Familial cold autoinflammatory syndrome-2 (FCAS2) is caused by heterozygous mutation in the NLRP12 gene on chromosome 19q13. It is a rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalised exposure to cold (this could be simply walking down a supermarket aisle with refrigerators).
It was first discovered in 2008 by Jeru et al. [Download full PDF here] who reported 2 unrelated families from Guadeloupe with a periodic fever syndrome using a candidate gene approach. Inheritance was autosomal dominant. Affected 10-year-old twin boys in one family had onset in the first days of life of episodic fever, arthralgia, and myalgia. Episodes developed after generalized exposure to cold. Urticaria was observed 2 times in each patient, and both had bilateral sensorineural hearing loss. Headache and severe lower limb pain occurred during and between episodes. Serum C-reactive protein (CRP; 123260) and IgD were normal. The affected father had attacks lasting 2 to 3 days during childhood, and had episodes of fever and urticaria triggered by mild physical activity as an adult. His audiogram was normal. The proband of the second family was a 9-year-old girl with episodic fever since the first year of life. Episodes were triggered by cold exposure and associated with abdominal pain, vomiting, arthralgia, buccal aphthous ulcers, and lymphadenopathy. Serum CRP was found to be increased during attacks. Her father also had attacks.
Cases have been reported in the United States (2), Guadelope (5), Italy (4), Armenia (2), France (6), United Kingdom (2/3), Argentina (1) and China (3). Locations of the other cases are not in the literature.
Symptoms include headache, neuropapillitis, conjunctivitis, oral ulcers, sensorineural deafness, thoracic pain, dyspnea, diarrhea, abdominal pain, arthritis, arthralgia, myalgia, lymphadenopathy, Splenomagaly, increased APRs, toxic synovitis. This list is not exhaustive.
FCAS2 is currently a lifelong condition. Some drugs are available to give symptom relief. Currently they are Colchicine, Anakinra (brand name Kineret), Tocilizumab (brand name Actemra) and Ilaris (canakinumab), Most of these drugs are extremely expensive and none of them are specifically for FCAS2. Ilaris costs $29,300 per injection in the United States and an injection is required each month.
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