Chronic infantile neurological cutaneous and articular syndrome Q87.8

CINCA syndrome, also known as NOMID, is a clinically severe, autosomal dominant, periodic fever syndrome caused by GOF mutations of the NLP3 gene and its gene product cryopyrin, which may manifest itself at birth as an extremely chronic, recurrent multisystemic disease. The clinical picture belongs to the family of cryopathies (CAPS), which also includes the mildest form, familial autoinflammatory cold syndrome 1 (CAPS) and Muckle-Wells syndrome.

CINCA is caused by genetically heterogeneous mutations of the NLP3 gene, which is mapped on gene locus 1q44. >50% of cases are due to de novo mutations. The mutation leads to disorders of the protein cryopyrin, a regulator of inflammatory reactions (see inflammasome, see NLRP3) with activation of NLP3 inflammasomes and an overproduction of interleukin-1beta.

Rapidly changing maculo-papular or urticarial exanthema, arthropathy, neurological disorders due to chronic aseptic menigitides, facial dysmorphia, mental retardation, lymphadenopathy and hepatosplenomegaly (see below fever syndromes, hereditary, periodic).

Non-specific picture with superficial, perivasal and interstitial, mostly neutrophilic infiltrates, with low leukocytoclasia; neutrophilic epitheliotropy (also in the eccrine sweat glands) is not uncommon; deposits of IgM and _C3 on the basement membrane can be detected.

Non-steroidal anti-inflammatory drugs and corticoids.

In case of sufficient response adjustment to the recombinant IL-1 receptor antagonist Anakinra (Kineret®) at a dosage of 100mg/day s.c.

History: Already since pre-school age the meanwhile 49 years old patient suffers from recurrent exanthema of the trunk and the lower extremities which occurred in intervals of 1-3 months. Under NSAR passagere improvement. Significant clinical effects could be achieved with medium prednisolone doses.ER is considerably restricted in his ability to read, so that he can hardly pursue his profession as an employee of a computer company.

Uveitis was diagnosed at the age of 30. Furthermore, he has arterial hypertension, which has to be treated with a beta-blocker.

For 10 years the patient has been taking ibuprofen regularly, almost daily.

Reason for the visitation: renewed fever (>39°C), exhaustion and severe feeling of illness, acute painful swelling of both ankle joints, also of the metacarpophalangeal joints. Simultaneous urticarial exanthema with small spots on the trunk and extremities.

Laboratory: BSG: 50/110, CRP 65 mg/l, neutrophil leukocytosis, lymphopenia, erythrocyturia, discrete serum amyloid A elevation. Discrete ANA, ENA, C3,C4, RF. c-ANCA. p-ANCA.

Human genetic diagnosis: Detection of a mutation in exon 3 of the NLP3 (CIAS 1) gene.

Therapy: IL-1 receptor antagonist (anakinra) at a dose of 100mg/day s.c. Including surprisingly fast improvement of symptoms.

Note: Subsequently, analogous symptoms were also found in the patient's family.

1. Aksentijevich I et al (2002) De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 46: 3340-3348
2. Granel B et al (2003) CIAS1 Mutation in a Patient with Overlap between Muckle-Wells and Chronic Infantile Neurological Cutaneous and Articular Syndromes. Dermatology 206: 257-259
3. Lee AG et al (1999) Optic disc edema in neonatal onset multisystem inflammatory disease (NOMID). J Neuroophthalmol 19: 180-181
4. Prieur A et al (1987) A chronic infantile neurological, cutaneous and articular (CINCA) syndrome. Scand J Rheumatol Suppl 66: 57-68