BI25 Immunotherapy-associated Sweet syndrome in a patient with metastatic melanoma

Abstract

Ipilimumab, an anti-CTLA-4 monoclonal antibody, is used in the treatment of metastatic melanoma. As with other immune checkpoint inhibitors, it can cause a spectrum of immune-related adverse events (irAEs), including a cutaneous pathology, in 25% of patients. To date, there have been five case reports of Sweet syndrome solely due to ipilimumab therapy. We present a suspected further case in a patient with metastatic melanoma of unknown primary origin, who concurrently developed vitiligo. A 65-year-old man presented to the dermatology department with a 2-week history of a mildly tender, erythematous papulonodular rash localized to the right forearm. He had also developed extensive vitiligo on all limbs over a similar period of time. Histology from a skin punch biopsy demonstrated a predominantly neutrophilic dermal inflammatory infiltrate without features of vasculitis, confirming Sweet syndrome. There were no recent medication changes or disease recurrence on repeat imaging. Nine months prior, the patient had been diagnosed with cerebral and pulmonary metastatic melanoma of unknown primary origin (BRAF V600 mutation positive). He underwent an evacuation of a left temporal cortical mass and subsequent stereotactic radiosurgery. The oncology team then commenced ipilimumab (3 mg kg–1) and nivolumab (1 mg kg–1) every 21 days. Four cycles were completed until discontinuation after 3 months due to multiple severe irAEs, namely, panhypopituitarism and liver toxicity. He was commenced on 80 mg (1 mg kg–1) oral prednisolone, which was slowly reduced over subsequent months and completed a few weeks prior to the development of Sweet syndrome and vitiligo. We prescribed topical clobetasol propionate 0.05% once daily, with resolution of Sweet syndrome after 2 months. The oncology team elected to withhold further immunotherapy due to the multiple irAEs, instead monitoring for melanoma recurrence by serial radiological imaging. The five previously documented cases of ipilimumab-associated Sweet syndrome report an average time to clinical presentation of 8.9 weeks. Our case differs as the patient developed Sweet syndrome 5 months after the discontinuation of immunotherapy. However, the development of any cutaneous adverse effect may have been masked by high-dose steroids for the other systemic irAEs soon after the fourth cycle of treatment. Despite a lack of temporality between immunotherapy and Sweet syndrome in our case, the addition of vitiligo at the same presentation suggests an irAE. This case highlights the importance of monitoring patients on immunotherapy for dermatological side-effects and working closely with oncology colleagues to manage these complex cases.