Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review

Abstract

IntroductionThe 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 etiologyThe 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.ConclusionPrognosis 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.

Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings

“…One fetus had a suspected Diamond-Blackfan anemia that was postnatally confirmed. Postnatal investigation showed suspicion of Chronic Infantile Neurological and Auricular syndrome in one baby but this was not genetically verified [26]. In three babies the etiology of the anemia remained unknown and persisted postnatally in one case.…”

Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets

“…Patients that have gain-of-function mutations in NLRP3 develop systemic auto-inflammatory syndromes called cryopyrin-associated periodic syndromes (CAPS; Finetti, Omenetti, Federici, Caorsi, & Gattorno, 2016). The NLRP3 gain-of-function mutations result in the spontaneous NLRP3 inflammasome formation without the addition of Signal 2.…”

“…Treatment with rilonacept, canakinumab or anakinra, compounds that act to suppress IL‐1β have greatly improved the life expectancy of CAPS patients, indicating that uncontrolled inflammation is damaging. Interestingly, patients with the most severe form of CAPS also display disruption of mental development (Finetti et al, ). This suggests that excessive IL‐1β production is detrimental to neuronal development and impairs health.…”

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

“…Different from the clinical manifestations of this patient, chilblains and intracranial calci cation are not present in SoJIA or CINCA; leukocytosis, destructive arthritis, or macrophage activation syndrome (MAS) are noted in SoJIA [4][5][6]; visual impairment, sensor neural deafness or progressive chronic meningitis have been commonly reported in CINCA [5]. Chronic kidney disease due to amyloidosis has been rarely reported in SoJIA, which is common in CINCA (Table 2) [8].…”