Generalized pustular psoriasis treated with ustekinumab

Generalized pustular psoriasis (GPP) is a rare and severe form of psoriasis that is frequently refractory to treatment. Ustekinumab is a fully human monoclonal antibody that binds with high affinity to the p40 subunit of interleukin (IL)‐12 and IL‐23.1 It has been shown to be safe and effective for the treatment of chronic plaque psoriasis.2 We report a case of a 90‐year‐old woman who initially presented in late 2009 with GPP. She had no preceding history of psoriasis and no obvious precipitating factors such as infection, drugs or recent systemic corticosteroid therapy. Physical examination revealed widespread urticated plaques with sheets of studded pustules on the patient's trunk, arms and legs (Fig. 1). Approximately 35% of her body surface area was affected. Widespread studded pustules on an erythematous base affecting the thighs bilaterally. The patient was commenced on ciclosporin A (CsA) (Neoral©; Novartis Pharmaceuticals Ltd, Camberley, Surrey, UK) at 2.5 mg/kg and her skin dramatically improved. Three months later, methotrexate was added with an initial test dose of 2.5 mg/week and subsequently increased to 10 mg/week with folic acid supplementation. Unfortunately, the patient's psoriasis flared upon weaning of the CsA despite the dose of methotrexate being increased to 20 mg/week. After 6 months of therapy, methotrexate was discontinued because of lack of efficacy, and acitretin 30 mg was commenced in addition to the existing dosage of CsA. The psoriasis improved, allowing the CsA to be tapered off, but the patient then developed hepatic dysfunction, which required discontinuation of acitretin. The patient was restarted on CsA at 2.5 mg/kg. She subsequently developed nausea and acute kidney injury on CsA, requiring discontinuation of the drug. She was commenced on adalimumab 40 mg/week in February 2011 after initial loading doses; unfortunately, after 14 months of adalimumab therapy, she developed widespread pustulation requiring inpatient hospital care. Her skin improved with the addition of CsA at 2.5 mg/kg. The pustular psoriasis again flared 12 months later, and adalimumab was stopped. The patient was commenced on ustekinumab 45 mg every 12 weeks, following an initial loading dose of 45 mg and another 45 mg at month 1. Her skin rapidly cleared after 4 weeks, and CsA was discontinued. Her skin remains clear 2.5 years later on ustekinumab 45 mg every 12 weeks. There are multiple reports of ustekinumab triggering pustular psoriasis,3 4 and there is only one previously published case report of GPP being successfully treated with ustekinumab; this was a 47‐year‐old man with plaque psoriasis that decompensated into pustular psoriasis. Although anti‐tumour necrosis factor agents (anti‐TNFs) are used to treat GPP, there are reports of these drugs actually triggering GPP.5 In conclusion, we report a case of a patient with GPP that was refractory to methotrexate therapy and required discontinuation of acitretin and CsA because of adverse effects. Although the patient's disease was initially controlled on adalimumab, it subsequently flared despite the addition of CsA to adalimumab therapy. The patient had a rapid and sustained response to ustekinumab therapy, and her skin has remained clear on a maintenance dose of ustekinumab. Our case highlights that ustekinumab can be a useful drug to treat this condition and should be considered in patients refractory to other systemic agents. Conflict of interest: the authors declare that they have no conflicts of interest.