Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment

Abstract

Objective: To report 77 patients with multiple sclerosis (MS) who developed skin-related adverse events (AEs) following treatment with cladribine.

Methods: We evaluated our prospective bicentric cladribine cohort. Cladribine-treated patients with a skin AE were identified.

Results: Two hundred thirty-nine cladribine-treated patients with MS were evaluated. Seventy-seven patients (32%) showed at least 1 skin AE at median 1 month after cladribine initiation (range: 1-12). Within first 3 months following last cladribine exposition, hair thinning (n = 28, 12%), skin rash (n = 20; 8%), mucositis (n = 13, 5%), and pruritus (n = 6, 3%) were observed. Furthermore, 35 patients (15%) developed herpes virus infections (time since last cladribine exposition: median 83 [range: 10-305]). In 15 patients, herpes zoster infection was severe (CTCAE grade ≥ 3) and required hospitalization. Delayed skin AEs (≥3 months after a cladribine treatment cycle) involved 1 case of leukocytoclastic vasculitis and 2 cases of alopecia areata. Finally, 2 patients presented with in total 3 isolated precancerous lesions (1 leukoplakia simplex and 2 actinic keratosis) and 1 patient developed a squamous cell carcinoma.

Conclusion: Skin AEs are common in patients with MS treated with cladribine. Until risk management plans have been adjusted to include these phenomena, clinicians should perform a thorough clinical follow-up and in suspicious cases seek early interdisciplinary support. In light of the observed delayed skin reactions, we further emphasize the necessity of careful clinical surveillance of cladribine-treated patients for yet undescribed secondary autoimmune events.

Classification of evidence: This study provides Class IV evidence that skin-related AEs are frequent in patients with MS following cladribine in a real-world setting.

Figure. Cladribine-Related Skin Reactions

(A) Acneiform eruption consisted of follicle-based papules without comedones and lesions typically occurred on the face, scalp, chest, and back, sparing the extremities. (B) Representative images of 1 patient, experiencing diffuse skin rash. (C) Nummular eczema typically occurred as itchy coin-sized round- to ovoid-shaped red plaques in 2 cladribine-treated individuals. (D) An example of a female patient with severe and unbearable itching. (E) Disseminated herpes zoster infection of left Th1 to Th4 dermatomes. (F) Representative images of herpes simplex infection following cladribine treatment. (G) Typical presentation of a leukocytoclastic vasculitis with palpable purpura, accompanied by pain and burning at both legs, in a 42-year-old female cladribine-treated patient with MS. (H) A case of alopecia areata with typical hair loss in one round spot on the scalp. (I) Oral leukoplakia simplex in a 41-year-old cladribine-treated patient. Typical white changes of the buccal mucosa are depicted (black arrows). (J) Actinic keratosis manifested as a rough, dry patch of skin, of approximately 1.5 cm in diameter in a 41-year-old cladribine-treated patient. (K) A 69-year-old female patient with MS developed squamous cell carcinomas on sun-exposed skin (hand and legs), appearing as hyperkeratotic plaque with central ulceration and/or crusted surface.