Case presentation

A 69-year-old female patient with a history of hypothyroidism, type 2 diabetes mellitus, and hypertension developed a maculopapular rash in the bilateral axilla, groin, neck, and scalp (Figures 1, 2). The rash progressed to painful, pruritic bullae that ruptured. There was involvement of more than 10% of the body surface area. The patient had been diagnosed with primary adenocarcinoma of the lung with metastasis to the chest wall and left gluteal region and was on long-term therapy with pembrolizumab due to high programmed death-ligand 1 (PD-L1) expression in the tumor. The patient had been on pembrolizumab therapy for four years before developing the skin lesions. Therapy with pembrolizumab was initiated every 21 days, and 55 cycles of this treatment had been completed. It is interesting to note that the patient also developed a symblepharon on the right eye for which she received topical steroids and cyclosporine eye drops (Figure 3).

Figure 1: Before topical steroid therapy.

Figure 2: After topical steroid therapy and discontinuation of pembrolizumab.

Figure 3: Symblepharon of the right eye (arrow).

After undergoing a punch biopsy and direct immunofluorescence study, showing subepidermal bullous dermatosis with eosinophils and IgA deposition, suggestive of linear IgA bullous dermatosis (LABD), both IgG and IgA linear deposits were present in the basement membrane. Indirect immunofluorescence showed reactivity consistent with pemphigus and pemphigoid/linear IgA disease. Enzyme assay for BP180, BP230, collagen VII, dsg1, and dsg3 was also negative. A paraneoplastic pemphigoid panel was performed, with negative indirect immunofluorescence staining and a negative IgG envoplakin antibody by enzyme-linked immunosorbent assay (ELISA). LABD was now a confirmed diagnosis.

Dermatological evaluation was done, and the patient was initially treated with a topical steroid and oral antibiotics; however, her skin lesions did not improve on topical therapy alone. Pembrolizumab therapy was also temporarily discontinued for nearly two months, which prevented further progression of the rash. The patient's rash resolved with topical medium- and high-intensity corticosteroid ointments (Figures 1, 2).

After confirmation of the diagnosis, treatment for bullous dermatosis was initiated with dapsone. Dapsone has been shown to benefit patients with autoimmune inflammatory conditions and neutrophilic infiltrates. Dapsone was then switched to colchicine due to a concern for G6PD deficiency-related hemolytic anemia. Maintenance therapy with colchicine in combination with topical steroids stopped the recurrence of the rash, and pembrolizumab therapy was resumed after two months.