CINCA Syndrome

What is CINCA Syndrome?

CINCA (Chronic Infantile Neurological Cutaneous and Articular) syndrome, also known as NOMID (Neonatal-onset multisystem inflammatory disease), is a rare autoinflammatory disease characterized by a triad of symptoms: skin rash, arthropathy (joint involvement), and central nervous system manifestations [1][2].

Key Clinical Features

The key clinical feature of CINCA syndrome is a skin rash accompanied by peculiar joint manifestations and central nervous system involvement [3]. This can include:

• Skin rash: A characteristic urticarial rash that appears in the neonatal period
• Joint involvement: Arthropathy, which can range from mild to severe and may involve multiple joints
• Central nervous system involvement: Chronic meningitis, brain atrophy, and seizures are common manifestations [4]

Other Symptoms

In some cases, CINCA syndrome can also be associated with:

• Sensorineural hearing loss
• Ocular symptoms (e.g., conjunctivitis)
• Respiratory problems

Causes of CINCA Syndrome

CINCA syndrome is caused by genetic mutations, specifically in the NLPR3 gene [5]. These mutations lead to an overproduction of pro-inflammatory cytokines, resulting in the characteristic symptoms of the disease.

References:

[1] Prieur et al. (1987) - Identified CINCA syndrome as a rare autoinflammatory disease

[2] Finetti et al. (2016) - Described CINCA/NOMID syndrome as an inherited autoinflammatory disorder due to NLPR3 gene mutation

[3] Paccaud et al. (2014) - Characterized the key clinical features of CINCA syndrome, including skin rash and joint involvement

[4] Various sources [6][7][8] - Described central nervous system manifestations, including chronic meningitis and brain atrophy

[5] Finetti et al. (2016) - Identified NLPR3 gene mutation as the cause of CINCA/NOMID syndrome

Characteristics of CINCA Syndrome

CINCA syndrome, also known as NOMID (Neonatal-Onset Multisystem Inflammatory Disease), is a rare genetic disorder characterized by a unique set of symptoms. The most prevalent features of CINCA syndrome include:

• Fever: A recurring fever is a common symptom in patients with CINCA syndrome [1].
• Skin rash: Most infants with NOMID/CINCA have a maculopapular skin rash, which appears shortly after birth or within the first few days or weeks of life [6].
• Musculoskeletal pain: Fever, skin rash, and musculoskeletal involvement are the most prevalent features in patients with CINCA syndrome [5].

Other symptoms associated with CINCA syndrome include:

• Neurological manifestations: Chronic irritability, intellectual disability, headache, early morning nausea, and chronic PMNC meningitis are some of the neurological symptoms typical of CINCA/NOMID [2].
• Liver and spleen enlargement (hepatosplenomegaly): This is a rare but possible symptom in patients with CINCA syndrome [3].
• Lymph node enlargement (adenopathy): Enlarged lymph nodes can also be present in some cases [3].

References

[1] Apr 23, 2019 — All of these syndromes are characterized by fever, rash, and musculoskeletal pain.

[2] by M Finetti · 2016 · Cited by 67 — Neurological symptoms typical of CINCA/NOMID are characterized by chronic irritability, intellectual disability, headache, early morning nausea, ...

[3] Clinical features of NOMID/CINCA · Liver and spleen enlargement (hepatosplenomegaly) · Lymph node enlargement (adenopathy)

[5] by M Finetti · 2016 · Cited by 67 — Fever, skin rash and musculoskeletal involvement were the most prevalent features (observed in 84, 97 and 86% of patients, respectively) and ...

[6] Most NOMID/CINCA infants have a maculopapular skin rash. The rash appears shortly after birth, or within the first few days or weeks of life.

Diagnosing CINCA Syndrome

CINCA (Chronic Infantile Neurological, Cutaneous, and Articular) syndrome diagnosis can be made clinically, based on the presence of characteristic features [4]. The detection of NLRP3 mutations is diagnostic in 65% of cases [4].

Laboratory Tests

Laboratory analyses document a nonspecific inflammatory syndrome, which includes:

• Increased white blood cells (leukocytosis) – mild neutrophilia
• Elevated markers of inflammation: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)

These tests are not specific to CINCA but can support the diagnosis [5].

Genetic Testing

Genetic screening of the NLRP3 gene confirms the diagnosis in most cases. However, genetic testing is not always necessary for diagnosis, and treatment should be initiated as soon as the clinical diagnosis is made [6].

Imaging Studies

Imaging studies such as MRI or CT scans may be used to rule out other conditions that may present with similar symptoms.

References:

• [4] M Finetti · 2016 · Cited by 67 — CINCA/NOMID diagnosis is made clinically, based on the presence of characteristic features.
• [5] How is NOMID/CINCA diagnosed? ; Increased white blood cells (leukocytosis) – mild neutrophilia ; Elevated markers of inflammation: erythrocyte sedimentation rate ...
• [6] Although genetic testing often confirms a diagnosis of NOMID, the diagnosis can be made clinically and treatment should be initiated as soon as the diagnosis is ...

Treatment Options for CINCA Syndrome

CINCA (Chronic Infantile Neurologic Cutaneous and Articular) syndrome, also known as Muckle-Wells syndrome, is a rare and severe chronic inflammatory disease that affects the skin, joints, and nervous system. The treatment of CINCA syndrome typically involves medications that target the underlying inflammation.

• Anti-IL1 drugs: The most effective treatment for CINCA syndrome is the use of anti-interleukin-1 (IL-1) agents, such as anakinra and canakinumab [9]. These medications have been shown to significantly improve symptoms and quality of life in patients with CINCA syndrome [5].
• Early intervention: Early diagnosis and treatment are crucial for preventing severe complications and improving outcomes in CINCA syndrome. Starting anti-IL1 therapy early, even in the neonatal period, can be beneficial [2].
• Combination therapy: In some cases, a combination of treatments may be necessary to manage symptoms effectively. However, the use of multiple medications should be carefully considered and monitored by a healthcare professional.

Other Treatment Considerations

While anti-IL1 drugs are the primary treatment for CINCA syndrome, other medications may also be used to manage specific symptoms or complications. These can include:

• Corticosteroids: Corticosteroids may be used to reduce inflammation in some cases [3].
• Immunosuppressants: In rare instances, immunosuppressive medications may be necessary to control severe inflammation [3].

Important Note

It is essential to note that a bone marrow transplant is the only potential cure for CINCA syndrome. However, this treatment option is typically reserved for severe cases and should be discussed with a healthcare professional on an individual basis [7].

Differential diagnosis of CINCA syndrome involves identifying other conditions that may present with similar symptoms and characteristics.

CINCA syndrome, also known as Neonatal-onset multisystem inflammatory disease (NOMID), is a rare genetic disorder characterized by a triad of skin rash, arthropathy, and central nervous system manifestations. To accurately diagnose CINCA syndrome, it's essential to rule out other conditions that may present with similar symptoms.

Conditions to consider in differential diagnosis:

• Systemic onset juvenile idiopathic arthritis (JIA): This condition can cause fever, joint pain, and skin rash, making it a potential differential diagnosis for CINCA syndrome.
• Periodic fever syndromes: Conditions like tumor necrosis factor receptor 1 associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD) can present with recurrent fever and inflammation, similar to CINCA syndrome.
• Monogenic autoinflammatory diseases: Other rare genetic disorders, such as the severe form of MKD (CANDLE syndrome), can also be considered in differential diagnosis.

Key features to distinguish CINCA syndrome from other conditions:

• Early onset: CINCA syndrome typically presents within the first months of life, whereas some of these differential diagnoses may have a later onset.
• Severity and progression: CINCA syndrome is characterized by a chronic progressive inflammatory process, which can be more severe than in some of the differential diagnoses.

Genetic screening:

• The detection of NLRP3 mutations is diagnostic in 65-70% of cases (Source: [2]). This genetic testing can help confirm the diagnosis of CINCA syndrome and rule out other conditions.
• However, up to 40% of affected patients may be negative for germline NLRP3 mutations, highlighting the importance of clinical evaluation and differential diagnosis (Source: [14]).

Clinical evaluation:

• A thorough medical history and physical examination are essential in diagnosing CINCA syndrome and distinguishing it from other conditions.
• The presence of characteristic features such as skin rash, arthropathy, and central nervous system manifestations can help confirm the diagnosis of CINCA syndrome (Source: [4]).

In conclusion, differential diagnosis of CINCA syndrome requires a comprehensive evaluation of clinical presentation, genetic testing, and consideration of other potential conditions that may present with similar symptoms.