Immune-related alopecia (areata and universalis) in cancer patients receiving immune checkpoint inhibitors

Abstract

CTLA-4, PD-1, and PD-L1 monoclonal antibodies, commonly known as immune checkpoint inhibitors, are used for the treatment of various malignancies. The mechanism of action involves the inhibition of negative regulators of immune activation, which results in many patients developing immune-related adverse events (irAEs) including endocrinopathies, pneumonitis, colitis, hepatitis and dermatologic events. Dermatologic irAEs include maculopapular rash, pruritus, vitiligo, blistering disorders, mucocutaneous lichenoid eruptions, rosacea, and exacerbation of psoriasis. Alopecia secondary to immune checkpoint inhibitors has been reported in 1.0-1.6% of patients. We characterize four cases of alopecia areata (AA) secondary to immune checkpoint inhibitors with images, histology, and concomitant nail findings, including the first report of anti-PD-L1 therapy induced AA, and a review of the literature. Patients treated with immune checkpoint inhibitors, singly or in combination, who developed partial or complete alopecia (areata and universalis-type) during treatment for their underlying cancer were analyzed (N=4). Three (75%) patients had AA, while one (25%) had universalis-type. Two patients had resolution after topical, oral, or intralesional therapies and one patient had resolution after discontinuation of immunotherapy; all regrown hair exhibited poliosis. One (25%) patient had coincident onychodystrophy. This report describes a series of four patients who developed partial or complete alopecia (i.e. areata and universalis-type) during treatment with immune-checkpoint inhibitor therapies for cancer. Recognition and management of hair-related irAEs are important for pretherapy counseling and interventions that would contribute to maintaining optimal health-related quality of life.

Lupus‐like cutaneous reaction following pembrolizumab: An immune‐related adverse event associated with anti‐PD‐1 therapy

“…The most frequent immune‐mediated skin reactions of PD‐1 inhibitors are lichenoid reactions, vitiligo, eczema and pruritus . Bullous pemphigoid, alopecia areata and Stevens‐Johnson syndrome/toxic epidermal necrolysis have also been reported . Under the microscope, lichenoid tissue reactions are commonly seen in association with PD‐1 inhibitor therapy .…”

Lack of an association between alopecia areata and visceral or hematopoietic cancers

“…It is known that treatment of cancers with immune checkpoint inhibitors such as tumor necrosis factor-α, cytotoxic T-lymphocyte-associated protein-4, programmed cell death protein and ligand, can induce AA. 5 Induction of AA was likely due to activation of the inflammatory response and exposure of hair follicle antigens leading to loss of immune privilege. 5 …”

“…5 Induction of AA was likely due to activation of the inflammatory response and exposure of hair follicle antigens leading to loss of immune privilege. 5 …”

Blue hair pigmentation as inmunorelated adverse event in patient with non-small cell lung cancer (NSCLC) treated with anti- PD1 immunotherapy: a case report

“…The most frequently affected organ is the skin and hair. 6 At the level of the hair, the alopecia is the most frequent global effect, 7 although there are also changes in the structure (becoming more brittle and brittle) or in color (both hyper and hypopigmentation). They are usually reversible after discontinuation of the treatment.…”