Ibrutinib-associated sever skin toxicity: A case of multiple inflamed skin lesions and cellulitis in a 68-year-old male patient with relapsed chronic lymphocytic leukemia - Case report and literature review

J Oncol Pharm Pract. 2020 Mar;26(2):487-491. doi: 10.1177/1078155219856422. Epub 2019 Jun 19.

Abstract

Introduction: Ibrutinib is an oral inhibitor of Bruton's tyrosine kinase that is used for a variety of B cell hematological malignancies. Skin and subcutaneous tissue manifestations have been reported and were witnessed in up to 32% of the patients on ibrutinib. The mechanism in which ibrutinib can cause skin toxicities has been thought due to the inhibition of epidermal growth factor; c-Kit and platelet-derived growth factor receptor). Here, we report a case of an elderly chronic lymphocytic leukemia patient who developed multiple inflamed lesions and lower limb cellulitis in 100 days after initiating ibrutinib therapy.

Case report: A 68-year-old male patient with relapsed chronic lymphocytic leukemia was started on ibrutinib 420 mg orally daily following multiple lines of therapy. Three months following ibrutinib, the patient developed multiple hyper pigmented lesions over both forearms then over both thighs; buttocks and lower limbs. The lesions were labeled as ecthyma and cellulitis that started as papules, which progressed to pustules.

Management and outcomes: The patient required admission in which he received prolonged course of antibiotics. Biopsy from the wound showed soft tissue fragment infiltrated by acute and chronic inflammatory cells with necrosis; rare foreign body giant cells and granulation tissue formation; suggestive of abscess. Subsequently, ibrutinib was stopped permanently.

Discussion: This is the first case description of an ibrutinib-associated sever skin toxicity in Qatar. The provided information regarding the clinical descriptions of toxicity profiles in general and skin-based in particular is valuable information for daily clinical practice, especially when selecting the optimum first-line treatment for the patient.

Keywords: Bruton’s tyrosine kinase inhibitor; Ibrutinib; cellulitis; chronic lymphocytic leukemia; skin; toxicity.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Aged
  • Cellulitis / chemically induced*
  • Cellulitis / diagnosis
  • Ecthyma / chemically induced*
  • Ecthyma / diagnosis
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy*
  • Piperidines
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / adverse effects*
  • Pyrimidines / adverse effects*
  • Skin / drug effects
  • Skin / pathology

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine