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Asymptomatic Purpuric Eruption on the Scalp of a Middle-aged Man

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A man in his 60s presented to the clinic with a several-day history of nontender, nonitchy purpuric rash on his scalp. The patient denied using any over-the-counter or prescription topicals at the affected sites before the onset of the eruption except for petroleum jelly. His medical history was significant for chronic lymphocytic leukemia (CLL) and allergic contact dermatitis. The patient reported being started on ibrutinib and allopurinol therapy 6 weeks prior to the rash onset for treatment of CLL. Physical examination revealed multiple purpuric, nonblanchable macules and patches on the frontal, vertex, temporal, and parietal scalp (Figure, A). A punch biopsy specimen from the scalp was obtained for histopathologic analysis (Figure, B).

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C. Ibrutinib-induced toxic effects

Ibrutinib is a selective Bruton tyrosine kinase inhibitor used for treatment of several lymphoproliferative disorders, including CLL, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia. Skin eruptions represent a frequent adverse effect of the medication and are seen in up to 47% of patients who take it.1

A retrospective cohort study by Iberri et al2 reported 2 main types of skin eruptions associated with ibrutinib use: an asymptomatic, nonpalpable, petechial rash, and a palpable, purpuric eruption resembling leukocytoclastic vasculitis (LCV). The nonpalpable eruption had late rash onset (80 days after initiation of the drug on average) and mild associated symptoms. The palpable eruption was associated with earlier rash onset (15 days after initiation of the drug on average) and worse severity, requiring temporary interruption of ibrutinib therapy in some of the patients. All the patients who required temporary interruption of therapy were able to resume ibrutinib.2 Histopathology of the eruptions revealed perivascular and interstitial inflammation and erythrocyte extravasation with no evidence of LCV.

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Article Information

Corresponding Author: Evgeniya Teterina Mohammed, MD, Kaplan-Amonette Department of Dermatology, University of Tennessee Health Science Center, 930 Madison Ave, Ste 840, Memphis, TN 38163 (eteteri1@uthsc.edu).

Published Online: February 18, 2021. doi:10.1001/jamaoncol.2020.6773

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Wang  ML , Rule  S , Martin  P ,  et al.  Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma.   N Engl J Med. 2013;369(6):507-516. doi:10.1056/NEJMoa1306220PubMedGoogle ScholarCrossref
2.
Iberri  DJ , Kwong  B , Stevens  L ,  et al.  Ibrutinib-associated rash: a single-centre experience of clinicopathological features and management.   Br J Haematol. 2018;180(1):164-166. doi:10.1111/bjh.14302PubMedGoogle ScholarCrossref
3.
Parra  CE , Newsom  E , Lee  EH , Allan  JN , Minkis  K .  Association of Ibrutinib Treatment With Bleeding Complications in Cutaneous Surgery.   JAMA Dermatol. 2017;153(10):1069-1070. doi:10.1001/jamadermatol.2017.1877PubMedGoogle ScholarCrossref
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Byrd  JC , Furman  RR , Coutre  SE ,  et al.  Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.   N Engl J Med. 2013;369(1):32-42. doi:10.1056/NEJMoa1215637PubMedGoogle ScholarCrossref
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Singer  S , Tan  SY , Dewan  AK ,  et al.  Cutaneous eruptions from ibrutinib resembling egfr inhibitor-induced dermatologic adverse events.   J Am Acad Dermatol. 2019;S0190-9622(19)33308-0. doi:10.1016/j.jaad.2019.12.031PubMedGoogle Scholar
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Lacouture  ME .  Mechanisms of cutaneous toxicities to EGFR inhibitors.   Nat Rev Cancer. 2006;6(10):803–812. doi:10.1038/nrc1970Google Scholar
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Fang  SY , Wu  CS , Liu  YS , Wei  KC .  Epidermal growth factor receptor (EGFR) inhibitor induced purpuric drug eruption: three case reports.   Medicine (Baltimore). 2019;98(47):e18112. doi:10.1097/MD.0000000000018112PubMedGoogle Scholar
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Goeser  MR , Laniosz  V , Wetter  DA .  A practical approach to the diagnosis, evaluation, and management of cutaneous small-vessel vasculitis.   Am J Clin Dermatol. 2014;15(4):299-306. doi:10.1007/s40257-014-0076-6PubMedGoogle ScholarCrossref
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Cines  DB , Blanchette  VS .  Immune thrombocytopenic purpura.   N Engl J Med. 2002;346(13):995-1008. doi:10.1056/NEJMra010501PubMedGoogle ScholarCrossref
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