Pemphigus vegetans

Background

This rare form of pemphigus vulgaris has two variants. In both types, oral lesions are common. The tounge may also be involved having a cerebriform pattern. Thickening of the scalp and vulva may occur.

Neumann type Initial vesicular erosive lesions resembling pemphigus vulgaris evolving into vegetating plaques Ab directed against 130 and 85 kd polypeptides of the pemphigus vulgaris antigen

Hallopeau type Initial pustual lesions with benign course and few relapses Ab directed against 130 kd polypeptide

In the Neumann type, there are intraepidermal vesicles with suprabasilar acantholysis. No eosinophilic microabscesses are present. In the Hallopeau type, eosinophilic spongiosis and microabscesses are present. In the later vegetative plaques, there is prominent epidermal hyperplasia with hyperkeratosis, papillomatosis, and occasional acantholysis.

The pathologist must distinguish this from pyodermatitis-pyostomatitis vegetans. This disorder has annular pustular lesions occurring with vegetating oral lesions. It has been associated with inflammatory bowel disease. Histologically, there is only focal acantholysis with variable epithelial hyperplasia and more inflammatory cells than pemphigus vulgaris.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/
Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

DISEASE ASSOCIATIONS CHARACTERIZATION

ACNE

A case of pyoderma vegetans associated with acne conglobata.

Fujita M, Okamoto S.

Department of Dermatology, School of Medicine, Chiba University, Japan.
J Dermatol 1990 Jul;17(7):429-34 Abstract quote
A 41-year-old man visited our clinic because of vegetating plaques resembling pemphigus vegetans on his sacral and perianal areas.

He had also suffered from acne conglobata since adolescence. A biopsy specimen taken from the perianal area showed marked acanthosis, exocytosis, and inflammatory infiltrates in the dermis, but no acantholysis. Direct and indirect immunofluorescent tests were negative for anti-intercellular antibodies. Bacterial cultures from the lesions showed many different types of organisms.

We diagnosed the case as pyoderma vegetans and discussed the relationship between pyoderma vegetans and other pyoderma.

CAPTOPRIL

Captopril-induced pemphigus vegetans with Charcot-Leyden crystals.

Pinto GM, Lamarao P, Vale T.

Department of Dermatology, Curry Cabral Hospital, Lisboa, Portugal.
J Am Acad Dermatol 1992 Aug;27(2 Pt 2):281-4 Abstract quote
A 78-year-old woman developed intertriginous vegetating plaques, mouth ulcers, and a cerebriform tongue after 11 months of captopril therapy.

Findings of clinical, histologic, and immunofluorescence testing were consistent with a diagnosis of pemphigus vegetans. In addition, Charcot-Leyden crystals were observed within some of the intraepidermal, eosinophilic abscess cavities, which were bordered by granular cells undergoing keratinization. The skin lesions cleared rapidly after discontinuation of captopril.

To the best of our knowledge, this report describes the first case of pemphigus vegetans induced by captopril.

MALIGNANCY

Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy.

Bastiaens MT, Zwan NV, Verschueren GL, Stoof TJ, Nieboer C.

Department of Dermatology, Free University Hospital, Amsterdam, The Netherlands.
Int J Dermatol 1994 Mar;33(3):168-71 Abstract quote
BACKGROUND. Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics.

METHODS. Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded.

RESULTS. Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature.

CONCLUSIONS. Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.

PATHOGENESIS CHARACTERIZATION

COMPLEMENT

Epidermal antigens and complement-binding anti-intercellular antibodies in pemphigus vegetans, Hallopeau type.
Hashizume H, Iwatsuki K, Takigawa M.

Department of Dermatology, Hamamatsu University School of Medicine, Japan.
Br J Dermatol 1993 Dec;129(6):739-43 Abstract quote
The serum of a 34-year-old woman with the Hallopeau type of pemphigus vegetans (PVg) contained antibodies against a 130-kDa polypeptide in human epidermal lysates, as revealed by Western blot analysis. The serum strongly fixed complement in vitro, and the PVg lesional skin contained a predominance of complement-fixing IgG2 and IgG4.

Although the antigens reactive with sera from PVg and pemphigus vulgaris were the same, strong fixation of complement by PVg antibodies, due to the presence of complement-dependent IgG subclasses, and subsequent in situ activation of complement, might explain the marked infiltration of neutrophils and eosinophils in PVg.

CLINICAL VARIANTS CHARACTERIZATION

BALANITIS, CHRONIC

Chronic balanitis owing to pemphigus vegetans.

Castle WN, Wentzell JM, Schwartz BK, Clendenning WE, Selikowitz SM.

J Urol 1987 Feb;137(2):289-91 Abstract quote
Pemphigus is an autoimmune bullous dermatosis in which intercellular antibodies are associated with loss of intercellular cohesion. Pemphigus vegetans, a rare variant of pemphigus, is manifested by vegetating plaques, usually in intertriginous areas of patients who probably have an increased resistance to the disease.

We report a case of chronic balanitis owing to pemphigus vegetans, and discuss proposed pathogenic mechanisms and treatment.

CHILDHOOD

Pemphigus vegetans in a child.

Sillevis Smitt JH, Mulder TJ, Albeda FW, Van Nierop JC.

Department of Dermatology, University of Amsterdam, The Netherlands.
Br J Dermatol 1992 Sep;127(3):289-91 Abstract quote
Pemphigus vegetans was diagnosed in a 12-year-old boy based on clinical, histopathological and immunohistological findings.

To our knowledge, this is the first case of juvenile pemphigus vegetans to be published in the literature. Suggested treatment with prednisone and azathioprine was refused, and the patient was treated with a decoction of herbs prescribed by a practitioner of traditional Chinese herbal medicine. This treatment gave excellent results. Possible active components of the treatment are discussed.

SPECIAL STAINS/
IMMUNOPEROXIDASE CHARACTERIZATION

DIRECT IMMUNOFLUORESCENCE

Unusual immunofluorescence findings in pemphigus vegetans.

Larsen FS, Clausen J.
Dermatologica 1983;166(5):247-9 Abstract quote
An 84-year-old man with massive verrucous lesions in the intertriginous areas is reported. The clinical, histological and electron microscopical findings indicated pemphigus vegetans.

However, in addition to the intraepidermal findings direct immunofluorescence showed a linear deposit of IgG and C3 at the basement membrane.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSIS

Pemphigus vegetans. Neumann type and Hallopeau type.

Ahmed AR, Blose DA.
Int J Dermatol 1984 Mar;23(2):135-41 Abstract quote
Two cases of pemphigus vegetans are presented, one of the Neumann type and one of the Hallopeau type. The differences between the two subsets are clinical presentation and course. Patients with the Hallopeau type often have a relatively benign disease, require lower doses of systemic corticosteroids, and usually have a prolonged remission. Patients with the Neumann type have a course similar to pemphigus vulgaris, need higher doses of systemic corticosteroids, and have relapses and remissions.

The histologic findings in the vegetating lesions are similar in both types. The immunopathologic features of both types are indistinguishable and similar to pemphigus vulgaris. IgM staining of eosinophilic microabscesses was observed in one case.

TREATMENT

DAPSONE

Pemphigus vegetans: its relationship to eosinophilic spongiosis and favorable response to dapsone.

Pearson RW, O'Donoghue M, Kaplan SJ.
Arch Dermatol 1980 Jan;116(1):65-8 Abstract quote
Two cases of pemphigus vegetans are presented. One, an example of the Hallopeau type of the disease, was found to have early lesions that simulated eosinophilic spongiosis clinically and histologically.

The other had lesions that were largely confined to the oral mucosa and was also considered to be the Hallopeau type of the disease in a limited form. The cases of these two patients were compared with a typical case of eosinophilic spongiosis.

All were controlled with dapsone therapy.

ETRETINATE

Successful treatment of pemphigus vegetans by addition of etretinate to systemic steroids.

Ichimiya M, Yamamoto K, Muto M.

Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan.
Clin Exp Dermatol 1998 Jul;23(4):178-80 Abstract quote
Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by flaccid bullae, which become eroded and form vegetations or papillomatous proliferations, especially in the intertriginous areas. Oral administration of corticosteroids alone does not always induce disease remission in pemphigus vegetans.

We report a 44-year-old Japanese man with pemphigus vegetans. Although corticosteroid therapy resulted in healing of the oral ulcers and skin bullae, verrucous vegetations continued to develop. In contrast, by combining corticosteroid with etretinate, verrucous vegetations improved.

Thus we propose that the combination therapy of steroid and etretinate might be an effective adjunct in the therapy of pemphigus vegetans.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

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Last Updated January 11, 2006

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DISEASE ASSOCIATIONS	CHARACTERIZATION
ACNE
A case of pyoderma vegetans associated with acne conglobata. Fujita M, Okamoto S. Department of Dermatology, School of Medicine, Chiba University, Japan.	J Dermatol 1990 Jul;17(7):429-34 Abstract quote A 41-year-old man visited our clinic because of vegetating plaques resembling pemphigus vegetans on his sacral and perianal areas. He had also suffered from acne conglobata since adolescence. A biopsy specimen taken from the perianal area showed marked acanthosis, exocytosis, and inflammatory infiltrates in the dermis, but no acantholysis. Direct and indirect immunofluorescent tests were negative for anti-intercellular antibodies. Bacterial cultures from the lesions showed many different types of organisms. We diagnosed the case as pyoderma vegetans and discussed the relationship between pyoderma vegetans and other pyoderma.
CAPTOPRIL
Captopril-induced pemphigus vegetans with Charcot-Leyden crystals. Pinto GM, Lamarao P, Vale T. Department of Dermatology, Curry Cabral Hospital, Lisboa, Portugal.	J Am Acad Dermatol 1992 Aug;27(2 Pt 2):281-4 Abstract quote A 78-year-old woman developed intertriginous vegetating plaques, mouth ulcers, and a cerebriform tongue after 11 months of captopril therapy. Findings of clinical, histologic, and immunofluorescence testing were consistent with a diagnosis of pemphigus vegetans. In addition, Charcot-Leyden crystals were observed within some of the intraepidermal, eosinophilic abscess cavities, which were bordered by granular cells undergoing keratinization. The skin lesions cleared rapidly after discontinuation of captopril. To the best of our knowledge, this report describes the first case of pemphigus vegetans induced by captopril.
MALIGNANCY
Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy. Bastiaens MT, Zwan NV, Verschueren GL, Stoof TJ, Nieboer C. Department of Dermatology, Free University Hospital, Amsterdam, The Netherlands.	Int J Dermatol 1994 Mar;33(3):168-71 Abstract quote BACKGROUND. Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics. METHODS. Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded. RESULTS. Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature. CONCLUSIONS. Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.

Neumann type	Initial vesicular erosive lesions resembling pemphigus vulgaris evolving into vegetating plaques	Ab directed against 130 and 85 kd polypeptides of the pemphigus vulgaris antigen
Hallopeau type	Initial pustual lesions with benign course and few relapses	Ab directed against 130 kd polypeptide

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

CLINICAL VARIANTS	CHARACTERIZATION
BALANITIS, CHRONIC
Chronic balanitis owing to pemphigus vegetans. Castle WN, Wentzell JM, Schwartz BK, Clendenning WE, Selikowitz SM.	J Urol 1987 Feb;137(2):289-91 Abstract quote Pemphigus is an autoimmune bullous dermatosis in which intercellular antibodies are associated with loss of intercellular cohesion. Pemphigus vegetans, a rare variant of pemphigus, is manifested by vegetating plaques, usually in intertriginous areas of patients who probably have an increased resistance to the disease. We report a case of chronic balanitis owing to pemphigus vegetans, and discuss proposed pathogenic mechanisms and treatment.
CHILDHOOD
Pemphigus vegetans in a child. Sillevis Smitt JH, Mulder TJ, Albeda FW, Van Nierop JC. Department of Dermatology, University of Amsterdam, The Netherlands.	Br J Dermatol 1992 Sep;127(3):289-91 Abstract quote Pemphigus vegetans was diagnosed in a 12-year-old boy based on clinical, histopathological and immunohistological findings. To our knowledge, this is the first case of juvenile pemphigus vegetans to be published in the literature. Suggested treatment with prednisone and azathioprine was refused, and the patient was treated with a decoction of herbs prescribed by a practitioner of traditional Chinese herbal medicine. This treatment gave excellent results. Possible active components of the treatment are discussed.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSIS
Pemphigus vegetans. Neumann type and Hallopeau type. Ahmed AR, Blose DA.	Int J Dermatol 1984 Mar;23(2):135-41 Abstract quote Two cases of pemphigus vegetans are presented, one of the Neumann type and one of the Hallopeau type. The differences between the two subsets are clinical presentation and course. Patients with the Hallopeau type often have a relatively benign disease, require lower doses of systemic corticosteroids, and usually have a prolonged remission. Patients with the Neumann type have a course similar to pemphigus vulgaris, need higher doses of systemic corticosteroids, and have relapses and remissions. The histologic findings in the vegetating lesions are similar in both types. The immunopathologic features of both types are indistinguishable and similar to pemphigus vulgaris. IgM staining of eosinophilic microabscesses was observed in one case.
TREATMENT
DAPSONE
Pemphigus vegetans: its relationship to eosinophilic spongiosis and favorable response to dapsone. Pearson RW, O'Donoghue M, Kaplan SJ.	Arch Dermatol 1980 Jan;116(1):65-8 Abstract quote Two cases of pemphigus vegetans are presented. One, an example of the Hallopeau type of the disease, was found to have early lesions that simulated eosinophilic spongiosis clinically and histologically. The other had lesions that were largely confined to the oral mucosa and was also considered to be the Hallopeau type of the disease in a limited form. The cases of these two patients were compared with a typical case of eosinophilic spongiosis. All were controlled with dapsone therapy.
ETRETINATE
Successful treatment of pemphigus vegetans by addition of etretinate to systemic steroids. Ichimiya M, Yamamoto K, Muto M. Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan.	Clin Exp Dermatol 1998 Jul;23(4):178-80 Abstract quote Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by flaccid bullae, which become eroded and form vegetations or papillomatous proliferations, especially in the intertriginous areas. Oral administration of corticosteroids alone does not always induce disease remission in pemphigus vegetans. We report a 44-year-old Japanese man with pemphigus vegetans. Although corticosteroid therapy resulted in healing of the oral ulcers and skin bullae, verrucous vegetations continued to develop. In contrast, by combining corticosteroid with etretinate, verrucous vegetations improved. Thus we propose that the combination therapy of steroid and etretinate might be an effective adjunct in the therapy of pemphigus vegetans.