Anakinra improves sensory deafness in a Japanese patient with Muckle‐Wells syndrome, possibly by inhibiting the cryopyrin inflammasome

Abstract

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients withMWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1␤ (IL-1␤). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C-reactive protein, serum amyloid A, and IL-1␤, and she had a heterozygous mutation in the CIAS1 gene, with C-to-T transversion at nucleotide position 778, encoding an arginineto-tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL-1␤, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.

An Integrated Classification of Pediatric Inflammatory Diseases, Based on the Concepts of Autoinflammation and the Immunological Disease Continuum

“…Given the aforementioned critical involvement of IL-1 and the NALP3 inflammasome in NOMID/CINCA pathogenesis, it is not surprising that anakinra and rilonacept have also been used therapeutically in a number of diseases, which are associated with excessive IL-1␤ production, including MWS (61)(62)(63)(64)(65)(66)(67)(68), FCAS (64,69 -73), NOMID/ CINCA (74 -76), and Schnitzler's syndrome (77-79). Not surprisingly, these lessons from pediatric arthritis/ inflammation have been successfully applied to adult patients with NALP3 inflammasome-related diseases, including gout and pseudogout (80,81).…”

Cryopyrin-associated periodic syndromes: background and therapeutics

“…Anakinra prevented cold-associated acute inflammation in patients with FCAS [41] and also effectively improved symptoms in patients with CINCA syndrome [42]. In some, but not all, cases of MWS, recovery from deafness following treatment with anakinra was reported, which greatly encouraged patients who had suffered from inflammatory symptoms for many years [43][44][45]. However, in a severe case of CINCA, only a limited effect of anakinra was reported [46].…”

Critical appraisal of canakinumab in the treatment of adults and children with cryopyrin-associated periodic syndrome (CAPS)

“…19,20 In about one-third of cases of MWS the hearing loss may be partially reversible. [21][22][23] In NOMID, NSAIDs, antihistamines, corticosteroids, colchicine, methotrexate and other immunosuppressive medications are marginally effective and do not change the disease course. One case report showed that etanercept, a tumor necrosis factor soluble receptor, was effective, mainly for the joints.…”