P091 Posterior reversible encephalopathy syndrome (PRES) presenting in a patient with psoriasis receiving ustekinumab

Abstract A 68-year-old patient with psoriasis and psoriatic arthritis presented to acute medicine after a short history of severe dizziness and headache. They were established on treatment with subcutaneous ustekinumab 45 mg every 12 weeks. Clinical examination showed no focal deficits in cranial nerve, motor or sensory function; however, Romberg’s sign was positive. Of note, her blood pressure on admission was 194/98 mmHg. Computed tomography of the brain showed atypical low attenuation in the white matter with relative sparing of the posterior territories. Subsequent magnetic resonance imaging (MRI) confirmed bilateral, symmetrical subcortical and deep white matter hyperintensities suggesting an atypical distribution of posterior reversible encephalopathy syndrome (PRES). Prochlorperazine 5 mg three times daily and amlodipine 10 mg once daily were commenced and ustekinumab suspended. At clinic follow-up 2 weeks later her symptoms had resolved. PRES is characterized by rapid onset over hours of a constellation of neurological symptoms including headache, nausea, visual disturbance, encephalopathy and seizures. These are accompanied by specific MRI findings of focal subcortical vasogenic oedema, which is often not restricted to the ‘posterior’ parietal and occipital lobes. Severe hypertension is commonly seen. A number of possible triggers have been identified, with autoimmune disease and immunosuppressive agents being found in approximately 45% of patients. The pathophysiology of this increasingly described entity remains controversial. The leading two theories are (i) cytotoxic endothelial injury from recruitment and activation of proinflammatory cytokines and T lymphocytes leading to blood–brain barrier dysfunction and (ii) rapidly developing hypertension leading to impairment of cerebral autoregulation causing cerebral hyperperfusion and vasogenic oedema. However, PRES can occur in the absence of hypertension. A consistent finding is that prompt neurological recovery can be obtained upon withdrawal of the suspected causative agent, which highlights the importance of an awareness of the association with biologic agents. PRES has been described in patients using adalimumab, infliximab and ustekinumab, most commonly in the context of inflammatory bowel disease. To our knowledge this is the second case of PRES reported in a patient with psoriasis treated with ustekinumab, with PRES being recorded as a serious adverse event in the phase III PHOENIX 2 study (ClinicalTrials.gov identifier: NCT00307437). Ustekinumab has a favourable safety profile. However, it is important that clinicians are aware of this rare debilitating neurological adverse event, so prompt withdrawal of possible triggers including biologic agents can be made to facilitate neurological recovery. The half-life of ustekinumab is problematic for prompt withdrawal and there remain questions regarding ongoing management of the patient’s inflammatory dermatosis and arthritis, as case reports document worsening of PRES on reintroduction of traditional immunosuppressive systemic agents.