YM Son, et al Ann Dermatol Vol. 23, Suppl. 3, 2011 http://dx.doi.org/10.5021/ad.2011.23.S3.S310 CASE REPORT The Neumann Type of Pemphigus Vegetans Treated with Combination of Dapsone and Steroid Young-Min Son, M.D., Hong-Kyu Kang, M.D., Jeong-Hwan Yun, M.D., Joo-Young Roh, M.D., Jong-Rok Lee, M.D. Department of Dermatology, Gachon University of Medicine and Science, Gil Hospital, Incheon, Korea Pemphigus vegetans is a rare variant of pemphigus vulgaris INTRODUCTION and is characterized by vegetating lesions in the inguinal folds and mouth and by the presence of autoantibodies Pemphigus diseases are a group of autoimmune disorders against desmoglein 3. Two clinical subtypes of pemphigus that have certain common features, and these diseases are vegetans exist, which are initially characterized by flaccid considered to be potentially fatal1,2. Pemphigus vegetans bullae and erosions (the Neumann subtype) or pustules (the is a variant of pemphigus vulgaris and is the rarest form of Hallopeau subtype). Both subtypes subsequently develop pemphigus; Pemphigus vegetans comprises less than 1∼ into hyperpigmented vegetative plaques with pustules and 2% of all pemphigus cases1,3,4. This variant is charac- hypertrophic granulation tissue at the periphery of the terized by flaccid bullae or pustules that erode to form hy- lesions. Oral administration of corticosteroids alone does not pertrophic papillated plaques that predominantly involve always induce disease remission in patients with pemphigus the intertriginous areas, the scalp, and the face; in 60∼ vegetans. We report here on a 63-year-old woman with 80% of all cases, the oral mucosa are also affected5,6. pemphigs vegetans. She had a 2-year history of vegetating, Clinically, two subtypes are recognized: the Neumann papillomatous plaques on the inguinal folds and erosions of and Hallopeau subtypes1,3. The Neumann type is charac- the oral mucosa. The enzyme-linked immunosorbent assay terized by bullae that extend and coalesce; they then was positive for anti-desmoglein 3, but it was negative for evolve to vegetating masses which become dry, hyper- anti-desmoglein 1. She was initially treated with systemic keratotic, and fissured. The Hallopeau type is characteri- steroid, but no improvement was observed. The patient was zed by a polycyclic eruption of pustules that form firm then successfully treated with a combination of systemic pink papillomas which progressively flatten and change to steroid and dapsone with a good clinical response. (Ann dark brown plaques with a benign course and few Dermatol 23(S3) S310∼S313, 2011) relapses4,7,8. We report here on a 63-year-old woman with a Neumman -Keywords- type of pemphigus vegetans who was was successfully Dapsone, Pemphigus vegetans treated with dapsone. CASE REPORT Received December 2, 2010, Revised January 14, 2011, Accepted for publication January 18, 2011 A 63-year-old woman presented with a 2-year history of Corresponding author: Jong-Rok Lee, M.D., Department of Der- vegetating, papillomatous plaques on the inguinal folds matology, Gachon University of Medicine and Science, Gil Hospital, and erosions of the oral mucosa, tongue, and perioral 1198 Guwol-dong, Namdong-gu, Incheon 405-760, Korea. Tel: area. The cutaneous lesions started with vesicles and 82-32-460-3114, Fax: 82-32-460-2001, E-mail: [email protected] bullae that extended peripherally and later formed the This is an Open Access article distributed under the terms of the vegetating lesions. No other lesions on the skin were seen, Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0) which permits unrestricted and there was no history of other skin disease. She had no non-commercial use, distribution, and reproduction in any medium, family history of a blistering disorder. On physical exami- provided the original work is properly cited. nation, there were oozing, erosive vesicles on the lip and S310 Ann Dermatol The Neumann Type of Pemphigus Vegetans Treated with Combination of Dapsone and Steroid Fig. 1. Oozing erosive vesicles on the lip (A) and hypertrophic verrucous vegetative plaques on the inguinal folds (B). Fig. 2. (A) A biopsy of an erosive vesicle from the lip showed a suprabasal cleft with scattered acantholytic cells (H&E, ×20). (B, C) A biopsy of the vegetating plaque from the inguinal folds showed a hyperplastic epidermis, eosinophilic spongiosis, and intraepithelial abscesses packed with eosinophils. Eosinophils also dominated the dense inflammatory infiltrate in the papillary dermis (H&E, ×10, ×20). hypertrophic verrucous vegetative plaques on the inguinal recombinant purified desmoglein (Dsg) 1 and Dsg3 folds (Fig. 1). Laboratory assessments showed an absolute (Medical & Biological Laboratories corporation, Nagoya, eosinophil count of 20.7% (normal range: 0∼5%) and a Japan) were positive for Dsg3 (a titer of 172.2 U/ml) but lymphocyte count of 17.6% (normal range: 20∼44%). not Dsg 1. Based on the clinical, histopathologic, and The results of routine serum chemistry, including liver ELISA findings, pemphigus vegetans as a definite diagnosis function tests, were within the normal ranges. was made. Biopsy specimens were obtained from the erosive vesicles The patient was treated with oral methylprednisolone 16 on the lip and a verrucous plaque on the inguinal folds. mg daily, but no improvement was observed after 7 days The histologic findings of the erosive vesicles from the lip of treatment. Subsequently, treatment with a combination revealed a suprabasal cleft with scattered acantholytic of oral methylprednisolone 12 mg daily and dapsone 50 cells (Fig. 2A). Biopsy of the vegetating plaque from the mg daily was started. The erosive vesicular and verrrucous inguinal folds showed massive papillomatosis and spon- lesions were healed 3 weeks after this combination giosis, as well as eosinophilic granulocytes throughout the therapy (Fig. 3). During treatment, the eosinophil count entire thickness of the epithelium. In addition to eosino- returned to normal. The doses of methylprednisolone philic spongiosis, we also found sharply bordered, eosino- were tapered to 8 mg daily without the appearance of philic abscesses in all the layers of the epidermis. Eosino- new lesions. The patient is presently well controlled on phils also dominated the dense inflammatory infiltrate in maintenance therapy of 4 mg methlyprednisolone and 50 the papillary dermis (Fig. 2B). Antibodies to desmoglein 1 mg dapsone daily. She has not had any recurrence of the and 3 were analyzed using a specific enzyme-linked lesions since. immunosorbent assay (ELISA). The results of ELISA with Vol. 23, Suppl. 3, 2011 S311 YM Son, et al Fig. 3. (A, B) The lesion improved and disappeared 3 weeks after treatment. DISCUSSION pemphigus vegetans seem to differ from those of the vulgaris type by an eosinophic response, formation of Pemphigus vegetans is a rare clinical form of pemphigus microabscesses, and the extent of vesiculation3,4. The and is characterized by verrucous intertriginous plaques1,2. immunofluorescence findings in pemphigus vegetans are Analysis of the demographic and clinical data of the indistinguishable from those of pemphigus vulgaris3,11. reported cases of pemphigus vegetans in the literature Direct immunofluorescence demonstrates deposition of reveals that individuals of all ages, including children, can IgG and C3 on the cell surface of keratinocytes. Indirect be affected by the disease9,10. immunofluorescence reveals circulating antiepithelial Pemphigus vegetans is classified based on the initial cell-surface IgG4,11. However, our patient refused skin clinical picture and disease course as the Neumman type biopsy for immunofluorescence because of her economic or Hallopeau type2,7. Consistent with Neumann type dis- status, so an immunofluorescence study was not per- ease, our patient had initial mucosal erosions and dissemi- formed. nated, slightly rupturing blisters on the intertriginous It might be difficult to make a diagnosis precisely due to areas, which formed the basis for papillomatous vege- the varied clinical presentation and the histopathological tations4,5. Oral involvement is present in nearly all pemphi- resemblance to other conditions. Some diseases or disor- gus vegetans cases. A characteristic feature of pemphigus ders have to be differentiated from pemphigus vegetans1,2. vegetans is the cerebriform tongue, which is characterized These include the vegetating lesions of other bullous auto- by a pattern of sulci and gyri on the dorsum of the immune skin diseases, such as bullous pemphigoid or IgA tongue9,10. pemphigus, the chronic inflammatory plaques in Haiely- Pemphigus vegetans is caused by intercellular autoanti- Haiely disease, and especially vegetating pyoderma1,3. bodies primarily against desmogleins 1 and 3, which are Making the differential diagnosis from pyostomatitis vege- adhesion molecules in the desmosomes of keratino- tans is especially important. Both conditions show similar cytes1,2,4. Previous studies have consistently reported auto- clinical and histopathological findings, and only direct antibodies against desmoglein 3 in patients with pemphi- and indirect immunofluorescence studies enable the clini- gus vegetans, and our patient was no exception. Autoanti- cian to distinguish between these two disorders. Only the bodies against desmoglein 1, desmocollin 1 and 2, and lesions of pemphigus vegetans characteristically show periplakin have occasionally been detected in previously epithelial intercellular