NLRC4-associated Autoinflammatory Disease, NLRC4-associated Macrophage Activation-like Syndrome (NLRC4-MAS)

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Acronym:
NLRC4-AID, NLRC4-MAS

SAID group:
NLRC4-associated autoinflammatory diseases, Macrophage Activation Diseases

Gene:
NLRC4 (aka SCAN4, CARD12)

Inheritance:
Autosomal dominant.

Ethnicity:
Not noted.

Frequency:
Unknown-rare

Timing of symptoms:
Injury, surgery or other stressors (physical or emotional) can trigger systemic flares of fever and macrophage activation syndrome (MAS)-like symptoms that can persist for weeks. [95]

Age of onset:
Infancy, early childhood - some at birth. [94] [95]

Skin cutaneous:
Evanescent rash with occasional dermatographism, with a notable urticarial rash during disease flares. [94] Adult with seronegative psoriatic arthritis, and erythematous plaques. [95]

Neurologic:
Recurrent fevers, starting in early infancy. [94] [95] Uncommon for other CNS symptoms. [98].

Auditory:
Not noted [94] [95] [98]

Ophthalamic:
Not noted [94] [95] [98]

Cardiopulmonary:
Risk for multiple-organ failure, disseminated intravascular coagulation (DIC), macrophage activation syndrome (MAS)-like attacks, with Acute Respiratory Distress Syndrome (ARDS). [95]

Abdominal:
Failure to thrive, or challenges with weight gain is common. Vomiting and diarrhea during flares. Splenomegaly, transaminitis. Inflammatory infiltrates are noted in the intestine. Duodenitis, neonatal-onset enterocolitis noted (may resolve after 1 yr of age). [94] [95] [98] High risk for multiple organ failure with MAS-like attacks. [95]

Lymphatic:
Splenomegaly.[94] [95] Lymphadenopathy may occur. [98]

Joints bones muscles cartilage:
Short stature, low weight in one case. [95] Arthralgia, myalgia, and psoriatic arthriitis noted in an adult patient. [95]

Vasculitis:
Not noted [94], [95]

Amyloidosis:
Not noted [94], [95]

Abnormal labs:
High (during flares): CRP, ESR, IL-18, triglycerides, ferritin (extreme ferritinemia), ALT, AST. Over-production of IL-1β and IL-18. Low during MAS-like flares): hemoglobin, platelets (thromobocytopenia), anemia, leukopenia. Normal NK cell function. [94].

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