058 Life-threateningneurological impairment as a primary manifestation of adult onset Still’sdisease: successfully treated with anakinra

Abstract

Background: Adult onset Still's disease (AOSD) is a rare immunologic disorder characterised by high spiking fever, evanescent rash, arthritis, lymphadenopathy, myalgia and leucocytosis. Central nervous system (CNS) involvement is rare and difficult to diagnose due to protean manifestations and a lack of specific clinical and radiological features. Previously reported presentations include cranial nerve palsies, seizures, aseptic meningoencephalitis, Miller-Fisher syndrome and cerebral microangiopathy secondary to thrombotic thrombocytopaenic purpura (TTP). Severe or fatal neurological involvement is atypical but has been reported in the context of macrophage activation syndrome (MAS, a form of haemophagocytic lymphohistiocytosis [HLH]) and TTP. Anakinra, an interleukin-1 (IL-1) receptor antagonist, is safe and effective in the management of both AOSD and AOSD-related MAS. We report a case of AOSD with life-threatening neurological impairment, without evidence of concomitant MAS or coagulopathy, which responded rapidly and fully to anakinra. Methods: A 38-year-old man with known AOSD was admitted to hospital with a flare, having failed to respond to oral prednisolone 40mg daily over the preceding week. Clinical features were typical, including arthralgia, quotidian fever >39 8C, rash, sore throat and mild abdominal discomfort. Investigations demonstrated elevated white cell count at 31x109/L, neutrophils 29x109L, CRP 319mg/L, ferritin 705ng/ml, fasting triglyceride 1.2mmol/L, thrombocytopaenia and splenomegaly. Results: Despite intravenous methylprednisolone, azathioprine, and empirical antibiotic, he deteriorated with hyperpyrexia, rising CRP and ferritin, worsening thrombocytopaenia, and confusion. Anakinra was commenced on day six (100mg daily subcutaneously) and antimicrobials were changed to cover CNS infection. Coma ensued on day 7 and he was intubated and transferred to intensive care. MRI demonstrated diffuse symmetrical white matter lesions involving the cerebral hemispheres, brainstem and cerebellar peduncles. CSF showed polymorphonuclear leucocytosis with elevated protein. Gram stain and viral PCR were negative. EEG findings were in keeping with encephalopathy. Bone marrow revealed reactive changes without evidence of haemophagocytosis. He did not meet the 2004 criteria for HLH, and H score was 117, translating to a very low probability (4.93%) of HLH. There was no evidence of TTP. Anakinra was escalated to 100mg TDS on day 10, alongside IV immunoglobulin 400mg/Kg daily days 8-12 and methylprednisolone 1g daily days 8-10. Inflammatory markers and fever improved rapidly from day 10, with remarkable neurological recovery over the following two weeks. Anakinra was continued following discharge, with azathioprine and prednisolone, and he returned to work one month later. MRI on day 31 demonstrated only a small residual abnormality in the corpus callosum. Upon neuroradiology review, MRI lesions were felt to represent direct inflammatory manifestations of AOSD, on the basis of their non-specific inflammatory appearance and rapid resolution. Conclusion: To our knowledge, no previous cases have been reported of life-threatening CNS involvement of AOSD, in the absence of MAS or coagulopathy, treated successfully with anakinra.