Original Article
Carbon Dioxide Laser Treatment in Hailey-Hailey Disease: A Series of 8 Patients
Tratamiento de la enfermedad de Hailey-Hailey con láser de dióxido de carbono: tratamiento en 8 pacientes
M. Pretel-Irazabal
, J.M. Lera-Imbuluzqueta, A. España-Alonso
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Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, Spain
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A. Presentaba lesiones en la región axilar.B. Lesiones en la región submamaria. C. Lesiones en la superficie posterior del tronco. D, E y F. Imagen de las lesiones 9 meses después de realizar el tratamiento. Nótese la gran mejoría de las lesiones y las zonas de hipo/hiperpigmentación residual que ha dejado la abrasión. A pesar de los cambios de coloración, la paciente decidió realizar una nueva sesión de tratamiento en otras localizaciones.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Pretel-Irazabal, J.M. Lera-Imbuluzqueta, A. España-Alonso" "autores" => array:3 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Pretel-Irazabal" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Lera-Imbuluzqueta" ] 2 => array:2 [ "nombre" => "A." 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B, Multiple lesions on a patient's leg.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Aguado, P. Espinosa, A. Romero-Maté, J.C. Tardío, S. Córdoba, J. Borbujo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Aguado" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Espinosa" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Romero-Maté" ] 3 => array:2 [ "nombre" => "J.C." "apellidos" => "Tardío" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Córdoba" ] 5 => array:2 [ "nombre" => "J." 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Pretel-Irazabal, J.M. Lera-Imbuluzqueta, A. España-Alonso" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Pretel-Irazabal" "email" => array:1 [ 0 => "mpretel@unav.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Lera-Imbuluzqueta" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "España-Alonso" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la enfermedad de Hailey-Hailey con láser de dióxido de carbono: tratamiento en 8 pacientes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2782 "Ancho" => 1555 "Tamanyo" => 381604 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A, 63-year-old patient with inguinal Hailey-Hailey disease. B, Photo taken 1 month after treatment with carbon dioxide laser skin resurfacing. Note the postoperative erythema.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hailey-Hailey disease (HHD), or familial benign pemphigus, is a rare autosomal dominant blistering skin disorder caused by a mutation in the gene encoding a Ca<span class="elsevierStyleSup">2+</span>-dependent ATPase located within the Golgi apparatus.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Patients develop blisters and erosions, which predominantly affect the large skinfolds, and in particular axillary and inguinal folds. It is a chronic condition, characterized by recurrent flares generally triggered by factors such as friction, sweating, heat, stress, local infection, and UV radiation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">HHD is difficult to treat. The literature contains many accounts of different topical and systemic treatments being used to control disease flares. Treatments include antibiotics and antivirals to treat secondary bacterial and viral infections; botulinum toxin to minimize aggravating factors, such as excessive sweating,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> and immunomodulators, such as corticosteroids,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> ciclosporin,<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> and tacrolimus<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–12</span></a> to reduce the associated inflammatory response. Photodynamic therapy has also been tested, but with little success.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> The above treatments, however, only result in temporary improvements in symptoms; they do not alter the course of disease, and they only rarely lead to long-term remission.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Surgical treatment of HHD should be considered in patients who do not respond to general measures or to conventional oral or topical treatments. Several cases published in recent years have shown carbon dioxide (CO<span class="elsevierStyleInf">2</span>) laser skin resurfacing to be effective in HHD. We present a series of 8 cases of HHD treated with this technique and conclude that it is a safe and effective treatment option in this setting.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We performed a retrospective study of patients with HHD treated with CO<span class="elsevierStyleInf">2</span> laser resurfacing at Clínica Universitaria de Navarra in Spain between 1999 and 2011.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis of HHD was based on clinical and histological criteria (coalescing blistering lesions, typically located in the skinfolds, that rupture to form erosions; histology showing intraepidermal blisters associated with acantholytic cells; a negative direct immunofluorescence test; and the absence of other diseases that could explain the manifestations of HHD).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patients were all aged over 18 years, had disabling symptoms that interfered with activities of daily living, and had not responded to conventional topical or systemic treatment (topical and oral corticosteroids and antibiotics). They had no concomitant conditions.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We studied 8 patients (4 men and 4 women), with a mean age of 50.7 years (range, 27-69 years). Mean age at the time of diagnosis was 35.5 years. Half of the patients had a family history of HHD. Lesions affected the groin in 100% of cases, the axillae in 87%, the genital area in 75%, the perianal area in 50%, and the trunk and arms in 25% each. Several areas were affected in a considerable number of cases (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). All the patients signed an informed consent form before undergoing laser treatment. They were examined by an anesthesiologist, who confirmed their suitability for general or spinal anesthesia. The areas to be treated, generally the axillae (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>) and genitocrural area (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), were marked before the procedure. In 1 patient with a particularly severe form of HHD, treatment also targeted the thorax, arms, legs, neck, and back (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). This patient asked for treatment to be targeted at more visible areas, namely the back, the abdomen, and the elbow and knee pits, even though she had been informed that the procedure would probably result in textural changes to the skin and hypopigmentation and/or hyperpigmentation (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The procedure was performed under general or spinal anesthesia, depending on the location of the lesions. Local anesthesia was used in patients with lesions confined to small areas. All areas were disinfected with povidone iodine before treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">A continuous-wave CO<span class="elsevierStyleInf">2</span> laser with computerized scanning (Sharplan SilkTouch laser; Sharplan Lasers, Inc.) was used in all cases. The procedure was performed with a 200-mm handpiece, an output power of 20 to 25<span class="elsevierStyleHsp" style=""></span>W, a pulse duration of 450<span class="elsevierStyleHsp" style=""></span>ms, and a spot diameter of 9<span class="elsevierStyleHsp" style=""></span>mm. The laser was connected to a plume removal system. Two to 3 passes were used in most cases; after each pass, all traces of abraded skin were removed using saline-moistened gauze. At the end of each session, the skin had a yellowish appearance with red pinpoint dots. Topical gentamicin was applied to the treated area, which was covered with Linitul or Mepitel dressings covered with gauze.</p><p id="par0050" class="elsevierStylePara elsevierViewall">All the patients received prophylactic antibiotic treatment and analgesics (metamizole or morphine derivatives) after the procedure. Topical gentamicin and dressings were applied daily for a week, during which time the patients remained in hospital.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Considerable improvement was observed in almost all patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In 1 patient, new lesions developed at the edge of the treated area several days after the procedure. Local recurrence was observed in 3 patients (38%) 6 months after treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The lesions were successfully treated in a second CO<span class="elsevierStyleInf">2</span> laser session involving more passes than in the first session. The poorest outcomes were observed in patients who had been treated at the beginning of the study period, possibly because the lower output powers used initially were insufficient.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Postoperative pain was moderate to intense in most patients, with analgesics being required in some cases. Complete reepithelialization was observed within 7 to 10 days in the majority of cases. The average time missed from work was 7 weeks.</p><p id="par0065" class="elsevierStylePara elsevierViewall">None of the patients developed postoperative contact dermatitis or bacterial, viral, or fungal infections. Three patients developed postinflammatory hyperpigmentation, which improved with time. Permanent mild hypopigmentation was observed in 1 patient and a small hypertrophic scar in the elbow pit in another. The scar responded very well to corticosteroid injections. Treatment satisfaction—assessed by questionnaire after several years of follow-up—was high in almost all cases. Six of the 8 patients rated the treatment outcome as satisfactory; 4 of these had a clinical improvement of more than 75%, while 2 had a clinical improvement of between 50% and 75%; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The patients were followed for between 1 and 12 years.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">HHD is a rare hereditary blistering skin disease. It runs a chronic course, with periods of remission punctuated by flares triggered by friction, sweating, heat, stress, local infection, UV radiation, or skin conditions such as contact dermatitis.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Patients with HDD have severely impaired quality of life. The lesions are painful and cause continuous discomfort as they are located in areas prone to friction from clothes. Furthermore, they frequently become infected, causing an unpleasant smell that can be highly distressing for patients.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Treatment outcomes in HDD are not very satisfactory, and in many cases, the lesions are aggravated by friction and bacterial, viral, or fungal infections. Avoidance of trauma and the treatment of secondary infections with antiseptic products and topical or systemic antibiotics can help to improve lesions. Long-term remission, however, is rare.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Satisfactory results have been reported patients treated with botulinum toxin,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> which reduces excessive sweating, an aggravating factor in HHD. Treatment with topical and oral corticosteroids or with immunomodulators, such as ciclosporin<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> and tacrolimus,<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–12</span></a> may reduce the inflammatory response associated with the disease. Effective results have been reported for other drugs, such as dapsone, methotrexate,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and retinoids,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> but the evidence is limited to isolated, anecdotal cases. However, none of these treatments alter the course of the disease; they provide only temporary relief from symptoms.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Surgical treatment is indicated in cases of HHD that are refractory to general measures and conventional oral or topical treatment. The surgical removal of lesions followed by skin grafting has produced successful outcomes in some patients,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> but the cosmetic and functional sequelae of surgery have led to the search for more superficial ablative techniques that would be equally effective but less aggressive.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Several reports of the use of dermabrasion to treat HHD have been published.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> Dermabrasion may be an effective treatment for lesions confined to small areas and it does not cause the highly visible scars associated with conventional surgery and skin grafts; it is also associated with a lower risk of scar retraction. Another advantage is that a skin donor site is not required. However, since the depth of skin removal in dermabrasion is highly dependent on the surgeon, there is an increased risk of secondary scarring. Furthermore, hemostasis is not attained and there is a greater risk of infection due to the dispersion of abraded tissue.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Laser therapy offers significant advantages over dermabrasion. On the one hand, it allows more precise control of treatment depth, thereby minimizing the risk of inadvertent penetration of the reticular dermis and scarring. On the other hand, treatment depth is predictable during each pass of the laser, making the technique more reproducible and less operator-dependent than dermabrasion and other techniques.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Two types of lasers are used for ablative skin resurfacing: the erbium:yttrium-aluminum-garnet (Er:YAG) laser and the CO<span class="elsevierStyleInf">2</span> laser. Both are used for cosmetic and therapeutic purposes (e.g., photorejuvenation and removal of skin hamartomas).</p><p id="par0110" class="elsevierStylePara elsevierViewall">The Er:YAG laser emits light with a wavelength of 2940<span class="elsevierStyleHsp" style=""></span>nm and permits precise ablation of tissue with minimal thermal damage to adjacent skin. The depth of penetration is more superficial than that achieved with the CO<span class="elsevierStyleInf">2</span> laser and hemostasis is not attained. Only 1 study to date has shown Er:YAG laser treatment to be effective in HHD.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The CO<span class="elsevierStyleInf">2</span> laser emits light with a wavelength of 10600<span class="elsevierStyleHsp" style=""></span>nm, which is largely absorbed by water in the tissues.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> It is used for skin rejuvenation and offers precise control of ablation depth and thermal damage.</p><p id="par0120" class="elsevierStylePara elsevierViewall">It offers several advantages over other lasers and techniques, including hemostasis in the treated area, greater reproducibility of results, and less operator dependency. Furthermore, when used with a plume removal system, it is cleaner—and associated with less biological risk—than dermabrasion.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In recent years, several reports of cases of HHD treated with CO<span class="elsevierStyleInf">2</span> lasers have been published.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24–30</span></a> In most of the cases, the treatment was very effective and associated with few adverse effects.</p><p id="par0130" class="elsevierStylePara elsevierViewall">We used the Sharplan Silk Touch laser with computerized scanning in our series. To minimize lateral thermal damage and consequently the risk of scarring and pigmentary changes in such cases, the pulse duration should be shorter than the thermal relaxation time of the target tissue (approximately 200-600<span class="elsevierStyleHsp" style=""></span>ms for skin).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The depth of ablation using this approach is 80 to 100 <span class="elsevierStyleHsp" style=""></span>μm with 2 passes and 150 <span class="elsevierStyleHsp" style=""></span>μm with 3 passes.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> We used 3 passes.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Based on our experience, we believe that an aggressive approach, consisting of 3 passes with a laser output power of at least 25<span class="elsevierStyleHsp" style=""></span>W, is necessary for CO<span class="elsevierStyleInf">2</span> laser resurfacing to be effective in HHD. Such an approach is sufficient to reach the deep papillary dermis and to cause fibrous bands of scar tissue in the treated area. A certain degree of thermal damage is also believed to be necessary to achieve good results and prevent recurrence. Insufficient thermal damage could explain why recurrence is sometimes observed in cases treated with lower output powers or short pulse durations. In our series, recurrence was more common in such cases. Specifically, new lesions appeared in patients who were treated with fewer than 3 passes and with an output power of less than 25<span class="elsevierStyleHsp" style=""></span>W. Recurrence is also common at the edges of treated areas. These lesions improve with time, and if they persist, they can be treated in a second laser session if the patient so wishes. Adverse effects associated with CO<span class="elsevierStyleInf">2</span> laser resurfacing can be of a short or long duration. Short-term complications include erythema, pruritus, acneiform eruptions, infections, and allergic or irritant contact dermatitis.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> All the patients in our series developed intense erythema that lasted for several months. No postoperative infections were observed, but it should be noted that all the patients received prophylactic antibiotics after the procedure.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Postoperative wound care is easier with CO<span class="elsevierStyleInf">2</span> laser therapy than with other techniques, such as dermabrasion, because it is associated with less bleeding, exudation, and crusting. In our series, open dressings were used to protect the wounds until complete reepithelialization.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Closed methods (semi-occlusive dressings) have been reported to result in less postoperative pain and faster reepithelialization. They are, however, more expensive and also associated with a higher rate of infection.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> In our patients, the treated areas healed in approximately 10 days.</p><p id="par0150" class="elsevierStylePara elsevierViewall">The main limitation of CO<span class="elsevierStyleInf">2</span> laser resurfacing in HHD is that it is a painful procedure. While topical anestetics can relieve a certain amount of pain, they are generally insufficient in larger areas or in areas in which more than 2 passes are used; in such cases, general or locoregional anesthesia is indicated. Postoperative pain tends to last for 10 to 14 days. In our series, most of the patients rated the pain as moderate or severe.</p><p id="par0155" class="elsevierStylePara elsevierViewall">The long-term adverse effects caused by CO<span class="elsevierStyleInf">2</span> laser therapy include erythema, hypopigmentation, hyperpigmentation, and permanent scarring.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> The incidence of postoperative hyperpigmentation varies according to skin type, with figures ranging between 26% and 36%; this adverse effect is more common in patients with dark skin.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Hyperpigmentation tends to be transient and generally resolves with time. Hypopigmentation has been reported in between 8% and 19% of patients and is related to ablation depth.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Because an aggressive approach is necessary to achieve good results, patients will almost certainly experience pigmentary or textural changes. Hyperpigmentation was observed in practically all the patients in our series; hypopigmentation was also seen, but in fewer cases. Skin changes due to CO<span class="elsevierStyleInf">2</span> laser resurfacing improve with time. However, as HHD affects areas that are normally covered, these changes are generally well tolerated by the patient.</p><p id="par0160" class="elsevierStylePara elsevierViewall">While certain textural changes were observed in our patients, only 1 patient developed a scar. This was located in an elbow pit and responded well to corticosteroid injections. No scars were observed in areas that are more prone to scarring, such as the back and the thorax.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Some authors have indicated that deep ablation, extending as far as the hair follicle, is necessary to prevent recurrence in Darier disease and HHD<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>; we agree with their opinion that these depths are necessary to achieve favorable outcomes.</p><p id="par0225" class="elsevierStylePara elsevierViewall">A small number of cases have reported the successful use of CO<span class="elsevierStyleInf">2</span> lasers in HHD and other acantholytic disorders.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24–30</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In all cases reported to date, the lesions treated covered less extensive areas than in our series. Furthermore, all the reports in the literature have described the treatment of lesions in the axillary, genitocrural, and submammary areas. In our series, 1 of the patients had extensive lesions that also affected the back, the neckline, the arms, and the abdomen. Treatment outcomes were good and the adverse effects were acceptable.</p><p id="par0175" class="elsevierStylePara elsevierViewall">The underlying mechanism through which laser therapy causes lesions to improve or disappear is not yet fully understood. It is known that ablation of the epidermis and dermis leads to reepithelialization based on cells from skin appendages. Under normal conditions, reepithelialization after deep erosion of the epidermis occurs through the expansion of keratinocytes derived from follicular stem cells.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The question that remains unanswered is why the new epidermis in patients with HHD is not defective, given that this disease is based on germinal mutations,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> present in every cell. It would be logical to assume that follicular and interfollicular stem cells would carry the same mutation. One hypothesis is that the mutation exists in both types of cells but is not expressed in follicular cells. Several types of epidermal cell clones (mutated and unmutated) may exist, and unmutated cells would possibly have a greater chance of surviving when there is dermal and epidermal damage followed by wound healing.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> If this were the case, unmutated clones would replace the defective clones in treated areas. We think that it would be interesting to explore this hypothesis in future studies.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Some authors have reported that successfully treated lesions are replaced by atrophic scars.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The area of fibrous tissue might harden the skin in this area, making it more resistant and consequently less prone to external mechanical damage. Another theory is that the destruction of eccrine glands could, at least in part, explain the success of CO<span class="elsevierStyleInf">2</span> laser therapy, as it would reduce triggers such as sweating.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Nevertheless, biopsies of treated areas have shown the persistence of eccrine glands.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Taken together, the above hypotheses suggest that treatment with CO<span class="elsevierStyleInf">2</span> laser may affect the threshold expression of the HHD mutation by inducing physical changes in the treated skin.</p><p id="par0190" class="elsevierStylePara elsevierViewall">CO<span class="elsevierStyleInf">2</span> laser skin resurfacing in HHD is a reproducible, operator-independent technique. It provides a bloodless surgical field and offers acceptable cosmetic results and long-term effectiveness, with few adverse effects. Given that HHD is an incurable condition, we believe that CO<span class="elsevierStyleInf">2</span> laser skin surfacing is a good alternative for cases that do not respond to conventional treatments. Patients should be informed that the energy required for effective treatment may cause textural and pigmentary skin changes. In general, this may not be a problem because the lesions are frequently located in unexposed areas, but the possible consequences should be considered in other, more visible, areas.</p><p id="par0195" class="elsevierStylePara elsevierViewall">The main limitations of this study are its retrospective design and the fact that we did not compare CO<span class="elsevierStyleInf">2</span> laser therapy with other treatment modalities.</p><p id="par0200" class="elsevierStylePara elsevierViewall">We believe that our findings are of interest as our series is the largest reported to date of HHD treated with CO<span class="elsevierStyleInf">2</span> laser resurfacing. Furthermore, we have provided the first-ever report of this modality being used to treat extensive lesions involving areas beyond the intertriginous areas.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of humans and animals</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that no tests were carried out in humans or animals for the purpose of this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Confidentiality of data</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of patient data and that all the patients included in this study have been appropriately informed and gave written informed consent to participate in this study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors obtained informed consent from the patients and/or subjects referred to in this article. This documentation is held by the corresponding author.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of Interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres104073" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Patients and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec91639" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres104074" "titulo" => array:5 [ 0 => "Resumen" 1 => "Introducción y objetivos" 2 => "Pacientes y método" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec91638" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of humans and animals" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-07-11" "fechaAceptado" => "2012-11-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec91639" "palabras" => array:3 [ 0 => "Laser therapy" 1 => "Carbon dioxide laser therapy" 2 => "Hailey-Hailey disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec91638" "palabras" => array:3 [ 0 => "Láser" 1 => "Dióxido de carbono" 2 => "Enfermedad de Hailey-Hailey" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0015">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hailey-Hailey disease (HHD), or benign familial pemphigus, is a rare autosomal dominant genodermatosis characterized by the formation of blisters. Eruptions are usually located in large skin folds, and when blisters become infected the condition can be very painful and disabling. HHD is difficult to treat. Many topical and systemic treatments have been used to bring exacerbations under control, but none have achieved medium- to long-term remission.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of 8 patients with HHD treated with carbon dioxide laser therapy in our hospital between 1999 and 2011. The patients’ mean age was 50.7 years. The 4 men and 4 women were followed for between 1 and 12 years.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Satisfactory outcomes were achieved for 6 of the patients. Clinical improvement was observed in more than 75% of the affected area in 4 patients and in 50% to 75% of the area in 2 patients. The effect of treatments was maintained over time. The poorest outcomes were observed in patients treated at lower potencies. When blistering recurred after treatment, a second laser session achieved a good response. We observed no adverse events other than slight changes in skin texture and pigmentation.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Carbon dioxide laser therapy was safe and effective in producing medium- to long-term improvement in HHD symptoms that were refractory to conventional treatments.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introducción y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Hailey-Hailey (EHH) o pénfigo familiar benigno es un rara genodermatosis ampollosa con herencia autonómica dominante. Cursa erosiones cutáneas, localizadas principalmente en los grandes pliegues, que se sobreinfectan y pueden ser muy dolorosas e incapacitantes para los pacientes. Es una patología difícil de tratar y aunque se han usado múltiples tratamientos tópicos y sistémicos para controlar los brotes de la enfermedad, ninguno de ellos consigue remisiones a medio-largo plazo.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Pacientes y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Realizamos un estudio retrospectivo de una serie de 8 casos de EHH tratados con láser CO2 en nuestro centro desde 1999 a 2011. Los pacientes tratados tenían una media de edad de 50,7 años, siendo 4 de ellos hombres y 4 mujeres. El seguimiento de los pacientes osciló entre 1 y 12 años.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De los 8 pacientes tratados, 6 obtuvieron unos resultados satisfactorios (4 pacientes con mejoría clínica > 75% y 2 pacientes entre 50-75%). Esta eficacia se mantuvo a lo largo del tiempo. Los peores resultados se observaron en los pacientes tratados con potencias más bajas. Las zonas con recidiva de la enfermedad después del tratamiento, se trataron con una segunda sesión de láser con buena respuesta. No observamos efectos adversos, salvo ligeros cambios texturales y de la pigmentación.</p> <span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El láser de CO2 es un tratamiento eficaz y seguro a medio-largo plazo en los casos de EHH sintomáticos y refractarios a tratamientos convencionales.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pretel-Irazabal M, et al. Tratamiento de la enfermedad de Hailey-Hailey con láser de dióxido de carbono: tratamiento en 8 pacientes. Actas Dermosifiliogr. 2013;104:325–33.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2333 "Ancho" => 1583 "Tamanyo" => 391463 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A, 56-year-old patient with severe Hailey-Hailey disease affecting both axillae. B, Photograph taken 1 month after treatment with carbon dioxide laser skin resurfacing. Note the considerable improvement in lesions and the small area of local recurrence in the armpit. The patient decided not to undergo partial treatment of this small area in a second laser session.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2187 "Ancho" => 1583 "Tamanyo" => 292484 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A, 47-year-old patient with axillary Hailey-Hailey disease. B, Outcome 1 year after treatment with carbon dioxide laser skin resurfacing. Note the postinflammatory hyperpigmentation with no evidence of recurrence.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2782 "Ancho" => 1555 "Tamanyo" => 381604 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A, 63-year-old patient with inguinal Hailey-Hailey disease. B, Photo taken 1 month after treatment with carbon dioxide laser skin resurfacing. Note the postoperative erythema.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 3452 "Ancho" => 2667 "Tamanyo" => 702198 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A 29-year-old patient with Hailey-Hailey disease. A, Lesions in the axillary area. B, Lesions in the submammary region. C, Lesions on the posterior aspect of the trunk. D, E, F. Appearance of lesions 9 months after treatment with carbon dioxide laser skin resurfacing. Note the considerable improvement in the lesions and the areas of residual hypopigmentation and hyperpigmentation. Despite these skin changes, the patient decided to undergo further treatment of lesions in other areas.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age, y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age at Diagnosis, y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Lesion Site \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Prior Treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CO<span class="elsevierStyleInf">2</span> Laser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Family History \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AxillaeGroinScrotumPerianal region \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral antibioticsTopical antifungalPimecrolimus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Axillae: 2-3 passes at 25<span class="elsevierStyleHsp" style=""></span>WGroin, scrotum, perineum: 5-6 passes at 25<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GroinAxillae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral corticosteroidsDapsone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Groin: 5 passes at 20<span class="elsevierStyleHsp" style=""></span>WAxillae: 6 passes at 20<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FatherSiblings \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AxillaeArmsGenitals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsAcitretin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Right axilla: 2 passes at 25<span class="elsevierStyleHsp" style=""></span>W, 1 localized pass at 25<span class="elsevierStyleHsp" style=""></span>WLeft axilla: first pass, 20<span class="elsevierStyleHsp" style=""></span>W; second pass, 25<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BackNeckAxillaeGroinVulvaArmsAbdomenChestKnee pits \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral corticosteroidsTopical antifungal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First session: groin + vulva at 25<span class="elsevierStyleHsp" style=""></span>W, 15<span class="elsevierStyleHsp" style=""></span>W, 15<span class="elsevierStyleHsp" style=""></span>WSecond session: axillae + abdomen + submammary region at 25<span class="elsevierStyleHsp" style=""></span>W, 25<span class="elsevierStyleHsp" style=""></span>W, 25<span class="elsevierStyleHsp" style=""></span>WThird session: back + abdomen + knee pits + elbow pits + upper thighs at 25<span class="elsevierStyleHsp" style=""></span>W, 25<span class="elsevierStyleHsp" style=""></span>W, 25<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GrandmotherMotherUncles/auntsSister \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NeckAxillaeGroinScrotumPerianal regionBack \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral antibioticsTopical and oral antifungalsAcitretinThalidomideDermabrasion of inguinal and perianal areas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2001: groin, axillae, inguinoscrotal regionLocal anesthesia: 3 passes at 20<span class="elsevierStyleHsp" style=""></span>W for perineum and 3 passes at 20<span class="elsevierStyleHsp" style=""></span>W for axillae2002: axillae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GroinPerineumAxillae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral corticosteroidsTopical and oral antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Groin: 20<span class="elsevierStyleHsp" style=""></span>W, 20<span class="elsevierStyleHsp" style=""></span>W, 18<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NephewSiblings \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AxillaeGroinScrotumPerianal region \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral corticosteroidsBotulinum toxin (axillae)Dermabrasion of axillae and groin (with recurrence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scrotum and perineumGroinAxillae: 2 passes at 20<span class="elsevierStyleHsp" style=""></span>W (left) and1 pass at 20<span class="elsevierStyleHsp" style=""></span>W (right)Right axillaScrotum and groin: 3 passes at 20<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FatherUncles/auntsSisters \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GroinVulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical and oral antibioticsTopical and oral corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Groin: 20<span class="elsevierStyleHsp" style=""></span>W, 20<span class="elsevierStyleHsp" style=""></span>W, 15<span class="elsevierStyleHsp" style=""></span>W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab185631.png" ] ] 1 => 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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Recovery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Adverse Effects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Improvement, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patient Satisfaction \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">><span class="elsevierStyleHsp" style=""></span>75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50%-75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local (axillary area) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50%-75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Small hypertrophic scar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Textural changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">><span class="elsevierStyleHsp" style=""></span>75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local (axillary area) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25%-50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">><span class="elsevierStyleHsp" style=""></span>75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local (axillary, \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">scrotal, inguinal areas) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypopigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">><span class="elsevierStyleHsp" style=""></span>75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypopigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><<span class="elsevierStyleHsp" style=""></span>25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab185630.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Results of Treatment With Carbon Dioxide (CO<span class="elsevierStyleInf">2</span>) Laser in Hailey-Hailey Disease.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:38 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z. 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| año/Mes | Html | Total | |
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| 2024 Noviembre | 15 | 18 | 33 |
| 2024 Octubre | 104 | 51 | 155 |
| 2024 Septiembre | 104 | 32 | 136 |
| 2024 Agosto | 151 | 80 | 231 |
| 2024 Julio | 131 | 38 | 169 |
| 2024 Junio | 139 | 35 | 174 |
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| 2024 Marzo | 110 | 28 | 138 |
| 2024 Febrero | 102 | 30 | 132 |
| 2024 Enero | 106 | 41 | 147 |
| 2023 Diciembre | 122 | 22 | 144 |
| 2023 Noviembre | 109 | 32 | 141 |
| 2023 Octubre | 119 | 37 | 156 |
| 2023 Septiembre | 150 | 39 | 189 |
| 2023 Agosto | 86 | 40 | 126 |
| 2023 Julio | 125 | 42 | 167 |
| 2023 Junio | 100 | 24 | 124 |
| 2023 Mayo | 140 | 28 | 168 |
| 2023 Abril | 105 | 30 | 135 |
| 2023 Marzo | 94 | 32 | 126 |
| 2023 Febrero | 77 | 32 | 109 |
| 2023 Enero | 99 | 29 | 128 |
| 2022 Diciembre | 82 | 37 | 119 |
| 2022 Noviembre | 40 | 40 | 80 |
| 2022 Octubre | 65 | 29 | 94 |
| 2022 Septiembre | 44 | 40 | 84 |
| 2022 Agosto | 50 | 46 | 96 |
| 2022 Julio | 43 | 53 | 96 |
| 2022 Junio | 40 | 28 | 68 |
| 2022 Mayo | 86 | 48 | 134 |
| 2022 Abril | 88 | 42 | 130 |
| 2022 Marzo | 105 | 67 | 172 |
| 2022 Febrero | 79 | 40 | 119 |
| 2022 Enero | 65 | 46 | 111 |
| 2021 Diciembre | 81 | 49 | 130 |
| 2021 Noviembre | 69 | 51 | 120 |
| 2021 Octubre | 88 | 62 | 150 |
| 2021 Septiembre | 53 | 35 | 88 |
| 2021 Agosto | 48 | 48 | 96 |
| 2021 Julio | 24 | 33 | 57 |
| 2021 Junio | 49 | 30 | 79 |
| 2021 Mayo | 36 | 37 | 73 |
| 2021 Abril | 91 | 35 | 126 |
| 2021 Marzo | 74 | 44 | 118 |
| 2021 Febrero | 93 | 18 | 111 |
| 2021 Enero | 48 | 17 | 65 |
| 2020 Diciembre | 36 | 19 | 55 |
| 2020 Noviembre | 34 | 17 | 51 |
| 2020 Octubre | 25 | 12 | 37 |
| 2020 Septiembre | 34 | 16 | 50 |
| 2020 Agosto | 36 | 16 | 52 |
| 2020 Julio | 22 | 16 | 38 |
| 2020 Junio | 29 | 16 | 45 |
| 2020 Mayo | 26 | 11 | 37 |
| 2020 Abril | 37 | 15 | 52 |
| 2020 Marzo | 28 | 14 | 42 |
| 2020 Febrero | 9 | 2 | 11 |
| 2020 Enero | 6 | 2 | 8 |
| 2019 Diciembre | 8 | 3 | 11 |
| 2019 Noviembre | 4 | 2 | 6 |
| 2019 Septiembre | 4 | 2 | 6 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 1 | 5 |
| 2019 Junio | 4 | 5 | 9 |
| 2019 Mayo | 6 | 19 | 25 |
| 2019 Abril | 4 | 3 | 7 |
| 2019 Marzo | 4 | 9 | 13 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 4 | 0 | 4 |
| 2018 Octubre | 3 | 2 | 5 |
| 2018 Septiembre | 3 | 0 | 3 |
| 2018 Junio | 0 | 7 | 7 |
| 2018 Mayo | 0 | 27 | 27 |
| 2018 Abril | 0 | 6 | 6 |
| 2018 Marzo | 1 | 4 | 5 |
| 2018 Febrero | 35 | 4 | 39 |
| 2018 Enero | 48 | 16 | 64 |
| 2017 Diciembre | 45 | 16 | 61 |
| 2017 Noviembre | 41 | 5 | 46 |
| 2017 Octubre | 46 | 8 | 54 |
| 2017 Septiembre | 36 | 8 | 44 |
| 2017 Agosto | 45 | 17 | 62 |
| 2017 Julio | 29 | 204 | 233 |
| 2017 Junio | 48 | 37 | 85 |
| 2017 Mayo | 63 | 13 | 76 |
| 2017 Abril | 62 | 11 | 73 |
| 2017 Marzo | 46 | 23 | 69 |
| 2017 Febrero | 197 | 8 | 205 |
| 2017 Enero | 97 | 11 | 108 |
| 2016 Diciembre | 110 | 8 | 118 |
| 2016 Noviembre | 197 | 11 | 208 |
| 2016 Octubre | 191 | 17 | 208 |
| 2016 Septiembre | 233 | 25 | 258 |
| 2016 Agosto | 235 | 13 | 248 |
| 2016 Julio | 131 | 24 | 155 |
| 2016 Junio | 8 | 14 | 22 |
| 2016 Mayo | 6 | 23 | 29 |
| 2016 Abril | 7 | 0 | 7 |
| 2016 Marzo | 3 | 0 | 3 |
| 2016 Febrero | 4 | 3 | 7 |
| 2016 Enero | 7 | 2 | 9 |
| 2015 Diciembre | 8 | 0 | 8 |
| 2015 Noviembre | 11 | 1 | 12 |
| 2015 Octubre | 11 | 0 | 11 |
| 2015 Septiembre | 13 | 2 | 15 |
| 2015 Agosto | 14 | 4 | 18 |
| 2015 Julio | 296 | 130 | 426 |
| 2015 Junio | 236 | 30 | 266 |
| 2015 Mayo | 317 | 35 | 352 |
| 2015 Abril | 173 | 8 | 181 |
| 2015 Marzo | 246 | 4 | 250 |
| 2015 Febrero | 217 | 6 | 223 |
| 2015 Enero | 119 | 5 | 124 |
| 2014 Diciembre | 117 | 4 | 121 |
| 2014 Noviembre | 114 | 7 | 121 |
| 2014 Octubre | 160 | 6 | 166 |
| 2014 Septiembre | 137 | 7 | 144 |
| 2014 Agosto | 157 | 7 | 164 |
| 2014 Julio | 158 | 6 | 164 |
| 2014 Junio | 139 | 14 | 153 |
| 2014 Mayo | 168 | 6 | 174 |
| 2014 Abril | 163 | 9 | 172 |
| 2014 Marzo | 169 | 11 | 180 |
| 2014 Febrero | 171 | 14 | 185 |
| 2014 Enero | 107 | 15 | 122 |
| 2013 Diciembre | 85 | 15 | 100 |
| 2013 Noviembre | 106 | 13 | 119 |
| 2013 Octubre | 86 | 13 | 99 |
| 2013 Septiembre | 88 | 7 | 95 |
| 2013 Agosto | 29 | 17 | 46 |
| 2013 Julio | 12 | 15 | 27 |
| 2013 Junio | 8 | 3 | 11 |
| 2013 Mayo | 6 | 6 | 12 |
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