Paraneoplastic Pemphigus Revealed by Anti-programmed Death-1 Pembrolizumab Therapy for Cutaneous Squamous Cell Carcinoma Complicating Hidradenitis Suppurativa

Abstract

A 64-year-old patient developed a widespread autoimmune mucocutaneous blistering disease 3 weeks after the initiation of the anti-programmed death-1 (anti-PD-1) pembrolizumab therapy administered for a locally advanced cutaneous squamous cell carcinoma (SCC) of the buttocks arising from hidradenitis suppurativa. A diagnosis of paraneoplastic pemphigus (PNP) was made based on the presence of a suprabasal acantholysis associated with intercellular deposits of immunoglobulin G and C3 on basement membrane zone. Analysis of the patient's sera was positive on monkey bladder and detected circulating antibodies against desmoglein 3 and desmoplakin I prior to the initiation of pembrolizumab. At that time, the patient had few localized blisters limited to the peri-tumoral skin of the buttocks with acantholysis but without in vivo immune deposits. Pembrolizumab therapy was discontinued and a complete remission of PNP was obtained using oral steroids. Reintroduction of pembrolizumab resulted in flare of PNP. Given the close temporal relation between pembrolizumab initiation and the subsequent clinical expression of a widespread PNP, the patient was diagnosed with pre-existing subclinical PNP exacerbated by PD-1 inhibitor. The extreme rarity of PNP in the setting of cutaneous SCC and the effects of challenge, dechallenge, and rechallenge of pembrolizumab argue in favor of a checkpoint inhibitor related adverse effect. Our case is the first PNP associated with anti-PD-1 therapy and serological follow-up suggest that one infusion of pembrolizumab is sufficient to allow clinical expression of underlying pemphigus auto-immunity.

Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa

“…All the case reports and series met the minimum quality assessment standard and were included in the meta-analysis ( Supplementary Table S1 ) [ 2 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Selection bias cannot be excluded as most authors did not explicitly explain their selection method; therefore, there is a possibility that some cases of cSCC arising from HS wounds were not reported, underestimating the total number of cases currently in the literature.…”

Paraneoplastic pemphigus manifesting in a patient treated with pembrolizumab for urothelial carcinoma

“…Infrequently, subclinical PNP and PNP-like irAEs with absence of mucositis have been described in the context of ICI therapy. 2 , 6 , 7 , 8 …”

Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma

“…According to a recently published review, 21 cases of BP have been described in association with PD-1 inhibitors (10 cases were associated with pembrolizumab, 9 cases with nivolumab, one case with durvalumab, and one with atezolizumab) ( 14 ). A few other studies have described two cases of atypical PV in patients treated with anti-PD-1 (one related to nivolumab and one with pembrolizumab), one report of PNP with pembrolizumab, and two cases of mucous membrane pemphigoid (MMC) associated with pembrolizumab ( 15 , 16 ). Among the data presented in our clinical experience, we observed two cases of PB related to PD-1 inhibitor therapy (one case with nivolumab and one with pembrolizumab) (data not published).…”