INTRODUCTION
Immune checkpoint inhibitors (ICIs) have altered the landscape for treating advanced malignant tumors. ICIs are monoclonal antibodies that target cytotoxic T lymphocyte-associate antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death ligand 1 (PD-L1),1 Adverse cutaneous events from ICIs are among the earliest and most common from these medications.2 In this report, we present a case of ICI-related plaque psoriasis and palmoplantar pustulosis (PPP) following pembrolizumab therapy for recurrent cutaneous squamous cell carcinoma of the face and the use of topical tapinarof cream 1% for the treatment of both conditions.
CASE REPORT
An 83-year-old Caucasian male with a history of numerous cutaneous squamous cell carcinomas (SCC) presented with a recurrent well-differentiated cutaneous SCC of the left central malar cheek with new onset facial numbness for 3 to 4 weeks. The site was initially treated with surgery in 2014. He underwent re-excision with Mohs procedure in Sept 2021, requiring three stages. After the procedure, he exhibited paresthesia and pain at the site of surgery. He then underwent an MRI of the head and neck, which revealed perineural invasion with nerve enhancement and thickening. Subsequent positron emission tomography (PET) scan and clinical exam revealed no clinical lymph node involvement. Given perineural invasion without lymph node involvement, the tumor was staged as T3N0M0 (Stage III) according to the AJCC-8 staging system for cutaneous SCC of the head and neck.3 He underwent complete full excision with clearance and then initiated immune checkpoint inhibitor (ICI) pembrolizumab 200 mg every 3 weeks from January 2022 to November 2022 without disease progression. The patient stopped pembrolizumab in November 2022 due to the development of a progressive rash rated as a Grade 3 ICI-related adverse event. He then presented in March 2023 with scaly nummular pink plaques involving his extremities and trunk, as well as erythematous patches, vesicles, pustules, and erosions with collarettes of scale on the palms and soles with significant pain while walking (Figure 1A). Exam findings were consistent with ICI-induced plaque psoriasis and palmoplantar pustulosis. The patient was then treated with tapinarof cream 1% daily to the affected areas for one month with significant improvement in lesion appearance and pain while walking (Figure 1B).
DISCUSSION
Pembrolizumab is a monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1) and prevents the inhibition of the cytotoxic T cell response allowing the immune system to eliminate tumor cells.1 While there is an important therapeutic benefit of pembrolizumab, adverse cutaneous effects are seen in nearly 17% of patients.2 Pembrolizumab is also less commonly known to cause or exacerbate psoriasis in patients.2 Cases of palmoplantar pustulosis (PPP) specifically following pembrolizumab therapy are rare but have also been reported.4 Treatment for psoriasis or PPP from pembrolizumab consists of stopping the offending drug and utilizing topical/oral corticosteroid therapy, methotrexate, and various biologics.2
In PPP, the primary area of inflammation is the acrosyringium indicating that eccrine sweat glands contribute to skin immunity and barrier function. Abnormalities of the gland in the palmoplantar region promote the development of vesicles and pustules filled with neutrophils or eosinophils.5 Biopsies of these lesions show increased production of several cytokines, including interleukin-8 (IL-8), IL-1alpha, IL-1beta, IL-17A-F, IL-22, IL-23A, and IL-23 receptor.6 While the role of the IL-17 pathway in the pathogenesis of PPP is not fully clear, several studies have found a significant increase in the expression of IL-17A in the palms and
