Definition
Cryopyrinopathies (or CAPS for Cryopyrin-Associated Periodic Syndrome) are rare auto-inflammatory genetic diseases associated with mutations in the NLRP3 gene.
When they were described, they were classically grouped into 3 clinical entities: familial cold urticaria (or FCAS), Muckle-Wells syndrome and chronic infantile neurological, cutaneous and articular syndrome (CINCA), the most common form. rare and most severe.
In practice, the first two are close and are often family forms (transmitted in a dominant mode) while CINCA mainly affects isolated patients (by neomutation).
Epidemiology
It is estimated that there are a hundred people with this disease in France and between 300 and 500 worldwide. The disease is cosmopolitan: it affects all countries of the world.
Genetic
The mutations are in the NLRP3 gene.
In family forms, they are transmitted from generation to generation according to a dominant mode and begin early in life.
In the CINCA form, the mutation appears during embryogenesis and the children who are born affected are often the only ones in their family.
There are forms of cold urticaria/Muckle wells appearing in adulthood by so-called "somatic" (i.e. acquired) mutation and the patients are therefore the only ones affected in their family.
Clinical
Symptoms are favored by environmental cold. The most common symptoms (in more than 95% of cases) is hives, favored by the cold.
Muckle-Wells syndrome and cold urticaria are characterized in addition to urticaria by recurrent fevers or chills, deafness, eye inflammation, headaches, joint pain and sometimes mouth ulcers +/- genitals.
CINCA syndrome begins at birth and is characterized by the presence of inflammation of the central nervous system (chronic meningitis), skin involvement (diffuse urticaria without itching), joint involvement ( deforming arthritis and arthropathy preferentially affecting the knees) and an unusual shape of the face, characterized by the presence of frontal bumps and saddle nose (too hollow nose).
All patients have inflammation in the blood, often chronic with elevated C-reactive protein.
In cases of prolonged chronic inflammation, they may develop inflammatory amyloidosis (AA amyloidosis)
Diagnostic
It is based on the detection of a mutation in the NLRP3 gene. It is recommended to do this by next-generation sequencing of the panel type, which makes it possible to see any somatic mutations.
Evolution
AA amyloidosis can complicate all forms of CAPS, including somatic NLRP3 mutation, and lead to disease discovery; the associated suggestive symptoms being deafness and cold urticaria.
Treatment
Treatment is based on interleukin 1 inhibitors, which have shown spectacular efficacy in these patients. Unfortunately, central nervous system damage and deafness are rarely reversible, especially if there is a long delay between the onset of symptoms and the start of treatment.