Cutaneous and Subcutaneous Toxicities of Pembrolizumab

Epidemiology

Approximately 34 % of patients receiving PD‑1 inhibition with pembrolizumab develop any cutaneous adverse event (e.g., rash, pruritus, vitiligo) [1][2][3][4].
The most common manifestations are:
- Erythematous rash in ~15 % of patients,
- Pruritus in 13–20 %, and
- Vitiligo in up to 25 % of melanoma patients [2][3].
Severe (grade 3‑4) skin reactions are uncommon, occurring in < 3 % of patients treated with pembrolizumab monotherapy [2][4].

Early‑onset toxicities typically appear within the first few weeks of therapy, but can also arise after several months [2][4].
Extensive cutaneous involvement (affecting > 30 % of body surface area) warrants urgent evaluation for life‑threatening conditions such as Stevens‑Johnson syndrome, toxic epidermal necrolysis, or DRESS [2][5].

Perform a comprehensive skin and subcutaneous examination, documenting number, size, distribution, and characteristics of any nodules or lesions 2.
Rule out alternative causes (infection, other drug reactions, cutaneous metastases, systemic diseases) [2][4].
Obtain a skin/subcutaneous biopsy for histopathology—especially for grade 3‑4 lesions—to confirm non‑caseating granulomas or other immune‑mediated patterns 4.
Assess for systemic sarcoidosis with complete blood count, liver and renal panels, and chest imaging 5.

Continue pembrolizumab with close monitoring; consider low‑dose systemic corticosteroids (e.g., prednisone ≈ 10 mg) if symptomatic [no citation – omitted].

Administer a short course of systemic glucocorticoids, which usually resolves lesions while allowing continuation of pembrolizumab [no citation – omitted].

Do not permanently discontinue pembrolizumab for mild‑to‑moderate skin toxicities that respond to treatment 6.
Do not delay treatment of severe reactions, as they can rapidly progress to life‑threatening conditions 5.
Advise patients to avoid harsh soaps or alcohol‑based cleansers that may exacerbate irritation 6.

Development of vitiligo in melanoma patients correlates with improved clinical response to pembrolizumab [2][3]4.
Sarcoid‑like granulomatous reactions may reflect an effective anti‑tumor immune response rather than disease progression [no citation – omitted].

Continuous monitoring throughout therapy is essential, as new dermatologic adverse events can arise at any time, not solely within the first 12 weeks 7.
The incidence of sarcoid‑like reactions is likely under‑reported because systematic dermatologic assessment is not routinely performed in clinical trials [2][3].