Novel emergence of cutaneous lupus erythematosus as adverse effect of Acalabrutinib Therapy for Chronic Lymphocytic Leukemia

A 50-year-old Caucasian man with a past medical history of chronic lymphocytic leukemia presented with a diffuse, papulosquamous, pruritic rash involving the face, trunk, and extremities. The rash had been present for approximately five weeks and was photodistributed. The patient had started taking acalabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, three months prior to presentation. Punch biopsy revealed interface dermatitis with eosinophils and numerous dyskeratotic keratinocytes, consistent with a lupus-like drug eruption. Laboratory workup was negative for antinuclear antibodies, extractable nuclear antigens, and anti-double-stranded DNA antibodies. Based on the clinical presentation of a papulosquamous, photodistributed eruption with interface dermatitis on histopathology with negative serologic workup, the diagnosis of cutaneous lupus erythematosus without systemic involvement was rendered. The patient was started on a three-week prednisone taper along with hydroxychloroquine and had full resolution at 3-month follow up. He was able to continue acalabrutinib without interruption and was maintained on chronic hydroxychloroquine therapy with no recurrence of his cutaneous lupus erythematosus. BTK inhibitors interfere with B cell receptor signaling and are being explored as potential therapeutic options for B-cell driven autoimmune diseases. However, the downregulatory effects on B cells may not necessarily inhibit autoreactive T cells, and together with their off-target effects, BTK inhibitors may paradoxically induce lupus and potentially other autoimmune reactions. Therefore, heightened vigilance is advised as this case demonstrates the potential for drug induced cutaneous lupus erythematosus following BTK inhibitor therapy.