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

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.

Ibrutinib-induced polyneuropathy: A case report

“…Severe skin toxicity, 13 autoimmune cytopenia, 14 severe arthritic syndrome, 15 autoimmune myelitis 16 and progressive multifocal leukoencephalopathy 17 due to ibrutinib, have also been reported.…”

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“…Second-generation BTK inhibitors seek to improve upon first-generation agents like ibrutinib by having less cardiotoxicity, fewer AEs that result in stopping treatment, and fewer off-target effects. For example, ibrutinib inhibits the activity of 3 major off-targets: epidermal growth factor, which can result in severe skin toxicities 13 ; interleukin-2 inducible kinase, which impairs natural killer cells' cytotoxic abilities 14 ; and the Tec family of kinases, decreasing their ability to aid in phosphorylation. 15 In updated results of the ASPEN trial presented at this year's virtual American Society of Clinical Oncology (ASCO) 2020 Annual Meeting, zanubrutinib (Brukinsa), the most recent second-generation BTK inhibitor to hit the US market, was shown to have a survival advantage over ibrutinib in patients with Waldenström macroglobulinemia who lacked the MYD88 mutation typically associated with successful treatment.…”

Ibrutinib skin toxicities: Report of two cases

“…1 The histopathologic description of these skin lesions is still limited to case reports and small case series, but appears to have a broad spectrum, including perivascular dermatitis, leukocytoclastic vasculitis, panniculitis, epidermal necrosis similar to what is seen within the spectrum of toxic erythema of chemotherapy, neutrophilic dermatosis, pseudolymphoma and granulomatous inflammation, and acneiform eruption/folliculitis similar to what is seen in anti-epidermal growth factor receptor (EGFR) therapy. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Here, we describe the histopathology of ibrutinib-related skin lesions in two patients.…”

“…1,7,8 Clinical descriptions of these skin lesions are highly variable, including pruritus, maculopapular rash, papulo-nodular lesions, petechiae/ecchymoses, acneiform eruptions, and others. [1][2][3][4][5][6][7][8][9][10][11][12] Iberri et al described two main ibrutinib-related skin rashes in CLL and MCL patients: a non-palpable asymptomatic rash, and a palpable pruritic rash. 7 The rash is generally mild (grades 1-2), but can be severe in rare cases (grade 3), resulting in discontinuation or titration of ibrutinib.…”