Background/Purpose: CAPS is a rare autoinflammatory disease associated with mutations in the NLRP3 gene that result in overactivation of the inflammasome, increased secretion of IL-1beta and IL-18, and systemic inflammation. Muckle-Wells syndrome (MWS) is a rare autosomal dominant disease which causes sensorineural deafness, recurrent hives, and joint pain. CNS manifestations are one of the prominent clinical features in children with CINCA/NOMID, but they have been described only rarely in patients with FCAS and MWS.

Methods: Here we present the imagination findings of CNS involvement in a family whose 11 members have MWS. Clinical data was collected during the course of ongoing patient care.

Results: We evaluated the clinical features of 11 patients who were referred to our center. The median age of the patients was 25 years (range: 9–65years). The ratio of females /males was 1.2 (6/5). All patients had arthritis with exacerbation on exposure to cold and ocular involvement, mostly in the form of conjunctivitis and far less commonly uveitis, irideal synechiae, band keratopathy, cataract, and impaired vision. The median age of onset of arthritis was 7 years (2-30y), the median age of onset of ocular involvement was 8 years (2-45 y). Hearing loss in 73.6% of patients was detected, with a 15 years (12-63 y) as the median age of onset. All patients except one had urticarial rash. The median age of onset of urticarial rash was 8 years (7-30 y). Three patients had recurrent headache attacks. Neurological examination was normal in all and cranial MR was obtained in 8 out of 11 patients. While 4 out of 8 patients had normal MR findings; the enlargement of the ventricles and gliotic focus in the subcortical white matter associated with a deepening of the cerebral sulci in 2 patients; enlarged ventricles and cerebellomedullary cisterns in 2 patients were detected. There was no mutation detected in the study of MEFV (all exons), TNFRSF1A (exons 2-to-7), MVK (all exons), NLRP3 (all exons), NOD2 (exons 4, 8 and 9) and PSTPIP1 (exons 10 and 11) genes. Anakinra was started in 6 patients and two patients were treated with canakunimab . Following anti-IL1 treatment, attacks of arthritis and urticaria are getting fully under control, advances in keratopathy and hearing loss could be partially controlled.

Conclusion: CAPS are usually inherited disorders caused by an autosomal dominant mutation. Neurological manifestations may be one of the major clinical features and were mostly reported in cases with CINCA/NOMID. Currently, there is no fixed demarcation between FCAS and MWS or MWS and CINCA/NOMID. Distinguishing between these cryopyrinopathies may be difficult because they have symptoms in common. During attacks, patients develop severe headaches and will have findings of ‘aseptic’ meningitis in the cerebrospinal fluid (CSF), with predominately neutrophils and eosinophils cellular infiltrate. Our three cases had recurrent headache and two of them had enlarged ventricles and cerebellomedullary cisterns in cranial MR. Although neurological findings was reported rarely in cases with MWS, cranial MR should be requested in patients with MWS who has headache.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cns-manifestations-of-patients-with-muckle-wells-syndrome/