DermDx: Irritative Lesions on the Abdomen, Genitals

Pemphigus vegetans is a rare variant of pemphigus vulgaris, an autoimmune bullous disease of the skin and mucous membranes.1-2 This disease presents as a reactive pattern of the skin in response to the autoimmune insult incurred in pemphigus vulgaris. The...

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Pemphigus vegetans is a rare variant of pemphigus vulgaris, an autoimmune bullous disease of the skin and mucous membranes.^1-2 This disease presents as a reactive pattern of the skin in response to the autoimmune insult incurred in pemphigus vulgaris. The vegetans variant occurs in less than 5% of all pemphigus vulgaris cases, and only 1% to 2% of cases are seen in children, with the vast majority of cases presenting in middle-aged women.^{2- 4} These epidemiologic characteristics are similar to pemphigus vulgaris, in which the average age of onset in the United States ranges from 50 to 60 years of age, with women 5 times more likely to be affected then men.⁵ If left untreated, pemphigus vulgaris has been shown to be uniformly fatal within 5 years as a result of the severe blistering of the skin and mucous membranes that is seen in the disease, which leads to malnutrition, dehydration, and sepsis.⁵ 

Pemphigus vegetans is characterized by purulent lesions that evolve to form vegetative plaques, often affecting intertriginous areas, including the axillary, anogenital, inguinal, and mammary regions, as well as areas on the scalp and face.^{2, 5-6} When the disease spreads to include mucosal sites, areas of involvement can include the oropharyngeal, upper esophageal, vaginal, nasal, and conjunctival mucosa, with the oropharyngeal mucosa being the most commonly affected. Additionally, cerebriform changes of the tongue and desquamative gingivitis can also be observed.⁷ Although many different manifestations of the disease are possible, the most characteristic finding seen in pemphigus vegetans is the presence of vegetating plaques at the site of cutaneous erosions. 

Pemphigus vegetans is categorized under 1 of 2 subtypes: Neumann and Hallopeau. The Neuman subtype is more aggressive and occurs more frequently.² Early manifestations of disease may resemble pemphigus vulgaris with the formation of vesicles and bullae; however in Neuman pemphigus vegetans these lesions will progress to form dry, hyperkeratotic plaques with fissures that persist for long periods of time.⁷ Additionally, periorificial papillomatous vegetations are often present.¹ The Hallopeau pemphigus vegetans subtype is less aggressive and is characterized by pustules that evolve into vegetations, usually involving the intertriginous areas.^1-2 

As with pemphigus vulgaris, the pathogenesis of pemphigus vegetans involves autoantibodies against desmoglein 3 (Dsg3) +/- desmoglein 1 (Dsg1).¹ Mucosal dominant disease is associated with Dsg3 antibodies, while mucocutaneous disease is associated with Dsg3 and Dsg1. Some cases of pemphigus vegetans are associated with IgG and IgA antibodies against desmocollins, although this association has yet to be clearly elucidated.¹ The mechanisms surrounding the autoimmune system’s attack on desmogleins are unknown, although certain MHC class II molecules have been implicated in pemphigus vulgaris and could potentially play a role in pemphigus vegetans as well (HLA DRB1*0402 and DQB1*0503).¹ 

The paucity of research on the epidemiologic characteristics of pemphigus vegetans has made it difficult to identify associated risk factors. It is assumed that the risk factors for pemphigus vegetans are the same as those of pemphigus vulgaris, which have been more extensively studied. Risk factors for pemphigus vulgaris are associated with herpes simplex virus, exposure to pesticides and metal vapor, and an increased number of pregnancies.^8,9

Punch or shave biopsy obtained from an affected area in a patient with pemphigus vegetans followed by histopathologic examination may or may not demonstrate epidural blister formation; however, suprabasal acantholysis resulting in a blister just above the basal cell layer is usually seen.⁷ While the basal keratinocytes remain attached to the basement membrane by hemidesmosomes, they lose attachments to each other, resulting in the “row of tombstones” that is classically described in pemphigus vulgaris.¹⁰ Additionally, most blisters will demonstrate a neutrophilic and or eosinophilic pustule or abscess in the epidermis with associated acantholysis and epidermal hyperplasia.^1,3

Because the occurrence of pemphigus vegetans is so rare, it is important to consider diseases that can cause a similar presentation when formulating a differential. The exclusion of more common diseases on the differential is a large part of the process that must occur to accurately diagnose pemphigus vegetans. Bacterial infections caused by enterococcus faecalis, E coli, morganella morganii, and gram-postive cocci, as well as multiple types of fungal infections, should be considered on the differential with pemphigus vegetans. Other diseases to test for and rule out include vegetating herpes simplex infection, acrodermatitis continua supperativa, proderma gangraneosum, Bowen’s disease, and squamous cell carcinoma.¹

The diagnosis of pemphigus vegetans is confirmed via the identification of autoantibodies to the keratinocyte cell surface, either by direct/indirect immunofluorescence or ELISA. Skin biopsy followed by immunofluorescence microscopy stains keratinocytes positive for IgA and IgG antibody, and, sometimes, C3 intracellular deposits in the epidermis.^7,9 Further confirmation for a diagnosis of pemphigus vegetans can be obtained with ELISA detection of anti-Dsg3 and/or anti-Dsg1 antibodies, similar to the ELISA findings seen in pemphigus vulgaris.¹ Of note, antigen-specific ELISAs have been found to be more sensitive and specific (>97%) for pemphigus vulgaris than indirect immunofluorescence; however, there has been limited use of it as a diagnostic tool for pemphigus vegetans.⁷ 

Treatment for pemphigus vegetans is similar to the treatment for pemphigus vulgaris—long-term systemic corticosteroids.^1,4 The initial treatment typically consists of a high-dose systemic corticosteroid, such as prednisolone, along with a steroid-sparing immunosuppressant, such as azathioprine.² However, long-term treatment with systemic corticosteroids is associated with adverse side effects, so the risks and benefits of treatment must be considered and the patient counseled appropriately. In addition to steroid therapy, antibiotics should be administered if a coexisting infection is present.³ As always, supportive care with intravenous fluids and nutritional supplementation should be administered as necessary. 

In this case, a biopsy of the lesion was performed and histopathologic examination showed a “row of tombstones” appearance. Direct immunofluorescence microscopy stained positive for IgA and IgG antibodies and anti-Dsg3 antibodies were detected with ELISA. After ruling out other diagnoses, the patient was found to have pemphigus vegetans. She was started on high-dose corticosteroid therapy and the lesions are improving.

Thanh Dang, BA, is a medical student, Joan Fernandez, BS, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

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9. Marchalik R, Reserva J, Plummer MA, Braniecki M. Pemphigus vegetans with coexistent herpes simplex infection and deep venous thrombosis of the lower extremities. BMJ Case Reports. 2015 Jul 15;2015. 
10. Clinical and pathological study of autoimmune vesiculobullous disorders. J Pakistan Assoc Dermatol. 2017;27:270