De novo subacute cutaneous lupus erythematosus‐like eruptions in the setting of programmed death‐1 or programmed death ligand‐1 inhibitor therapy: clinicopathological correlation

Abstract

Summary Immune checkpoint inhibitors (ICI) may cause eruptions resembling cutaneous autoimmune diseases. There are six cases of immunotherapy‐associated subacute cutaneous lupus erythematosus (SCLE) in the literature. We present details of five patients referred to the Skin Toxicity Program at the Dana‐Farber Cancer Institute/Brigham and Women’s Cancer Center who developed de novo immunotherapy‐associated SCLE‐like eruptions, along with clinicopathological correlation and highlight potential mechanistic features and important diagnostic points. Two patients were maintained on topical corticosteroids, antihistamines and photoprotection. One had complete clearance and two had improvement with addition of hydroxychloroquine. Four patients continued their immunotherapy uninterrupted, while one had immunotherapy suspended for a month before restarting at full dose. Histopathologically, this series illustrates the temporal evolution of ICI‐induced immune cutaneous reactions with SCLE subtype. Looking beyond the universally present lichenoid infiltrate, features of evolving SCLE were evident. We hypothesize that programmed death‐1 blockade may induce immunological recognition of previously immunologically tolerated drug antigens, leading to epitope spreading and the SCLE phenotype.

Subacute Cutaneous Lupus Erythematosus-Like Eruption Induced by Durvalumab: A Case Report and Literature Review

“…The period of ICIs use before the onset of SCLE appears longer, averaging 4 months (2 weeks to 20 months). 8,9 In our case, anti-cancer drugs consisting cytotoxic chemotherapies and durvalumab were the new medications initiated before the skin eruption in preceding 3 months and 2 months, respectively. However, DI-SCLE due to chemotherapeutic agents is uncommon, with few published cases associated with taxanes, tamoxifen, capecitabine, 5-fluorouracil, pemetrexed, and carboplatin.- 10 There is no report on etoposide-associated SCLE in the literature.…”

“…Moreover, anti-Ro/SSA can be positive in up to 80% in patients with ICIs-associated SCLE, whereas anti-La/SSB positivity occurs in only 25%. 9 The percentage of anti-Ro/SSA and ANA positivity among DI-SCLE associated with other drugs and ICIs-related SCLE were roughly the same, at 80% and 82%, respectively. However, positive anti-La/SSB is more common in classic DI-SCLE, accounting for approximately 48%.…”

“…Interface dermatitis with foci of vacuolar alteration of basal keratinocytes alternating with areas of lichenoid dermatitis, prominent epidermal atrophy, follicular plugging, and mild or absent basement membrane thickening are all classic features of SCLE skin biopsy. 9 The median time interval between drug exposure and the appearance of drug-induced SCLE (DI-SCLE) was reported to be 6 weeks (3 days to 11 years). The period of ICIs use before the onset of SCLE appears longer, averaging 4 months (2 weeks to 20 months).…”

“…However, HCQ administered at 200-400 mg/day has been employed with good outcome and without any adverse events. 9,[24][25][26][27][28] In a previous study, approximately 40% showed serologic improvement at the 8month follow-up in drug-induced CLE with positive anti-Ro/SSA. 29 In conclusion, ICIs are increasingly used in cancer therapy, the clinical-pathologic correlation is important to diagnose specific dermatologic adverse events.…”

Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

“…The detection of vasculitis only depends on imaging methods in a few cases; biopsy is required to confirm a diagnosis in some patients. Considering systemic vasculitides may result in severe organ damage, treatment of ICI may be discontinued, with the remedy therapy of hydroxychloroquine, glucocorticoid, and plasma exchange ( 63 , 64 ). It should be noted that acral vasculitis with digital ischemia could be concurrent with cancer ( 65 , 66 ); discontinuation of ICIs and steroid therapy might distinguish ICI-induced vasculitis and others.…”