LAUSR

Pyoderma gangrenosum is an inflammatory dermatosis characterised by painful, non-healing skin ulceration. There are no evidence-based or expert consensus guidelines to direct management and treatment failure is common. Approximately 50% of pyoderma gangrenosum sufferers have a recognised disease association such as inflammatory bowel disease or polymyalgia rheumatica. Polymyalgia rheumatica is a chronic inflammatory condition characterised by fatigue, pain and stiffness in the neck and proximal joints. This second most common rheumatic disease in the elderly is associated with giant cell arteritis in about 20% of cases. Treatment is unsatisfactory with many patients experiencing corticosteroid toxicity from prolonged courses required to maintain remission. A 69 year-old man with a history of gout, polymyalgia rheumatica and renal impairment presented with a sloughy painful penile ulcer along the inferior corona measuring 25 9 12 mm which appeared 8 months earlier and was enlarging progressively (Fig. 1). Previous treatments included numerous courses of antibiotics and topical corticosteroids. Polymyalgia rheumatica medications (of 3 years) included methotrexate (15 mg/week) and prednisolone (6 mg/day). Initial laboratory investigations revealed erythrocyte sedimentation rate (ESR) 38, C-reactive protein (CRP) 16 and rheumatoid factor 23. Immunoserology and sexual health screens were negative. Swabs from the ulcer base showed heavy growth of mixed flora. Histopathology revealed ulceration with bland-appearing keratinocytes in the epithelium. The ulcer base contained a mixed inflammatory cell infiltrate, granulation tissue and ectatic vessels, but no granulomas. Viropathic changes were not observed, and various pathogen stains were negative. A diagnosis of pyoderma gangrenosum was made based on clinico-pathological and microbiological correlation. The patient was initially prescribed topical clobetasol. After 2 weeks, the ulcer had expanded, so ciclosporin (100mg/day) was commenced. Five weeks later, the lesions were 25% smaller but still very painful. There was no further response after 4 more weeks, so ciclosporin was stopped prednisolone was tapered, and he was commenced on tildrakizumab 100 mg subcutaneously on a 0, 4, then 12 weekly schedule. At week 6 (after 2 doses), prednisolone was discontinued, and methotrexate was reduced to 10mg weekly. At week 24 (after 3 doses), the ulceration had almost completely re-epithelialised (Fig. 2). Methotrexate was stopped without polymyalgia rheumatica relapse. He received the 4th dose at week 28. At this timepoint, ESR was 2 and CRP 8. The ulceration had healed completely at week 32. There were no adverse events, and the patient discontinued topical treatment. Elevated IL-23 expression, Th17-cell recruitment and IL-23/IL-17 inflammatory axis disturbance have been implicated in pyoderma gangrenosum pathogenesis. Tildrakizumab is a monoclonal antibody that neutralises IL23 activity through IL-23p19 receptor inactivation. While the IL-12/IL-23p40 inhibitor ustekinumab has been successfully used to treat pyoderma gangrenosum, this is the first report of a selective anti-IL-23 biologic for refractory pyoderma gangrenosum treatment. The profound response seen justifies further clinical studies to investigate the efficacy and safety of tildrakizumab in pyoderma gangrenosum. Interestingly, tildrakizumab enabled cessation of prednisolone and methotrexate without polymyalgia rheumatica relapse. A decreased regulatory T-cell count and a markedly increased Th17-cell response are observed in polymyalgia rheumatica. Tildrakizumab’s inhibition of the IL-23/IL-17 axis and hence Th17-cell activity may