2197 Letter urticaria were most pronounced at the patient’s face, trunk, and lower limbs and would intensify during recurrent attacks of fever (Figure 1D). Acute-phase reactants were constantly elevated [C-reactive protein (CRP) up to 170 mg/l, serum amyloid A (SAA) up to 567 mg/l]. Failure to thrive, mild splenomegaly, and refractory iron-deficiency anemia, without a detectable source of infection, led to no definitive diagnosis, and an extensive investigation for autoantibodies and complement defects was negative. During early childhood she developed arthritis of both knees and excessive hyperostosis of the patella and distal femur (Figure 1H, 1I), which led to constant pain and finally required surgery. She developed bilateral chronic uveitis with secondary band keratopathy (Figure 1A) and optic neuritis, which led to a significant visual impairment with optic nerve atrophy. At age 5 years the clinical diagnosis of CINCA syndrome was made and later confirmed by genetic testing, indicating a novel NLRP3 mutation A439P. Short stature, frontal bossing of the skull, characteristic flattening of the nasal bridge, clubbing of the fingers and delayed closure of the fontanelles (at age 10 years) contributed to the clinical picture. Episodes of transient sudden deafness preceded bilateral sensorineural hearing loss, especially in the higher frequency range (Figure 1B), and brain magnetic resonance imaging showed diffuse cortical atrophy and ventriculomegaly (Figure 1C). At age 12 the patient developed a pauci-immune crescent glomerulonephritis with diffuse extracapillary necrosis and accompanying vasculitis without amyloidosis (Figure 1E, 1F). Renal function was stabilized by 3 pulses of cyclophosphamide 500 mg, but mild proteinuria and reduced creatinine clearance remained.

An association of autoinflammatory diseases such as familial Mediterranean fever and vasculitis has been described5, but this is the first report of vasculitis in a patient with CINCA syndrome. Despite various treatments (including corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, and cyclosporine), persistent uveitis, polyarticular arthropathy, and patellar overgrowth continued to be major complaints, temporarily confining the patient to a wheelchair. She suffered frequent episodes of headaches related to chronic aseptic meningitis. Treatment with a soluble tumor necrosis factor (TNF)-receptor immunoglobulin fusion protein (etanercept, 50 mg weekly) or with a monoclonal antibody against TNF-a (adalimumab, 40 mg subcutaneously biweekly) led to mild improvement of symptoms but no reduction in CRP and SAA levels.