Cryopyrin-associated periodic syndrome pathophysiology

The exact pathogenesis of cryopyrin-associated periodic syndrome is not fully understood. However, it occurs due to the dysregulation of innate immune system. NLRP3 gene encoding a protein called cryopyrin involved in the pathogenesis of this disorder.

• Inflammation is the complex immunological response of vascular tissues to harmful stimuli. Normally, it protects the organism from the injurious stimuli as well as initiates the healing process for the tissue.

• The exact pathogenesis of the cryopyrin-associated periodic syndrome is not completely understood. However, it occurs due to the dysregulation of innate immune system.^[1]
• Mutations in the NLRP3 gene cause abnormal activation of the inflammasome, the molecular platform that plays a pivotal role in inflammation.
• This leads to the overexpression of the key proinflammatory cytokine, interleukin (IL)-1β.
• Excessive amounts of IL-1β triggers the uncontrolled release of inflammatory cytokines, which act synergistically with IL-1β inducing the inflammatory process. This process is mainly mediated via the recruitment and activation of neutrophils.

• Cryopyrin-associated periodic syndrome is transmitted in the autosomal dominant pattern.^[2][3]
• NLRP3 gene encoding a protein called cryopyrin (also known as nacht domain-, leucine-rich repeat- and pyrin domain-containing protein 3 [NALP3] or pyrin domain-containing apoptotic protease activating factor 1-like protein [PYPAF1] involved in the pathogenesis of this disorder.
• Cryopyrin is derived from the Greek words for icy cold and fire. The recurrent episodes of this disease are usually triggered by cold.

• Conditions associated with Familial Cold Autoinflammatory Syndrome (FCAS) include:^[4]
  • Mild hearing loss
• Conditions associated with Muckle-Wells Syndrome include:^[5]
  • Hearing loss
  • Secondary amyloidosis
• Conditions associated with Neonatal Onset Multi-system Autoinflammatory Disease (NOMID) include:^[6][4]
  • Developmental delay
  • Seizure
  • Hydrocephalus
  • Chronic aseptic meningitis
  • Uveitis
  • Pericarditis
  • Destructive arthropathy
  • Secondary amyloidosis

• Individual cutaneous lesion in CAPS are rose or red macule or papule or plaques.^[7]

• Histology of urticarial lesions consists of dense neutrophilic infiltrate in perivascular area and interstitium.^[7]

Template:WH Template:WS