Cryopyrin-associated periodic syndrome

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Cryopyrin-associated periodic syndrome
Other namesCAPS[1]
Cryopyrin-associated periodic syndrome is autosomal dominant in inheritance
SpecialtyDermatology, medical genetics Edit this on Wikidata

Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by

familial cold autoinflammatory syndrome (FCAS, formerly termed familial cold-induced urticaria), the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID, also called chronic infantile neurologic cutaneous and articular syndrome or CINCA) that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway, and keratoendotheliitis fugax hereditaria
in which the autoinflammatory symptoms affect only the anterior segment of the eye.

Signs and symptoms

The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients with systemic involvement from 16 countries,

seizure, hydrocephalus or intellectual disability; 40% of cases), and AA amyloidosis (4% of cases).[citation needed
]

In keratoendotheliitis fugax hereditaria, systemic symptoms are not reported whereas the patients experience periodical transient inflammation of the corneal endothelium and stroma, leading to short term blurring of vision and, after repeated attacks, to central corneal stromal opacities in some patients.[3]

Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary.[4][5]

Pathogenesis

Cryopyrin-associated periodic syndromes are associated with a gain-of-function missense mutation in exon 3 of

interleukin 1 inflammasome.[2][6] In keratoendotheliitis fugax hereditaria, the mutation occurs in exon 1.[3] Intracellular formation of the interleukin 1 inflammasome leads to the activation of the potent pro-inflammatory cytokines interleukin 1β and interleukin-18 through a cascade involving caspase 1. The IL-1 inflammasome may also be released from activated macrophages, amplifying the cytokine production cascade.[7] The mutation in NLRP3 leads to aberrant constitutive formation of this inflammasome.[8][9]

Up to 170 heterogenous mutations in NLRP3 have been identified. Some reports suggest rare mutations are more frequently associated with a severe phenotype,[10] and some mutations are associated with distinct phenotypes, probably reflecting the differential impact of the mutation on the activity of the inflammasome in the context of individual genetic background.[2][3] Inheritance of these disorders is autosomal dominant with variable penetrance.[citation needed]

Diagnosis

Because CAPS is extremely rare and has a broad clinical presentation, it is difficult to diagnose, and a significant delay exists between symptom onset and definitive diagnosis.[11] There are currently no clinical or diagnostic criteria for CAPS based solely on clinical presentation. Instead, diagnosis is made by genetic testing for NLRP3 mutations. Acute phase reactants and white blood cell count are usually persistently elevated, but this is aspecific for CAPS.[citation needed]

Treatment

Since interleukin 1β plays a central role in the pathogenesis of the disease, therapy typically targets this cytokine in the form of monoclonal antibodies (such as canakinumab[12][13]), binding proteins/traps (such as rilonacept[14]), or interleukin 1 receptor antagonists (such as anakinra[15][16][17][18]). These therapies are generally effective in alleviating symptoms and substantially reducing levels of inflammatory indices. Case reports suggest that thalidomide[19] and the anti-IL-6 receptor antibody tocilizumab[20] may also be effective.

References

  1. ^ RESERVED IU. "Orphanet: Cryopyrin associated periodic syndrome". www.orpha.net. Retrieved April 27, 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. ^
    S2CID 206850668
    .
  3. ^
    PMID 29366613
    .
  4. PMID 10486324
    .
  5. PMID 22997256
    .
  6. PMID 11687797
    .
  7. S2CID 13022253
    .
  8. PMID 38321014
    .
  9. PMID 31086329
    .
  10. ^ "Infevers". fmf.igh.cnrs.fr. Archived from the original on October 21, 2016. Retrieved October 21, 2016.
  11. S2CID 6670512
    .
  12. S2CID 28667263
    .
  13. PMID 24906637
    .
  14. PMID 18668535
    .
  15. S2CID 34516905
    .
  16. PMID 15541451
    .
  17. PMID 16899778
    .
  18. PMID 16284353
    .
  19. S2CID 30354429
    .
  20. PMID 16802372
    .

External links

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