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Review
, 11 (1), 167

Chronic Infantile Neurological Cutaneous and Articular (CINCA) Syndrome: A Review

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Review

Chronic Infantile Neurological Cutaneous and Articular (CINCA) Syndrome: A Review

Martina Finetti et al. Orphanet J Rare Dis.

Abstract

Introduction: The Chronic Infantile Neurological Cutaneous and Articular (CINCA, or Neonatal-onset multisystem inflammatory disease NOMID) is a rare autoinflammatory disease identified in 1987 by Prieur et al., typically characterized by the triad of skin rash, arthropathy and central nervous system manifestations. It represents the most severe phenotype of the cryopyrin-associated periodic syndrome (CAPS).

Clinical description and etiology: The syndrome is due to autosomal dominant gain of function mutations in NLRP3, which encodes a key component of the innate immunity that regulates the activation and secretion of interleukin (IL)-1β. From the first days of life, patients display an urticarial rash in association with chronic inflammation with a typical facies featured by frontal bossing and saddle back nose. The CNS manifestations include chronic aseptic meningitis leading to brain atrophy, mental delay and sensorineural hearing loss. Chronic polyarthritis and alteration of the growth cartilage also may be present. CINCA/NOMID diagnosis is made clinically, based on the presence of characteristic features. The detection of NLRP3 mutations is diagnostic in 65-70% of cases. Indeed, up to 40% of affected patients are negative for germline NLRP3 mutations and several subjects are carriers of somatic mosaicism. Due to the pivotal role of Cryopyrin in the control of Caspase-1 activation and the massive secretion of active IL-1β observed in cryopyrin-mutated individuals, anti-IL1 treatment represents the standard therapy.

Conclusion: Prognosis of CINCA/NOMID syndrome has been changed by the availability of anti-IL1 drugs. Nowadays, the use of anti-IL-1 drugs has sensibly reduced the risk of developing main complications such as severe intellectual disability, hearing-loss and amyloidosis, if treatment is started early on.

Keywords: Aseptic meningitis; Autoinflammation; Cryopyrinopathies; Hearing loss; IL-1; Urticarial rash.

Figures

Fig. 1
Fig. 1
Urticarial rash of CAPS patient
Fig. 2
Fig. 2
Typical CINCA/NOMID “facies” featured by frontal bossing, large cephalic perimeter and saddle-back nose
Fig. 3
Fig. 3
MR features of CINCA/NOMID brain (subdural fluid collections, leptomeningeal contrast, papilledema, coclear enhancement)
Fig. 4
Fig. 4
Schematic illustration of the NLRP3 inflammasome activation

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