Pruritus in Dermatology: Part 2—Diseases and Their Treatment

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"apellidos" => "Navarro-Triviño" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<elsevierMultimedia ident="fig0030"></elsevierMultimedia>" ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023002247?idApp=UINPBA000044" "url" => "/00017310/0000011400000007/v1_202307101051/S0001731023002247/v1_202307101051/es/main.assets" ] ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => " Pruritus in Dermatology: Part 2—Diseases and Their Treatment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T613" "paginaFinal" => "T626" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "F.J. Navarro-Triviño" "autores" => array:1 [ 0 => array:3 [ "nombre" => "F.J." "apellidos" => "Navarro-Triviño" "email" => array:1 [ 0 => "fntmed@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Eczema de Contacto e Inmunoalergia, Dermatología, Hospital Universitario San Cecilio, Granada, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prurito en dermatología. Enfermedades y su tratamiento. Parte 2" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 750 "Ancho" => 1333 "Tamanyo" => 85437 ] ] ] ] "textoCompleto" => "IntroductionBiologics that target cytokines of the Th2 pathway such as IL-4, IL-13, and IL-31, opioid agonists/antagonists, NK-1 receptor antagonists, GABAergic receptors such as pregabalin and gabapentin, JAK1 inhibitors such as upadacitinib, abrocitinib, and baricitinib, anti-IL-17 antibodies such as ixekizumab, phototherapy, and classic immunosuppressants such as cyclosporin, are among the therapeutic options currently available. This article will detail the recommended treatments according to the underlying disease.Atopic DermatitisPruritus is one of the diagnostic criteria for atopic dermatitis (AD). Between 87% and 100% of patients suffer from it.<a class="elsevierStyleCrossRef" href="#bib0575">1</a> It is mainly nonhistaminergic. Cytokines such as IL-4, IL-13, IL-31, and thymic stromal lymphopoietin (TSLP) are important pruritogenic mediators in AD.<a class="elsevierStyleCrossRef" href="#bib0580">2</a> Intracellular signaling is mainly via JAK1,<a class="elsevierStyleCrossRef" href="#bib0585">3</a> although the cannabinoid receptors CB1 and CB2, or opioid receptors KOR have also been identified. NK-1 antagonists improve pruritus without improving eczema. There is overexpression of PAR2<a class="elsevierStyleCrossRef" href="#bib0590">4</a> and TRPV3.<a class="elsevierStyleCrossRef" href="#bib0595">5</a> TRPV3 increases expression of SERPIN E1 (adipokines in keratinocytes), mainly in dry skin, induced by release of natriuretic polypeptide b (NPPB) in the nerve endings. Calcitonin gene related peptide (CGRP) and substance P (SP) are also overexpressed.Antimicrobial peptides participate in cutaneous neuropoiesis. Cathelicidin LL-37 increases expression of semaphorin A, and β-defensins inhibit production of growth factors such as NGF or artemin.<a class="elsevierStyleCrossRef" href="#bib0600">6</a> They also induce secretion of pruritogenic cytokines such as IL-4, IL-13, and IL-31. This neuroinflammatory environment—cutaneous hyperinnervation and disproportionate excitation of nerve endings—gives rise to sensitization to pruritus in patients with AD, marked by hyperactivity of the thalamus, prefrontal cortex, and cingulate cortex.<a class="elsevierStyleCrossRefs" href="#bib0605">7,8</a>It is a complex task to compare results on improvement in pruritus across the different trials of these new molecules for the treatment of AD. These treatments are detailed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Oral upadacitinib showed the best results in monotherapy and in combination with corticosteroids, and at 52 weeks. A study has been published of dupilumab with 4-year data, with an improvement in NRS≥4 with respect to baseline in 69% of patients,<a class="elsevierStyleCrossRef" href="#bib0615">9</a> and with tralokinumab at 3 years in 58% of patients (data not published). Lebrikizumab, which is not included as it is not available commercially, showed a ≥4-point reduction in NRS at 16 weeks in 70% of patients.<a class="elsevierStyleCrossRef" href="#bib0620">10</a> Treatment of pruritus in patients with AD is still considered an unmet need, where combination with NK-1R and GABAergic antagonists, and even opioid derivatives may break the itch-scratch cycle and achieve an NRS of 0–1.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Allergic Contact DermatitisThe chemokine, IFNγ inducible protein 10 (CXL10), has been linked with pruritus in allergic contact dermatitis.<a class="elsevierStyleCrossRef" href="#bib0625">11</a> IL-31 and TSLP also act as pruritogens. Overexpression of MrgprX2 has been detected. Allergens are able to induce different inflammatory responses.<a class="elsevierStyleCrossRef" href="#bib0630">12</a> Fragrances trigger the type 2 inflammatory pathway, whereas nickel and isothiazolinones induce the type 1 pathway. This raises the possibility of targeted therapy with molecules such as dupilumab, for example.Drug-Induced PruritusApproximately 5% of cases of pruritus are caused by drugs. This may be through pruritogenic metabolites, photodermatoses, liver toxicity, or xerosis. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists the main pruritus-inducing drugs.<a class="elsevierStyleCrossRef" href="#bib0635">13</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>UrticariaThis is primarily a histamine-mediated pruritus where mastocytes and basophils orchestrate the process. Recently, IL-4<a class="elsevierStyleCrossRef" href="#bib0640">14</a> and CGRP have been recognized as pruritogenic mediators in urticaria. New targets such as Mrgpr,<a class="elsevierStyleCrossRef" href="#bib0645">15</a> Bruton tyrosine kinase (BTK),<a class="elsevierStyleCrossRef" href="#bib0650">16</a> and spleen tyrosine kinase (SYK),<a class="elsevierStyleCrossRef" href="#bib0655">17</a> appear to be promising. Dupilumab has shown significant results for this condition,<a class="elsevierStyleCrossRef" href="#bib0660">18</a> as have biologic agents that target IL-5.<a class="elsevierStyleCrossRef" href="#bib0665">19</a>Lichen Simplex ChronicusIn this disease, expression of GRPR+ neurons and TRPV1 and PTRA1 is increased. A small fiber neuropathy caused by decreased expression of NGF has been considered.<a class="elsevierStyleCrossRef" href="#bib0670">20</a> Chronic scratching induces the release of pruritogens by keratinocytes following direct damage to the epidermal barrier. The inflammatory infiltrate is predominantly type 2. IL-31 is the cytokine responsible for the chronic status of pruritus. The recommended treatments are presented in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>PsoriasisBetween 60% and 90% of patients report pruritus.<a class="elsevierStyleCrossRef" href="#bib0675">21</a> There is overexpression of SP, TSLP, and IL-31,<a class="elsevierStyleCrossRef" href="#bib0680">22</a> while expression of KOR/dynorphin and NPY is reduced. CGRP participates in the induction of pruritus at the nerve endings. Dorsal root ganglion neurons express IL-17 receptors.<a class="elsevierStyleCrossRef" href="#bib0685">23</a> Up to 70% of patients treated with ixekizumab show a reduction in pruritus.<a class="elsevierStyleCrossRef" href="#bib0690">24</a> Bimekizumab achieved a pruritus score of 0 on the P-SIM scale in 32.2% of patients at Week 16 and in 60% of patients at Week 48.<a class="elsevierStyleCrossRef" href="#bib0695">25</a> IL-22 appears to activate GPRP+ neurons and enhance the pruritogenic signal. Those patients with refractory pruritus may obtain clinical benefit from NK-1 receptor antagonists or opioid derivatives.Mycosis Fungoides/Sezary SyndromeUp to 88% of patients with these conditions report pruritus,<a class="elsevierStyleCrossRef" href="#bib0700">26</a> which is considered a factor for worse prognosis. It is more frequent in variants such as the folliculotropic one,<a class="elsevierStyleCrossRef" href="#bib0705">27</a> and in advanced stages of the disease. IL-31 and SP are the main pruritogens. High levels of IL-4, IL-2, and IFNγ have been detected in Sezary syndrome.<a class="elsevierStyleCrossRef" href="#bib0710">28</a> A certain polarization toward Th2 has been reported, and this could explain the eosinophilia (factor for worse prognosis).<a class="elsevierStyleCrossRef" href="#bib0715">29</a> However, patients treated with dupilumab have shown a worsening of the disease.<a class="elsevierStyleCrossRef" href="#bib0720">30</a> Other mediators involved are PAR2 and GRPR+ neurons, while an MOR/KOR imbalance may also occur.<a class="elsevierStyleCrossRef" href="#bib0705">27</a> Aprepitant<a class="elsevierStyleCrossRef" href="#bib0725">31</a> has shown significant results in the reduction of pruritus (regimen 125-80-80mg/every 2 weeks). Mirtazapine, GABAergic agents, opioid agents, and thalidomide can be considered as additions to the base treatment.Pruritus in Keloid ScarsTranscriptomic techniques have demonstrated an inflammatory neurogenic microenvironment, with predominance of Th2 lymphocytes and mastocytes. NGF and SP are overexpressed, and IL4Rα, tryptase, and periostin levels are elevated.<a class="elsevierStyleCrossRef" href="#bib0730">32</a> Polarization of macrophages toward M2 enhances the type 2 inflammatory response, triggering secretion of TGF-β by fibroblasts, which in turn induce IL-31 release. Thermal sensitivity tests have shown an alteration in the C fibers. There is a decreased density of intraepidermal fibers. Both phototherapy<a class="elsevierStyleCrossRef" href="#bib0735">33</a> and dupilumab<a class="elsevierStyleCrossRef" href="#bib0740">34</a> significantly decrease pruritus. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the different treatments available.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Pruritus and Autoimmune DiseasesUp to 57% of patients with connective tissue diseases are affected by pruritus, as a result of pruritogen release or triggering/worsening by intake of drugs such as antimalarials or calcium antagonists.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">A.Dermatomyositis (DM): Up to 90% of patients with DM are affected by pruritus,<a class="elsevierStyleCrossRef" href="#bib0745">35</a> mainly in photoexposed areas. The severity of pruritus correlates with the severity of DM. There are no differences between the classic and amyopathic form. It appears as a premonitory form, during the disease, or as a paraneoplastic condition. IL-31 has been identified as a pruritogen.<a class="elsevierStyleCrossRef" href="#bib0750">36</a> Reduction in intraepidermal nerve fibers without any changes in peptidergic fibers points to a possible small fiber neuropathy.<a class="elsevierStyleCrossRef" href="#bib0755">37</a></li><li class="elsevierStyleListItem" id="lsti0010">B.Systemic sclerosis: Pruritus occurs in 62.3% of patients with this disease.<a class="elsevierStyleCrossRef" href="#bib0760">38</a> It shows neuropathic characteristics and presents mainly on the head, trunk, and arms. Patients with pruritus show greater skin, gastrointestinal, and/or pulmonary involvement. The chronic nature of pruritus is related to the presence of anti-centromere antibodies.<a class="elsevierStyleCrossRef" href="#bib0765">39</a> A regeneration of C fibers and an increase in the neuronal population occur.</li><li class="elsevierStyleListItem" id="lsti0015">C.Cutaneous lupus erythematosus: Of patients with this disease, 76.8% are affected by pruritus, which is of moderate or severe intensity in half of these.<a class="elsevierStyleCrossRef" href="#bib0770">40</a> The scalp is the most common site. A decrease in the number of small fibers and a decrease in intraepidermal nerve fibers have been detected.<a class="elsevierStyleCrossRef" href="#bib0775">41</a> Photosensitivity and use of antimalarial agents are trigger factors. These patients show high levels of IL-31.<a class="elsevierStyleCrossRef" href="#bib0780">42</a></li><li class="elsevierStyleListItem" id="lsti0020">D.Morphea: Between 46% and 52.2% of patients with morphea experience pruritus,<a class="elsevierStyleCrossRef" href="#bib0785">43</a> which is more prevalent in adults than in children. Improvement with phototherapy suggests a cytokine-mediated neurogenic inflammation.</li><li class="elsevierStyleListItem" id="lsti0025">E.Sjögren syndrome: Between 38.3% and 41.6% of patients with this syndrome also experience pruritus,<a class="elsevierStyleCrossRef" href="#bib0790">44</a> particularly with the primary form. It is the second most common skin manifestation after xerosis. It has been described as a small fiber neuropathy.<a class="elsevierStyleCrossRef" href="#bib0795">45</a> Paraneoplastic pruritus should be considered given the risk of lymphomas and thyroid cancer.<a class="elsevierStyleCrossRef" href="#bib0800">46</a></li></ul>The recommended treatments for pruritus in these patients are apremilast, gabapentin, pregabalin, naltrexone, and thalidomide as an addition to the base treatment. Oral and topical JAK inhibitors appear promising.Pruritus and Chronic Kidney DiseaseModerate to severe pruritus is present in 38.2% of patients on hemodialysis,<a class="elsevierStyleCrossRef" href="#bib0805">47</a> with mortality as high as 17%.<a class="elsevierStyleCrossRef" href="#bib0810">48</a> There are 4 theories to explain this type of pruritus<a class="elsevierStyleCrossRef" href="#bib0815">49</a>: toxin build-up, peripheral neuropathy, immune system dysregulation, and opioid imbalance. Recently, p-cresyl sulfate and indoxyl sulfate have been proposed as 2 uremic toxins that could be implicated in both pruritus and cardiovascular risk.<a class="elsevierStyleCrossRef" href="#bib0820">50</a><a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> shows the recommended treatments.<a class="elsevierStyleCrossRefs" href="#bib0825">51–53</a><elsevierMultimedia ident="fig0015"></elsevierMultimedia>Cholestatic PruritusThis pruritus presents at palmoplantar sites, although it can be generalized. Primary biliary cirrhosis or primary sclerosing cholangitis show elevated levels of autotaxin,<a class="elsevierStyleCrossRef" href="#bib0840">54</a> an enzyme that metabolizes lysophosphatidylcholine into lysophosphatidic acid able to activate TRPV4. Naltrexone has been shown to be effective in uremic pruritus.<a class="elsevierStyleCrossRef" href="#bib0845">55</a> The most important pruritogenic pathway is binding of bile acids to MrgprX4.<a class="elsevierStyleCrossRef" href="#bib0850">56</a> Rifampicin decreases the activity of autotaxin.<a class="elsevierStyleCrossRef" href="#bib0855">57</a><a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a> shows the recommended treatments.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Pruritus and PregnancyBetween 18% and 40% of pregnant women experience pruritus at some point during gestation.<a class="elsevierStyleCrossRef" href="#bib0860">58</a> Some of the most important types are summarized below.<a class="elsevierStyleCrossRef" href="#bib0865">59</a><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the different treatments available.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030">A.Atopic rash during pregnancy: This is the most frequent type. A history of AD is present in 20%. Type 2 inflammation predominates. Onset is usually during the second/third trimester. There are 2 main forms of presentation: eczematous form localized on the face, neck, presternal region, and flexural areas; and the prurigo type on extension surfaces and the trunk. There is a risk of infectious complications such as eczema herpeticum. There is no risk to the fetus.</li><li class="elsevierStyleListItem" id="lsti0035">B.Polymorphous rash during pregnancy: This is a self-limiting process with pruritic urticarial papules and plaques. Onset is usually during the third trimester or immediately postpartum. The eczematous lesions are located on the abdomen (over stretch marks if present) and the periumbilical region, without blistering. The rash may be confused with an initial state of pemphigoid gestationis. There is no risk to the fetus.</li><li class="elsevierStyleListItem" id="lsti0040">C.Pemphigoid gestationis: This is an uncommon self-limiting disease caused by IgG autoantibodies to the BP180 protein. Recurrence in successive pregnancies is 30–50%, with an early and severe onset. Polymorphic urticarial papules and plaques form on the periumbilical region, abdomen, and limbs. The mucosa may be involved. Biopsy with IFD shows linear deposition of IgG and C3 at the dermoepidermal junction. The antibodies can be detected by ELISA (specificity 94–98%; sensitivity 86–97%). This is considered a high-risk pregnancy. There is a risk to the fetus.</li><li class="elsevierStyleListItem" id="lsti0045">D.Intrahepatic cholestasis: This affects 0.3–5.6% of pregnant women. Bile salts are the main pruritogen. Onset occurs during the second/third trimester through activation of the MrgprX4 receptor. Measurement of bile acids in maternal blood is the key to diagnosis. If the concentration of bile acids in blood is >100mmol/L and 37 weeks of gestation have been completed, induction of pregnancy can be considered. There is a risk to the fetus.</li><li class="elsevierStyleListItem" id="lsti0050">E.Dermatoses that worsen during pregnancy: AD, psoriasis, dermatomyositis, urticaria, lichen planus, mastocytosis can all worsen during pregnancy.</li></ul><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Paraneoplastic PruritusPruritus that has an onset before or during the tumor process but that is not the result of either infiltration by tumor cells or treatment administered is denoted paraneoplastic pruritus.<a class="elsevierStyleCrossRef" href="#bib0870">60</a> It resolves after tumor remission and reappears if there is recurrence. Hematologic neoplastic and gastrointestinal disorders are the most frequent neoplasms where this occurs. In up to 5.9% of cases, pruritus is generalized. Thirty percent of patients with Hodgkin lymphoma, 40% with essential thrombocytosis, and 15–50% of those with non-Hodgkin lymphoma and polycythemia vera (with characteristic aquagenic pruritus,<a class="elsevierStyleCrossRef" href="#bib0875">61</a> more severe in carriers of the JAK2 V617F mutation), also have pruritus. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the different treatments available.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Chronic Prurigo (Nodularis)T lymphocytes, mastocytes, and eosinophils in histopathology studies confirm the type 2 inflammatory environment, where cytokines such as IL-4 and IL-31 appear to play an important role, as well as IL-17 and IL-22.<a class="elsevierStyleCrossRef" href="#bib0880">62</a> Overexpression of SP+ and CGRP+ peptidergic neurons has been detected. There is dermal hyperinnervation and a reduction in the density of epidermal nerve fibers as a result of an imbalance between neuronal growth factors and repulsion factors.<a class="elsevierStyleCrossRef" href="#bib0885">63</a> Although JAK inhibitors have not been included in <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>, a case report was recently published of good response to baricitinib.<a class="elsevierStyleCrossRef" href="#bib0890">64</a> Therapies that target IL-31 have been demonstrated to be effective.<a class="elsevierStyleCrossRef" href="#bib0895">65</a> Nemolizumab is a monoclonal antibody that binds to the IL-31α receptor.<a class="elsevierStyleCrossRef" href="#bib0900">66</a> AD and prurigo nodularis are the main therapeutic focus. The results of the phase 3 study for AD showed a decrease of 42.8% (in combination with topical corticosteroids) in the pruritus score at 16 weeks compared with baseline (in the placebo arm, the reduction was 20%).<a class="elsevierStyleCrossRef" href="#bib0905">67</a> The results of the phase 2 study of prurigo nodularis showed a decrease of 53% at Week 4 (compared with 20.2% in the placebo group).<a class="elsevierStyleCrossRef" href="#bib0910">68</a> Vixarelimab (KPL-716)<a class="elsevierStyleCrossRef" href="#bib0915">69</a> is a subcutaneously administered monoclonal antibody that binds to OSMRβ. A phase 2 study of prurigo nodularis is currently active (but not recruiting).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Pruritus and Bullous PemphigoidThis is characterized by predominance of a type 2 inflammatory environment, the intensity of which correlates with dermal periostin build-up and infiltrates of eosinophils, basophils, and Th2 lymphocytes. IL-4 and IL-31 act as pruritogens. Dupilumab has been shown to be effective in this type of dermatosis.<a class="elsevierStyleCrossRef" href="#bib0920">70</a>Anogenital PruritusThis type of pruritus can be a manifestation of either a local dermatosis or a systemic one.<a class="elsevierStyleCrossRef" href="#bib0925">71</a> The acute forms are more common in association with infections and contact dermatitis whereas the chronic ones are psychogenic, neoplastic, or chronic inflammatory dermatoses. Detailed medical history and targeted additional tests are key to ensure an appropriate therapeutic approach. The area requires special care with sitz baths, avoiding the use of toilet paper, drying of the area without intense friction, avoiding wet wipes and other disinfectants, short fingernails, avoiding coffee, chocolate, citric fruits, soft drinks and food rich in dairy products, and the use of zinc oxide 10–20% powders several times a day.Treatment of the underlying cause, application of topical corticosteroids, topical calcineurin inhibitors, antifungal agents, local anesthetics such as lidocaine, and even topical capsaicin 0.006% are some of the recommendations. The use of selective serotonin reuptake inhibitors (SSRIs) (sertraline, paroxetine, fluoxetine), amitriptyline, doxepin, mirtazapine, or injection of methylene blue 0.5–1% is reserved for refractory cases.<a class="elsevierStyleCrossRef" href="#bib0930">72</a> Physiotherapy targeting the pelvic flood may be a useful option for idiopathic female genital pruritus.Basic (General) Care of the Patient with Pruritus<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055">-Avoid smoking, alcohol, caffein and other stimulants, spices, and stress.</li><li class="elsevierStyleListItem" id="lsti0060">-Showering is better than taking a bath, with warm water and for 10min at most.</li><li class="elsevierStyleListItem" id="lsti0065">-Shower with detergent-free soap (Syndet), shower oils, or cleansing cream. Avoid the use of perfumed products and irritative substances such as sodium lauryl sulfate. Likewise, preferably use pH neutral soaps.</li><li class="elsevierStyleListItem" id="lsti0070">-Emollient creams or hypoallergenic salves, free of fragrances and preservatives with a high sensitization potential such as isothiazolinones. The ingredients may include soothing ingredients (see below).</li><li class="elsevierStyleListItem" id="lsti0075">-Soft and loose-fitting cotton clothing; avoid synthetic and tight-fitting materials.</li></ul>Treatments for Localized PruritusMenthol 1% lotion applied 3–4 times a day (acts via the TRPM8 pathway<a class="elsevierStyleCrossRef" href="#bib0935">73</a>). In patients over 2 years of age, the following options are available:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080">-Topical anesthetics: Application to localized not too extensive areas due to risk of systemic effects. It is necessary to take care with sensitization to these products.</li><li class="elsevierStyleListItem" id="lsti0085">-Polidocanol 2–10% is a nonionic surfactant used in sclerotherapy with moisturizing and anesthetic properties.</li><li class="elsevierStyleListItem" id="lsti0090">-Compounded formulation of lidocaine 2.5–5%+amitriptyline 5%+ketamine 5–10% o/w cream<a class="elsevierStyleCrossRef" href="#bib0940">74</a> for transdermal application. Apply 3 times/day, never to more than 30% of the body surface area.</li><li class="elsevierStyleListItem" id="lsti0095">-Pramoxine 1% lotion, cream, foam, gels. Apply 3–4 times a day.</li><li class="elsevierStyleListItem" id="lsti0100">-Lidocaine 2–5%. Apply 2–4 times a day. Take care with the possibility of methemoglobinemia if high doses of Emla® (lidocaine+procaine) are applied in young patients.</li></ul>Topical antihistamines are not recommended in children.<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0105">-Diphenhydramine 1–2%, 3–4 times a day. Photosensitivity and urticaria due to sensitization are the most common adverse effects.</li><li class="elsevierStyleListItem" id="lsti0110">-Doxepin 5% cream 4 times a day, with at least 3–4 hours between applications. Risk of contact dermatitis, anticholinergic effects of local sensation of burning/itching. Should not be applied to more than 10% of the body surface area.</li></ul>Topical anti-inflammatory agents and capsaicin:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0115">-Topical corticosteroids: These can be applied with wet bandages or injected (triamcinolone acetonide) in the case of thick lesions. High potency corticosteroids are associated with greater risk of stretch marks and suppression of the hypothalamic–pituitary–adrenal axis.</li><li class="elsevierStyleListItem" id="lsti0120">-Topical calcineurin inhibitors (TCI): Tacrolimus and pimecrolimus. Application twice a day. Pruritus or a local burning sensation may present during the first applications. This sensation can be reduced with the administration of acetylsalicylic acid 500mg, initially, and by avoiding alcohol consumption during treatment.</li><li class="elsevierStyleListItem" id="lsti0125">-Capsaicin 0.025% cream<a class="elsevierStyleCrossRef" href="#bib0945">75</a>: Repeated application (3–4 times a day, tolerance is improved by applying Emla® 30–60min earlier) induces TRPV1 activation with subsequent SP depletion, desensitizing the nerve fibers. It is indicated in neuropathic pruritus (notalgia paresthetica, brachioradial pruritus, postherpetic pruritus). It can also be used in aquagenic or uremic pruritus and prurigo nodularis.</li></ul>AntihistaminesThese are drugs that target the H1 receptor by competing with histamine. They are recommended as first-line treatment in most situations. Cetirizine and rupatadine inhibit PAF action,<a class="elsevierStyleCrossRef" href="#bib0950">76</a> cetirizine and desloratadine decrease IL-4 and IL-13 secretion,<a class="elsevierStyleCrossRef" href="#bib0955">77</a> fexofenadine inhibits tryptase release, and ebastine inhibits the Th2-lymphocyte mediated inflammatory pathway.<a class="elsevierStyleCrossRef" href="#bib0960">78</a>PhototherapyBoth narrow-band (NB) UVB (311mm) and UVA (340–400mm) are considered second-line treatments in many dermatoses with associated pruritus. UVA1 decreases levels of IL-4, IL-13, IL-17 and IL-23.<a class="elsevierStyleCrossRef" href="#bib0965">79</a> Repeated exposure to sub-erythematogenic doses both of UVA1 and NB-UVB decrease IL-31 concentration, whereas high doses have the opposite effect, in particular with UVB. A decrease has been demonstrated in degranulation of IgE-dependent mastocytes and a decrease in migration of Langerhans cells to the epidermis. Another finding is decreased expression of MOR and increased expression of dynorphin with phototherapy. Phototherapy plays a neuromodulatory role, decreasing release of NGF while increasing release of semaphorin A, giving rise to a decreased density of intraepithelial nerve fibers.<a class="elsevierStyleCrossRef" href="#bib0970">80</a> Excimer lamps also decrease the density of intraepithelial nerve fibers.Opioid DerivativesThe mu opioid receptor (MOR) antagonists and the kappa opioid receptor (KOR) agonists have been shown to be very useful given their role as central pruritus regulators. <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a><a class="elsevierStyleCrossRefs" href="#bib0975">81–89</a> shows detailed information on this useful antipruritic therapy.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>AntidepressantsResults have been published for uremic, cholestatic, or paraneoplastic pruritus. The peak of the effect is reached after 4–6 weeks. Side effects limit their use, particularly in the case of SSRIs and mirtazapine. These agents are less effective than pregabalin or gabapentin in neuropathic pruritus. The results of an analysis of 35 studies are shown in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>.<a class="elsevierStyleCrossRef" href="#bib1020">90</a><elsevierMultimedia ident="tbl0030"></elsevierMultimedia>Thalidomide/LenalidomideThere are more publications and information in the case of refractory prurigo nodularis.<a class="elsevierStyleCrossRef" href="#bib1025">91</a> The thalidomide dose is 50–300mg/day, with an average dose of 100mg/day, followed by NB-UVB phototherapy. It has a good profile in oncology patients and those with HIV. The main drawbacks are teratogenicity and neuropathy. Lenalidomide is an interesting option given its low cost and lower rate of neuropathy.Apremilast/Difamilast/RoflumilastApremilast is indicated for psoriasis, psoriatic arthritis, and Behçet disease. It has not shown significant results either in AD or pruritus of unknown origin.<a class="elsevierStyleCrossRef" href="#bib1030">92</a> Difamilast ointment is in development for AD.<a class="elsevierStyleCrossRef" href="#bib1035">93</a> Off-label use of oral roflumilast has been reported for nummular eczema<a class="elsevierStyleCrossRef" href="#bib1040">94</a> and hidradenitis suppurativa.<a class="elsevierStyleCrossRef" href="#bib1045">95</a> Roflumilast cream is in development for psoriasis.<a class="elsevierStyleCrossRef" href="#bib1050">96</a>AntineuralgicsThe gamma aminobutyric acid analogs, gabapentin and pregabalin, are recommended for neuropathic-type pruritus and brachioradial pruritus, cholestatic and uremic pruritus, and pruritus of unknown origin.<a class="elsevierStyleCrossRef" href="#bib1055">97</a> Release of SP or CGRP is decreased,<a class="elsevierStyleCrossRef" href="#bib1060">98</a> whereas the inhibitory capacity of GABA+ interneurons is increased. They bind to protein α2δ of the voltage-gated calcium channels. The gabapentin dose is 300mg/every 8h (maximum dose 3600mg/day) and the pregabalin dose is 75mg/day with increases up to 225mg/day according to tolerance (maximum dose 300mg/day). The dose should be tapered prior to withdrawal of the drug.Classic ImmunosuppressantsThese agents are widely used in dermatology as corticosteroid sparing agents<a class="elsevierStyleCrossRef" href="#bib1065">99</a> or in monotherapy. Physicians should be familiar with the particular characteristics of each of them<a class="elsevierStyleCrossRef" href="#bib1070">100</a>:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0130">A.Ciclosporin: According to the Summary of Product Characteristics, this is indicated for AD in patients aged 16 years and above at doses of 3–5mg/kg/day, spread over 2–3 doses. It inhibits lymphocyte, eosinophil, and mastocyte infiltrates, inhibits NK1-R and IL-31R expression, inhibits IL-31 secretion, and inhibits intraepidermal nerve fiber elongation.<a class="elsevierStyleCrossRef" href="#bib1075">101</a> Given its mechanism of action, neuroinflammatory pruritus is considered the type that shows best response. Up to 78% of patients treated with this drug show a reduction in pruritus.<a class="elsevierStyleCrossRef" href="#bib1080">102</a></li><li class="elsevierStyleListItem" id="lsti0135">B.Methotrexate: This drug is indicated according to the Summary of Product Characteristics for psoriasis. The mean dose used is 15mg/week. The anti-inflammatory infiltrate makes it a good choice for treatment of neuroinflammatory pruritus, even at low doses. Good outcomes have been achieved in cases of pruritus of unknown origin in elderly individuals<a class="elsevierStyleCrossRef" href="#bib1085">103</a> and in prurigo nodularis.<a class="elsevierStyleCrossRef" href="#bib1090">104</a></li><li class="elsevierStyleListItem" id="lsti0140">C.Azathioprine: This agent does not include any dermatologic indications in its Summary of Product Characteristics. It has been shown to significantly reduce itching in patients with intractable pruritus<a class="elsevierStyleCrossRef" href="#bib1095">105</a> and in primary biliary cirrhosis.</li><li class="elsevierStyleListItem" id="lsti0145">D.Mofetil mycophenolate: This is the prodrug of mycophenolic acid, which inhibits inosine-5-monophosphate dehydrogenase and decreases T and B lymphocyte proliferation; this may be useful in patients with neuroinflammatory pruritus as is the case in AD<a class="elsevierStyleCrossRef" href="#bib1100">106</a> and autoimmune diseases.</li></ul>NK-1 Receptor AntagonistsAprepitant<a class="elsevierStyleCrossRef" href="#bib1105">107</a> is the most widely used of these agents and has the most publications on its use. It is dispensed in a 3-tablet blister (125-80-80mg). The regimen is not defined, as there are publications of cycles of 3 tablets every 1 or 2 weeks and 80mg/day. The best responses have been observed for paraneoplastic pruritus<a class="elsevierStyleCrossRef" href="#bib1110">108</a> and pruritus induced by cancer treatments,<a class="elsevierStyleCrossRef" href="#bib1115">109</a> although these results are disputed. Serlopitant appears to be superior to aprepitant.<a class="elsevierStyleCrossRef" href="#bib1120">110</a> Doses of 5mg for prurigo nodularis have shown significant reductions in pruritus compared with placebo. The results of the EPIONE study with tradipitant in 2021 did not show significant results in AD,<a class="elsevierStyleCrossRef" href="#bib1125">111</a> and it is currently under development for gastrointestinal disorders.AntibioticsDoxycycline and minocycline: These agents exercise an antipruritic and neuroprotective effect through regulation of the microglial cell population in the intramedullary posterior horn.<a class="elsevierStyleCrossRef" href="#bib1130">112</a> Doxycycline inhibits PAR2 implicated in pruritus mediation.Erythromycin and azithromycin: These agents have been shown to be effective in pruritus associated with atypical forms of pityriasis rosada<a class="elsevierStyleCrossRef" href="#bib1135">113</a> and chronic lichenoid pityriasis.<a class="elsevierStyleCrossRef" href="#bib1140">114</a> The immunomodulatory effect is attributed to interaction with phospholipids and with the transcription factors AP-1, NFκB, and proinflammatory cytokines.Antagonists of the Serotonin 5HT-3 ReceptorOndansetron, tropisetron, and granisetron have been used in isolated cases with contradictory results. These agents are not recommended except in pruritus associated with chronic renal disease and cholestatic pruritus.ConclusionsBreaking the itch-scratch cycle can be a therapeutic challenge. The key to success is choosing the appropriate treatment for each patient.Conflicts of InterestThe author declares that he has no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:38 [ 0 => array:3 [ "identificador" => "xres1927793" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1927792" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1661951" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1927794" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0015" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1661950" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Atopic Dermatitis" ] 7 => array:2 [ "identificador" => "sec0015" "titulo" => "Allergic Contact Dermatitis" ] 8 => array:2 [ "identificador" => "sec0020" "titulo" => "Drug-Induced Pruritus" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Urticaria" ] 10 => array:2 [ "identificador" => "sec0030" "titulo" => "Lichen Simplex Chronicus" ] 11 => array:2 [ "identificador" => "sec0035" "titulo" => "Psoriasis" ] 12 => array:2 [ "identificador" => "sec0040" "titulo" => "Mycosis Fungoides/Sezary Syndrome" ] 13 => array:2 [ "identificador" => "sec0045" "titulo" => "Pruritus in Keloid Scars" ] 14 => array:2 [ "identificador" => "sec0050" "titulo" => "Pruritus and Autoimmune Diseases" ] 15 => array:2 [ "identificador" => "sec0055" "titulo" => "Pruritus and Chronic Kidney Disease" ] 16 => array:2 [ "identificador" => "sec0060" "titulo" => "Cholestatic Pruritus" ] 17 => array:2 [ "identificador" => "sec0065" "titulo" => "Pruritus and Pregnancy" ] 18 => array:2 [ "identificador" => "sec0070" "titulo" => "Paraneoplastic Pruritus" ] 19 => array:2 [ "identificador" => "sec0075" "titulo" => "Chronic Prurigo (Nodularis)" ] 20 => array:2 [ "identificador" => "sec0080" "titulo" => "Pruritus and Bullous Pemphigoid" ] 21 => array:2 [ "identificador" => "sec0085" "titulo" => "Anogenital Pruritus" ] 22 => array:2 [ "identificador" => "sec0090" "titulo" => "Basic (General) Care of the Patient with Pruritus" ] 23 => array:2 [ "identificador" => "sec0095" "titulo" => "Treatments for Localized Pruritus" ] 24 => array:2 [ "identificador" => "sec0100" "titulo" => "Antihistamines" ] 25 => array:2 [ "identificador" => "sec0105" "titulo" => "Phototherapy" ] 26 => array:2 [ "identificador" => "sec0110" "titulo" => "Opioid Derivatives" ] 27 => array:2 [ "identificador" => "sec0115" "titulo" => "Antidepressants" ] 28 => array:2 [ "identificador" => "sec0120" "titulo" => "Thalidomide/Lenalidomide" ] 29 => array:2 [ "identificador" => "sec0125" "titulo" => "Apremilast/Difamilast/Roflumilast" ] 30 => array:2 [ "identificador" => "sec0130" "titulo" => "Antineuralgics" ] 31 => array:2 [ "identificador" => "sec0135" "titulo" => "Classic Immunosuppressants" ] 32 => array:2 [ "identificador" => "sec0140" "titulo" => "NK-1 Receptor Antagonists" ] 33 => array:2 [ "identificador" => "sec0145" "titulo" => "Antibiotics" ] 34 => array:2 [ "identificador" => "sec0150" "titulo" => "Antagonists of the Serotonin 5HT-3 Receptor" ] 35 => array:2 [ "identificador" => "sec0155" "titulo" => "Conclusions" ] 36 => array:2 [ "identificador" => "sec0160" "titulo" => "Conflicts of Interest" ] 37 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-01-09" "fechaAceptado" => "2023-03-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1661951" "palabras" => array:11 [ 0 => "Pruritus" 1 => "Atopic dermatitis" 2 => "Contact dermatitis" 3 => "Psoriasis" 4 => "Chronic prurigo" 5 => "Lichen simplex chronicus" 6 => "Urticaria" 7 => "Mycosis fungoides" 8 => "Cholestatic pruritus" 9 => "Pregnancy" 10 => "Uremic pruritus" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1661950" "palabras" => array:11 [ 0 => "Prurito" 1 => "Dermatitis atópica" 2 => "Dermatitis de contacto" 3 => "Psoriasis" 4 => "Prurigo crónico" 5 => "Liquen simple crónico" 6 => "Urticaria" 7 => "Micosis fungoides" 8 => "Prurito colestásico" 9 => "Embarazo" 10 => "Prurito urémico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Pruritus is the main symptom of many dermatologic and systemic diseases. Atopic dermatitis, psoriasis, contact dermatitis, urticaria, lichen simplex chronicus, mycosis fungoides, scars, autoimmune diseases, kidney or liver diseases among others are all associated with itch that may require different approaches to management. Although antihistamines seem to be the first line of therapy, in reality their role is limited to urticaria and drug-induced reactions. In fact, the pathophysiologic mechanisms of each of the conditions covered in this review will differ. Recent years have seen the emergence of new drugs whose efficacy and safety profiles are very attractive for the management of pruritus in clinical practice. Clearly, we are at a critical moment in dermatology, in which we have the chance to be more ambitious in our goals when treating patients with pruritus." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El prurito es el síntoma principal en múltiples enfermedades dermatológicas y sistémicas. La dermatitis atópica, la psoriasis, la dermatitis de contacto, la urticaria, el liquen simple crónico, la micosis fungoides, las cicatrices, las enfermedades autoinmunes, la enfermedad renal o hepática crónica, entre otras, asocian prurito que puede requerir un manejo terapéutico distinto. Aunque los antihistamínicos parecen ser la primera línea de tratamiento, en realidad su papel queda limitado a la urticaria y reacciones por fármacos, ya que los mecanismos fisiopatológicos de cada una de las entidades tratadas a lo largo de este manuscrito serán distintas. En estos últimos años han aparecido nuevas moléculas para el tratamiento del prurito, con perfiles de eficacia y seguridad muy atractivos para su uso en práctica clínica. Sin duda, es un momento crucial para el desarrollo de la dermatología en el campo del prurito, y una oportunidad para ser más exigentes con los objetivos a alcanzar en estos pacientes." ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1917 "Ancho" => 3338 "Tamanyo" => 730375 ] ] "descripcion" => array:1 [ "en" => "Decrease of ≥4 points on NRS according to publications of the different clinical trials of new treatments for AD." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1142 "Ancho" => 2343 "Tamanyo" => 192884 ] ] "descripcion" => array:1 [ "en" => "Recommended treatment for lichen simplex chronicus." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 657 "Ancho" => 1407 "Tamanyo" => 87750 ] ] "descripcion" => array:1 [ "en" => "Treatments recommended for pruritus in kidney disease. a Although expert panels continue to recommend ondansetron as second-line therapy, the most recent Cochrane review concludes that it is not an effective drug in the treatment of uremic pruritus.<a class="elsevierStyleCrossRef" href="#bib0835">53</a>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1132 "Ancho" => 2345 "Tamanyo" => 171083 ] ] "descripcion" => array:1 [ "en" => "Recommended treatment for cholestatic pruritus." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1177 "Ancho" => 2343 "Tamanyo" => 184813 ] ] "descripcion" => array:1 [ "en" => "Treatment recommended for prurigo. a Triamcinolone acetonide 10mg/mL (dilution recommended) for isolated lesions. b Mainly SSRIs and mirtazapine. c Currently in development." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antibiotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Penicillin G, amoxicillin, ampicillin, cefotaxime, ceftazidime, erythromycin, ciprofloxacin, vancomycin, clindamycin, tetracyclines, minocycline, metronidazole, rifampicin, trimethoprim/sulfamethoxazole, antifungals, antimalarials (chloroquine, hydroxychloroquine, mepacrine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amlodipine, diltiazem, verapamil, clonidine, methyldopa, amiodarone, captopril, enalapril, lisinopril, candesartan, irbesartan, flecainide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lipid-lowering agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clofibrate, fenofibrate, fluvastatin, pravastatin, lovastatin, simvastatin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose-lowering agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metformin, gliclazide, tolbutamide, glimepiride \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiuricosuric agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alopurinol, colchicine, probenecid, tiopronin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neuroleptics, antiepileptics, and antipsychotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amitriptyline, citalopram, fluoxetine, paroxetine, sertraline, carbamazepine, phenytoin, topiramate, chlorpromazine, phenothiazine, risperidone, haloperidol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Opioids and analgesics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Morphine, codeine, fentanyl, oxycodone, tramadol, aspirin, celecoxib, diclofenac, ketoprofen, naproxen, piroxicam \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immunosuppressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methotrexate, ciclosporin, cyclophosphamide, mofetil mycophenolate, tacrolimus, thalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hormones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Danazol, estrogens, progesterone, testosterone, corticosteroids, tamoxifen, clomiphene, oral contraceptives \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cancer treatments and biologic agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5-Fluoracyl, chlorambucil, gemcitabine, nilotinib, vemurafenib, paclitaxel, tamoxifen, temsirolimus, ipilimumab, cetuximab, erlotinib, rituximab, panitumumab, gefitinib, adalimumab, infliximab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Miscellaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enoxaparin, hydroxyethyl starch (HES), iodine contrast, pentoxifylline, ticlopidine, interleukin-2, antithyroid agents \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210409.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main Drugs Associated with Triggering Pruritus." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: IL-13, interleukin-13; IL-31, interleukin-31; TRPV1, transient receptor potential vanilloid 1." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Effect/therapeutic target \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intralesional corticosteroids (triamcinolone acetonide) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vasoconstriction, increased collagenase activity, antimitotic activity of fibroblasts, reduced expression of IL-31 and IL-13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tissue necrosis by freezing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Botulinic A toxin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inhibits connective tissue growth factor expression, reduces the levels of substance P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Agonist of central inhibitory interneurons, decreases neuropathic type pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperbaric oxygen therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduces inflammatory environment, vasodilator, decreases expression of TRPV1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pulsed laser light \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inhibits expression of connective tissue growth factor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5-Fluoracyl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inhibits cell proliferation and induces fibroblast apoptosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Silicone patches \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increases epidermal hydration (decreases fibroblast activity) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210405.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatments Available for Pruritus in Keloid Scars." ] ] 7 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dermatosis gestational \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First line \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Second line \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Third line \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atopic rash during pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EmollientsMedium-potency topical corticosteroid(Oral corticosteroids<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> if outbreak is severe) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cetirizine, loratadine, levocetirizine (FDA category B)Phototherapy<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ciclosporin (FDA Category C)Azathioprine (FDA Category C)Dupilumab (real-world evidence)<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polymorphous rash during pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EmollientsCetirizine, loratadine, desloratadineMedium-potency topical corticosteroid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral corticosteroid (prednisone) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pemphigoid gestationis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EmollientsHigh-potency topical corticosteroidCetirizine, loratadine, desloratadine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral corticosteroid (prednisone)Topical tacrolimus (not more than 5g per day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Azathioprine (FDA Category C)Dapsone (FDA Category C)<a class="elsevierStyleCrossRef" href="#tblfn0020">d</a>Intravenous immunoglobulinsOmalizumab (FDA Category B)Dupilumab<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a>Rituximab<a class="elsevierStyleCrossRef" href="#tblfn0025">e</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intrahepatic cholestasis during pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral ursodesoxycholic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rifampicin (FDA Category C) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210406.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Oral glucocorticoids 0.5–2mg/kg/day with particular care during the first trimester. Use in uncontrolled pruritus for a short period of time. It has been associated with cleft palate and low weight at birth. It increases the risk of gestational diabetes, preeclampsia, and premature birth with premature breaking of water." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "During treatment with phototherapy, it is necessary to administer folic acid supplement 0.8mg/day because this treatment reduces levels of folic acid in blood. Facial photoprotection is recommended to avoid melasma." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "The current experience is from real clinical practice, and although data show that dupilumab is a safe drug during gestation, experts recommend an individual benefit-risk assessment in each patient." ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "Concomitant administration of vitamin E 800U/day and vitamin C 1g/day reduces the risk of methemoglobinemia during treatment with dapsone." ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "e" "nota" => "It is recommended to administer rituximab 12 months before attempting to become pregnant. This recommendation may be difficult to achieve in clinical practice." ] ] ] "descripcion" => array:1 [ "en" => "Recommended Treatments for Different Gestational Dermatoses that Present with Pruritus." ] ] 8 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: DRESS, drug reaction with eosinophilia and systemic symptoms; MAOI, monoaminooxidase inhibitors." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Posology \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main precautions \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hydroxyzine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–50mg/night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liver failure, kidney failure, risk of convulsions, risk of arrhythmia and QT prolongation. Avoid alcohol intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paroxetine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–20mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid with linezolid and MAOI (serotoninergic syndrome), interaction with tamoxifen, glaucoma, unstable epilepsy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluvoxamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–100mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid with linezolid and MAOI (serotoninergic syndrome), glaucoma, unstable epilepsy, QT prolongation, interaction with clopidogrel \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sertraline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–50mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid with pimozide and with MAOI, unstable epilepsy, risk of bleeding, liver failure, kidney failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–100mg/night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recent myocardial infarction, avoid with MAOI, severe liver failure, cardiac arrhythmia, hypotension, urinary retention, hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doxepin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50mg/night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Constipation, xerostomia, urinary retention, arrythmias, glaucoma, cholestatic jaundice, hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mirtazapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15mg/night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid with MAOI, risk of agranulocytosis, unstable epilepsy, liver failure, kidney failure, elevated blood glucose, cardiac diseases, severe toxicoderma, avoid alcohol intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">300–600mg/8h (maximum 3600mg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DRESS, acute pancreatitis, unstable epilepsy, control if concomitant opioid administration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pregabalin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75–600mg/day (divided in 3 doses) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe toxicoderma, dizziness, somnolence, blurred vision, congestive heart failure, control if concomitant opioid administration. Avoid alcohol consumption \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thalidomide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–200mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral neuropathy, teratogenic, thromboembolic phenomena, hypothyroidism, severe toxicodermas, herpes zoster, progressive multifocal leukoencephalopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naloxone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8–2mg/intravenous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physical dependence, dizziness, hypotension, hypertension, tachycardia, pulmonary edema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naltrexone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–100mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liver failure, physical dependence, avoid using with thalidomide, hydroxyzine, doxepin, amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aprepitant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">125-80-80mg in cycles of 1 or 2 weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pharmacological interactions (CYP3A4), hiccups, constipation, headache \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210408.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommended Treatment for Paraneoplastic Pruritus. Bear in Mind Precautions to Ensure Appropriate Selection of the Patient Profile." ] ] 9 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mechanism of action \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Route of administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication in the summary of product characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Off-label use in pruritus \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KOR agonist</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Difelikefalin<a class="elsevierStyleCrossRef" href="#bib0760">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uremic pruritus in patients on hemodialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nalfurafin<a class="elsevierStyleCrossRef" href="#bib0765">39</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholestatic pruritus and pruritus of hepatic origin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nalmefene<a class="elsevierStyleCrossRef" href="#bib0770">40</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tablets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction in alcohol consumption \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholestatic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KOR agonist/MOR antagonist</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nalbufin<a class="elsevierStyleCrossRef" href="#bib0775">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uremic pruritus in patients on hemodialysisPrurigo nodularis<a class="elsevierStyleCrossRef" href="#bib0795">45</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Butorfanol<a class="elsevierStyleCrossRef" href="#bib0780">42</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral/intranasal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intractable pruritusCholestatic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MOR antagonist/KOR antagonist</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naloxone<a class="elsevierStyleCrossRef" href="#bib0785">43</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reversal of side effects of opioids or intoxication \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drug-induced pruritusBrachioradial pruritusCholestatic pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naltrexone<a class="elsevierStyleCrossRef" href="#bib0790">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tablets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alcoholism, opiate dependence treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drug-induced pruritusCholestaticHaley-HaleyLichen planopilarisPsoriasisDarier \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210410.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Opioids, Mechanism of Action, and Uses in Pruritus." ] ] 10 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations; AD, atopic dermatitis; SSRI, selective serotonin reuptake inhibitors; HIV, human immunodeficiency virus." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Uses in clinical practice \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluoxetine (SSRI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aquagenic pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluvoxamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25–100mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic pruritus in patients with AD, lymphomas, paraneoplastic pruritus, psychiatric patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paroxetine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pruritus of unknown origin, psychogenic pruritus, paraneoplastic pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sertraline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75–100mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uremic pruritus and cholestatic pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brachioradial pruritus, lichen amyloidosis, uremic pruritus, notalgia paresthetica, post-stroke pruritus, mycosis fungoides, HIV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doxepin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–20mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uremic pruritus, pruritus of unknown origin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nortriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vulvar pruritus of unknown origin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mirtazapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15–30mg/day (at night) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychogenic pruritus, pruritus of unknown origin, paraneoplastic pruritus, nighttime pruritus of unknown origin \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3210407.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main Antidepressants Used for Treatment of Pruritus." ] ] 11 => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 750 "Ancho" => 1333 "Tamanyo" => 85437 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:114 [ 0 => array:3 [ "identificador" => "bib0575" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Itch characteristics in atopic dermatitis: results of a web-based questionnaire" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2008.08941.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2009" "volumen" => "160" "paginaInicial" => "642" "paginaFinal" => "644" "link" => array:1 [ …1] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0580" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mediators of chronic pruritus in atopic dermatitis: getting the itch out?" 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Pruritus in Dermatology: Part 2—Diseases and Their Treatment

Prurito en dermatología. Enfermedades y su tratamiento. Parte 2

F.J. Navarro-Triviño

Unidad de Eczema de Contacto e Inmunoalergia, Dermatología, Hospital Universitario San Cecilio, Granada, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Biologics that target cytokines of the Th2 pathway such as IL-4&#44; IL-13&#44; and IL-31&#44; opioid agonists&#47;antagonists&#44; NK-1 receptor antagonists&#44; GABAergic receptors such as pregabalin and gabapentin&#44; JAK1 inhibitors such as upadacitinib&#44; abrocitinib&#44; and baricitinib&#44; anti-IL-17 antibodies such as ixekizumab&#44; phototherapy&#44; and classic immunosuppressants such as cyclosporin&#44; are among the therapeutic options currently available&#46; This article will detail the recommended treatments according to the underlying disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Atopic Dermatitis</span><p id="par0010" class="elsevierStylePara elsevierViewall">Pruritus is one of the diagnostic criteria for atopic dermatitis &#40;AD&#41;&#46; Between 87&#37; and 100&#37; of patients suffer from it&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">1</span></a> It is mainly nonhistaminergic&#46; Cytokines such as IL-4&#44; IL-13&#44; IL-31&#44; and thymic stromal lymphopoietin &#40;TSLP&#41; are important pruritogenic mediators in AD&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">2</span></a> Intracellular signaling is mainly via JAK1&#44;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">3</span></a> although the cannabinoid receptors CB1 and CB2&#44; or opioid receptors KOR have also been identified&#46; NK-1 antagonists improve pruritus without improving eczema&#46; There is overexpression of PAR2<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">4</span></a> and TRPV3&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">5</span></a> TRPV3 increases expression of SERPIN E1 &#40;adipokines in keratinocytes&#41;&#44; mainly in dry skin&#44; induced by release of natriuretic polypeptide b &#40;NPPB&#41; in the nerve endings&#46; Calcitonin gene related peptide &#40;CGRP&#41; and substance P &#40;SP&#41; are also overexpressed&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Antimicrobial peptides participate in cutaneous neuropoiesis&#46; Cathelicidin LL-37 increases expression of semaphorin A&#44; and &#946;-defensins inhibit production of growth factors such as NGF or artemin&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">6</span></a> They also induce secretion of pruritogenic cytokines such as IL-4&#44; IL-13&#44; and IL-31&#46; This neuroinflammatory environment&#8212;cutaneous hyperinnervation and disproportionate excitation of nerve endings&#8212;gives rise to sensitization to pruritus in patients with AD&#44; marked by hyperactivity of the thalamus&#44; prefrontal cortex&#44; and cingulate cortex&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It is a complex task to compare results on improvement in pruritus across the different trials of these new molecules for the treatment of AD&#46; These treatments are detailed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; Oral upadacitinib showed the best results in monotherapy and in combination with corticosteroids&#44; and at 52 weeks&#46; A study has been published of dupilumab with 4-year data&#44; with an improvement in NRS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4 with respect to baseline in 69&#37; of patients&#44;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">9</span></a> and with tralokinumab at 3 years in 58&#37; of patients &#40;data not published&#41;&#46; Lebrikizumab&#44; which is not included as it is not available commercially&#44; showed a &#8805;4-point reduction in NRS at 16 weeks in 70&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">10</span></a> Treatment of pruritus in patients with AD is still considered an unmet need&#44; where combination with NK-1R and GABAergic antagonists&#44; and even opioid derivatives may break the itch-scratch cycle and achieve an NRS of 0&#8211;1&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Allergic Contact Dermatitis</span><p id="par0025" class="elsevierStylePara elsevierViewall">The chemokine&#44; IFN&#947; inducible protein 10 &#40;CXL10&#41;&#44; has been linked with pruritus in allergic contact dermatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">11</span></a> IL-31 and TSLP also act as pruritogens&#46; Overexpression of MrgprX2 has been detected&#46; Allergens are able to induce different inflammatory responses&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">12</span></a> Fragrances trigger the type 2 inflammatory pathway&#44; whereas nickel and isothiazolinones induce the type 1 pathway&#46; This raises the possibility of targeted therapy with molecules such as dupilumab&#44; for example&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Drug-Induced Pruritus</span><p id="par0030" class="elsevierStylePara elsevierViewall">Approximately 5&#37; of cases of pruritus are caused by drugs&#46; This may be through pruritogenic metabolites&#44; photodermatoses&#44; liver toxicity&#44; or xerosis&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists the main pruritus-inducing drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Urticaria</span><p id="par0035" class="elsevierStylePara elsevierViewall">This is primarily a histamine-mediated pruritus where mastocytes and basophils orchestrate the process&#46; Recently&#44; IL-4<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">14</span></a> and CGRP have been recognized as pruritogenic mediators in urticaria&#46; New targets such as Mrgpr&#44;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">15</span></a> Bruton tyrosine kinase &#40;BTK&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">16</span></a> and spleen tyrosine kinase &#40;SYK&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">17</span></a> appear to be promising&#46; Dupilumab has shown significant results for this condition&#44;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">18</span></a> as have biologic agents that target IL-5&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Lichen Simplex Chronicus</span><p id="par0040" class="elsevierStylePara elsevierViewall">In this disease&#44; expression of GRPR<span class="elsevierStyleSup">&#43;</span> neurons and TRPV1 and PTRA1 is increased&#46; A small fiber neuropathy caused by decreased expression of NGF has been considered&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">20</span></a> Chronic scratching induces the release of pruritogens by keratinocytes following direct damage to the epidermal barrier&#46; The inflammatory infiltrate is predominantly type 2&#46; IL-31 is the cytokine responsible for the chronic status of pruritus&#46; The recommended treatments are presented in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Psoriasis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Between 60&#37; and 90&#37; of patients report pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">21</span></a> There is overexpression of SP&#44; TSLP&#44; and IL-31&#44;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">22</span></a> while expression of KOR&#47;dynorphin and NPY is reduced&#46; CGRP participates in the induction of pruritus at the nerve endings&#46; Dorsal root ganglion neurons express IL-17 receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">23</span></a> Up to 70&#37; of patients treated with ixekizumab show a reduction in pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">24</span></a> Bimekizumab achieved a pruritus score of 0 on the P-SIM scale in 32&#46;2&#37; of patients at Week 16 and in 60&#37; of patients at Week 48&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">25</span></a> IL-22 appears to activate GPRP<span class="elsevierStyleSup">&#43;</span> neurons and enhance the pruritogenic signal&#46; Those patients with refractory pruritus may obtain clinical benefit from NK-1 receptor antagonists or opioid derivatives&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Mycosis Fungoides&#47;Sezary Syndrome</span><p id="par0050" class="elsevierStylePara elsevierViewall">Up to 88&#37; of patients with these conditions report pruritus&#44;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">26</span></a> which is considered a factor for worse prognosis&#46; It is more frequent in variants such as the folliculotropic one&#44;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">27</span></a> and in advanced stages of the disease&#46; IL-31 and SP are the main pruritogens&#46; High levels of IL-4&#44; IL-2&#44; and IFN&#947; have been detected in Sezary syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">28</span></a> A certain polarization toward Th2 has been reported&#44; and this could explain the eosinophilia &#40;factor for worse prognosis&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">29</span></a> However&#44; patients treated with dupilumab have shown a worsening of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">30</span></a> Other mediators involved are PAR2 and GRPR<span class="elsevierStyleSup">&#43;</span> neurons&#44; while an MOR&#47;KOR imbalance may also occur&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">27</span></a> Aprepitant<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">31</span></a> has shown significant results in the reduction of pruritus &#40;regimen 125-80-80<span class="elsevierStyleHsp" style=""></span>mg&#47;every 2 weeks&#41;&#46; Mirtazapine&#44; GABAergic agents&#44; opioid agents&#44; and thalidomide can be considered as additions to the base treatment&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pruritus in Keloid Scars</span><p id="par0055" class="elsevierStylePara elsevierViewall">Transcriptomic techniques have demonstrated an inflammatory neurogenic microenvironment&#44; with predominance of Th2 lymphocytes and mastocytes&#46; NGF and SP are overexpressed&#44; and IL4R&#945;&#44; tryptase&#44; and periostin levels are elevated&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">32</span></a> Polarization of macrophages toward M2 enhances the type 2 inflammatory response&#44; triggering secretion of TGF-&#946; by fibroblasts&#44; which in turn induce IL-31 release&#46; Thermal sensitivity tests have shown an alteration in the C fibers&#46; There is a decreased density of intraepidermal fibers&#46; Both phototherapy<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">33</span></a> and dupilumab<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">34</span></a> significantly decrease pruritus&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the different treatments available&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pruritus and Autoimmune Diseases</span><p id="par0060" class="elsevierStylePara elsevierViewall">Up to 57&#37; of patients with connective tissue diseases are affected by pruritus&#44; as a result of pruritogen release or triggering&#47;worsening by intake of drugs such as antimalarials or calcium antagonists&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">A&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Dermatomyositis &#40;DM&#41;&#58;</span> Up to 90&#37; of patients with DM are affected by pruritus&#44;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">35</span></a> mainly in photoexposed areas&#46; The severity of pruritus correlates with the severity of DM&#46; There are no differences between the classic and amyopathic form&#46; It appears as a premonitory form&#44; during the disease&#44; or as a paraneoplastic condition&#46; IL-31 has been identified as a pruritogen&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">36</span></a> Reduction in intraepidermal nerve fibers without any changes in peptidergic fibers points to a possible small fiber neuropathy&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">B&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Systemic sclerosis&#58;</span> Pruritus occurs in 62&#46;3&#37; of patients with this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">38</span></a> It shows neuropathic characteristics and presents mainly on the head&#44; trunk&#44; and arms&#46; Patients with pruritus show greater skin&#44; gastrointestinal&#44; and&#47;or pulmonary involvement&#46; The chronic nature of pruritus is related to the presence of anti-centromere antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">39</span></a> A regeneration of C fibers and an increase in the neuronal population occur&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">C&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cutaneous lupus erythematosus&#58;</span> Of patients with this disease&#44; 76&#46;8&#37; are affected by pruritus&#44; which is of moderate or severe intensity in half of these&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">40</span></a> The scalp is the most common site&#46; A decrease in the number of small fibers and a decrease in intraepidermal nerve fibers have been detected&#46;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">41</span></a> Photosensitivity and use of antimalarial agents are trigger factors&#46; These patients show high levels of IL-31&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">42</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">D&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Morphea&#58;</span> Between 46&#37; and 52&#46;2&#37; of patients with morphea experience pruritus&#44;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">43</span></a> which is more prevalent in adults than in children&#46; Improvement with phototherapy suggests a cytokine-mediated neurogenic inflammation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">E&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Sj&#246;gren syndrome&#58;</span> Between 38&#46;3&#37; and 41&#46;6&#37; of patients with this syndrome also experience pruritus&#44;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">44</span></a> particularly with the primary form&#46; It is the second most common skin manifestation after xerosis&#46; It has been described as a small fiber neuropathy&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">45</span></a> Paraneoplastic pruritus should be considered given the risk of lymphomas and thyroid cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">46</span></a></p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">The recommended treatments for pruritus in these patients are apremilast&#44; gabapentin&#44; pregabalin&#44; naltrexone&#44; and thalidomide as an addition to the base treatment&#46; Oral and topical JAK inhibitors appear promising&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Pruritus and Chronic Kidney Disease</span><p id="par0095" class="elsevierStylePara elsevierViewall">Moderate to severe pruritus is present in 38&#46;2&#37; of patients on hemodialysis&#44;<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">47</span></a> with mortality as high as 17&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">48</span></a> There are 4 theories to explain this type of pruritus<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">49</span></a>&#58; toxin build-up&#44; peripheral neuropathy&#44; immune system dysregulation&#44; and opioid imbalance&#46; Recently&#44; p-cresyl sulfate and indoxyl sulfate have been proposed as 2 uremic toxins that could be implicated in both pruritus and cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">50</span></a><a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows the recommended treatments&#46;<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">51&#8211;53</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Cholestatic Pruritus</span><p id="par0100" class="elsevierStylePara elsevierViewall">This pruritus presents at palmoplantar sites&#44; although it can be generalized&#46; Primary biliary cirrhosis or primary sclerosing cholangitis show elevated levels of autotaxin&#44;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">54</span></a> an enzyme that metabolizes lysophosphatidylcholine into lysophosphatidic acid able to activate TRPV4&#46; Naltrexone has been shown to be effective in uremic pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">55</span></a> The most important pruritogenic pathway is binding of bile acids to MrgprX4&#46;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">56</span></a> Rifampicin decreases the activity of autotaxin&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">57</span></a><a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows the recommended treatments&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Pruritus and Pregnancy</span><p id="par0105" class="elsevierStylePara elsevierViewall">Between 18&#37; and 40&#37; of pregnant women experience pruritus at some point during gestation&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">58</span></a> Some of the most important types are summarized below&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">59</span></a><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the different treatments available&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">A&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Atopic rash during pregnancy&#58;</span> This is the most frequent type&#46; A history of AD is present in 20&#37;&#46; Type 2 inflammation predominates&#46; Onset is usually during the second&#47;third trimester&#46; There are 2 main forms of presentation&#58; eczematous form localized on the face&#44; neck&#44; presternal region&#44; and flexural areas&#59; and the prurigo type on extension surfaces and the trunk&#46; There is a risk of infectious complications such as eczema herpeticum&#46; There is no risk to the fetus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">B&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Polymorphous rash during pregnancy&#58;</span> This is a self-limiting process with pruritic urticarial papules and plaques&#46; Onset is usually during the third trimester or immediately postpartum&#46; The eczematous lesions are located on the abdomen &#40;over stretch marks if present&#41; and the periumbilical region&#44; without blistering&#46; The rash may be confused with an initial state of pemphigoid gestationis&#46; There is no risk to the fetus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">C&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pemphigoid gestationis&#58;</span> This is an uncommon self-limiting disease caused by IgG autoantibodies to the BP180 protein&#46; Recurrence in successive pregnancies is 30&#8211;50&#37;&#44; with an early and severe onset&#46; Polymorphic urticarial papules and plaques form on the periumbilical region&#44; abdomen&#44; and limbs&#46; The mucosa may be involved&#46; Biopsy with IFD shows linear deposition of IgG and C3 at the dermoepidermal junction&#46; The antibodies can be detected by ELISA &#40;specificity 94&#8211;98&#37;&#59; sensitivity 86&#8211;97&#37;&#41;&#46; This is considered a high-risk pregnancy&#46; There is a risk to the fetus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">D&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Intrahepatic cholestasis&#58;</span> This affects 0&#46;3&#8211;5&#46;6&#37; of pregnant women&#46; Bile salts are the main pruritogen&#46; Onset occurs during the second&#47;third trimester through activation of the MrgprX4 receptor&#46; Measurement of bile acids in maternal blood is the key to diagnosis&#46; If the concentration of bile acids in blood is &#62;100<span class="elsevierStyleHsp" style=""></span>mmol&#47;L and 37 weeks of gestation have been completed&#44; induction of pregnancy can be considered&#46; There is a risk to the fetus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">E&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Dermatoses that worsen during pregnancy&#58;</span> AD&#44; psoriasis&#44; dermatomyositis&#44; urticaria&#44; lichen planus&#44; mastocytosis can all worsen during pregnancy&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Paraneoplastic Pruritus</span><p id="par0135" class="elsevierStylePara elsevierViewall">Pruritus that has an onset before or during the tumor process but that is not the result of either infiltration by tumor cells or treatment administered is denoted paraneoplastic pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">60</span></a> It resolves after tumor remission and reappears if there is recurrence&#46; Hematologic neoplastic and gastrointestinal disorders are the most frequent neoplasms where this occurs&#46; In up to 5&#46;9&#37; of cases&#44; pruritus is generalized&#46; Thirty percent of patients with Hodgkin lymphoma&#44; 40&#37; with essential thrombocytosis&#44; and 15&#8211;50&#37; of those with non-Hodgkin lymphoma and polycythemia vera &#40;with characteristic aquagenic pruritus&#44;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">61</span></a> more severe in carriers of the JAK2 V617F mutation&#41;&#44; also have pruritus&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the different treatments available&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Chronic Prurigo &#40;Nodularis&#41;</span><p id="par0140" class="elsevierStylePara elsevierViewall">T lymphocytes&#44; mastocytes&#44; and eosinophils in histopathology studies confirm the type 2 inflammatory environment&#44; where cytokines such as IL-4 and IL-31 appear to play an important role&#44; as well as IL-17 and IL-22&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">62</span></a> Overexpression of SP<span class="elsevierStyleSup">&#43;</span> and CGRP<span class="elsevierStyleSup">&#43;</span> peptidergic neurons has been detected&#46; There is dermal hyperinnervation and a reduction in the density of epidermal nerve fibers as a result of an imbalance between neuronal growth factors and repulsion factors&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">63</span></a> Although JAK inhibitors have not been included in <a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#44; a case report was recently published of good response to baricitinib&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">64</span></a> Therapies that target IL-31 have been demonstrated to be effective&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">65</span></a> Nemolizumab is a monoclonal antibody that binds to the IL-31&#945; receptor&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">66</span></a> AD and prurigo nodularis are the main therapeutic focus&#46; The results of the phase 3 study for AD showed a decrease of 42&#46;8&#37; &#40;in combination with topical corticosteroids&#41; in the pruritus score at 16 weeks compared with baseline &#40;in the placebo arm&#44; the reduction was 20&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">67</span></a> The results of the phase 2 study of prurigo nodularis showed a decrease of 53&#37; at Week 4 &#40;compared with 20&#46;2&#37; in the placebo group&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">68</span></a> Vixarelimab &#40;KPL-716&#41;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">69</span></a> is a subcutaneously administered monoclonal antibody that binds to OSMR&#946;&#46; A phase 2 study of prurigo nodularis is currently active &#40;but not recruiting&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Pruritus and Bullous Pemphigoid</span><p id="par0145" class="elsevierStylePara elsevierViewall">This is characterized by predominance of a type 2 inflammatory environment&#44; the intensity of which correlates with dermal periostin build-up and infiltrates of eosinophils&#44; basophils&#44; and Th2 lymphocytes&#46; IL-4 and IL-31 act as pruritogens&#46; Dupilumab has been shown to be effective in this type of dermatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">70</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Anogenital Pruritus</span><p id="par0150" class="elsevierStylePara elsevierViewall">This type of pruritus can be a manifestation of either a local dermatosis or a systemic one&#46;<a class="elsevierStyleCrossRef" href="#bib0925"><span class="elsevierStyleSup">71</span></a> The acute forms are more common in association with infections and contact dermatitis whereas the chronic ones are psychogenic&#44; neoplastic&#44; or chronic inflammatory dermatoses&#46; Detailed medical history and targeted additional tests are key to ensure an appropriate therapeutic approach&#46; The area requires special care with sitz baths&#44; avoiding the use of toilet paper&#44; drying of the area without intense friction&#44; avoiding wet wipes and other disinfectants&#44; short fingernails&#44; avoiding coffee&#44; chocolate&#44; citric fruits&#44; soft drinks and food rich in dairy products&#44; and the use of zinc oxide 10&#8211;20&#37; powders several times a day&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Treatment of the underlying cause&#44; application of topical corticosteroids&#44; topical calcineurin inhibitors&#44; antifungal agents&#44; local anesthetics such as lidocaine&#44; and even topical capsaicin 0&#46;006&#37; are some of the recommendations&#46; The use of selective serotonin reuptake inhibitors &#40;SSRIs&#41; &#40;sertraline&#44; paroxetine&#44; fluoxetine&#41;&#44; amitriptyline&#44; doxepin&#44; mirtazapine&#44; or injection of methylene blue 0&#46;5&#8211;1&#37; is reserved for refractory cases&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">72</span></a> Physiotherapy targeting the pelvic flood may be a useful option for idiopathic female genital pruritus&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Basic &#40;General&#41; Care of the Patient with Pruritus</span><p id="par0160" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">Avoid smoking&#44; alcohol&#44; caffein and other stimulants&#44; spices&#44; and stress&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">Showering is better than taking a bath&#44; with warm water and for 10<span class="elsevierStyleHsp" style=""></span>min at most&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">Shower with detergent-free soap &#40;Syndet&#41;&#44; shower oils&#44; or cleansing cream&#46; Avoid the use of perfumed products and irritative substances such as sodium lauryl sulfate&#46; Likewise&#44; preferably use pH neutral soaps&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">Emollient creams or hypoallergenic salves&#44; free of fragrances and preservatives with a high sensitization potential such as isothiazolinones&#46; The ingredients may include soothing ingredients &#40;see below&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">Soft and loose-fitting cotton clothing&#59; avoid synthetic and tight-fitting materials&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Treatments for Localized Pruritus</span><p id="par0190" class="elsevierStylePara elsevierViewall">Menthol 1&#37; lotion applied 3&#8211;4 times a day &#40;acts via the TRPM8 pathway<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">73</span></a>&#41;&#46; In patients over 2 years of age&#44; the following options are available&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">Topical anesthetics&#58; Application to localized not too extensive areas due to risk of systemic effects&#46; It is necessary to take care with sensitization to these products&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Polidocanol 2&#8211;10&#37; is a nonionic surfactant used in sclerotherapy with moisturizing and anesthetic properties&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Compounded formulation of lidocaine 2&#46;5&#8211;5&#37;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>amitriptyline 5&#37;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ketamine 5&#8211;10&#37; o&#47;w cream<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">74</span></a> for transdermal application&#46; Apply 3 times&#47;day&#44; never to more than 30&#37; of the body surface area&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">Pramoxine 1&#37; lotion&#44; cream&#44; foam&#44; gels&#46; Apply 3&#8211;4 times a day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">Lidocaine 2&#8211;5&#37;&#46; Apply 2&#8211;4 times a day&#46; Take care with the possibility of methemoglobinemia if high doses of Emla&#174; &#40;lidocaine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>procaine&#41; are applied in young patients&#46;</p></li></ul></p><p id="par0220" class="elsevierStylePara elsevierViewall">Topical antihistamines are not recommended in children&#46;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Diphenhydramine 1&#8211;2&#37;&#44; 3&#8211;4 times a day&#46; Photosensitivity and urticaria due to sensitization are the most common adverse effects&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Doxepin 5&#37; cream 4 times a day&#44; with at least 3&#8211;4 hours between applications&#46; Risk of contact dermatitis&#44; anticholinergic effects of local sensation of burning&#47;itching&#46; Should not be applied to more than 10&#37; of the body surface area&#46;</p></li></ul></p><p id="par0235" class="elsevierStylePara elsevierViewall">Topical anti-inflammatory agents and capsaicin&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">Topical corticosteroids&#58; These can be applied with wet bandages or injected &#40;triamcinolone acetonide&#41; in the case of thick lesions&#46; High potency corticosteroids are associated with greater risk of stretch marks and suppression of the hypothalamic&#8211;pituitary&#8211;adrenal axis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">Topical calcineurin inhibitors &#40;TCI&#41;&#58; Tacrolimus and pimecrolimus&#46; Application twice a day&#46; Pruritus or a local burning sensation may present during the first applications&#46; This sensation can be reduced with the administration of acetylsalicylic acid 500<span class="elsevierStyleHsp" style=""></span>mg&#44; initially&#44; and by avoiding alcohol consumption during treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">-</span><p id="par0250" class="elsevierStylePara elsevierViewall">Capsaicin 0&#46;025&#37; cream<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">75</span></a>&#58; Repeated application &#40;3&#8211;4 times a day&#44; tolerance is improved by applying Emla&#174; 30&#8211;60<span class="elsevierStyleHsp" style=""></span>min earlier&#41; induces TRPV1 activation with subsequent SP depletion&#44; desensitizing the nerve fibers&#46; It is indicated in neuropathic pruritus &#40;notalgia paresthetica&#44; brachioradial pruritus&#44; postherpetic pruritus&#41;&#46; It can also be used in aquagenic or uremic pruritus and prurigo nodularis&#46;</p></li></ul></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Antihistamines</span><p id="par0255" class="elsevierStylePara elsevierViewall">These are drugs that target the H1 receptor by competing with histamine&#46; They are recommended as first-line treatment in most situations&#46; Cetirizine and rupatadine inhibit PAF action&#44;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">76</span></a> cetirizine and desloratadine decrease IL-4 and IL-13 secretion&#44;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">77</span></a> fexofenadine inhibits tryptase release&#44; and ebastine inhibits the Th2-lymphocyte mediated inflammatory pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">78</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Phototherapy</span><p id="par0260" class="elsevierStylePara elsevierViewall">Both narrow-band &#40;NB&#41; UVB &#40;311<span class="elsevierStyleHsp" style=""></span>mm&#41; and UVA &#40;340&#8211;400<span class="elsevierStyleHsp" style=""></span>mm&#41; are considered second-line treatments in many dermatoses with associated pruritus&#46; UVA1 decreases levels of IL-4&#44; IL-13&#44; IL-17 and IL-23&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">79</span></a> Repeated exposure to sub-erythematogenic doses both of UVA1 and NB-UVB decrease IL-31 concentration&#44; whereas high doses have the opposite effect&#44; in particular with UVB&#46; A decrease has been demonstrated in degranulation of IgE-dependent mastocytes and a decrease in migration of Langerhans cells to the epidermis&#46; Another finding is decreased expression of MOR and increased expression of dynorphin with phototherapy&#46; Phototherapy plays a neuromodulatory role&#44; decreasing release of NGF while increasing release of semaphorin A&#44; giving rise to a decreased density of intraepithelial nerve fibers&#46;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">80</span></a> Excimer lamps also decrease the density of intraepithelial nerve fibers&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Opioid Derivatives</span><p id="par0265" class="elsevierStylePara elsevierViewall">The mu opioid receptor &#40;MOR&#41; antagonists and the kappa opioid receptor &#40;KOR&#41; agonists have been shown to be very useful given their role as central pruritus regulators&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a><a class="elsevierStyleCrossRefs" href="#bib0975"><span class="elsevierStyleSup">81&#8211;89</span></a> shows detailed information on this useful antipruritic therapy&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Antidepressants</span><p id="par0270" class="elsevierStylePara elsevierViewall">Results have been published for uremic&#44; cholestatic&#44; or paraneoplastic pruritus&#46; The peak of the effect is reached after 4&#8211;6 weeks&#46; Side effects limit their use&#44; particularly in the case of SSRIs and mirtazapine&#46; These agents are less effective than pregabalin or gabapentin in neuropathic pruritus&#46; The results of an analysis of 35 studies are shown in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">90</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Thalidomide&#47;Lenalidomide</span><p id="par0275" class="elsevierStylePara elsevierViewall">There are more publications and information in the case of refractory prurigo nodularis&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">91</span></a> The thalidomide dose is 50&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; with an average dose of 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; followed by NB-UVB phototherapy&#46; It has a good profile in oncology patients and those with HIV&#46; The main drawbacks are teratogenicity and neuropathy&#46; Lenalidomide is an interesting option given its low cost and lower rate of neuropathy&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Apremilast&#47;Difamilast&#47;Roflumilast</span><p id="par0280" class="elsevierStylePara elsevierViewall">Apremilast is indicated for psoriasis&#44; psoriatic arthritis&#44; and Beh&#231;et disease&#46; It has not shown significant results either in AD or pruritus of unknown origin&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">92</span></a> Difamilast ointment is in development for AD&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">93</span></a> Off-label use of oral roflumilast has been reported for nummular eczema<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">94</span></a> and hidradenitis suppurativa&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">95</span></a> Roflumilast cream is in development for psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">96</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Antineuralgics</span><p id="par0285" class="elsevierStylePara elsevierViewall">The gamma aminobutyric acid analogs&#44; gabapentin and pregabalin&#44; are recommended for neuropathic-type pruritus and brachioradial pruritus&#44; cholestatic and uremic pruritus&#44; and pruritus of unknown origin&#46;<a class="elsevierStyleCrossRef" href="#bib1055"><span class="elsevierStyleSup">97</span></a> Release of SP or CGRP is decreased&#44;<a class="elsevierStyleCrossRef" href="#bib1060"><span class="elsevierStyleSup">98</span></a> whereas the inhibitory capacity of GABA<span class="elsevierStyleSup">&#43;</span> interneurons is increased&#46; They bind to protein &#945;2&#948; of the voltage-gated calcium channels&#46; The gabapentin dose is 300<span class="elsevierStyleHsp" style=""></span>mg&#47;every 8<span class="elsevierStyleHsp" style=""></span>h &#40;maximum dose 3600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; and the pregabalin dose is 75<span class="elsevierStyleHsp" style=""></span>mg&#47;day with increases up to 225<span class="elsevierStyleHsp" style=""></span>mg&#47;day according to tolerance &#40;maximum dose 300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; The dose should be tapered prior to withdrawal of the drug&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Classic Immunosuppressants</span><p id="par0290" class="elsevierStylePara elsevierViewall">These agents are widely used in dermatology as corticosteroid sparing agents<a class="elsevierStyleCrossRef" href="#bib1065"><span class="elsevierStyleSup">99</span></a> or in monotherapy&#46; Physicians should be familiar with the particular characteristics of each of them<a class="elsevierStyleCrossRef" href="#bib1070"><span class="elsevierStyleSup">100</span></a>&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">A&#46;</span><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Ciclosporin&#58;</span> According to the Summary of Product Characteristics&#44; this is indicated for AD in patients aged 16 years and above at doses of 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#44; spread over 2&#8211;3 doses&#46; It inhibits lymphocyte&#44; eosinophil&#44; and mastocyte infiltrates&#44; inhibits NK1-R and IL-31R expression&#44; inhibits IL-31 secretion&#44; and inhibits intraepidermal nerve fiber elongation&#46;<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">101</span></a> Given its mechanism of action&#44; neuroinflammatory pruritus is considered the type that shows best response&#46; Up to 78&#37; of patients treated with this drug show a reduction in pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">102</span></a></p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">B&#46;</span><p id="par0300" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Methotrexate&#58;</span> This drug is indicated according to the Summary of Product Characteristics for psoriasis&#46; The mean dose used is 15<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#46; The anti-inflammatory infiltrate makes it a good choice for treatment of neuroinflammatory pruritus&#44; even at low doses&#46; Good outcomes have been achieved in cases of pruritus of unknown origin in elderly individuals<a class="elsevierStyleCrossRef" href="#bib1085"><span class="elsevierStyleSup">103</span></a> and in prurigo nodularis&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">104</span></a></p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">C&#46;</span><p id="par0305" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Azathioprine&#58;</span> This agent does not include any dermatologic indications in its Summary of Product Characteristics&#46; It has been shown to significantly reduce itching in patients with intractable pruritus<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">105</span></a> and in primary biliary cirrhosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">D&#46;</span><p id="par0310" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Mofetil mycophenolate&#58;</span> This is the prodrug of mycophenolic acid&#44; which inhibits inosine-5-monophosphate dehydrogenase and decreases T and B lymphocyte proliferation&#59; this may be useful in patients with neuroinflammatory pruritus as is the case in AD<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">106</span></a> and autoimmune diseases&#46;</p></li></ul></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">NK-1 Receptor Antagonists</span><p id="par0315" class="elsevierStylePara elsevierViewall">Aprepitant<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">107</span></a> is the most widely used of these agents and has the most publications on its use&#46; It is dispensed in a 3-tablet blister &#40;125-80-80<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; The regimen is not defined&#44; as there are publications of cycles of 3 tablets every 1 or 2 weeks and 80<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; The best responses have been observed for paraneoplastic pruritus<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">108</span></a> and pruritus induced by cancer treatments&#44;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">109</span></a> although these results are disputed&#46; Serlopitant appears to be superior to aprepitant&#46;<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">110</span></a> Doses of 5<span class="elsevierStyleHsp" style=""></span>mg for prurigo nodularis have shown significant reductions in pruritus compared with placebo&#46; The results of the EPIONE study with tradipitant in 2021 did not show significant results in AD&#44;<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">111</span></a> and it is currently under development for gastrointestinal disorders&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Antibiotics</span><p id="par0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Doxycycline and minocycline&#58;</span> These agents exercise an antipruritic and neuroprotective effect through regulation of the microglial cell population in the intramedullary posterior horn&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">112</span></a> Doxycycline inhibits PAR2 implicated in pruritus mediation&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Erythromycin and azithromycin&#58;</span> These agents have been shown to be effective in pruritus associated with atypical forms of pityriasis rosada<a class="elsevierStyleCrossRef" href="#bib1135"><span class="elsevierStyleSup">113</span></a> and chronic lichenoid pityriasis&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">114</span></a> The immunomodulatory effect is attributed to interaction with phospholipids and with the transcription factors AP-1&#44; NF&#954;B&#44; and proinflammatory cytokines&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Antagonists of the Serotonin 5HT-3 Receptor</span><p id="par0330" class="elsevierStylePara elsevierViewall">Ondansetron&#44; tropisetron&#44; and granisetron have been used in isolated cases with contradictory results&#46; These agents are not recommended except in pruritus associated with chronic renal disease and cholestatic pruritus&#46;</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conclusions</span><p id="par0335" class="elsevierStylePara elsevierViewall">Breaking the itch-scratch cycle can be a therapeutic challenge&#46; The key to success is choosing the appropriate treatment for each patient&#46;</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conflicts of Interest</span><p id="par0340" class="elsevierStylePara elsevierViewall">The author declares that he has no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Atopic Dermatitis"
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          "titulo" => "Urticaria"
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          "identificador" => "sec0030"
          "titulo" => "Lichen Simplex Chronicus"
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          "titulo" => "Mycosis Fungoides&#47;Sezary Syndrome"
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          "titulo" => "Anogenital Pruritus"
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          "titulo" => "Thalidomide&#47;Lenalidomide"
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          "titulo" => "Apremilast&#47;Difamilast&#47;Roflumilast"
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          "titulo" => "Antineuralgics"
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          "titulo" => "Classic Immunosuppressants"
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          "titulo" => "NK-1 Receptor Antagonists"
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          "titulo" => "Antibiotics"
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    "fechaAceptado" => "2023-03-16"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1661951"
          "palabras" => array:11 [
            0 => "Pruritus"
            1 => "Atopic dermatitis"
            2 => "Contact dermatitis"
            3 => "Psoriasis"
            4 => "Chronic prurigo"
            5 => "Lichen simplex chronicus"
            6 => "Urticaria"
            7 => "Mycosis fungoides"
            8 => "Cholestatic pruritus"
            9 => "Pregnancy"
            10 => "Uremic pruritus"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1661950"
          "palabras" => array:11 [
            0 => "Prurito"
            1 => "Dermatitis at&#243;pica"
            2 => "Dermatitis de contacto"
            3 => "Psoriasis"
            4 => "Prurigo cr&#243;nico"
            5 => "Liquen simple cr&#243;nico"
            6 => "Urticaria"
            7 => "Micosis fungoides"
            8 => "Prurito colest&#225;sico"
            9 => "Embarazo"
            10 => "Prurito ur&#233;mico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pruritus is the main symptom of many dermatologic and systemic diseases&#46; Atopic dermatitis&#44; psoriasis&#44; contact dermatitis&#44; urticaria&#44; lichen simplex chronicus&#44; mycosis fungoides&#44; scars&#44; autoimmune diseases&#44; kidney or liver diseases among others are all associated with itch that may require different approaches to management&#46; Although antihistamines seem to be the first line of therapy&#44; in reality their role is limited to urticaria and drug-induced reactions&#46; In fact&#44; the pathophysiologic mechanisms of each of the conditions covered in this review will differ&#46; Recent years have seen the emergence of new drugs whose efficacy and safety profiles are very attractive for the management of pruritus in clinical practice&#46; Clearly&#44; we are at a critical moment in dermatology&#44; in which we have the chance to be more ambitious in our goals when treating patients with pruritus&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El prurito es el s&#237;ntoma principal en m&#250;ltiples enfermedades dermatol&#243;gicas y sist&#233;micas&#46; La dermatitis at&#243;pica&#44; la psoriasis&#44; la dermatitis de contacto&#44; la urticaria&#44; el liquen simple cr&#243;nico&#44; la micosis fungoides&#44; las cicatrices&#44; las enfermedades autoinmunes&#44; la enfermedad renal o hep&#225;tica cr&#243;nica&#44; entre otras&#44; asocian prurito que puede requerir un manejo terap&#233;utico distinto&#46; Aunque los antihistam&#237;nicos parecen ser la primera l&#237;nea de tratamiento&#44; en realidad su papel queda limitado a la urticaria y reacciones por f&#225;rmacos&#44; ya que los mecanismos fisiopatol&#243;gicos de cada una de las entidades tratadas a lo largo de este manuscrito ser&#225;n distintas&#46; En estos &#250;ltimos a&#241;os han aparecido nuevas mol&#233;culas para el tratamiento del prurito&#44; con perfiles de eficacia y seguridad muy atractivos para su uso en pr&#225;ctica cl&#237;nica&#46; Sin duda&#44; es un momento crucial para el desarrollo de la dermatolog&#237;a en el campo del prurito&#44; y una oportunidad para ser m&#225;s exigentes con los objetivos a alcanzar en estos pacientes&#46;</p></span>"
      ]
    ]
    "multimedia" => array:12 [
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        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1917
            "Ancho" => 3338
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Decrease of &#8805;4 points on NRS according to publications of the different clinical trials of new treatments for AD&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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            "Tamanyo" => 192884
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Recommended treatment for lichen simplex chronicus&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 657
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            "Tamanyo" => 87750
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Treatments recommended for pruritus in kidney disease&#46; <span class="elsevierStyleSup">a</span> Although expert panels continue to recommend ondansetron as second-line therapy&#44; the most recent Cochrane review concludes that it is not an effective drug in the treatment of uremic pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">53</span></a></p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1132
            "Ancho" => 2345
            "Tamanyo" => 171083
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Recommended treatment for cholestatic pruritus&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1177
            "Ancho" => 2343
            "Tamanyo" => 184813
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Treatment recommended for prurigo&#46; <span class="elsevierStyleSup">a</span> Triamcinolone acetonide 10<span class="elsevierStyleHsp" style=""></span>mg&#47;mL &#40;dilution recommended&#41; for isolated lesions&#46; <span class="elsevierStyleSup">b</span> Mainly SSRIs and mirtazapine&#46; <span class="elsevierStyleSup">c</span> Currently in development&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antibiotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Penicillin G&#44; amoxicillin&#44; ampicillin&#44; cefotaxime&#44; ceftazidime&#44; erythromycin&#44; ciprofloxacin&#44; vancomycin&#44; clindamycin&#44; tetracyclines&#44; minocycline&#44; metronidazole&#44; rifampicin&#44; trimethoprim&#47;sulfamethoxazole&#44; antifungals&#44; antimalarials &#40;chloroquine&#44; hydroxychloroquine&#44; mepacrine&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiovascular agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amlodipine&#44; diltiazem&#44; verapamil&#44; clonidine&#44; methyldopa&#44; amiodarone&#44; captopril&#44; enalapril&#44; lisinopril&#44; candesartan&#44; irbesartan&#44; flecainide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipid-lowering agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clofibrate&#44; fenofibrate&#44; fluvastatin&#44; pravastatin&#44; lovastatin&#44; simvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucose-lowering agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metformin&#44; gliclazide&#44; tolbutamide&#44; glimepiride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiuricosuric agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alopurinol&#44; colchicine&#44; probenecid&#44; tiopronin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuroleptics&#44; antiepileptics&#44; and antipsychotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amitriptyline&#44; citalopram&#44; fluoxetine&#44; paroxetine&#44; sertraline&#44; carbamazepine&#44; phenytoin&#44; topiramate&#44; chlorpromazine&#44; phenothiazine&#44; risperidone&#44; haloperidol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Opioids and analgesics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morphine&#44; codeine&#44; fentanyl&#44; oxycodone&#44; tramadol&#44; aspirin&#44; celecoxib&#44; diclofenac&#44; ketoprofen&#44; naproxen&#44; piroxicam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunosuppressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methotrexate&#44; ciclosporin&#44; cyclophosphamide&#44; mofetil mycophenolate&#44; tacrolimus&#44; thalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hormones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danazol&#44; estrogens&#44; progesterone&#44; testosterone&#44; corticosteroids&#44; tamoxifen&#44; clomiphene&#44; oral contraceptives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cancer treatments and biologic agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5-Fluoracyl&#44; chlorambucil&#44; gemcitabine&#44; nilotinib&#44; vemurafenib&#44; paclitaxel&#44; tamoxifen&#44; temsirolimus&#44; ipilimumab&#44; cetuximab&#44; erlotinib&#44; rituximab&#44; panitumumab&#44; gefitinib&#44; adalimumab&#44; infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Miscellaneous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enoxaparin&#44; hydroxyethyl starch &#40;HES&#41;&#44; iodine contrast&#44; pentoxifylline&#44; ticlopidine&#44; interleukin-2&#44; antithyroid agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
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            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Main Drugs Associated with Triggering Pruritus&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
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          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; IL-13&#44; interleukin-13&#59; IL-31&#44; interleukin-31&#59; TRPV1&#44; transient receptor potential vanilloid 1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Effect&#47;therapeutic target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intralesional corticosteroids &#40;triamcinolone acetonide&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vasoconstriction&#44; increased collagenase activity&#44; antimitotic activity of fibroblasts&#44; reduced expression of IL-31 and IL-13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cryotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tissue necrosis by freezing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Botulinic A toxin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibits connective tissue growth factor expression&#44; reduces the levels of substance P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonist of central inhibitory interneurons&#44; decreases neuropathic type pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyperbaric oxygen therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduces inflammatory environment&#44; vasodilator&#44; decreases expression of TRPV1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pulsed laser light&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibits expression of connective tissue growth factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5-Fluoracyl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibits cell proliferation and induces fibroblast apoptosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Silicone patches&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increases epidermal hydration &#40;decreases fibroblast activity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3210405.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Treatments Available for Pruritus in Keloid Scars&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dermatosis gestational&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Second line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Third line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atopic rash during pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EmollientsMedium-potency topical corticosteroid&#40;Oral corticosteroids<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> if outbreak is severe&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cetirizine&#44; loratadine&#44; levocetirizine &#40;FDA category B&#41;Phototherapy<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ciclosporin &#40;FDA Category C&#41;Azathioprine &#40;FDA Category C&#41;Dupilumab &#40;real-world evidence&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polymorphous rash during pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EmollientsCetirizine&#44; loratadine&#44; desloratadineMedium-potency topical corticosteroid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral corticosteroid &#40;prednisone&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pemphigoid gestationis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EmollientsHigh-potency topical corticosteroidCetirizine&#44; loratadine&#44; desloratadine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral corticosteroid &#40;prednisone&#41;Topical tacrolimus &#40;not more than 5<span class="elsevierStyleHsp" style=""></span>g per day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azathioprine &#40;FDA Category C&#41;Dapsone &#40;FDA Category C&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>Intravenous immunoglobulinsOmalizumab &#40;FDA Category B&#41;Dupilumab<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>Rituximab<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intrahepatic cholestasis during pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral ursodesoxycholic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rifampicin &#40;FDA Category C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3210406.png"
              ]
            ]
          ]
          "notaPie" => array:5 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Oral glucocorticoids 0&#46;5&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day with particular care during the first trimester&#46; Use in uncontrolled pruritus for a short period of time&#46; It has been associated with cleft palate and low weight at birth&#46; It increases the risk of gestational diabetes&#44; preeclampsia&#44; and premature birth with premature breaking of water&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">During treatment with phototherapy&#44; it is necessary to administer folic acid supplement 0&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;day because this treatment reduces levels of folic acid in blood&#46; Facial photoprotection is recommended to avoid melasma&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The current experience is from real clinical practice&#44; and although data show that dupilumab is a safe drug during gestation&#44; experts recommend an individual benefit-risk assessment in each patient&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Concomitant administration of vitamin E 800<span class="elsevierStyleHsp" style=""></span>U&#47;day and vitamin C 1<span class="elsevierStyleHsp" style=""></span>g&#47;day reduces the risk of methemoglobinemia during treatment with dapsone&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">It is recommended to administer rituximab 12 months before attempting to become pregnant&#46; This recommendation may be difficult to achieve in clinical practice&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Recommended Treatments for Different Gestational Dermatoses that Present with Pruritus&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; DRESS&#44; drug reaction with eosinophilia and systemic symptoms&#59; MAOI&#44; monoaminooxidase inhibitors&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Posology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main precautions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hydroxyzine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;night&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liver failure&#44; kidney failure&#44; risk of convulsions&#44; risk of arrhythmia and QT prolongation&#46; Avoid alcohol intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paroxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid with linezolid and MAOI &#40;serotoninergic syndrome&#41;&#44; interaction with tamoxifen&#44; glaucoma&#44; unstable epilepsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluvoxamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8211;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid with linezolid and MAOI &#40;serotoninergic syndrome&#41;&#44; glaucoma&#44; unstable epilepsy&#44; QT prolongation&#44; interaction with clopidogrel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sertraline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid with pimozide and with MAOI&#44; unstable epilepsy&#44; risk of bleeding&#44; liver failure&#44; kidney failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amitriptyline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8211;100<span class="elsevierStyleHsp" style=""></span>mg&#47;night&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recent myocardial infarction&#44; avoid with MAOI&#44; severe liver failure&#44; cardiac arrhythmia&#44; hypotension&#44; urinary retention&#44; hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doxepin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50<span class="elsevierStyleHsp" style=""></span>mg&#47;night&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Constipation&#44; xerostomia&#44; urinary retention&#44; arrythmias&#44; glaucoma&#44; cholestatic jaundice&#44; hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mirtazapine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15<span class="elsevierStyleHsp" style=""></span>mg&#47;night&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid with MAOI&#44; risk of agranulocytosis&#44; unstable epilepsy&#44; liver failure&#44; kidney failure&#44; elevated blood glucose&#44; cardiac diseases&#44; severe toxicoderma&#44; avoid alcohol intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&#8211;600<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;maximum 3600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DRESS&#44; acute pancreatitis&#44; unstable epilepsy&#44; control if concomitant opioid administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pregabalin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#8211;600<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;divided in 3 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe toxicoderma&#44; dizziness&#44; somnolence&#44; blurred vision&#44; congestive heart failure&#44; control if concomitant opioid administration&#46; Avoid alcohol consumption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#8211;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Peripheral neuropathy&#44; teratogenic&#44; thromboembolic phenomena&#44; hypothyroidism&#44; severe toxicodermas&#44; herpes zoster&#44; progressive multifocal leukoencephalopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naloxone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;intravenous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physical dependence&#44; dizziness&#44; hypotension&#44; hypertension&#44; tachycardia&#44; pulmonary edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naltrexone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#8211;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liver failure&#44; physical dependence&#44; avoid using with thalidomide&#44; hydroxyzine&#44; doxepin&#44; amitriptyline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aprepitant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">125-80-80<span class="elsevierStyleHsp" style=""></span>mg in cycles of 1 or 2 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pharmacological interactions &#40;CYP3A4&#41;&#44; hiccups&#44; constipation&#44; headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3210408.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Recommended Treatment for Paraneoplastic Pruritus&#46; Bear in Mind Precautions to Ensure Appropriate Selection of the Patient Profile&#46;</p>"
        ]
      ]
      9 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mechanism of action&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Route of administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication in the summary of product characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Off-label use in pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KOR agonist</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Difelikefalin<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parenteral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Uremic pruritus in patients on hemodialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nalfurafin<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parenteral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cholestatic pruritus and pruritus of hepatic origin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nalmefene<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tablets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in alcohol consumption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cholestatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KOR agonist&#47;MOR antagonist</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nalbufin<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parenteral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Uremic pruritus in patients on hemodialysisPrurigo nodularis<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Butorfanol<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parenteral&#47;intranasal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intractable pruritusCholestatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOR antagonist&#47;KOR antagonist</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naloxone<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parenteral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reversal of side effects of opioids or intoxication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug-induced pruritusBrachioradial pruritusCholestatic pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naltrexone<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tablets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alcoholism&#44; opiate dependence treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug-induced pruritusCholestaticHaley-HaleyLichen planopilarisPsoriasisDarier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Opioids&#44; Mechanism of Action&#44; and Uses in Pruritus&#46;</p>"
        ]
      ]
      10 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at6"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#59; AD&#44; atopic dermatitis&#59; SSRI&#44; selective serotonin reuptake inhibitors&#59; HIV&#44; human immunodeficiency virus&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Uses in clinical practice&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluoxetine &#40;SSRI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aquagenic pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluvoxamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8211;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic pruritus in patients with AD&#44; lymphomas&#44; paraneoplastic pruritus&#44; psychiatric patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paroxetine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pruritus of unknown origin&#44; psychogenic pruritus&#44; paraneoplastic pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sertraline&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Uremic pruritus and cholestatic pruritus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Amitriptyline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15&#8211;30<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;at night&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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Información del artículo

ISSN: 00017310
Idioma original: Inglés

DOI:10.1016/j.ad.2023.06.007

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2024 Enero	283	81	364
2023 Diciembre	245	62	307
2023 Noviembre	218	85	303
2023 Octubre	324	103	427
2023 Septiembre	247	83	330
2023 Agosto	238	108	346
2023 Julio	283	151	434
2023 Junio	126	81	207

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