Pemphigus foliaceus masquerading as IgA pemphigus and responding to dapsone.

A 14-year-old male presented with seven years history of recurrent episodes of fluid filled, itchy and eroded lesions over the body not responding to oral corticosteroids and azathioprine. Dermatological examination revealed crusted plaques and erosions in a seborrheic distribution. Histopathology of skin lesions and direct immunofluorescence were characteristic of pemphigus foliaceus. He was treated with dexamethasone pulse therapy with inadequate response. However, relapsing skin lesions revealed a circinate arrangement with a predilection to trunk and flexures. In view of clinical features suggestive of IgA pemphigus, he was started on dapsone, to which he responded dramatically in four weeks. However, repeat biopsy continued to reveal features of pemphigus foliaceus and ELISA for anti-desmoglein 1 antibodies was positive.

What was known?

Pemphigus foliaceus can have IgA pemphigus like clinical picture

Introduction

Pemphigus foliaceus is a rare autoimmune blistering disorder characterised histopathologically by subcorneal blisters and immunopathologically by IgG antibodies to desmoglein 1 (dsg-1).[1] It responds well to systemic corticosteroids. Immunoglobulin A (IgA) pemphigus is relatively a newly described intraepidermal blistering disorder characterised by IgA autoantibodies directed against desmosomal components, mainly desmocollin. It responds well to dapsone but poorly to steroids.[23] We report here an interesting case of histopathologically and immunopathologically proved Pemphigus foliaceus, clinically masquerading as IgA pemphigus responding poorly to systemic corticosteroids and responding well to dapsone.

Case Report

A 14-year-old male child presented with complaints of recurrent episodes of multiple, fluid filled lesions over trunk and scalp, since seven years. These lesions used to rupture spontaneously, leaving behind painful, burning erosions. Birth and developmental history was normal. No history of oral or genital ulceration, any drug intake prior to onset, photoexacerbation, koebnerisation or similar illness in family members was present. Dermatological examination revealed crusted plaques and erosions in a seborrheic distribution [Figures 1 and 2]. There was no mucosal involvement. Nikolsky's sign was positive.

Figure 1

Crusted plaques and erosions in seborrheic distribution

Figure 2

Similar lesions on trunk

Prior to present consultation, he had taken prednisolone 40 mg tablet, once a day along with supportive therapy with which he had only partial relief. He was also prescribed azathioprine 50 mg tablet once a day which was stopped after 10 weeks as he did not respond.

In view of above clinical picture, patient was evaluated with a clinical diagnosis of pemphigus foliaceus, and histopathology and direct immunofluorescence (DIF) confirmed the same. He was treated with dexamethasone pulse therapy. But after the second pulse, patient developed a relapse. He had also developed osteoporosis with impending spinal compression fracture with Cushingoid features [Figure 3]. Dermatological examination at the time of relapse revealed circinate pattern of lesions predominantly involving trunk and flexures [Figure 4]. Nikolsky's sign was negative. Oral mucosa and genitalia were normal. On the basis of these clinical findings, a diagnosis of IgA pemphigus was considered. Repeat biopsy, samples for DIF and ELISA for desmoglein antibodies were sent. Meanwhile, systemic steroids were stopped and he was started on Dapsone 100 mg tablet, daily. He responded dramatically within four weeks [Figure 5]. Repeat histopathology of lesional skin was consistent with pemphigus foliaceus revealing acantholysis in upper epidermis, complete loss of stratum corneum and subcorneal cleft filled with neutrophils [Figure 6]. Repeat DIF showed strong positivity for IgG, but was negative for IgA [Figures 7 and 8]. ELISA for anti dsg-1 antibodies was strongly positive with a titre of 215.5 units/ml (normal range <20 units/ml).

Figure 3

Cushingoid features

Figure 4

Later presentation of circinate lesions resembling IgA pemphigus

Figure 5

Complete resolution of lesions

Figure 6

Histopathology of lesion showing features of Pemphigus foliaceus. (H and E stain, ×100)

Figure 7

DIF showing IgG positivity

Figure 8

DIF showing IgA negativity

Discussion

Pemphigus foliaceus is clinically characterised by flaccid bullae with associated scaling and crusting. Seborrheic areas are initially involved, but it may later generalise.

IgA pemphigus is a variant, in which patients present with pruritic vesicles in annular or circinate configuration. IgA pemphigus is presently divided into two subtypes: Subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic (IEN) IgA dermatosis.[4] The SPD variant shows subcorneal acantholysis with pustules and intercellular IgA deposits in upper epidermis. The IEN variant is characterized by deep epidermal pustules and intercellular IgA deposits in the entire epidermis.[5] In the SPD variant, desmocollin 1 has been identified as the target autoantigen,[6] while in the IEN type, the autoantigen may be desmoglein 1 and 3 as reported by few studies.[7]

Both pemphigus foliaceus and IgA pemphigus are common in the middle age group, though they may occur in childhood also. Mucosal involvement is rare in both, as was in our patient. The evolving lesions of pruritic flaccid vesicles forming circinate crusted plaques, absence of Nikolsky's sign, site of predilection being axillae and groin were all suggestive of IgA pemphigus.

Since the clinical and histological differentiation of pemphigus foliaceus and IgA pemphigus might be difficult or even not possible, the diagnosis is based on immunological findings, which in this case was diagnostic of pemphigus foliaceus with complete absence of IgA. Cases of pemphigus foliaceus showing IgA deposition on immunofluorescence have been reported.[8] There are few case reports also showing coexisting IgA and IgG deposition in IgA pemphigus.[9]

Pemphigus foliaceus is generally regarded as a benign disease, which responds well to topical or oral steroids and to azathioprine or cyclophosphamide in severe cases. Dapsone has only been used as an adjuvant in few patients, especially those with pemphigus herpetiformis like lesions. Unlike IgG pemphigus, IgA pemphigus is often not controlled with corticosteroids alone. Sulphones appear to be effective as a single agent or in combination with other drugs.

A solitary report of a child with pemphigus foliaceus not responding to steroids but responding to dapsone has been documented earlier in literature.[10]

This case had clinical features of IgA pemphigus but repeated histological and DIF features were confirmatory of pemphigus foliaceus. It is therefore a rare instance of a DIF proven pemphigus foliaceus in a child, resembling IgA pemphigus, both clinically and therapeutically.

What is new?

Pemphigus foliaceus with IgA like clinical picture responds well to Dapsone