LAUSR

We report the case of a 51-year-old man with metastatic melanoma who presented with a cutaneous drug reaction consistent with acute localised exanthematous pustulosis (ALEP). The patient was diagnosed with a BRAF wild type (NRAS Q61R mutant) metastatic melanoma following his admission for headache, blurred vision and left leg weakness. Multiple brain metastases were discovered on computed tomography imaging. A clinical examination revealed no evidence of cutaneous metastasis. Staging positron emission tomography scans revealed low volume positive axillary and hilar nodes, with no other extracranial disease. He was managed with the excision of the frontal, cerebellar and parietal masses, followed by whole brain radiotherapy and 3-weekly infusions of pembrolizumab. His medical history included diabetes, hypertension and dyslipidemia. Three months after commencing pembrolizumab he presented with erythematous macules and pustules on his palms and soles. The eruption was occasionally pruritic but not painful. Although the eruption resembled palmoplantar pustulosis, he had no history of psoriasis. A histopathological examination of a 3-mm punch biopsy sample taken from the left palm showed an intraepidermal subcorneal vesicle containing a mild neutrophilic infiltrate and a few acantholytic keratinocytes (Fig. 1). The adjacent epidermis showed mild spongiosis and there was a mild, superficial dermal perivascular chronic inflammatory cell infiltrate. Psoriasiform hyperplasia and suprapapillary plate thinning, characteristically seen in psoriasis, was not detected. There was no sub-epidermal clefting, heavy eosinophilic infiltrate, dermal oedema, leukocytoclasis or vasculitis. No viral cytopathic changes or fungal elements were detected either. A histopathology examination of a right heel sample showed lichenoid inflammation consistent with a drug reaction. Differential diagnoses based on histology included acute generalised exanthematous pustulosis (AGEP), pustular psoriasis or eczema with impetiginsation. Based on clinical findings, the eruption was most consistent with a localised form of AGEP secondary to pembrolizumab. The patient was commenced on betamethasone dipropionate ointment used under occlusion and maintained on pembrolizumab. At 4 months follow up, he reported improvement with the intermittent use of topical steroids; no further pustules were seen and only mildly scaly plaques remained. AGEP is a rare cutaneous eruption characterised by disseminated non-follicular sterile pustules on a background of erythematous skin. AGEP is typically drug-induced, with antibiotics being the commonest offending agent. ALEP is a localised and milder variant of AGEP with similar histopathological features. A clinical and histological distinction between pustular psoriasis and AGEP or ALEP is often difficult. Pembrolizumab is a humanised monoclonal IgG4 antibody that functions as a T-cell checkpoint inhibitor, targeting the programmed cell death 1 receptor (PD-1). Pembrolizumab is currently approved for the treatment of advanced melanoma and non-small cell lung cancer. Cutaneous adverse reactions to pembrolizumab are common and are usually mild: a retrospective study reported that 42% of patients experienced a cutaneous reaction. Common skin reactions to anti-PD-1 agents include macular and papular eruptions, pruritus and hypopigmentation. There are no cases of AGEP or ALEP secondary to any of the approved anti-PD-1 antibodies (nivolumab and pembrolizumab) in the medical literature, although unspecified