No abstract

Importance Ibrutinib (Imbruvica®), a Bruton tyrosine kinase (BTK) inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well-tolerated but requires long-term treatment until disease progression or intolerable toxicity occurs. Little is known regarding its cutaneous adverse effects. Objective To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL. Design Prospective study of patients enrolled in a single-arm phase II clinical trial of ibrutinib for CLL between March 2014 and October 2015 Setting A single institution study at the National Institutes of Health. Participants The study evaluated 66 patients with CLL. Main outcomes and measures The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11question survey. In addition, the severity of nail changes was determined from a 0–3 rating scale for both onychoschizia and onychorrhexis. Results Among 66 patients, 44 (66.6%) reported brittle fingernails at a median of 6.5 months after starting ibrutinib (95% CI 6–12 months). 15 patients (22.7%) developed brittle toenails after a median of 9 months of ibrutinib therapy (95% CI 6–15). Textural hair changes were reported in 17 patients (25.7%), at a median of 9 months of ibrutinib treatment (95% CI 6–12). Conclusion and relevance Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits BTK by covalently binding to cysteine 481.Whether ibrutinib affects the hair and nails by binding and altering cysteine rich proteins of hair and nails or due to other off-target remains unknown.

Accurate diagnosis of connective tissue diseases is often challenging, and relies upon careful correlation between clinical and histopathological features, direct immunofluorescence studies and laboratory work‐up. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterised by an interface dermatitis although other histopathological patterns also exist, depending upon the clinical presentation, location and chronicity of the skin lesions. In this article, we review the clinical, serological, histopathological and direct immunofluorescence findings in LE‐specific and LE non‐specific skin lesions, with an emphasis upon lesser‐known variants, newly described features and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.