Case and Research Letter
Superficial Granulomatous Pyoderma. Report of 2 Cases Treated With Topical Tacrolimus
Pioderma granulomatoso superficial. Presentación de 2 casos tratados con tacrolimus tópico
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Presentación de 2 casos tratados con tacrolimus tópico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "721" "paginaFinal" => "724" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Superficial Granulomatous Pyoderma. 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Report of 2 Cases Treated With Topical Tacrolimus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "721" "paginaFinal" => "724" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "N. Ormaechea-Pérez, A. López-Pestaña, C. Lobo-Morán, A. Tuneu-Valls" "autores" => array:4 [ 0 => array:4 [ "nombre" => "N." "apellidos" => "Ormaechea-Pérez" "email" => array:1 [ 0 => "nereaorma@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "López-Pestaña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Lobo-Morán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Tuneu-Valls" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pioderma granulomatoso superficial. Presentación de 2 casos tratados con tacrolimus tópico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1221 "Ancho" => 1584 "Tamanyo" => 176373 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Plaques with ulcers on the buttocks. B, Horseshoe-shaped ulcer measuring 7<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cm with an atrophic center and erythematous-violaceous borders on the upper back. C, Predominantly follicular inflammatory infiltrate with rupture of the follicular epithelium and granulomatous reaction with giant cells (hematoxylin-eosin, original magnification ×100). D, Residual scars on the buttocks. E, cribriform scars on the back.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">To the Editor:</span></p><p id="par0005" class="elsevierStylePara elsevierViewall">Superficial granulomatous pyoderma (SGP) or pyoderma vegetans is a rare inflammatory disease first described by Wilson-Jones and Winkelmann in 1988.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although considered a superficial, vegetative variant of pyoderma gangrenosum (PG), SGP has distinguishing features such as a chronic and slowly progressive course, lack of association with other diseases, shallower ulcers, the presence on histology of characteristic 3-layered granulomas,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and better response to treatment (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">We present 2 cases of SGP that were successfully treated with topical tacrolimus, with no recurrence after 5 years.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 77-year-old man with a history of hypertension and type 2 diabetes mellitus presented in July 2003 with erosive papular lesions, some of them with follicular dominance. The lesions coalesced to form plaques prone to ulceration and the formation of crusts on the buttocks and scalp (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). On the upper back he had a horseshoe-shaped ulcer measuring 7<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cm with an atrophic center and erythematous-violaceous borders (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The lesions had first appeared several months earlier and had been treated with topical antibiotics and oral cephalosporins. No improvement was observed. Cultures for bacteria, fungi, and mycobacteria were negative. Skin biopsy revealed an acute and chronic inflammatory infiltrate that was predominantly follicular, with rupture of the follicular epithelium and a granulomatous reaction with giant cells (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). Results of laboratory tests were within the normal range. The patient received successive treatments with corticosteroids and topical antibiotics, oral tetracyclines, trimethoprim-sulfamethoxazole, colchicine, and isotretinoin, but little improvement was noted. Finally, after 6 months of treatment with topical tacrolimus 0.1% the lesions healed, leaving cribriform scars (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D and 1E).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case 2</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 33-year-old woman with a history of schizophrenia came to our clinic with lesions on the right breast that had appeared a year earlier. She reported a history of right breast abscess that had required drainage by her gynecologist. Since then she had had erosive lesions with erythematous-violaceous borders on the upper outer quadrant of the breast that had not improved with topical antibiotics (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Cultures for bacteria, fungi, and mycobacteria were negative. A biopsy revealed a dense, mixed dermal infiltrate of plasma cells and suppurative granulomas (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). No microorganisms or foreign bodies were observed. Laboratory tests revealed only subclinical hypothyroidism. Following application of tacrolimus 0.1% ointment twice daily for 12 months, the lesions resolved.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">SGP is a rare condition for which we found some 60 references in the literature. It usually presents on the trunk as a slow-growing, painless superficial ulcer with vegetative borders, although SGP lesions have been reported on the face, the limbs, and even the scrotum.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> When SGP is located on the face it is important to consider a diagnosis of Wegener disease.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although SGP has a more indolent course than PG and usually responds better to treatment, chronicity and recurrence are common.</p><p id="par0030" class="elsevierStylePara elsevierViewall">SGP rarely accompanies systemic diseases, although isolated cases have been associated with chronic lymphatic leukemia, polymyalgia rheumatica, IgA paraproteinemia, sarcoidosis, rheumatoid arthritis, and ulcerative colitis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Histology characteristically reveals a superficial dermal abscess or ulcer which tends to form granulomas in 3 layers: a central zone with neutrophils, cellular debris, and evidence of bleeding; a surrounding layer of histiocytes and giant cells; and an outer layer of plasma cells and eosinophils.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Although not all cases have this characteristic histology, granulomatous inflammation is a consistent finding. The presence of eosinophils, plasma cells, and granulomas and the lack of involvement of the hypodermis help differentiate SGP from PG.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Moreover, sinus tracts and foreign bodies such as hair, suture material, and vegetable matter are usually observed in SGP but not in PG.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In both PG and SGP, definitive diagnosis is by exclusion. Differential diagnosis should include mycobacterial and fungal infections, ulcerative sarcoidosis, foreign body granuloma, and halogenoderma.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The pathogenesis is unknown. Characteristics supporting the hypothesis that SGP has a different etiology to PG are the presence of foreign bodies and the inflammatory infiltrate composed of giant cells, plasma cells, and eosinophils, in addition to neutrophils. SGP therefore seems to be a local response of the skin to an as yet unidentified element or to a normal tissue that the disordered immune response identifies as foreign.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The treatment of SGP is different to that of PG.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Spontaneous healing is not unusual, although recurrence is common. SGP located on the face is more refractory to treatment.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> As in PG, surgical removal of SGP is not recommended because of the risk of pathergy. Since SGP has a more indolent clinical course than PG, aggressive treatments are not usually required in principle (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The response to topical corticosteroids is usually good, though slow.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Good responses to topical tacrolimus have also been reported.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,10</span></a> Our positive experience with tacrolimus in 2 patients leads us to think it could be considered a first-line treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, we have presented 2 cases of SGP, an uncommon diagnosis. We emphasize the favorable response to topical tacrolimus, although complete cure took several months to achieve.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Case 2" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ormaechea-Pérez N, et al. Pioderma granulomatoso superficial. Presentación de 2 casos tratados con tacrolimus tópico. Actas Dermosifiliogr. 2013;104:721–4.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1221 "Ancho" => 1584 "Tamanyo" => 176373 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Plaques with ulcers on the buttocks. B, Horseshoe-shaped ulcer measuring 7<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cm with an atrophic center and erythematous-violaceous borders on the upper back. C, Predominantly follicular inflammatory infiltrate with rupture of the follicular epithelium and granulomatous reaction with giant cells (hematoxylin-eosin, original magnification ×100). D, Residual scars on the buttocks. E, cribriform scars on the back.</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" => 1667 "Ancho" => 1252 "Tamanyo" => 259960 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Erosions and scabs on the upper outer quadrant of the breast. B, 3-layer granuloma composed of a central zone with neutrophils, a surrounding layer with granulomatous inflammation, and an outer layer of plasma cells and eosinophils (hematoxylin-eosin, original magnification ×40).</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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"><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">Type of Feature \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">Superficial Granulomatous Pyoderma \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">Pyoderma Gangrenosum \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">Signs and symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Superficial ulcer, clean base \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Deep ulcer, necrotic center \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Painless \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Painful \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Located on trunk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Located on lower limbs \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Single lesion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple lesions \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Less often associated with systemic disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated with inflammatory bowel disease, rheumatoid arthritis, lymphoid tumors, etc. \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Slow growth \t\t\t\t\t\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">Histology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic granulomatous inflammatory infiltrate (eosinophils, plasma cells) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute diffuse inflammatory infiltrate (neutrophils) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Formation of fistulous tracts \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 fistulous tracts \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foreign bodies such as hair and suture material may be found. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 foreign bodies \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">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical: corticosteroids, tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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: corticosteroids, tacrolimus \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral: corticosteroids, tetracyclines, dapsone, ciclosporin, infliximab, intravenous immunoglobulins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral: corticosteroids, ciclosporin, dapsone, clofazimine, minocycline, oral tacrolimus, mycophenolate mofetil, TNF, intravenous immunoglobulins \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">Prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent relapses \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent 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">Often requires maintenance treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] 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| 2022 Junio | 32 | 49 | 81 |
| 2022 Mayo | 66 | 78 | 144 |
| 2022 Abril | 116 | 57 | 173 |
| 2022 Marzo | 100 | 84 | 184 |
| 2022 Febrero | 111 | 43 | 154 |
| 2022 Enero | 125 | 62 | 187 |
| 2021 Diciembre | 104 | 80 | 184 |
| 2021 Noviembre | 113 | 52 | 165 |
| 2021 Octubre | 58 | 60 | 118 |
| 2021 Septiembre | 56 | 49 | 105 |
| 2021 Agosto | 51 | 34 | 85 |
| 2021 Julio | 58 | 34 | 92 |
| 2021 Junio | 72 | 39 | 111 |
| 2021 Mayo | 70 | 43 | 113 |
| 2021 Abril | 154 | 73 | 227 |
| 2021 Marzo | 102 | 25 | 127 |
| 2021 Febrero | 96 | 35 | 131 |
| 2021 Enero | 46 | 21 | 67 |
| 2020 Diciembre | 39 | 22 | 61 |
| 2020 Noviembre | 46 | 31 | 77 |
| 2020 Octubre | 59 | 12 | 71 |
| 2020 Septiembre | 42 | 10 | 52 |
| 2020 Agosto | 33 | 23 | 56 |
| 2020 Julio | 42 | 21 | 63 |
| 2020 Junio | 49 | 33 | 82 |
| 2020 Mayo | 31 | 24 | 55 |
| 2020 Abril | 45 | 28 | 73 |
| 2020 Marzo | 38 | 28 | 66 |
| 2020 Febrero | 5 | 7 | 12 |
| 2020 Enero | 4 | 8 | 12 |
| 2019 Diciembre | 8 | 9 | 17 |
| 2019 Noviembre | 4 | 8 | 12 |
| 2019 Octubre | 0 | 4 | 4 |
| 2019 Septiembre | 8 | 3 | 11 |
| 2019 Agosto | 6 | 4 | 10 |
| 2019 Julio | 3 | 7 | 10 |
| 2019 Junio | 6 | 6 | 12 |
| 2019 Mayo | 4 | 37 | 41 |
| 2019 Abril | 9 | 6 | 15 |
| 2019 Marzo | 4 | 5 | 9 |
| 2019 Febrero | 0 | 1 | 1 |
| 2019 Enero | 6 | 0 | 6 |
| 2018 Diciembre | 6 | 0 | 6 |
| 2018 Noviembre | 7 | 0 | 7 |
| 2018 Octubre | 4 | 0 | 4 |
| 2018 Septiembre | 3 | 1 | 4 |
| 2018 Agosto | 0 | 7 | 7 |
| 2018 Julio | 0 | 2 | 2 |
| 2018 Junio | 0 | 2 | 2 |
| 2018 Mayo | 0 | 5 | 5 |
| 2018 Abril | 0 | 10 | 10 |
| 2018 Marzo | 5 | 2 | 7 |
| 2018 Febrero | 63 | 10 | 73 |
| 2018 Enero | 86 | 7 | 93 |
| 2017 Diciembre | 95 | 7 | 102 |
| 2017 Noviembre | 67 | 8 | 75 |
| 2017 Octubre | 63 | 6 | 69 |
| 2017 Septiembre | 66 | 14 | 80 |
| 2017 Agosto | 80 | 19 | 99 |
| 2017 Julio | 64 | 11 | 75 |
| 2017 Junio | 62 | 27 | 89 |
| 2017 Mayo | 64 | 15 | 79 |
| 2017 Abril | 49 | 7 | 56 |
| 2017 Marzo | 49 | 25 | 74 |
| 2017 Febrero | 83 | 13 | 96 |
| 2017 Enero | 43 | 21 | 64 |
| 2016 Diciembre | 63 | 25 | 88 |
| 2016 Noviembre | 87 | 16 | 103 |
| 2016 Octubre | 121 | 11 | 132 |
| 2016 Septiembre | 210 | 15 | 225 |
| 2016 Agosto | 184 | 14 | 198 |
| 2016 Julio | 81 | 5 | 86 |
| 2016 Junio | 8 | 13 | 21 |
| 2016 Mayo | 6 | 12 | 18 |
| 2016 Abril | 5 | 1 | 6 |
| 2016 Marzo | 6 | 1 | 7 |
| 2016 Febrero | 5 | 18 | 23 |
| 2016 Enero | 5 | 4 | 9 |
| 2015 Diciembre | 15 | 4 | 19 |
| 2015 Noviembre | 23 | 1 | 24 |
| 2015 Octubre | 22 | 6 | 28 |
| 2015 Septiembre | 7 | 8 | 15 |
| 2015 Agosto | 4 | 2 | 6 |
| 2015 Julio | 97 | 9 | 106 |
| 2015 Junio | 69 | 8 | 77 |
| 2015 Mayo | 72 | 12 | 84 |
| 2015 Abril | 57 | 6 | 63 |
| 2015 Marzo | 39 | 4 | 43 |
| 2015 Febrero | 43 | 6 | 49 |
| 2015 Enero | 35 | 11 | 46 |
| 2014 Diciembre | 40 | 2 | 42 |
| 2014 Noviembre | 30 | 9 | 39 |
| 2014 Octubre | 36 | 9 | 45 |
| 2014 Septiembre | 40 | 5 | 45 |
| 2014 Agosto | 39 | 11 | 50 |
| 2014 Julio | 41 | 14 | 55 |
| 2014 Junio | 53 | 7 | 60 |
| 2014 Mayo | 38 | 7 | 45 |
| 2014 Abril | 37 | 6 | 43 |
| 2014 Marzo | 36 | 5 | 41 |
| 2014 Febrero | 29 | 4 | 33 |
| 2014 Enero | 27 | 2 | 29 |
| 2013 Diciembre | 19 | 8 | 27 |
| 2013 Noviembre | 3 | 2 | 5 |
| 2013 Octubre | 3 | 4 | 7 |
| 2013 Septiembre | 0 | 2 | 2 |
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