Cryopyrin-associated periodic syndrome (CAPS) belong to autoinflammatory diseases. In fact, CAPS is characterized by periodic and repeated episodes of fever, skin rash and musculoskeletal problems including arthritis. Besides, it has three subtypes that fall off under Cryopyrin-associated periodic syndrome (CAPS):
1- Familial cold autoinflammatory syndrome (FCAS)
2- Muckle wells syndrome (MWS)
3- Chronic infantile neurologic cutaneous articular syndrome OR Neonatal-onset multisystem inflammatory disease (CINCA/NOMID)
Therefore, some scientists proposed a term for these 3 diseases which is “NLRP3 associated autoinflammatory diseases” and it considers the responsible genes. As a matter of fact, CAPS result from gain-of-function mutation in the gene called CIAS1.
In fact, CAPS genetic disorder is very rare that it occurs for 1 in every million people. Above all, FCAS is considered a mild form of CAPS, while MWS might present with complications that lasts for long. Moreover, CINCA/NOMID is the most rare and severe form of CAPS genetic disorder. Furthermore, despite the fact that the 3 diseases have the same gene defected, each of them manifest in a different organ.
Symptoms of CAPS:
In general, CAPS genetic disorder starts right after birth where the baby experiences fever and rash without having any infection.
| FCAS | -Fever episodes that ends within a day |
| MWS | -Fever episodes that lasts 3 or more days -Arthritis (joint pain) -Progressive loss of hearing -Rare cases: Uveitis, papilledema, and optic atrophy |
| CINCA/NOMID | -Fever episodes that lasts 3 or 4 more days -Persistent inflammatory course with irregular flares -Erosive arthritis -Progressive loss of hearing -Uveitis, papilledema, and optic atrophy -Aseptic meningitis and increased intracranial pressure |
| ALL | -Fever -Fatigue -Flu-like symptoms -Skin rashes (urticaria, erythematous, edematous papule, plaque-like skin changes) -Ocular problems -Central nervous system problems -Extremities pain -Arthralgia -Myalgia -Rare cases: Anti-IL-1 Unresponsive bone deformities -Headache -Retardation, seizures, stroke and vascular occlusions |
What causes cryopyrin-associated periodic syndrome (CAPS):
In brief, CAPS is a genetic disease where there's a defect in a protein which controls inflammation. In other words, the defect is in the cryopyrin protein which is also called NLRP3 protein. To illustrate, to have a baby born with the disease, it's either by inheritance or a genetic mutation. Indeed, CAPS is an autosomal dominant disease where it's enough to have one copy mutated of the gene. Consequently, if one parent suffers from CAPS, the baby will definitely inherit this syndrome.
Diagnosis of cryopyrin-associated periodic syndrome (CAPS):
Certainly, a history regarding the symptoms the patient face (fever, hive rash, joint pain, etc...) or a physical examination during a fever episode is necessary to diagnose CAPS. Moreover, a blood test can reveal if the patient has any inflammation. Besides, it only makes sense to conduct a genetic test to confirm the mutation. Indeed, the criteria used for CAPS diagnosis are Eurofever/PRINTO criteria consisting of two sets. Additionally, the first is concerned with clinical issues while the other is concerned with clinical and genetic issues. Also, both sets propose efficiency of 100%.
Cryopyrin-associated periodic syndrome (CAPS) treatment:
Without a doubt, treatment with anti-interleukin (IL)-1 to antagonize the increase in IL-1 levels is the major approach. Thus, anakinra, canakinumab, and rilonacept are used as a treatment. Unfortunately, there exist no cure to end the disease so taking the treatment all life is vital. In general, you can't reverse any damage resulting including that of the eyes, ears, brain or bones, so detecting and treating CAPS genetic disease as early is possible is the mainstay. However, once arthritis or deafness are induced by the disease, it's possible to control them by physical therapy and hearing aids respectively.
How is it like to have CAPS?
In short, being a CAPS patient means you'll have a challenging life. Without doubt, this genetic disorder drastically affects your quality of life where you need to skip school frequently. In addition, it'll cost the parents finantionally and emotionally to live with a CAPS child. However, due to the developed treatments that can still be more advanced, sick children can enjoy life like normal children do.
Complications:
It's not safe to ignore treating the symptoms generated by this syndrome since it might cause:
- Amyloidosis
- Bones swelling
- Arthritis
- Loss of hearing
- Blindness
- Growth delay
References:
-Luheshi G, Rothwell N. Cytokines and fever. Int Arch Allergy Immunol. 1996 Apr;109(4):301-7. doi: 10.1159/000237256. PMID: 8634513.
-Bernheim HA, Block LH, Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979 Aug;91(2):261-70. doi: 10.7326/0003-4819-91-2-261. PMID: 223485.
