- Cryopyrin-associated periodic syndromes.

Cryopyrin-associated periodic syndromes (CAPSs)

CAPS includes a spectrum of conditions ranging from mild to severe, and includes three syndromes:

• FCAS.
•  MWS.
• CINCA/NOMID.

INCIDENCE/AETIOLOGY:

CAPS is extremely rare, with an incidence of probably <1 in 500,000.

CAPS is due to mutations in NLRP3/CIAS1 on chromosome 1q44, that encodes the key component of IL-1 activation complex: the inflammasome.

A dominant inheritance occurs in about 75% of patients with FCAS and MWS, whereas CINCA is usually due to de novo mutations 

.

CLINICAL PRESENTATION:-

Onset is in early infancy, often from birth; there is no sex bias.

Children present with a characteristic appearance of flattened nasal bridge and bossing of the skull.

•  FCAS: attacks of fever generally begin 1-3 hr after generalized cold exposure, urticarial rash, arthralgia and conjunctivitis, episodes are self-limited and generally resolve within 24 hr.
• MWS: daily attacks (afternoon/evenings), Acute symptoms include fever, urticarial rash, arthralgia and myalgia, conjunctivitis, headache and fatigue.Rash can be persistent.Deafness occurs later and is often missed in the early stages.
• CINCA/NOMID: continuous inflammation with additional severe chronic aseptic meningitis, raised intracranial pressure, uveitis, deafness and arthropathy.

DIAGNOSIS

• FCAS and MWS have mutations in NLRP3.
• Clinical diagnosis for CINCA/NOMID: mutations are found in only 50%.
•  Histopathologic examination reveals a perivascular neutrophilic infiltratewithout the mast cells or mast cell degranulation seen with true urticaria.

TREATMENT:

Treatment is IL-1 blockade with anakinra or with two other licensed therapies: the fully human anti IL-1beta antibody canakinumab; or IL-1 Trap) rilonacept(.

Not only controlling fever and rash, but also preventing end-organ damage.

PROGNOSIS:

•  25% develop AA amyloidosis.
•  Complications of chronic CNS inflammation: severe in CINCA, less in MWS.
• 40% sensorineural deafness;
• blindness due to optic atrophy or uveitis; developmental delay.
•  CINCA arthropathy: cartilage and bony overgrowth (patella), joint destruction can occur.
• MWS and CINCA: 17% clubbing of the finger nails.

 Ibrahim samaha

References:-

• Amanda K. Ombrello and Daniel L. Kastner , Hereditary Periodic Fever Syndromes and Other Systemic Autoinflammatory Diseases,Chapter 163,NELSON TEXTBOOK OF PEDIATRICS, TWENTIETH EDITION 2016
• Clarissa Pilkington, Kiran Nistala, Helen Lachman and Paul Brogan, Rheumatology , GREAT ORMOND STREET HANDBOOK OF PAEDIATRICS, 2nd  ed
• Osama Naga,Rheumatologic Disorders, Periodic Fever ,190-192 Pediatric Board Study Guide, A Last Minute Review
• Sujata Sawhney and Amita Aggarwal, Autoinflammatory Syndromes in Children, Pediatric Rheumatology,546-554 A Clinical Viewpoint,2017
• Ronald M. Laxer ,David D. Sherry  and Philip J. Hashkes,CH10 Autoinflammatory Syndromes,189-208 Pediatric Rheumatology in Clinical Practice,2nd ed 2016