TNF-alpha inhibitor induced pemphigoid in a patient with generalized granuloma annulare

Summary: We present a 62-year-old woman with a history of uveitis and hepatic artery pseudoaneurysm, who developed a sudden onset pruritic, erythematous skin eruption 3 weeks following initiation of adalimumab for the treatment of refractory generalized granuloma annulare (GA). Examination revealed brightly erythematous plaques involving the anterior chest and neck. Skin biopsy revealed eosinophilic spongiosis and superficial interstitial mixed inflammation with numerous eosinophils, in addition to, mid-deep dermal interstitial granulomatous inflammation, consistent with the patient’s known GA. On direct immunofluorescence, there was linear IgG and C3 basement membrane zone deposition and serologic studies demonstrated circulating IgG autoantibodies with an epidermal pattern on primate salt-split skin substrate. The clinical presentation and histopathologic and immunopathologic findings were supportive of a diagnosis of drug associated non-bullous pemphigoid (DABP) in the setting of anti-TNF-α therapy for treatment of GA. Although there are many reports of paradoxical autoimmune processes and adverse cutaneous eruptions related to anti-TNF-α agents, autoimmune bullous dermatoses are a rarely reported side effect. A 2020 Systematic review of DABP identified only 7 cases of DABP from anti-TNF-α therapies reported in the literature. This case highlights the importance of considering DABP in patients with new skin eruptions following initiation of anti-TNF-α therapies.