# Cutaneous Adverse Effects in Patients Treated with BTK Inhibitors

## TL;DR

This paper reviews skin-related side effects in patients taking BTK inhibitors, focusing on their frequency, severity, and management.

## Contribution

The paper provides a comprehensive overview of cutaneous adverse effects associated with newer BTK inhibitors compared to ibrutinib.

## Key findings

- Skin toxicities from BTK inhibitors are mostly mild and manageable with corticosteroids or dose adjustments.
- Second-generation BTK inhibitors like acalabrutinib and zanubrutinib show reduced toxicity compared to ibrutinib.
- Common skin symptoms include bruising, rash, infections, and nail or hair changes.

## Abstract

Patients treated with BTK inhibitors frequently demonstrate dermatologic toxicities, such as bruising, rash, infections, mucosal symptoms, neutrophilic dermatoses, vasculitis, infections, nail plate abnormalities and hair changes. In most cases, skin toxicities remain mild. Proactive management is crucial in order to limit dose-intensity modification. For most patients, these skin changes are benign and do not require treatment: discontinuation or topical or oral corticosteroid use should be considered until cutaneous symptoms disappear. However, in some patients, BTKi dose reduction, treatment interruption, or even cessation of treatment is recommended.

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles.