Track

Case Reports

Abstract

We present three cases of cutaneous toxicity associated with Bruton tyrosine kinase (BTK) inhibitor therapy, a notable but not well-established manifestation in dermatology. A 70-year-old woman on zanubrutinib subsequently developed slightly tender, ecchymotic, and purpuric plaques on her left arm after being on treatment for over a year. Biopsies showed an increase in dilated thin-walled dermal vessels with red blood cell thrombi, solar elastosis, and hemorrhage. A 64-year-old man who developed extensive genital and lower abdominal ecchymotic and edematous plaques after treatment with zanubrutinib for 3 months. His symptoms improved after cessation of treatment but recurred within eight days of restarting therapy, prompting discontinuation again. An 86-year-old woman on acalabrutinib developed purpuric patches on the shins and forearm after one year of treatment. Similar clinical presentations are documented in patients receiving other BTK inhibitors, such as ibrutinib and acalabrutinib, with reactions presenting weeks to years after treatment initiation. Ecchymotic plaques are also described within previously irradiated sites after starting a BTK inhibitor. Collectively, these cases identify a cutaneous toxicity of BTK inhibitors with clinical findings of edema and ecchymosis/purpura and pathologic findings of red blood cell thrombi, elastosis, edema, and red blood cell extravasation.  While still not well defined, this clinical-pathologic pattern reflects an off-target vasculopathy due to BTK inhibitors and is likely underreported.