Dermatology and Immunoglobulin Therapy: Who to Treat and How to Administer Immunoglobulins

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The circumscribed component is clearly visible in the plaques situated on a) the right side of the neck, and b) the right preauricular and parotic regions, including involvement of the pinna." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Aranegui, J. Jiménez-Reyes" "autores" => array:2 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Aranegui" ] 1 => array:2 [ "nombre" => "J." 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Navarro-Triviño, I. Pérez-López, R. Ruíz-Villaverde" "autores" => array:3 [ 0 => array:4 [ "nombre" => "F.J." "apellidos" => "Navarro-Triviño" "email" => array:1 [ 0 => "fntmed@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Pérez-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "R." 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Abbreviations: ASA, acetylsalicylic acid; TEN, toxic epidermal necrolysis." ] ] ] "textoCompleto" => "IntroductionImmunoglobulins have been used for more than 50 years in the indication of primary and secondary immune system deficiencies. Their introduction in the treatment of different skin diseases is more recent, mainly because of the lack of randomized, controlled clinical trials and also because of the high costs. In 2008, the first guideline for the clinical use of intravenous immunoglobulin (IVIG) was published. Since then, publications have appeared in a wide range of journals describing their use for different conditions in isolated cases or in case series, culminating in recent guidelines. Between 3000 and 10 000 healthy donors are required to obtain an immunoglobulin concentrate. The production standards (World Health Organization 1982) were updated by the Committee for Propietary Medicinal Products of the European Medicines Agency (CPMP/BPWG/859/), with the aim of maintaining a higher level of quality and maximum safety in the manufacturing process. Plasma is incubated for at least 60 days to detect possible seroconversion of infectious agents (HBV, HCV, HIV, parvovirus B12, etc.). The functional integrity of the preparation is also tested for neutralizing antibodies and other immunomodulatory and inflammatory properties with the aim of detecting possible abnormalities in the function of these immunoglobulins. The national health agencies are responsible for regulating the manufacturing process as well as screening for viruses. Serum from donors positive for viral infections by polymerase chain reaction techniques or with abnormal immunoglobulin function is directly discarded to maintain the quality of the product.Commercial IVIG preparations contain physiological quantities of all immunoglobulins except IgA, given that this immunoglobulin is responsible for anaphylactic reactions. The levels of this immunoglobulin should be kept as low as possible.The bioavailability of IVIG is 100% at the time of infusion and 70% to 80% at 24hours. On the fifth day, 50% of administered product has been cleared. Although the half-life is estimated between 18 and 32 days, conditions such as fever or infections increase catabolism and, therefore, decrease the half-life. IVIG can pass through the placenta and is excreted in breast milk. In terms of mechanism of action, the Fc region of IgG can change signaling and transduction signs in cells that express Fcγ receptors on their surface, thus inducing both immune-mediated and anti-inflammatory changes. However, the mechanism of action of IVIG has not been fully clarified in in vivo studies. Recently, Pérez et al.<a class="elsevierStyleCrossRef" href="#bib0275">1</a> published a very complete review of existing evidence of the use of IVIG in humans. The review aimed to provide the reader with a practical grounding in the use of this treatment in dermatology.Main Indications for Intravenous Immunoglobulins in DermatologyAlthough the list of skin diseases in which IVIG therapy has been reported as a treatment option is quite extensive (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>), use was almost always off label. Nevertheless, good outcomes have been reported in some cases. In this article, we highlight the most relevant publications with the corresponding level of evidence and strength of recommendation (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DermatomyositisLevel of Evidence IIA, Strength of Recommendation BOf all the skin diseases described in this article, dermatomyositis, along with autoimmune blistering diseases, is perhaps the one with the highest level of evidence for efficacy. Placebo-controlled studies<a class="elsevierStyleCrossRef" href="#bib0280">2</a> and multiple case series<a class="elsevierStyleCrossRef" href="#bib0285">3</a> have been published, reporting satisfactory outcomes. IVIG is indicated as first-line therapy in cases of dermatomyositis with severe muscular involvement (fulminant myolysis), inclusion body myositis, and polymyositis.<a class="elsevierStyleCrossRef" href="#bib0290">4</a> Cases of juvenile dermatomyositis,<a class="elsevierStyleCrossRef" href="#bib0295">5</a> idiopathic dermatomyositis, and paraneoplastic dermatomyositis have been described with good response to treatment. IVIG is administered as adjuvant therapy, never as monotherapy, in patients who have not responded adequately to systemic corticosteroids after 1 month or in patients who experience worsening of muscle symptoms on decreasing the corticosteroid dose. The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>. These agents are also useful in the treatment of skin manifestations associated with dermatomyositis, particularly when these are severe and extensive, even when muscular involvement is not present,<a class="elsevierStyleCrossRef" href="#bib0300">6</a> or in the treatment of dystrophic calcinosis<a class="elsevierStyleCrossRef" href="#bib0305">7</a> and calcinosis refractory to multiple immunosuppressants.<a class="elsevierStyleCrossRef" href="#bib0310">8</a> Good outcomes have also been reported in severe edematous dermatomyositis<a class="elsevierStyleCrossRef" href="#bib0315">9</a> and in dermatomyositis panniculitis.<a class="elsevierStyleCrossRef" href="#bib0320">10</a> According to the systematic review by Callander et al.,<a class="elsevierStyleCrossRef" href="#bib0325">11</a> IVIG therapy is an interesting alternative in the treatment of amyopathic dermatomyositis, as reported in isolated cases.<a class="elsevierStyleCrossRef" href="#bib0330">12</a> In the treatment of juvenile dermatomyositis, IVIG therapy occupies a position as an effective and safe alternative,<a class="elsevierStyleCrossRef" href="#bib0335">13</a> particularly when administered subcutaneously.<a class="elsevierStyleCrossRef" href="#bib0340">14</a> This route of administration represents a major breakthrough in terms of safety and low rate of side effects, and it also reduces the number of school days missed.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Autoimmune Blistering DiseasesLevel of Evidence iii, Strength of Recommendation CAutoimmune blistering diseases are the second group of diseases in which IVIG therapy is an interesting treatment alternative,<a class="elsevierStyleCrossRefs" href="#bib0345">15,16</a> particularly in the severe forms and forms refractory to systemic glucocorticosteroids in combination with immunosuppressants (azathioprine and mofetil mycophenolate). IVIG therapy in the field of autoimmune blistering diseases is considered second-line treatment, although severe cases of pemphigus vulgaris, pemphigus foliaceus, mucous membrane pemphigoid,<a class="elsevierStyleCrossRef" href="#bib0355">17</a> and acquired epidermolysis bullosa<a class="elsevierStyleCrossRef" href="#bib0360">18</a> have been published with good therapeutic response. Other indications with a lower level of evidence for the use of IVIG therapy are bullous pemphigoid, linear IgA disease, IgA pemphigus, and paraneoplastic pemphigus. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a> shows the posology of IVIG therapy in blistering diseases. However, the use of rituximab in this group of diseases has been a great advance in the treatment and outcomes in these patients, with long disease-free periods.<a class="elsevierStyleCrossRef" href="#bib0365">19</a> In patients with recalcitrant disease, the combination of rituximab and IVIG therapy has been shown to be effective,<a class="elsevierStyleCrossRefs" href="#bib0370">20,21</a> with complete and sustained responses; however, given the high cost of this combination, patients who would benefit from this therapeutic option should be selected appropriately. In our hospital, experience with the combination of rituximab and IVIG therapy, although limited to a small number of patients, has been satisfactory in those cases refractory to first-line drugs, as well as their possible combinations.In certain special situations, such as when systemic glucocorticosteroids are contraindicated (aseptic bone necrosis, difficult-to-control diabetes mellitus, and severe osteoporosis), IVIG therapy could be justified as first-line treatment. However, this should always be as an adjuvant to other drugs such as immunosuppressants or rituximab, never as monotherapy. Good response to treatment can be assessed by the absence of new lesions and epithelization of existing ones, along with decreased autoantibody titers (IgA measured by enzyme-linked immunosorbent assay) or the possibility of reducing the dose of systemic glucocorticosteroids without disease deterioration.IVIG therapy can also be indicated in gestational pemphigoid, a special situation given the therapeutic limitations associated with pregnancy, particularly when administration of glucocorticosteroids does not achieve sufficient disease control. The effectiveness of IVIG administration in cases of refractory gestational pemphigoid has been reported in several articles,<a class="elsevierStyleCrossRefs" href="#bib0380">22,23</a> in association with oral cyclosporin<a class="elsevierStyleCrossRef" href="#bib0390">24</a> or as monotherapy,<a class="elsevierStyleCrossRef" href="#bib0395">25</a> without any side effects for the neonate.Kawasaki DiseaseLevel of Evidence i, Strength of Recommendation AAmong the vasculitis syndromes, Kawasaki disease is the only one in which IVIG is considered first-line therapy.<a class="elsevierStyleCrossRef" href="#bib0400">26</a> Perhaps the most difficult aspect of this process is initial suspicion, as the patient may not meet all diagnostic criteria and therefore there is a delay in administration of treatment. The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>. Some authors suggest IVIG administration as a single perfusion for 10-12hours, always in combination with acetylsalicylic acid. There are predictive factors for resistance to IVIG therapy,<a class="elsevierStyleCrossRef" href="#bib0405">27</a> the most relevant currently being level of C-reactive protein (CRP) before starting treatment.<a class="elsevierStyleCrossRef" href="#bib0410">28</a> The aim of treatment is to avoid formation of coronary aneurysms and associated comorbidities (ischemia, rhythm disorders, etc.). Decreased levels of CRP in plasma are the best indicator of good response to treatment.Toxic Epidermal NecrolysisLevel of Evidence IIA, Strength of Recommendation BToxic epidermal necrolysis (TEN) is a severe toxicoderma with a mortality as high as 40% according to some published series. Apoptosis of keratinocytes is mediated by the action of Fas (CD95), granulysin, and annexin-1. Rapid identification of the process, withdrawal of the suspected causal drug, and admission to the intensive care unit for care of the patient as if they had severe burns are essential for improving the chance of survival. Several meta-analyses and systematic reviews have been published on the pharmacological treatment of TEN, given that major controversy exists as to the efficacy of administration of immunosuppressants during admission to hospital. The most recent clinical practice guidelines for TEN<a class="elsevierStyleCrossRef" href="#bib0415">29</a> confer IVIG therapy an important role if administered early at high doses (3mg/kg), as a single cycle, split over 3 days at a slow infusion speed. It is essential to be aware of the patient¿s comorbidities, in particular renal insufficiency, cardiovascular diseases, and diabetes mellitus,<a class="elsevierStyleCrossRef" href="#bib0420">30</a> as fractioning the dose over 3 to 5 days avoids decompensation due to fluid overload. The best sign for detecting suitable response to treatment is absence of epidermal detachment, as well as the start of re-epithelization of previously affected areas. Although numerous drugs have been used to treat this often fatal disease, basic skin and mucosal care, control of vital signs, and maintaining a good fluid and electrolyte balance seem to be the only interventions that have been shown to improve patient survival.<a class="elsevierStyleCrossRef" href="#bib0425">31</a>ScleromyxedemaLevel of Evidence iii, Strength of Recommendation CScleromyxedema is a rare disease consisting of fibroblast proliferation and mucin deposition in the skin and internal organs, with resulting progressive hardening and fibrosis. It is usually a disease that is hard to treat, as it does not respond to multiple immunosuppressants and so is associated with high morbidity and mortality. In 2000, the first report appeared of good response to IVIG therapy.<a class="elsevierStyleCrossRef" href="#bib0430">32</a> According to data published on patients with scleromyxedema with predominant neurocutaneous involvement, IVIG therapy is considered the treatment of choice, either alone or in combination with corticosteroids<a class="elsevierStyleCrossRef" href="#bib0435">33</a> or plasmapheresis.<a class="elsevierStyleCrossRef" href="#bib0440">34</a> The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>. As with other dermatoses, factors predictive of good response to treatment correspond to skin changes, as well as improved function of internal organs.Pyoderma GangrenosumLevel of Evidence iii, Strength of Recommendation CIVIG therapy can be considered as a treatment option in patients with severe pyoderma gangrenosum refractory to normal treatment (systemic glucocorticosteroids and oral cyclosporin A). The only reports correspond to single cases or small case series,<a class="elsevierStyleCrossRefs" href="#bib0445">35–37</a> all with severe pyoderma gangrenosum and good outcomes. It is recommended to administer IVIG therapy as an adjuvant to systemic glucocorticosteroids and/or cyclosporin A, although some cases of administration as monotherapy have been reported.Livedoid VasculopathyLevel of Evidence iii, Strength of Recommendation DLivedoid vasculopathy presents with painful ulcers, above all on the legs, and these have a major impact on the patient¿s quality of life. The lesions can be refractory to multiple treatments. IVIG therapy has been used in severe difficult-to-treat cases with good response to treatment, according to published series.<a class="elsevierStyleCrossRefs" href="#bib0460">38–40</a> IVIG therapy is increasingly seen as a treatment option in this difficult-to-treat disease.OthersThe scientific literature includes use of IVIG therapy in other diseases, with variable clinical response. However, the availability of new drugs with better response rates has displaced the use of IVIG therapy. These new options include in particular the use of dupilumab as an upcoming treatment of severe cases of atopic dermatitis<a class="elsevierStyleCrossRef" href="#bib0475">41</a> and the use of omalizumab in autoimmune urticaria.<a class="elsevierStyleCrossRef" href="#bib0480">42</a> Other diseases in which the role of IVIG therapy does not lead to similar therapeutic response to those described previously are systemic lupus erythematosus (level of evidence IIA, strength of recommendation C), particularly when associated with renal failure,<a class="elsevierStyleCrossRef" href="#bib0485">43</a> systemic sclerosis<a class="elsevierStyleCrossRef" href="#bib0490">44</a> (level of evidence I, strength of recommendation B), and the set of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis,<a class="elsevierStyleCrossRefs" href="#bib0495">45,46</a> such as granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis, and polyarteritis nodosa (PAN)-type vasculitis<a class="elsevierStyleCrossRef" href="#bib0505">47</a> (level of evidence IIA, strength of recommendation B), where use of IVIG therapy is more questionable. In these cases, therapy is mainly reserved for those cases with a fulminant presentation that do not improve with systemic glucocorticosteroids in combination with cyclophosphamide.Use of Intravenous ImmunoglobulinsGiven that there are several skin diseases that may benefit from IVIG therapy, it is necessary to be aware of certain characteristics summarized in the following points. For this review, we have referred to several articles related to the use of IVIG in dermatology. Of these, we would like to highlight 2 of these, the article by Pérez et al.<a class="elsevierStyleCrossRef" href="#bib0275">1</a> and the European guidelines for the use of IVIG in dermatology,<a class="elsevierStyleCrossRef" href="#bib0510">48</a> should the reader wish to go into more detail on the topicPosologyThe dose used in all indications, except Kawasaki disease and TEN is 2g/kg body weight and cycle. The dose is distributed over 3 to 5 days, such that 400mg/kg body weight is administered daily. It is important to remember that dose adjustment is not needed for comorbidities, although it is recommended to control the volume of fluid administered in patients with renal or heart failure.Rate of InfusionThe rate of infusion depends on the commercial preparation. An initial (first 30min) infusion rate of 0.8 drops/kg/min is recommended for preparations such as Flebogamma, with an increase to 1.6 drops/kg/min if well tolerated. For other preparations such as Privigen 10%, the initial rate of infusion is slower, 0.3 drops/kg/min, and this rate is increased if well tolerated after 30minutes, up to a maximum of 4.8drops/kg/min.Monitoring Before and During AdministrationIt is essential to record a full medical history by organ and body system to detect a personal history of heart disease, chronic renal failure, diabetes mellitus, liver diseases, or administration of other drugs. It is recommended to assess kidney and liver function and measure blood glucose, determine hematology and coagulation parameters, as well as IgA, viral serology (HIV, HBV, HCV), cryoglobulins, blood group, and screen for thrombophilia. The patient should have signed the informed consent once treatment has been explained, along with the potential associated benefits and risks. It is important to keep the batch label, as this can help determine whether there is a problem with production in the event of infections or other treatment-associated complications.Premedication and Grounds for Discontinuation Signs of toxicityPrior to IVIG infusion, it is recommended to intravenously administer 1 vial of Polaramine and paracetamol 1g. During treatment, blood pressure should be measured and the patient monitored for signs and symptoms that might induce suspicion of an adverse reaction, in particular, a sensation of chest oppression, rubeosis, hypotension, intense headache, or general progressive malaise. If any of these signs and symptoms appear, the rate of IVIG infusion should be reduced, and if they persist despite intravenous administration of Polaramine, corticosteroids, or even adrenaline, treatment should be suspended to due risk of anaphylactic shock.In those patients at risk of pulmonary thromboembolism, 500mL of intravenous saline should be administered before and after IVIG infusion. Acetylsalicylic acid 100mg or heparin calcium 1000IU should be administered for 3 consecutive days after treatment.Precautions and ContraindicationsIn elderly patients or those with heart or kidney disease, hypercoagulability, systemic lupus erythematosus, migraine, and rheumatoid arthritis, particular care should be taken during administration of the treatment. With regards contraindications, severe hypersensitivity to IVIG therapy, severe kidney failure, and IgA deficiency are the most important. The US Food and Drug Administration considered IVIG as a pregnancy category C product. It is not contraindicated during breast feeding. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a> presents the side effects associated with administration of IVIG therapy.<a class="elsevierStyleCrossRef" href="#bib0515">49</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Subcutaneous Immunoglobulins: What Are Their Advantages?There are many publications in the literature on the use of subcutaneous immunoglobulins as treatment for immunodeficiencies, myopathies, and other immune-mediated diseases.<a class="elsevierStyleCrossRefs" href="#bib0520">50–52</a> The use of this route of administration has opened up a new frontier in the use of immunoglobulins.<a class="elsevierStyleCrossRefs" href="#bib0535">53,54</a> Advantages include that no premedication is required, more physiological serum levels of IgG are obtained, and the patients’ quality of life is improved given they do not need to be admitted to hospital or attend a day hospital. Overall, this route of administration of immunoglobulins incurs lower health costs than IVIG. Infusion pumps are used to administer at a rate of between 15 and 25mL/h, distributing the total dose between different points of injection. Endovascular administration is contraindicated.The indication of subcutaneous immunoglobulins, like IVIG, includes immunodeficiency conditions and autoimmune and inflammatory processes. Subcutaneous immunoglobulin administration can also be considered as maintenance treatment after initiation with IVIG. A maximum infusion rate of 20-25mL/h is recommended. Examples include the following preparations: Hizentra, Gammanorm, Subcuvia, Subgam, Gamunex-C, and Gammagard Liquid (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>ConclusionsUse of IVIG therapy in dermatology has become a treatment alternative in a range of diseases. Despite the limited number of controlled clinical trials, in publications on its use, good outcomes are obtained, with the advantage that this therapy is considered safe. It is necessary to be aware of the characteristics of administration, as well as associated side effects, use it appropriately, and avoid the appearance of unwanted side effects. <a class="elsevierStyleCrossRef" href="#tbl0025">Table 4</a>.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1022269" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec980426" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1022268" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec980425" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Main Indications for Intravenous Immunoglobulins in Dermatology" "secciones" => array:8 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Dermatomyositis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Level of Evidence IIA, Strength of Recommendation B" ] ] ] 1 => array:3 [ "identificador" => "sec0025" "titulo" => "Autoimmune Blistering Diseases" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Level of Evidence iii, Strength of Recommendation C" ] ] ] 2 => array:3 [ "identificador" => "sec0035" "titulo" => "Kawasaki Disease" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Level of Evidence i, Strength of Recommendation A" ] ] ] 3 => array:3 [ "identificador" => "sec0045" "titulo" => "Toxic Epidermal Necrolysis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Level of Evidence IIA, Strength of Recommendation B" ] ] ] 4 => array:3 [ "identificador" => "sec0055" "titulo" => "Scleromyxedema" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Level of Evidence iii, Strength of Recommendation C" ] ] ] 5 => array:3 [ "identificador" => "sec0065" "titulo" => "Pyoderma Gangrenosum" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Level of Evidence iii, Strength of Recommendation C" ] ] ] 6 => array:3 [ "identificador" => "sec0075" "titulo" => "Livedoid Vasculopathy" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Level of Evidence iii, Strength of Recommendation D" ] ] ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Others" ] ] ] 6 => array:3 [ "identificador" => "sec0090" "titulo" => "Use of Intravenous Immunoglobulins" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Posology" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Rate of Infusion" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Monitoring Before and During Administration" ] 3 => array:2 [ "identificador" => "sec0110" "titulo" => "Premedication and Grounds for Discontinuation Signs of toxicity" ] 4 => array:2 [ "identificador" => "sec0115" "titulo" => "Precautions and Contraindications" ] ] ] 7 => array:2 [ "identificador" => "sec0120" "titulo" => "Subcutaneous Immunoglobulins: What Are Their Advantages?" ] 8 => array:2 [ "identificador" => "sec0125" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0130" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-04-02" "fechaAceptado" => "2017-11-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec980426" "palabras" => array:5 [ 0 => "Intravenous immunoglobulin therapy" 1 => "Dermatology" 2 => "Dermatomyositis" 3 => "Autoimmune bullous diseases" 4 => "Toxic epidermal necrolysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec980425" "palabras" => array:5 [ 0 => "Inmunoglobulinas intravenosas" 1 => "Dermatología" 2 => "Dermatomiositis" 3 => "Enfermedades autoinmunes ampollares" 4 => "Necrólisis epidérmica tóxica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Intravenous immunoglobulin (IVIG) replacement therapy has been used in immune deficiency diseases for more than 50 years. The indications for this treatment have evolved, however, and IVIG therapy is now used in various diseases in which the immune system plays a prominent role. IVIG therapy has carved out a niche in dermatology for the treatment of such conditions as dermatomyositis, autoimmune bullous diseases, and toxic epidermal necrolysis. Special attention has been paid to this therapy in recent years. New guidelines have been published and should be taken into consideration in dermatology. This review provides a practical guide to IVIG use in our specialty." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El uso de las inmunoglobulinas intravenosas en la medicina se remonta a hace más de 50 años, tras el uso como terapia sustitutiva en enfermedades inmunodeficientes. Sin embargo, las indicaciones de este tratamiento han evolucionado de tal manera que actualmente está dirigido a enfermedades donde el sistema inmune desempeña un papel relevante. En el campo de la dermatología se ha hecho un hueco interesante en algunas enfermedades, como la dermatomiositis, las enfermedades autoinmunes ampollares o la necrólisis epidérmica tóxica, entre otras. En los últimos años se ha prestado especial atención al uso de las inmunoglobulinas intravenosas, de hecho se han publicado recientemente nuevas guías sobre su uso, y qué consideraciones debemos tener en cuenta durante su uso en dermatología. Nuestra intención con este artículo es reflejar de una manera práctica el uso de las inmunoglobulinas intravenosas en la dermatología." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Navarro-Triviño FJ, Pérez-López I, Ruíz-Villaverde R. Dermatología e inmunoglobulinas. ¿A quién y cómo administrarlas?. Actas Dermosifiliogr. 2018;109:323–330." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Table Strength of Recommendation (Meaning) and Level of Scientific Evidence (Type of Study)" "identificador" => "sec0135" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2394 "Ancho" => 3174 "Tamanyo" => 342499 ] ] "descripcion" => array:1 [ "en" => "Therapeutic algorithm for administration of IVIG therapy in dermatology according to the number of cycles and duration of treatment. Abbreviations: ASA, acetylsalicylic acid; TEN, toxic epidermal necrolysis." ] ] 1 => array:8 [ "identificador" => "tbl0010" "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Main Off Label Indications for Use of IVIG in Dermatology \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Other Indications \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Atopic dermatitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune bullous diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Autoimmune urticaria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lupus erythematosus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ANCA-associated vasculitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Behçet disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kaposi sarcoma \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1737244.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main Skin Diseases for Which IVIG Can be of Use." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Disease \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Posology \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doses: 2mg/kg body weight. Distributed over 3-5 consecutive days (400mg/d) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune blistering diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cycles: 6 (6 months) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Interval: 4-6 weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Time: 18 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doses: 1.6-2mg/kg bodyweight as single infusion in 10-12h, or distributed over 3-5 days. Always combined with ASA 50mg/kg of bodyweight/d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cycles: 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doses: 3 mg/kg weight. Distributed over 3-5 consecutive days (400mg/kg/d) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cycles: 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1737245.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Posology of IVIG Therapy by Dermatosis." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "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="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Side effects<a class="elsevierStyleCrossRef" href="#bib0515">49</a></th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immediate reactions, first 24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">General. Flu-like symptoms with myalgia, arthralgia, fever, headache, shivers. Hoarseness, adenopathy, and palpitations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Urticaria, palmoplantar bullous eruption \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anaphylactic shock due to anti-IgA antibodies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnea, acute 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Late reactions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Aseptic meningitis and migraine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thromboembolic phenomena \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acute renal failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemolysis, transient neutropenia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hyponatremia, pseudohyponatremia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Infections associated with commercial preparation \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1737243.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main Side Effects of IVIG Therapy." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Disease \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Strength of Recommendation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level of Evidence \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune bullous diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic lupus erythematosus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ANCA-associated vasculitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1737246.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Strength of Recommendation and Level of Evidence for IVIG Therapy by Disease." ] ] 5 => array:5 [ "identificador" => "tbl0005" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Strength of Recommendation (Meaning) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A, Extremely recommendable B, Favorable recommendation C, Favorable recommendation but inconclusive D, Not recommended or approved \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Level of Evidence (Type of Study) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I, At least 1 randomized, controlled clinical trial with an appropriate design II-1, Well-designed, controlled but not randomized clinical trials II-2, Well-designed cohort or case-control studies, preferably multicenter II-3, Multiple series compared over time, with or without intervention, and surprising results in uncontrolled studies III, Opinions based on clinical experience, descriptive studies, clinical observations, or expert committee reports \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1737247.png" ] ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:54 [ 0 => array:3 [ "identificador" => "bib0275" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on the use of immunoglobulin in human disease: A review of evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.E. 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Practical Dermatology

Dermatology and Immunoglobulin Therapy: Who to Treat and How to Administer Immunoglobulins

Dermatología e inmunoglobulinas. ¿A quién y cómo administrarlas?

F.J. Navarro-Triviñoa,

Autor para correspondencia

fntmed@gmail.com

Corresponding author.

, I. Pérez-Lópezb, R. Ruíz-Villaverdeb

a Unidad de Dermatología Médico-Quirúrgica y Venereología, Hospital Comarcal Santa Ana, Motril, Spain

b Unidad de Gestión Clínica de Dermatología y Venereología, Complejo Hospitalario Universitario de Granada, Granada, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Therapeutic algorithm for administration of IVIG therapy in dermatology according to the number of cycles and duration of treatment&#46; Abbreviations&#58; ASA&#44; acetylsalicylic acid&#59; TEN&#44; toxic epidermal necrolysis&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Immunoglobulins have been used for more than 50 years in the indication of primary and secondary immune system deficiencies&#46; Their introduction in the treatment of different skin diseases is more recent&#44; mainly because of the lack of randomized&#44; controlled clinical trials and also because of the high costs&#46; In 2008&#44; the first guideline for the clinical use of intravenous immunoglobulin &#40;IVIG&#41; was published&#46; Since then&#44; publications have appeared in a wide range of journals describing their use for different conditions in isolated cases or in case series&#44; culminating in recent guidelines&#46; Between 3000 and 10&#160;000 healthy donors are required to obtain an immunoglobulin concentrate&#46; The production standards &#40;World Health Organization 1982&#41; were updated by the Committee for Propietary Medicinal Products of the European Medicines Agency &#40;CPMP&#47;BPWG&#47;859&#47;&#41;&#44; with the aim of maintaining a higher level of quality and maximum safety in the manufacturing process&#46; Plasma is incubated for at least 60 days to detect possible seroconversion of infectious agents &#40;HBV&#44; HCV&#44; HIV&#44; parvovirus B12&#44; etc&#46;&#41;&#46; The functional integrity of the preparation is also tested for neutralizing antibodies and other immunomodulatory and inflammatory properties with the aim of detecting possible abnormalities in the function of these immunoglobulins&#46; The national health agencies are responsible for regulating the manufacturing process as well as screening for viruses&#46; Serum from donors positive for viral infections by polymerase chain reaction techniques or with abnormal immunoglobulin function is directly discarded to maintain the quality of the product&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Commercial IVIG preparations contain physiological quantities of all immunoglobulins except IgA&#44; given that this immunoglobulin is responsible for anaphylactic reactions&#46; The levels of this immunoglobulin should be kept as low as possible&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The bioavailability of IVIG is 100&#37; at the time of infusion and 70&#37; to 80&#37; at 24<span class="elsevierStyleHsp" style=""></span>hours&#46; On the fifth day&#44; 50&#37; of administered product has been cleared&#46; Although the half-life is estimated between 18 and 32 days&#44; conditions such as fever or infections increase catabolism and&#44; therefore&#44; decrease the half-life&#46; IVIG can pass through the placenta and is excreted in breast milk&#46; In terms of mechanism of action&#44; the Fc region of IgG can change signaling and transduction signs in cells that express Fc&#947; receptors on their surface&#44; thus inducing both immune-mediated and anti-inflammatory changes&#46; However&#44; the mechanism of action of IVIG has not been fully clarified in in vivo studies&#46; Recently&#44; P&#233;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> published a very complete review of existing evidence of the use of IVIG in humans&#46; The review aimed to provide the reader with a practical grounding in the use of this treatment in dermatology&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Main Indications for Intravenous Immunoglobulins in Dermatology</span><p id="par0020" class="elsevierStylePara elsevierViewall">Although the list of skin diseases in which IVIG therapy has been reported as a treatment option is quite extensive &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>&#41;&#44; use was almost always off label&#46; Nevertheless&#44; good outcomes have been reported in some cases&#46; In this article&#44; we highlight the most relevant publications with the corresponding level of evidence and strength of recommendation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Dermatomyositis</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Level of Evidence IIA&#44; Strength of Recommendation B</span><p id="par0025" class="elsevierStylePara elsevierViewall">Of all the skin diseases described in this article&#44; dermatomyositis&#44; along with autoimmune blistering diseases&#44; is perhaps the one with the highest level of evidence for efficacy&#46; Placebo-controlled studies<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">2</span></a> and multiple case series<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> have been published&#44; reporting satisfactory outcomes&#46; IVIG is indicated as first-line therapy in cases of dermatomyositis with severe muscular involvement &#40;fulminant myolysis&#41;&#44; inclusion body myositis&#44; and polymyositis&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a> Cases of juvenile dermatomyositis&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> idiopathic dermatomyositis&#44; and paraneoplastic dermatomyositis have been described with good response to treatment&#46; IVIG is administered as adjuvant therapy&#44; never as monotherapy&#44; in patients who have not responded adequately to systemic corticosteroids after 1 month or in patients who experience worsening of muscle symptoms on decreasing the corticosteroid dose&#46; The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#46; These agents are also useful in the treatment of skin manifestations associated with dermatomyositis&#44; particularly when these are severe and extensive&#44; even when muscular involvement is not present&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a> or in the treatment of dystrophic calcinosis<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">7</span></a> and calcinosis refractory to multiple immunosuppressants&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> Good outcomes have also been reported in severe edematous dermatomyositis<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">9</span></a> and in dermatomyositis panniculitis&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">10</span></a> According to the systematic review by Callander et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a> IVIG therapy is an interesting alternative in the treatment of amyopathic dermatomyositis&#44; as reported in isolated cases&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a> In the treatment of juvenile dermatomyositis&#44; IVIG therapy occupies a position as an effective and safe alternative&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">13</span></a> particularly when administered subcutaneously&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">14</span></a> This route of administration represents a major breakthrough in terms of safety and low rate of side effects&#44; and it also reduces the number of school days missed&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Autoimmune Blistering Diseases</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Level of Evidence <span class="elsevierStyleSmallCaps">iii</span>&#44; Strength of Recommendation <span class="elsevierStyleSmallCaps">C</span></span><p id="par0030" class="elsevierStylePara elsevierViewall">Autoimmune blistering diseases are the second group of diseases in which IVIG therapy is an interesting treatment alternative&#44;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">15&#44;16</span></a> particularly in the severe forms and forms refractory to systemic glucocorticosteroids in combination with immunosuppressants &#40;azathioprine and mofetil mycophenolate&#41;&#46; IVIG therapy in the field of autoimmune blistering diseases is considered second-line treatment&#44; although severe cases of pemphigus vulgaris&#44; pemphigus foliaceus&#44; mucous membrane pemphigoid&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a> and acquired epidermolysis bullosa<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a> have been published with good therapeutic response&#46; Other indications with a lower level of evidence for the use of IVIG therapy are bullous pemphigoid&#44; linear IgA disease&#44; IgA pemphigus&#44; and paraneoplastic pemphigus&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a> shows the posology of IVIG therapy in blistering diseases&#46; However&#44; the use of rituximab in this group of diseases has been a great advance in the treatment and outcomes in these patients&#44; with long disease-free periods&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">19</span></a> In patients with recalcitrant disease&#44; the combination of rituximab and IVIG therapy has been shown to be effective&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">20&#44;21</span></a> with complete and sustained responses&#59; however&#44; given the high cost of this combination&#44; patients who would benefit from this therapeutic option should be selected appropriately&#46; In our hospital&#44; experience with the combination of rituximab and IVIG therapy&#44; although limited to a small number of patients&#44; has been satisfactory in those cases refractory to first-line drugs&#44; as well as their possible combinations&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In certain special situations&#44; such as when systemic glucocorticosteroids are contraindicated &#40;aseptic bone necrosis&#44; difficult-to-control diabetes mellitus&#44; and severe osteoporosis&#41;&#44; IVIG therapy could be justified as first-line treatment&#46; However&#44; this should always be as an adjuvant to other drugs such as immunosuppressants or rituximab&#44; never as monotherapy&#46; Good response to treatment can be assessed by the absence of new lesions and epithelization of existing ones&#44; along with decreased autoantibody titers &#40;IgA measured by enzyme-linked immunosorbent assay&#41; or the possibility of reducing the dose of systemic glucocorticosteroids without disease deterioration&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">IVIG therapy can also be indicated in gestational pemphigoid&#44; a special situation given the therapeutic limitations associated with pregnancy&#44; particularly when administration of glucocorticosteroids does not achieve sufficient disease control&#46; The effectiveness of IVIG administration in cases of refractory gestational pemphigoid has been reported in several articles&#44;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">22&#44;23</span></a> in association with oral cyclosporin<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">24</span></a> or as monotherapy&#44;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">25</span></a> without any side effects for the neonate&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Kawasaki Disease</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Level of Evidence <span class="elsevierStyleSmallCaps">i</span>&#44; Strength of Recommendation A</span><p id="par0045" class="elsevierStylePara elsevierViewall">Among the vasculitis syndromes&#44; Kawasaki disease is the only one in which IVIG is considered first-line therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">26</span></a> Perhaps the most difficult aspect of this process is initial suspicion&#44; as the patient may not meet all diagnostic criteria and therefore there is a delay in administration of treatment&#46; The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#46; Some authors suggest IVIG administration as a single perfusion for 10-12<span class="elsevierStyleHsp" style=""></span>hours&#44; always in combination with acetylsalicylic acid&#46; There are predictive factors for resistance to IVIG therapy&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">27</span></a> the most relevant currently being level of C-reactive protein &#40;CRP&#41; before starting treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">28</span></a> The aim of treatment is to avoid formation of coronary aneurysms and associated comorbidities &#40;ischemia&#44; rhythm disorders&#44; etc&#46;&#41;&#46; Decreased levels of CRP in plasma are the best indicator of good response to treatment&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Toxic Epidermal Necrolysis</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Level of Evidence IIA&#44; Strength of Recommendation B</span><p id="par0050" class="elsevierStylePara elsevierViewall">Toxic epidermal necrolysis &#40;TEN&#41; is a severe toxicoderma with a mortality as high as 40&#37; according to some published series&#46; Apoptosis of keratinocytes is mediated by the action of Fas &#40;CD95&#41;&#44; granulysin&#44; and annexin-1&#46; Rapid identification of the process&#44; withdrawal of the suspected causal drug&#44; and admission to the intensive care unit for care of the patient as if they had severe burns are essential for improving the chance of survival&#46; Several meta-analyses and systematic reviews have been published on the pharmacological treatment of TEN&#44; given that major controversy exists as to the efficacy of administration of immunosuppressants during admission to hospital&#46; The most recent clinical practice guidelines for TEN<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">29</span></a> confer IVIG therapy an important role if administered early at high doses &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#44; as a single cycle&#44; split over 3 days at a slow infusion speed&#46; It is essential to be aware of the patient¿s comorbidities&#44; in particular renal insufficiency&#44; cardiovascular diseases&#44; and diabetes mellitus&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">30</span></a> as fractioning the dose over 3 to 5 days avoids decompensation due to fluid overload&#46; The best sign for detecting suitable response to treatment is absence of epidermal detachment&#44; as well as the start of re-epithelization of previously affected areas&#46; Although numerous drugs have been used to treat this often fatal disease&#44; basic skin and mucosal care&#44; control of vital signs&#44; and maintaining a good fluid and electrolyte balance seem to be the only interventions that have been shown to improve patient survival&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Scleromyxedema</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Level of Evidence <span class="elsevierStyleSmallCaps">iii</span>&#44; Strength of Recommendation C</span><p id="par0055" class="elsevierStylePara elsevierViewall">Scleromyxedema is a rare disease consisting of fibroblast proliferation and mucin deposition in the skin and internal organs&#44; with resulting progressive hardening and fibrosis&#46; It is usually a disease that is hard to treat&#44; as it does not respond to multiple immunosuppressants and so is associated with high morbidity and mortality&#46; In 2000&#44; the first report appeared of good response to IVIG therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">32</span></a> According to data published on patients with scleromyxedema with predominant neurocutaneous involvement&#44; IVIG therapy is considered the treatment of choice&#44; either alone or in combination with corticosteroids<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">33</span></a> or plasmapheresis&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">34</span></a> The posology is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#46; As with other dermatoses&#44; factors predictive of good response to treatment correspond to skin changes&#44; as well as improved function of internal organs&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pyoderma Gangrenosum</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Level of Evidence <span class="elsevierStyleSmallCaps">iii</span>&#44; Strength of Recommendation C</span><p id="par0060" class="elsevierStylePara elsevierViewall">IVIG therapy can be considered as a treatment option in patients with severe pyoderma gangrenosum refractory to normal treatment &#40;systemic glucocorticosteroids and oral cyclosporin A&#41;&#46; The only reports correspond to single cases or small case series&#44;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">35&#8211;37</span></a> all with severe pyoderma gangrenosum and good outcomes&#46; It is recommended to administer IVIG therapy as an adjuvant to systemic glucocorticosteroids and&#47;or cyclosporin A&#44; although some cases of administration as monotherapy have been reported&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Livedoid Vasculopathy</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Level of Evidence <span class="elsevierStyleSmallCaps">iii</span>&#44; Strength of Recommendation D</span><p id="par0065" class="elsevierStylePara elsevierViewall">Livedoid vasculopathy presents with painful ulcers&#44; above all on the legs&#44; and these have a major impact on the patient¿s quality of life&#46; The lesions can be refractory to multiple treatments&#46; IVIG therapy has been used in severe difficult-to-treat cases with good response to treatment&#44; according to published series&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">38&#8211;40</span></a> IVIG therapy is increasingly seen as a treatment option in this difficult-to-treat disease&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Others</span><p id="par0070" class="elsevierStylePara elsevierViewall">The scientific literature includes use of IVIG therapy in other diseases&#44; with variable clinical response&#46; However&#44; the availability of new drugs with better response rates has displaced the use of IVIG therapy&#46; These new options include in particular the use of dupilumab as an upcoming treatment of severe cases of atopic dermatitis<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">41</span></a> and the use of omalizumab in autoimmune urticaria&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">42</span></a> Other diseases in which the role of IVIG therapy does not lead to similar therapeutic response to those described previously are systemic lupus erythematosus &#40;level of evidence IIA&#44; strength of recommendation C&#41;&#44; particularly when associated with renal failure&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">43</span></a> systemic sclerosis<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> &#40;level of evidence I&#44; strength of recommendation B&#41;&#44; and the set of anti-neutrophil cytoplasmic autoantibody &#40;ANCA&#41;-associated small-vessel vasculitis&#44;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">45&#44;46</span></a> such as granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis&#44; and polyarteritis nodosa &#40;PAN&#41;-type vasculitis<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a> &#40;level of evidence IIA&#44; strength of recommendation B&#41;&#44; where use of IVIG therapy is more questionable&#46; In these cases&#44; therapy is mainly reserved for those cases with a fulminant presentation that do not improve with systemic glucocorticosteroids in combination with cyclophosphamide&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Use of Intravenous Immunoglobulins</span><p id="par0075" class="elsevierStylePara elsevierViewall">Given that there are several skin diseases that may benefit from IVIG therapy&#44; it is necessary to be aware of certain characteristics summarized in the following points&#46; For this review&#44; we have referred to several articles related to the use of IVIG in dermatology&#46; Of these&#44; we would like to highlight 2 of these&#44; the article by P&#233;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> and the European guidelines for the use of IVIG in dermatology&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a> should the reader wish to go into more detail on the topic</p><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Posology</span><p id="par0080" class="elsevierStylePara elsevierViewall">The dose used in all indications&#44; except Kawasaki disease and TEN is 2<span class="elsevierStyleHsp" style=""></span>g&#47;kg body weight and cycle&#46; The dose is distributed over 3 to 5 days&#44; such that 400<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight is administered daily&#46; It is important to remember that dose adjustment is not needed for comorbidities&#44; although it is recommended to control the volume of fluid administered in patients with renal or heart failure&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Rate of Infusion</span><p id="par0085" class="elsevierStylePara elsevierViewall">The rate of infusion depends on the commercial preparation&#46; An initial &#40;first 30<span class="elsevierStyleHsp" style=""></span>min&#41; infusion rate of 0&#46;8 drops&#47;kg&#47;min is recommended for preparations such as Flebogamma&#44; with an increase to 1&#46;6 drops&#47;kg&#47;min if well tolerated&#46; For other preparations such as Privigen 10&#37;&#44; the initial rate of infusion is slower&#44; 0&#46;3 drops&#47;kg&#47;min&#44; and this rate is increased if well tolerated after 30<span class="elsevierStyleHsp" style=""></span>minutes&#44; up to a maximum of 4&#46;8<span class="elsevierStyleHsp" style=""></span>drops&#47;kg&#47;min&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Monitoring Before and During Administration</span><p id="par0090" class="elsevierStylePara elsevierViewall">It is essential to record a full medical history by organ and body system to detect a personal history of heart disease&#44; chronic renal failure&#44; diabetes mellitus&#44; liver diseases&#44; or administration of other drugs&#46; It is recommended to assess kidney and liver function and measure blood glucose&#44; determine hematology and coagulation parameters&#44; as well as IgA&#44; viral serology &#40;HIV&#44; HBV&#44; HCV&#41;&#44; cryoglobulins&#44; blood group&#44; and screen for thrombophilia&#46; The patient should have signed the informed consent once treatment has been explained&#44; along with the potential associated benefits and risks&#46; It is important to keep the batch label&#44; as this can help determine whether there is a problem with production in the event of infections or other treatment-associated complications&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Premedication and Grounds for Discontinuation Signs of toxicity</span><p id="par0095" class="elsevierStylePara elsevierViewall">Prior to IVIG infusion&#44; it is recommended to intravenously administer 1 vial of Polaramine and paracetamol 1<span class="elsevierStyleHsp" style=""></span>g&#46; During treatment&#44; blood pressure should be measured and the patient monitored for signs and symptoms that might induce suspicion of an adverse reaction&#44; in particular&#44; a sensation of chest oppression&#44; rubeosis&#44; hypotension&#44; intense headache&#44; or general progressive malaise&#46; If any of these signs and symptoms appear&#44; the rate of IVIG infusion should be reduced&#44; and if they persist despite intravenous administration of Polaramine&#44; corticosteroids&#44; or even adrenaline&#44; treatment should be suspended to due risk of anaphylactic shock&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In those patients at risk of pulmonary thromboembolism&#44; 500<span class="elsevierStyleHsp" style=""></span>mL of intravenous saline should be administered before and after IVIG infusion&#46; Acetylsalicylic acid 100<span class="elsevierStyleHsp" style=""></span>mg or heparin calcium 1000<span class="elsevierStyleHsp" style=""></span>IU should be administered for 3 consecutive days after treatment&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Precautions and Contraindications</span><p id="par0105" class="elsevierStylePara elsevierViewall">In elderly patients or those with heart or kidney disease&#44; hypercoagulability&#44; systemic lupus erythematosus&#44; migraine&#44; and rheumatoid arthritis&#44; particular care should be taken during administration of the treatment&#46; With regards contraindications&#44; severe hypersensitivity to IVIG therapy&#44; severe kidney failure&#44; and IgA deficiency are the most important&#46; The US Food and Drug Administration considered IVIG as a pregnancy category C product&#46; It is not contraindicated during breast feeding&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a> presents the side effects associated with administration of IVIG therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Subcutaneous Immunoglobulins&#58; What Are Their Advantages&#63;</span><p id="par0110" class="elsevierStylePara elsevierViewall">There are many publications in the literature on the use of subcutaneous immunoglobulins as treatment for immunodeficiencies&#44; myopathies&#44; and other immune-mediated diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">50&#8211;52</span></a> The use of this route of administration has opened up a new frontier in the use of immunoglobulins&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">53&#44;54</span></a> Advantages include that no premedication is required&#44; more physiological serum levels of IgG are obtained&#44; and the patients&#8217; quality of life is improved given they do not need to be admitted to hospital or attend a day hospital&#46; Overall&#44; this route of administration of immunoglobulins incurs lower health costs than IVIG&#46; Infusion pumps are used to administer at a rate of between 15 and 25<span class="elsevierStyleHsp" style=""></span>mL&#47;h&#44; distributing the total dose between different points of injection&#46; Endovascular administration is contraindicated&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The indication of subcutaneous immunoglobulins&#44; like IVIG&#44; includes immunodeficiency conditions and autoimmune and inflammatory processes&#46; Subcutaneous immunoglobulin administration can also be considered as maintenance treatment after initiation with IVIG&#46; A maximum infusion rate of 20-25<span class="elsevierStyleHsp" style=""></span>mL&#47;h is recommended&#46; Examples include the following preparations&#58; Hizentra&#44; Gammanorm&#44; Subcuvia&#44; Subgam&#44; Gamunex-C&#44; and Gammagard Liquid &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">Use of IVIG therapy in dermatology has become a treatment alternative in a range of diseases&#46; Despite the limited number of controlled clinical trials&#44; in publications on its use&#44; good outcomes are obtained&#44; with the advantage that this therapy is considered safe&#46; It is necessary to be aware of the characteristics of administration&#44; as well as associated side effects&#44; use it appropriately&#44; and avoid the appearance of unwanted side effects&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of Interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            1 => "Dermatology"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intravenous immunoglobulin &#40;IVIG&#41; replacement therapy has been used in immune deficiency diseases for more than 50 years&#46; The indications for this treatment have evolved&#44; however&#44; and IVIG therapy is now used in various diseases in which the immune system plays a prominent role&#46; IVIG therapy has carved out a niche in dermatology for the treatment of such conditions as dermatomyositis&#44; autoimmune bullous diseases&#44; and toxic epidermal necrolysis&#46; Special attention has been paid to this therapy in recent years&#46; New guidelines have been published and should be taken into consideration in dermatology&#46; This review provides a practical guide to IVIG use in our specialty&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El uso de las inmunoglobulinas intravenosas en la medicina se remonta a hace m&#225;s de 50 a&#241;os&#44; tras el uso como terapia sustitutiva en enfermedades inmunodeficientes&#46; Sin embargo&#44; las indicaciones de este tratamiento han evolucionado de tal manera que actualmente est&#225; dirigido a enfermedades donde el sistema inmune desempe&#241;a un papel relevante&#46; En el campo de la dermatolog&#237;a se ha hecho un hueco interesante en algunas enfermedades&#44; como la dermatomiositis&#44; las enfermedades autoinmunes ampollares o la necr&#243;lisis epid&#233;rmica t&#243;xica&#44; entre otras&#46; En los &#250;ltimos a&#241;os se ha prestado especial atenci&#243;n al uso de las inmunoglobulinas intravenosas&#44; de hecho se han publicado recientemente nuevas gu&#237;as sobre su uso&#44; y qu&#233; consideraciones debemos tener en cuenta durante su uso en dermatolog&#237;a&#46; Nuestra intenci&#243;n con este art&#237;culo es reflejar de una manera pr&#225;ctica el uso de las inmunoglobulinas intravenosas en la dermatolog&#237;a&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Navarro-Trivi&#241;o FJ&#44; P&#233;rez-L&#243;pez I&#44; Ru&#237;z-Villaverde R&#46; Dermatolog&#237;a e inmunoglobulinas&#46; &#191;A qui&#233;n y c&#243;mo administrarlas&#63;&#46; Actas Dermosifiliogr&#46; 2018&#59;109&#58;323&#8211;330&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Therapeutic algorithm for administration of IVIG therapy in dermatology according to the number of cycles and duration of treatment&#46; Abbreviations&#58; ASA&#44; acetylsalicylic acid&#59; TEN&#44; toxic epidermal necrolysis&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Main Off Label Indications for Use of IVIG in Dermatology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Other Indications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune bullous diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Autoimmune urticaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systemic sclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANCA-associated vasculitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Beh&#231;et disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kaposi sarcoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1737244.png"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Main Skin Diseases for Which IVIG Can be of Use&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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        "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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Posology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Doses&#58; 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight&#46; Distributed over 3-5 consecutive days &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune blistering diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cycles&#58; 6 &#40;6 months&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Interval&#58; 4-6 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Time&#58; 18 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Doses&#58; 1&#46;6-2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg bodyweight as single infusion in 10-12<span class="elsevierStyleHsp" style=""></span>h&#44; or distributed over 3-5 days&#46; Always combined with ASA 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg of bodyweight&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cycles&#58; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Doses&#58; 3 mg&#47;kg weight&#46; Distributed over 3-5 consecutive days &#40;400<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cycles&#58; 1&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="spar0025" class="elsevierStyleSimplePara elsevierViewall">Posology of IVIG Therapy by Dermatosis&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
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        "tabla" => array:1 [
          "tablatextoimagen" => 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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Side effects<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immediate reactions&#44; first 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">General&#46; Flu-like symptoms with myalgia&#44; arthralgia&#44; fever&#44; headache&#44; shivers&#46; Hoarseness&#44; adenopathy&#44; and palpitations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Urticaria&#44; palmoplantar bullous eruption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anaphylactic shock due to anti-IgA antibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dyspnea&#44; acute 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Late reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aseptic meningitis and migraine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Thromboembolic phenomena&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Acute renal failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemolysis&#44; transient neutropenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hyponatremia&#44; pseudohyponatremia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Infections associated with commercial preparation&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="spar0030" class="elsevierStyleSimplePara elsevierViewall">Main Side Effects of IVIG Therapy&#46;</p>"
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        "etiqueta" => "Table 4"
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            "identificador" => "at4"
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        "tabla" => array:1 [
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                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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Strength of Recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level of Evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dermatomyositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune bullous diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kawasaki disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic epidermal necrolysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Scleromyxedema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pyoderma gangrenosum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vasculopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic sclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ANCA-associated vasculitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&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="spar0035" class="elsevierStyleSimplePara elsevierViewall">Strength of Recommendation and Level of Evidence for IVIG Therapy by Disease&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0005"
        "tipo" => "MULTIMEDIATABLA"
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        "mostrarDisplay" => true
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            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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Strength of Recommendation &#40;Meaning&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A&#44; Extremely recommendable<br>B&#44; Favorable recommendation<br>C&#44; Favorable recommendation but inconclusive<br>D&#44; Not recommended or approved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Level of Evidence &#40;Type of Study&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I&#44; At least 1 randomized&#44; controlled clinical trial with an appropriate design<br>II-1&#44; Well-designed&#44; controlled but not randomized clinical trials<br>II-2&#44; Well-designed cohort or case-control studies&#44; preferably multicenter<br>II-3&#44; Multiple series compared over time&#44; with or without intervention&#44; and surprising results in uncontrolled studies<br>III&#44; Opinions based on clinical experience&#44; descriptive studies&#44; clinical observations&#44; or expert committee reports&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:54 [
            0 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on the use of immunoglobulin in human disease&#58; A review of evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;E&#46; P&#233;rez"
                            1 => "J&#46;S&#46; Orange"
                            2 => "F&#46; Bonilla"
                            3 => "J&#46; Chinen"
                            4 => "I&#46;K&#46; Chinn"
                            5 => "M&#46; Dorsey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2016.09.023"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2017"
                        "volumen" => "139"
                        "paginaInicial" => "S1"
                        "paginaFinal" => "S46"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28041678"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A controlled trial of high-dose intravenous immune infusions as treatment for dermatomyositis"
                      "autores" => array:1 [
                        0 => array:2 [
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                          "autores" => array:6 [
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Información del artículo

ISSN: 15782190
Idioma original: Inglés

DOI:10.1016/j.adengl.2018.03.010

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