Linear IgA disease associated with membranous glomerulonephropathy

A 33‐year‐old Caucasian man developed an acute nephrotic syndrome with a proteinuria of 15 g/day. His past medical history was significant for a cholecystectomy secondary to complications of hypercholesterolemia, and his medications included niacinamide, simvastatin, and multivitamins. A renal biopsy revealed a membranous glomerulonephropathy, with thickening of the capillary loops by light microscopy and 4+ granular immunoglobulin G (IgG) staining of the capillary loops by immunofluorescence. Multiple discrete subepithelial deposits were also noted by electron microscopy. He was treated with cyclophosphamide, chlorambucil, and high dose steroids. Laboratory data at that time were notable for an elevated erythrocyte sedimentation rate (ESR), decreased albumin, a negative antinuclear antibody, and normal complement levels. His symptoms improved, and the proteinuria stabilized to 7 g/day. His systemic therapy was discontinued without a flare in his renal disease. Approximately 9 months later, he developed a pruritic, blistering eruption which began on his face and neck. An initial skin biopsy showed a subepidermal blister with many eosinophils and eosinophilic spongiosis. A direct immunofluorescence (DIF) study revealed linear deposits of IgG and IgA, and focally linear C3 at the basement membrane zone. This pattern was interpreted to be most consistent with bullous pemphigoid. He was referred to the Philadelphia VA Medical Center for further evaluation and treatment Cutaneous examination revealed multiple urticarial plaques with tense bullae studding the peripheral margin, in a rosette pattern, distributed on his face, trunk, groin, extremities, and feet, with one healing erosion on the hard palate. Laboratory data revealed abnormal, but stable, renal disease, with an elevated blood urea nitrogen (21.1) and creatinine (1.5). Serum IgA was elevated (400), and serum albumin (3.3) and a total protein (5.5) were decreased. A second skin biopsy from a blister edge demonstrated a subepidermal bulla with numerous eosinophils and collections of neutrophils at the dermal papillae tips ( Fig. 1). DIF revealed 3+ linear IgA deposition at the basement membrane zone ( Fig. 2), and an indirect immunofluorescence study on monkey esophagus showed linear IgA deposition in the basement membrane zone. A diagnosis of linear IgA disease was made. Dapsone 50 mg p.o. daily was started, with a dramatic improvement on his blistering within 2 weeks. His renal disease remained stable