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Published on: February 5, 2020
Lichenoid Dermatologic Toxicity From Immune Checkpoint Blockade Therapy: A Detailed Examination of the
Michael T Tetzlaff1, Priyadharsini Nagarajan, Susan Chon
1*Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; Departments of †Dermatology, and ‡Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Abstract:
Immunotherapy targeting the programmed cell death 1 (PD-1) receptor has demonstrated tremendous promise in the treatment of advanced solid tumors. Dermatologic toxicities, however, are an emerging consequence of this therapy and have been clearly associated with immune checkpoint blockade antibodies. Distinctive clinical and histologic subtypes of dermatologic toxicity secondary to immunotherapy are emerging and include rare autoimmune bullous reactions (eg, bullous pemphigoid) and lichenoid eruptions. We report three patients who developed lichenoid dermatitis while receiving anti-PD-1 antibody therapy. The mean time to onset of lichenoid dermatologic toxicity was 42 days (range: 1-75 days) from initiation of anti-PD-1 antibody therapy. Lesions most frequently presented on the extremities and trunk as pustules, papules, and plaques. The face was not commonly involved. Of the five skin biopsies examined, all demonstrated dense band-like lymphocytic infiltrate, hyperkeratosis, hypergranulosis, saw-tooth rete ridge pattern, and dyskeratosis. Acanthosis was a feature in all of the skin biopsies, and in one, epidermal hyperplasia was prominent. In several skin biopsies, histologic features supporting a lichenoid drug eruption were present, including parakeratosis, spongiosis, periadnexal/perivascular inflammation, and eosinophils. Furthermore, the histologic features varied in skin biopsy specimens taken from the same patient at different sites, supporting a drug reaction. All patients' skin lesions improved with use of steroids: two were treated with topical steroids and one with systemic steroids. Recognition of the histopathologic patterns of dermatologic toxicities resulting from immune checkpoint blockade therapy will become increasingly important for ensuring appropriate management of dermatologic toxicities and optimal patient care.
Insights
Immune checkpoint blockade therapy, specifically anti-PD-1 antibodies, can cause lichenoid dermatitis. This therapy-induced skin condition often presents on the trunk and extremities and responds well to steroid treatment.
Area of Science:
- Oncology
- Dermatology
- Immunology
Background:
- Programmed cell death 1 (PD-1) receptor immunotherapy shows promise for advanced solid tumors.
- Dermatologic toxicities are an emerging side effect of immune checkpoint blockade antibodies.
- Distinctive subtypes of immunotherapy-induced dermatologic toxicity are being identified, including autoimmune bullous reactions and lichenoid eruptions.
Observation:
- Three patients developed lichenoid dermatitis during anti-PD-1 antibody therapy.
- Lichenoid toxicity onset averaged 42 days (range: 1-75 days) after therapy initiation.
- Lesions commonly appeared on extremities and trunk as pustules, papules, and plaques, with infrequent facial involvement.
Findings:
- Skin biopsies revealed dense band-like lymphocytic infiltrate, hyperkeratosis, hypergranulosis, saw-tooth rete ridge pattern, and dyskeratosis.
- Acanthosis was consistently observed, with prominent epidermal hyperplasia in one case.
- Histologic features suggested a lichenoid drug eruption, with variations between biopsy sites supporting a drug reaction.
Implications:
- Steroid treatment, both topical and systemic, led to improvement in all patients' skin lesions.
- Recognizing histopathologic patterns of dermatologic toxicities from immune checkpoint blockade is crucial.
- Appropriate management of these toxicities ensures optimal patient care during immunotherapy.
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