An intriguing case of blisters in a child: Uncovering the diagnosis of Immunoglobulin A epidermolysis bullosa acquisita by serration pattern analysis

Dear Editor,

Linear IgA disease (LAD) is a distinct sub-epidermal autoimmune blistering disease (AIBD), characterised by the linear deposition of IgA in the basement membrane zone (BMZ). Two immunopathological subgroups of LAD have been recognised based on immunoelectron microscopy: (i) lamina lucida-type and (ii) sublamina densa-type.¹ The former accounts for a vast majority of LADs; the pathogenic IgA autoantibodies react with the epidermal side (‘roof’ pattern) of the salt split skin substrate by indirect immunofluorescence (IIF) microscopy and target 97-kDa (LABD- 97) or 120-kDa (LAD-1). On the other hand, the sublamina densa-type of LAD reveals dermal staining of IgA (‘floor’ pattern) on salt split skin and targets type VII collagen, which is the antigenic target of epidermolysis bullosa acquisita (EBA).¹ The latter variant is known as ‘IgA-EBA.’ It is usually seen in adults, and its occurrence in children is extremely uncommon.² Here, we present a rare case of IgA-EBA in a child.

A 4-year-old girl was referred to our tertiary care centre with a complaint of blisters over the legs, face, and neck for 3 months. She had received age-appropriate immunisation and had no co-morbidities. There was no history of drug intake prior. The lesions started initially as itchy, transient wheals which subsequently blistered in the centre. She was treated in a primary healthcare facility with topical and oral steroids, resulting in partial improvement. Cutaneous examination revealed a few discrete, tense blisters over the shin with normal underlying skin [Figure 1]. Multiple post inflammatory, hypopigmented macules were also observed over the cheeks, chin, neck, chest, and abdomen. There was no milia, scarring or nail dystrophy. The oral and genital mucosae were normal. A provisional diagnosis of LAD was made. Histopathological examination revealed an intraepidermal blister containing mixed inflammatory infiltrate of neutrophils and few eosinophils. Direct immunofluorescence (DIF) microscopy from the perilesional skin biopsy showed linear staining of BMZ with IgA [Figure 2a], while IgG, IgM, C3 and fibrin were negative. The serration pattern analysis revealed a ‘u’ serration pattern [Figure 2b]. IIF microscopy using salt-split skin showed staining on the dermal side with IgA [Figure 2c]. The enzyme-linked immunosorbent assay (ELISA) for bullous pemphigoid (BP) 180 and 230 was negative. ELISA (with IgA antibodies) for type VII collagen was not performed due to the unavailability. A final diagnosis of IgA EBA was made. The child was started on oral dapsone (1 mg/ kg) along with topical fluticasone propionate 0.05% cream. There was significant improvement with no relapse of blisters at 6 months follow up.

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Figure 1:

Two tense blisters on the left leg.

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Figure 2a:

Photomicrograph showing linear staining of BMZ with IgA using fluorescein isothiocyanate conjugate (Fluorescein isothiocyanate conjugate, 200x).

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Figure 2b:

DIF microscopy showing ‘u’ serration pattern with IgA (Fluorescein isothiocyanate conjugate, 1000x).

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Figure 2c:

IIF on salt split skin showing ‘dermal’ staining with IgA (Fluorescein isothiocyanate conjugate, 200x).

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IgA EBA may be more common than previously anticipated; it accounted for 8.6% of all IgA-mediated subepidermal AIBD and 26.9% cases of EBA in a previous study.² The median age of onset of IgA EBA was 64 years; we could find only four cases of childhood IgA EBA in the literature [Table 1].^3-6 The clinical presentation of IgA EBA is heterogeneous with erythematous macules, vesicles, urticarial plaques, papules, and tense bullae, often showing annular configuration. The lesions may be generalised or confined to the extremities. Mucosal involvement has been reported in approximately 60% of cases. Caux et al.⁴ and Bauer et al.⁵ reported two children with IgA EBA who developed severe ocular involvement, leading to blindness.^4,5 Hence, it is very important to make an early and precise diagnosis of IgA EBA to prevent complications.

Advanced immunological tests often help to precisely diagnose IgA EBA. DIF microscopy reveals the exclusive or predominant deposition of IgA at the BMZ. Circulating autoantibodies can be demonstrated by IIF microscopy on salt-split skin in 50% of the cases and reveal immune deposits on the dermal side of the split. Though ELISA kits for the detection of IgG antibodies against type VII collagen are commercially available, they are not yet available for the detection of IgA antibodies.¹ Western blotting using recombinant antigens or dermal extracts is available only in certain specialised laboratories across the globe. In such cases, serration pattern analysis can be considered as a suitable alternative, as it is based on DIF microscopy and helps to differentiate EBA (‘u’ serration) from other subepidermal AIBDs, including lamina lucida type of LAD (‘n’ serration).⁷ Our patient revealed a ‘u’ serration pattern with IgA, confirming the diagnosis of IgA EBA.

Dapsone is the mainstay of therapy for IgA EBA. Approximately 50% of patients may not respond to dapsone. In such cases, colchicine, prednisolone, azathioprine, cyclosporine, and mycophenolate may be considered.^4-6 This case is presented for its rarity, as we could not find any other report of childhood IgA EBA from our country.⁷