同: CINCA

同: CINCA

WordNet

being long-lasting and recurrent or characterized by long suffering; "chronic indigestion"; "a chronic shortage of funds"; "a chronic invalid"
of long duration; "chronic money problems" (同)continuing
habitual; "a chronic smoker" (同)inveterate
of or relating to infants or infancy; "infantile paralysis"
being or befitting or characteristic of an infant; "infantile games"
a pattern of symptoms indicative of some disease
a complex of concurrent things; "every word has a syndrome of meanings"
relating to or existing on or affecting the skin; "cutaneous nerves"; "a cutaneous infection" (同)cutaneal, dermal

PrepTutorEJDIC

《語・句・節を対等に結んで》…『と』…,…や…,および / 《数詞を結合して》…『足す』…,…に加えて / …『しかも』…,…して,同時に… / 《時間的に》『そして』,それから,すると(and then) / 《当然の帰結として》…『ので』,…だから(and so) / 《おもに話》《命令文などの後で》『そうすれば』,そうしたら / 《追加・強調して》それに,しかも / 《対照的な内容を導いて》ところが,しかし(but) / 《譲歩的に》それなのに,それでいながら / 《A and Bで一体の関係を表して》《単数扱い》 / 《同一語を反復して多数・継続などを表して》 / 《同一の複数名詞を結合して変化・種類などを表して》 / 《話》《「形容詞+and+形容詞」の形で前の形容詞が後に副詞的に働く》 / 《話》《「動詞come, goなど+and+動詞」の形でandとその後の動詞が不定詞の働きをして》 / 《「動詞+and+動詞」の形で後の動詞が現在分詞の意を表して》 / 《話》《文頭において前の質問・意見などに同意を示して》そうとも,そして(Yes!and) / 《話》《文頭に置いて驚き・疑念・非難などを表して》ほんとうに;…なのに
(病気が)長期にわたる,慢性の / 《名詞の前にのみ用いて》常習の,癖になった
《名詞の前にのみ用いて》幼時の / 子供じみた;子供らしい
(疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態
皮膚の,皮膚を冒す

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/06 17:57:55」(JST)

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Neonatal onset multisystem inflammatory disease (abbreviated NOMID, also known as chronic infantile neurologic cutaneous and articular syndrome,^[1]^:149 or CINCA) is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period. Symptoms include skin rashes, severe arthritis, and chronic meningitis leading to neurologic damage. It is one of the cryopyrin-associated periodic syndromes.

NOMID can result from a mutation in the CIAS1 gene (also known as NLRP3 gene), which helps control inflammation. Mutations in this gene also cause familial cold urticaria and Muckle-Wells syndrome. NOMID has been successfully treated with the drug anakinra.

This syndrome is also known as the Prieur-Griscelli syndrome as it was first described by these authors in 1981.^[2]

Signs and symptoms

The age of onset is almost always before 3 months of age. Many infants are born preterm (1/3 cases) and dysmature. The babies are frequently small for dates. The placenta may be abnormal with non specific inflammation on histology. Umbilical cord anomalies have occasionally been reported. In severe cases signs in the brain may be detected on prenatal ultrasound.

The presentation is pleiomorphic making the diagnosis difficult but the most common features of this disease involve the skin, joints and central nervous system.

All have a maculopapular urticarial skin rash and is often present at birth (75% cases). It is probably more correctly described as an urticarial-like rash. The presence of the rash varies with time and biopsy of these skin lesions shows a perivascular inflammatory infiltrate including granulocytes.

In about 35-65% of cases arthritis occurs. Joint signs are variably expressed and can lead to transient swelling without sequelae between crises or to unpredictable anomalies of growth cartilage and long bones epiphyses suggestive of a pseudo-tumour. Biopsies reveal hypertrophic cartilage without inflammatory cells. This most commonly affects the large joints (knees, ankles, elbows, wrists) but may also involve the small joints of the hands and feet. It is usually bilateral and painful. A common and characteristic feature is are giant kneecaps. Severe cases may result in contractures (joint deformities).

Most patients eventually have neurological problems. These manifest themselves in three principal ways: chronic meningitis, involvement of the both the optic tract and eye and sensineural deafness. The chronic meningitis presents with the features of chronically raised intracranial pressure: chronic headaches, vomiting, ventriculomegaly, hydrocephalus, macromegaly, cerebral atrophy and optic atrophy. Some of these features may be evidence on prenatal ultrasound. In 50% intellectual deficit occurs. Seizures occur in 25% but other manifestations are rare. Histological examination shows infiltration of the meninges with polymorphs.

Ocular manifestations occur in 80% and include uveitis (70%), papillary involvement, conjunctivitis and optical neuritis. If untreated these may result in blindness (25%). The sensorineural hearing loss occurs in 75% and tends to be progressive leading to deafness in 20%.

Almost all the children are remarkably short and have growth delay. Fever is extremely common but inconstant and is most often mild. Anaemia is frequent. Other findings that have been reported include macrocephaly (95%), large fontanelle, prominent forehead, flattening of the nasal bridge (saddleback nose), short thick extremities and finger clubbing. The liver and/or spleen may be enlarged. Lymph node enlargement may also be present.

Later in life secondary amyloidosis may occur. Delayed puberty and secondary amenorrhoea is not uncommon. Hoarseness due to inflammation of the laryngeal cartilage has also been reported.

Possible causes

The disease is caused in 60% of cases by a mutated gene called CIAS1 that is known to be involved in other syndromes that appear somewhat similar, such as Muckle-Wells syndrome and familial cold urticaria. In many patients, the parents do not have the same mutation, indicating the problem was not inherited, even though it is a genetic disease.

CIAS1 is involved in controlling the immune system, which is why the mutation leads to out-of-control inflammation.

Diagnosis

The diagnosis is based on observing the patient and finding the constellation of symptoms and signs described above. A few blood tests help, by showing signs of long standing inflammation. There is no specific test for the disease, though now that the gene that causes the disease is known, that may change.

Routine laboratory investigations are non specific: anaemia, increased numbers of polymorphs, an elevated erythrocyte sedimentation rate and elevated concentrations of C reactive protein are typically all the abnormalities found. Lumbar puncture shows elevated levels of polymorphs (20-70% of cases) and occasionally raised eosinophil counts (0-30% of cases). CSF neopterin may be elevated.

The X ray changes are unique and charactistic of this syndrome. These changes include bony overgrowth due to premature ossification of the patella and the long bone epiphyses in very young children and bowing of long bones with widening and shortening periosteal reaction in older ones.

Audiometry shows a progressive sensineural deafness. Visual examination shows optic atrophy and an increase in the blind spot. CT is usually normal but may show enlargement of the ventricles. MRI with contrast may show enhancement of leptomeninges and cochlea consistent with chronic meningitis. EEG shows is non specific with slow waves and spike discharges.

Polymorphs tend to show increased expression of CD10.

Differential diagnosis

Aicardi-Goutières syndrome
Still's disease
Schnitzler syndrome
Hyperimmunoglobulin D syndrome
Familial Mediterranean Fever
Marshall's syndrome
Castleman's disease

Still's disease does not affect children under 6 months old.

Hyperimmunoglobulin D syndrome in 50% of cases is associated with mevalonate kinase deficiency which can be measured in the leukocytes.

Treatment

There have been attempts to control the inflammation using drugs that work in other conditions where inflammation is a problem. The most successful of these are steroids, but they have side effects when used long term. Other medications, including methotrexate, colchicine and canakinumab, have been tried with some success. Otherwise, the treatment is supportive, or aimed solely at controlling symptoms and maximizing function.

Prognosis

Overall, the prognosis for patients with NOMID is not good, though many (80%) live into adulthood, and a few appear to do relatively well. They are at risk for leukemia, infections, and some develop deposits of protein aggregated called amyloid, which can lead to kidney failure and other problems. The neurologic problems are most troubling. The finding that other diseases are related and a better understanding of where the disease comes from may lead to more effective treatments.

Epidemiology

This is a rare condition with an incidence estimated to be less than 1 in a million live births. About 100 cases have been reported worldwide. The bulk of cases are sporadic but familial forms with autosomal dominant transmission have also been described.

References

^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
^ Prieur AM, Griscelli C (1981) Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation. J. Pediat 99:79-83

External links

NOMID Alliance—Non-profit charity devoted to CAPS diseases
Neonatal Onset Multisystem Inflammatory Disease (NOMID) - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Notes

Online 'Mendelian Inheritance in Man' (OMIM) 607115
Goldbach-Mansky, R. et al. Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1{beta} Inhibition N Engl J Med 2006 355: 581-592.

UpToDate Contents

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1. 血清病および血清病様反応 serum sickness and serum sickness like reactions
2. クリオピリン関連周期性発熱症候群および関連疾患 cryopyrin associated periodic syndromes and related disorders
3. IPEX：免疫不全，多腺性内分泌障害、腸疾患、X連鎖 ipex immune dysregulation polyendocrinopathy enteropathy x linked
4. 全身型若年性特発性関節炎：臨床症状および診断 systemic onset juvenile idiopathic arthritis clinical manifestations and diagnosis
5. 周期性発熱症候群およびその他の自己炎症性疾患：概要 periodic fever syndromes and other autoinflammatory diseases an overview

English Journal

Musculoskeletal Symptoms in Patients with Cryopyrin-Associated Periodic Syndromes: Large Database Study.

Houx L1, Hachulla E2, Kone-Paut I3, Quartier P4, Touitou I5, Guennoc X6, Grateau G7, Hamidou M8, Neven B9, Berthelot JM10, Lequerré T11, Pillet P12, Lemelle I13, Fischbach M14, Duquesne A15, Le Blay P16, Le Jeunne C17, Stirnemann J18, Bonnet C19, Gaillard D20, Alix L21, Touraine R22, Garcier F23, Bedane C24, Jurquet AL25, Duffau P26, Smail A27, Frances C28, Le Rosey-Grall M29, Cathebras P30, Tran TA31, Morell-Dubois S32, Pagnier A33, Richez C34, Cuisset L35, Devauchelle-Pensec V36.
Arthritis & rheumatology (Hoboken, N.J.).Arthritis Rheumatol.2015 Aug 5. doi: 10.1002/art.39292. [Epub ahead of print]
OBJECTIVES: To determine the type and frequency of musculoskeletal symptoms at onset and during follow-up of cryopyrin-associated periodic syndromes (CAPS).METHODS: We retrospectively recorded the articular and muscular symptoms of patients with CAPS managed in French hospitals. Data were described
PMID 26245507

CAPS - pathogenesis, presentation and treatment of an autoinflammatory disease.

Kuemmerle-Deschner JB1.
Seminars in immunopathology.Semin Immunopathol.2015 Jul;37(4):377-85. doi: 10.1007/s00281-015-0491-7. Epub 2015 May 12.
The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare diseases. CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID), also known
PMID 25963520

Successful management of cryopyrin-associated periodic syndrome with canakinumab in infancy.

Kanariou M1, Tantou S2, Varela I2, Raptaki M2, Petropoulou C3, Nikas I4, Valari M5.
Pediatrics.Pediatrics.2014 Nov;134(5):e1468-73. doi: 10.1542/peds.2013-3185.
Neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic cutaneous and articular (CINCA) syndrome is a rare, early-onset autoinflammatory disorder and the most severe form of cryopyrin-associated periodic syndrome, which is associated with overproduction of interleukin (I
PMID 25349319

Japanese Journal

NOD蛋白質の機能から考える『自己炎症疾患』発症の分子メカニズム

増本純也,長谷川瑞穂,猪原直弘
日本臨床免疫学会会誌 = Japanese journal of clinical immunology 30(2), 68-77, 2007-04-28
… 炎症疾患（Familial cold autoinflammatory syndrome : FCAS), Muckle-Wells syndrome (MWS），新生児発症全身炎症疾患（Neonatal onset multisystem inflammatory disease : NOMID)/慢性乳児期発症神経皮膚関節症候群（Chronic infantile neurologic cutaneous and articular syndrome : CINCA）とNOD蛋白質の一つであるpy …
NAID 10019495134

Enhanced interleukin-1β and interleukin-18 release in a patient with chronic infantile neurologic, cutaneous, articular syndrome

JANSSEN R.
Arthritis Rheum 50, 3329-3333, 2004
NAID 30013441667

Related Pictures

Clubbingについて（結核画像シリーズ小休止） : 放浪→定住 Periodic fever, rash and arthropathy in a child: Diagnosis: Chronic infantile Cryopyrin Associated Periodic Syndrome (Familial Cold Urticaria, Familial Cold Cryopyrinopathies: Update on Pathogenesis and Treatment: Clinical Manifestations Clinical Manifestations and Longterm Followup of a Patient with CINCA/NOMID Syndrome Periodic fever, rash and arthropathy in a child: Diagnosis: Chronic infantile Clinical features of neonatal-onset multisystem inflammatory | Download Scientific Linkage of bacterial colonization of skin and the urticaria-like rash of NLRP3