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Correspondence Clinical Letters445 The Authors | Journal compilation Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1105PLEVA pemphigoides synchronous features of PLEVA and bullous pemphigoid DOI: 10.1111/ddg.12025 Dear Editors,We recently encountered a 12-year-old boy who simulta-neously displayed clinical and histopathological features of pityriasis lichenoides et varioliformis acuta (PLEVA) and bullous pemphigoid (BP).The boy presented with a mildly pruritic rash on his trunk, neck and proximal extremities. The skin changes had developed 2 weeks earlier on the chest and slowly progressed. After a week he had noted blisters on his legs. Shortly before the onset of the rash, he had a sore throat with slight fever (38.5 C). He was otherwise well, with no previous history of skin problems or allergies, and he was not on any medications.Skin examination revealed disseminated red-brown papu-les with some scaling and crust formation mainly on his trunk, neck and proximal extremities (Figure 1a, b). Furthermore, below the umbilicus and on the inner parts of the thighs, sever-al tense blisters were noted on affected but also on non-affected skin (Figure 1bd). Mucous membranes were not involved.Histopathologic examination of a biopsied papule show-ed a lichenoid lymphocytic infi ltrate with vacuolization of the basal layer of the epidermis and scattered apoptotic keratinocytes (Figure 2a). The lymphocytes were mainly CD-8 positive. Direct immunofl uorescence of perilesional skin revealed C3 deposits in a linear pattern at the dermo-epidermal junction (Figure 2b). Indirect immunofl uores-cence using monkey esophagus was positive in a pemphigoid pattern. ELISA investigations showed elevated BP180 IgG antibodies (47.17 U/ml, normal range 9.0 U/ml). BP230 IgG antibodies were within normal range. The clinical presentation with disseminated red-brown sca-ly papules on the trunk and light microscopic fi ndings were con-sistent with the diagnosis of PLEVA. However, the tense bullae, direct and indirect immunofl uorescence and the ELISA results were compatible with the diagnosis of bullous pemphigoid.Initial treatment with topical steroids (triamcinolone ace-tonide) and systemic clarithromycin (15 mg/kg/day) for 4 weeks produced little improvement. After changing to oral prednisone (0.5 mg/kg/day) and adding dapsone (1.5 mg/kg/day), the skin lesions slowly healed with residual hyperpigmentation over 4 weeks. Prednisone was reduced and stopped after a total of 6 weeks, whereas dapsone was given for a total of 10 months. During the treatment course, the level of BP180 IgG antibodies slowly returned to normal range ( 9.0 U/ml) over 6 months. Since stopping treatment, the patient has remained relapse-free with a total follow-up period of two years.According to the above described fi ndings and in analogy to the entity of lichen planus pemphigoides (LPP), we here pro-pose the term PLEVA pemphigoides for the condition seen in our patient. LPP is a rare autoimmune blistering disease that is characterized by the appearance of blistering skin lesions in patients with lichen planus 1. As proposed for the patho-genesis in LPP, we assume that the infl ammatory process of Clinical LettersFigure 1 Clinical presentation. Disseminated red-brown papules with scaling and crusts on the trunk and proximal extremities (a). Close-up view of the periumbilical area showing red-brown flat papules with central scaling as well as a solitary tense blis-ter below the umbilicus (b). Inner thighs with numerous tense blisters of varying size (c). Close up view of grouped blisters on otherwise mildly affected skin on the thighs (d).Correspondence Clinical Letters446 The Authors | Journal compilation Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1105PLEVA damages the dermoepidermal junction, thus exposing antigens (epitope spreading), which may evoke autoantibody formation 2, 3. Circulating antibodies against BP180 anti-gen have been detected in many cases of LPP and were present in our case of PLEVA pemphigoides 4, 5. These antibodies seem to be responsible for the development of secondary bull-ous pemphigoid with characteristic blister formation. As pre-viously described in patients with bullous pemphigoid 6 and LPP 5 we found a close correlation between the serum levels of antibodies against BP180 and disease activity, which adds further evidence for this new entity of PLEVA pemphigoides.In summary, we recommend a prompt skin biopsy for histopathology including direct immunofl uorescence and performing ELISA testing for BP180 IgG antibodies in pati-ents who present with clinical features of PLEVA and coexis-tent tense blisters.If there is evidence for a secondary autoimmune bliste-ring disease, treatment with systemic corticosteroids and/or dapsone may be more effective than traditional therapy for PLEVA, which generally includes UV phototherapy and/or systemic antibiotics.Stephan Nobbe1, Lisa Weibel1,2, Andreas Kuehne3, Sharon Gobbi1, Katrin Kerl1, Antonio Cozzio1(1) Department of Dermatology, University Hospital Zurich, Zurich, Switzerland(2) University Childrens Hospital Zurich, Zurich, Switzerland(3) Private Dermatology Practice, Buchs, SwitzerlandFigure 2 Histology and direct immunofluorescence. Lichenoid lymphocytic infiltrate with vacuolization of the basal layer of the epidermis and scattered apoptotic keratinocytes (a). C3 deposits in linear pattern at the dermoepidermal junction (b).Figure 1 Continued.Correspondence Clinical Letters447 The Authors | Journal compilation Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1105Correspondence toStephan Nobbe, MDUniversity Hospital Zurich, Department of DermatologyGloriastrasse 318091 Zurich, SwitzerlandE-mail: stephan.nobbeusz.chReferences1 Cohen DM, Ben-Amitai D, Feinmesser M, Zvulunov A. Child-hood Lichen planus pemphigoides: a case report and review of the literature. Pediatr Dermatol 2009; 5: 56974.2 Chan LS, Vanderlugt CJ, Hashimoto T, Nishikawa T, Zone JJ, Black MM, Wojnarowska F, Stevens SR, Chen M, Fairley JA, Woodley DT, Miller SD, Gordon KB. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol 1998; 110: 1039.3 Stingl G, Holubar K. Coexistence of lichen planus and bullous pemphigoid. An immunopathological study. Br J Dermatol 1975; 93: 31320.4 Zillikens D, Caux F, Mascaro JM, Wesselmann U, Schmidt E, Prost C, Callen JP, Brcker EB, Diaz LA, Giudice GJ. Autoan-tibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180. J Invest Dermatol 1999; 113: 11721.5 Barnadas MA, Ro E, Dalmau J, Dalmau J, Alomar A, Martnez L, Gelp C. Lichen planus pemphigoides: detection of anti-BP 180 antibodies by ELISA and immunoblotting tests. J Eur Acad Dermatol Venereol 2010; 24: 13601.6 Schmidt E, Obe K, Brcker EB, Zillikens D. Serum levels of auto-antibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol 2000; 136: 1748.Paradoxical reaction to etanercept: Development of pyoderma gangraenosum during therapy of psoriasis arthritisDOI: 10.1111/ddg.12032 Dear Editors,Etanercept (Enbrel) is approved for the treatment of refrac-tory moderate-to-severe psoriasis vulgaris, psoriatic arthri-tis, moderate to severe rheumatoid arthritis, as well as seve-re ankylosing spondylitis. In at least three case reports and numerous other individual patients etanercept has been used successfully to treat pyoderma gangrenosum 1, SAPHO-syndrome, PAPA syndrome, and hidradenitis suppurativa 2, sometimes in patients with concomitant chronic infl ammato-ry bowel disease or rheumatoid arthritis.A 58-year-old woman had a 34-year history of plaque psoriasis and a 15-year history of psoriatic arthritis. The joint disorder was treated with non-steroidal anti-infl amm-atory drugs (NSAID), methotrexate, and most recently lefl u-nomide, which was discontinued due to side effects. She was started on etanercept 50 mg subcutaneously once weekly, as well as with oral diclofenac. Treatment led to signifi cant im-provement of the joint symptoms and the psoriatic plaques. The Psoriasis Arthritis Disease Activity Score (DAS28) fell over a period of 12 weeks from 5.18 to 1.89. There were still solitary, slightly erythematous scaling lesions bilaterally on the elbows, knees, and shins. About one month before beginning etanercept thera-py, the patient had developed diarrhea. The results of a co-lonoscopy with a biopsy led to a diagnosis of microscopic colitis. This was successfully treated with the corticostero-id oral budesonide 3 mg/daily. Five months after beginning etanercept, the patient developed an abscess on the left temp-le. Her family doctor lanced the abscess. Later a 2 cm ulcer developed. When pressure was applied, pus appears at the margin (Figure 1). The ulcer had a vegetative and partly crusty base. There were also progressive, multiple, bizarrely confi gured ulcerations with bright red undermined borders and long fi stulous tracts in the groin and perivulvar region on both sides (Figure 2, 3). No comedones or nodules were found, ruling out acne inversa, for which the ulcerations on the temple would have also been atypical. A biopsy taken from the groin region showed minimally abnormal stratifi ca-tion of the epidermis; the dermis contained a diffuse, partly perivascular, lymphohistiocytic infl ammatory infi ltrate with Clinical LettersCorrespondence Clinical Letters448 The Authors | Journal compilation Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1105solitary eosinophils. The absence of neutrophils may have been due to prior treatment with steroids and other drugs. The results of direct immunofl uorescence were negative. The possibility of underlying hematological disease including monoclonal gammopathy was rule out based on the results of a blood differential and serum-protein electrophoresis with immunofi xation.We made a clinical diagnosis of pyoderma gangrenosum, discontinued etanercept and started oral prednisone 1 mg/kg of body weight, as well as topical antiseptic therapy with 0.1 % octenidine solution. This led to dramatic improve-ment of the ulcerations (Figure 4). Repeat colonoscopy show-ed infl ammation with tissue eosinophilia, most likely due to NSAID use, without specifi c histopathological changes suggesting microscopic colitis or ulcerative colitis. We thus stopped diclofenac treatment. We could not confi rm the presence of chronic infl ammatory bowel disease due to eta-nercept or metastatic Crohn 3 disease. The onset of chronic infl ammatory bowel disease during the use of TNF-alpha antagonists, including etanercept has been reported on oc-casion 46. Yet in our patient the bowel symptoms began before the patient started using etanercept.Figure 1 Purulent ulcer of the left temple/cheak region of about 2 x 3 cm diameter, newly arising following 5 months of therapy with etanercept because of proriasis arthritis.Figure 2 Ulceration and fistulation involving the groin and pe-rigenital region, newly arising during therapy with etanercept.Figure 4 Pyoderma gangraenosum affecting the right groin, healing 12 days after discontinuing etanercept and starting systemic steroid medication.Figure 3 Biopsied pyoderma gangraenosum affecting the right groin newly arising during therapy with etanercept.Correspondence Clinical Letters449 The Authors | Journal compilation Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1105The paradoxical onset of pyoderma gangrenosum has been reported in patients undergoing treatment for arthri-tis or ulcerative colitis using the TNF-alpha antagonists infl iximab 7, 8 and adalimumab 9, although to the best of our knowledge no association with etanercept has yet been reported. We believe that in our patient the pyoderma gan-grenosum either could have been triggered by etanercept or, at the very least the drug did not counteract the development of disease. A possible mechanism of induction of pyoderma gangrenosum due to etanercept use could be elevated pro-duction of interferon- or TNF-alpha T cells with the use of TNF-alpha antagonists 4, 6. There has also been discussion of activation of previously masked infl ammatory processes due to steroid therapy, once the steroids are discontinued and the patient is using a biological therapy. The activati-on of infectious agents as a pathomechanism has also been discussed 5. One could consider continuing the treatment of psoriatic arthritis with the biological agent ustekinumab, which is effective against the disease 10, in order to use an immunomodulatory mechanism other than the one involving inhibition of TNF-alpha 11.Lutz Kowalzick1, Julia Bertolini2, Christine Baumann3, Beate Walther4, Beate Truhm1, Lena Eickenscheidt1(1) Department of Dermatology and Allergology, HELIOS Vogtland-Klinikum Plauen GmbH, Plauen, Germany(2) Institute of Pathology, University of Leipzig, Germany(3) Practice for Internal Medicine and Rheumatology, Plauen(4) Department of Internal Medicine I, HELIOS Vogtland-Klini-kum Plauen GmbH, Plauen, GermanyCorrespondence toProf. Dr. med. habil. Lutz KowalzickKlinik fr Hautkrankheiten und AllergologieHELIOS Vogtland-Klinikum Plauen GmbHPostfach 100153 08505 Plauen, GermanyE-mail: lutz.kowalzickhelios-kliniken.deReferences1 Charles CA, Leon A, Banta MR, Kirsner RS. Etanercept for the treatment of refractory pyoderma gangraenosum: a brief series. Int J Dermatol 2007; 46: 10959.2 Giamerellos-Bourboulis EJ, Pelekanou E, Antopoulou A, Petropoulou H, Baziaka F, Karagini V, Stavrianeas N, Giamarel-lou H. An open-label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa. Brit J Dermatol 2008; 158: 56772.3 Siroy A, Warsman J. Metastatic Crohn Disease: a rare cutaneous entity. Arch Pathol Lab Med 2012

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