Ipilimumab-induced acute generalized exanthematous pustulosis in a patient with metastatic melanoma

Abstract

Ipilimumab is a new anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody that stimulates the immune response against melanoma. A 50-year-old man received ipilimumab for metastatic melanoma as part of a clinical trial. Two weeks after drug initiation, he developed a widespread oedematous erythema with sterile pustules. The histological examination showed subcorneal pustulosis formation with eosinophils. The clinical-pathological correlation was consistent with acute generalized exanthematous pustulosis. The symptoms resolved within 25 days after discontinuation of ipilimumab. We suspect that neutrophilic accumulation under the epidermis in this patient is a phenomenon similar to intraepithelial neutrophils aggregating on the surface epithelium over laminar propria in ipilimumab-induced colitis. To our knowledge, this is the first reported case of acute generalized exanthematous pustulosis associated with ipilimumab use in metastatic melanoma patients.

The Clinical and Histopathological Features of Cutaneous Immune-Related Adverse Events and Their Outcomes

“…Interestingly, cutaneous irAEs shared clinical and histopathological features with classical inflammatory eruptions. Although not observed in our study, there have been reports of sarcoidosis [16], Grover's disease [17][18][19], granuloma annulare [20], dermatomyositis [21,22], Sjögren's syndrome [23], pityriasis rubra pilaris [24], or acute generalized exanthematous pustulosis [25,26] induced by ICIs. Several reports [27][28][29] suggested that in superficial perivascular dermatitis induced by ICIs, there were increased numbers of CD4 + lymphocytes compared with CD8 + lymphocytes, as well as regulatory T cells.…”

Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

“…Lesions in the inflammatory category include DHR (as described earlier), dermatomyositis, neutrophilic dermatoses (e.g. Sweet syndrome and pyoderma gangrenosum), acute generalized exanthematous pustulosis (AGEP), acneiform eruptions, photosensitivity reactions, radiation‐associated dermatitis, lichenoid dermatitides, drug rash with eosinophilia and systemic symptoms (DRESS) and a CD30‐positive lymphoid reaction . Extremely rare were reports of an adverse cutaneous reaction that manifested as vasculitis with progression to Steven‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) .…”

Intracorneal pustular drug eruption associated with nivolumab in a patient with metastatic renal cancer

“…We assume that anti‐PD1 therapy modifies the homeostasis of the normal skin flora leading to a marked infiltration of neutrophils of the skin. Comparable hypotheses were proposed in a recent case of nivolumab‐induced intracorneal pustular drug eruption and in a patient with ipilimumab‐induced AGEP 1,7 . Furthermore, these previous cases highlight the importance of considering pustular drug eruptions as a differential diagnosis in patients with pustules or erythematous plaques who are receiving anti‐PD1 therapy.…”