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Case Reports

Abstract

Second generation Bruton’s tyrosine kinase (BTK) inhibitors (e.g. acalabrutinib, zanubrutinib) are a standard of care treatment option for malignant B-cell lymphoproliferative disorders including chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, and mantle cell lymphoma. While they have a more favorable cardiovascular profile as compared to their first-generation counterpart ibrutinib due to a more selective BTK binding mechanism, similar rates of adverse cutaneous reactions have been observed. The cutaneous adverse reactions for patients treated with BTK inhibitors that are well described in the literature include rash, ecchymosis, petechiae, and skin infections. Here we report both the clinical and histopathologic features of five patients who developed a novel diffuse purpuric and edematous eruption on the extremities while receiving treatment with BTK inhibitors. A subset of patients discontinued the medication with resolution of their cutaneous findings. The primary histopathologic findings include ectatic and proliferative lymphovascular channels, vascular congestion, focal intraluminal microthrombi or intraluminal fibrin deposition, and red blood cell extravasation. Next generation sequencing was performed on three biopsy samples and did not demonstrate any variants of known significance. As the clinical improvement of this lymphoproliferative reaction did coincide with either pausing or discontinuing treatment, we suspect that this finding is primarily caused by BTK inhibitor therapy, though the possibility of their underlying lymphoproliferative disorder being a predisposing factor for this cutaneous reaction cannot entirely be excluded, and further investigation is warranted.