Familial Cold Autoinflammatory Syndrome

Cold urticaria (essentially meaning cold hives) is a disorder where hives (urticaria) or large red welts form on the skin after exposure to a cold stimulus. The welts are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7mm in diameter to as big as about 27mm diameter or larger. This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to occur between ages 18–25, although it can occur as early as 5 years old in some cases. Life-threatening risks include suffocation resulting from pharyngeal angiooedema induced by cold foods or beverages, drowning after shock from swimming in cold water and anaphylactic shock. 'The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID.'' However, while these techniques assist in diagnosis, they do not provide information about temperature and stimulation time thresholds at which patients will start to develop symptoms.' Cold urticaria (essentially meaning cold hives) is a disorder where hives (urticaria) or large red welts form on the skin after exposure to a cold stimulus. The welts are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7mm in diameter to as big as about 27mm diameter or larger. This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to occur between ages 18–25, although it can occur as early as 5 years old in some cases. Life-threatening risks include suffocation resulting from pharyngeal angiooedema induced by cold foods or beverages, drowning after shock from swimming in cold water and anaphylactic shock. Cold urticaria may be divided into the following types: Primary cold contact urticaria is a cutaneous condition characterized by wheals, and occurs in rainy, windy weather, and after swimming in cold water and after contact with cold objects, including ice cubes. Secondary cold contact urticaria is a cutaneous condition characterized by wheals, due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia are extremely rare, and are then associated with other manifestations such as Raynaud's phenomenon or purpura. Reflex cold urticaria is a cutaneous condition in which generalized cooling of the body induces widespread welting. Familial cold urticaria (also properly known as familial cold autoinflammatory syndrome, FCAS) is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22 °C (72 °F). It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells syndrome and NOMID. It is rare and is estimated as having a prevalence of 1 per million people and mainly affects Americans and Europeans. FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44. The disease was described in The Lancet Volume 364 by Hoffman H.M. et al. The effect of FCAS on the quality of life of patients is far reaching. A survey of patients in the United States in 2008 found, 'To cope with their underlying disease and to try to avoid symptomatic, painful, flares patients reported limiting their work, school, family, and social activities. Seventy-eight percent of survey participants described an impact of the disease on their work, including absenteeism and impaired job advancement; frequently, they quit their job as a consequence of their disease'.