Cold temperature challenges for acquired cold urticaria.
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Cold Temperature↗
Biomedical subjects
Alan A Wanderer
Publications and source records attributed to Alan A Wanderer.
The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromes.
Acquired cold urticaria syndromes represent one of the more common forms of physical urticaria. The syndromes are heterogenous, and a diagnostic classification is presented to facilitate collation for future studies. Acquired cold urticaria represents an excellent reproducible in vivo model to investigate the mechanisms of urticaria. The discussion includes clinical manifestations, laboratory features, pathogenesis, and management of these disorders. A description of familial types, particularly familial cold auto-inflammatory syndrome (FCAS) that is manifested by cold-evoked signs and symptoms of chronic inflammation, is included. FCAS historically has been included with acquired cold urticaria, even though the exanthem of FCAS is maculopapular caused by leukocytic infiltration. FCAS has become an important investigative syndrome, as it represents a reproducible in vivo model of chronic inflammation.
Cold Temperature↗
Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P.
Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant inflammatory disease with a high degree of penetrance that is characterized by episodes of rash, arthralgia, fever, conjunctivitis, and leukocytosis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44, and subsequently the gene ( CIAS1) responsible for FCAS was identified. In this paper, we describe the physical and genetic mapping of the FCAS locus, and we report a large ancestral haplotype and a new disease-causing mutation. A BAC contig of approximately 3 Mb was developed and subsequently used for high throughput sequencing. We identified a critical region of 4 cM using rare crossover events in four large North American FCAS families. An unusually large shared haplotype (40 cM) was identified in three of the four families. We found a single heterozygous missense mutation (T1058C=L353P) in exon 3 of CIAS1 in all four families that is responsible for the large majority of FCAS cases described in the literature. We also report a comprehensive list of intragenic single nucleotide polymorphisms. The data provided here will assist others researching the 1q44 region and will aid clinicians in the diagnosis of FCAS.
Autoimmune Diseases↗
Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist.
BACKGROUND: Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant disorder characterised by recurrent episodes of rash, arthralgia, and fever after cold exposure. The genetic basis of this disease has been elucidated. Cryopyrin, the protein that is altered in FCAS, is one of the adaptor proteins that activate caspase 1, resulting in release of interleukin 1. METHODS: An experimental cold challenge protocol was developed to study the acute inflammatory mechanisms occurring after a general cold exposure in FCAS patients and to investigate the effects of pretreatment with an antagonist of interleukin 1 receptor (IL-1Ra). ELISA, real-time PCR, and immunohistochemistry were used to measure cytokine responses. FINDINGS: After cold challenge, untreated patients with FCAS developed rash, fever, and arthralgias within 1-4 h. Significant increases in serum concentrations of interleukin 6 and white-blood-cell counts were seen 4-8 h after cold challenge. Serum concentrations of interleukin 1 and cytokine mRNA in peripheral-blood leucocytes were not raised, but amounts of interleukin 1 protein and mRNA were high in affected skin. IL-1Ra administered before cold challenge blocked symptoms and increases in white-blood-cell counts and serum interleukin 6. INTERPRETATION: The ability of IL-1Ra to prevent the clinical features and haematological and biochemical changes in patients with FCAS indicates a central role for interleukin 1beta in this disorder. Involvement of cryopyrin in activation of caspase 1 and NF-kappaB signalling suggests that it might have a role in many chronic inflammatory diseases. RELEVANCE TO PRACTICE: These findings support a new therapy for a disorder with no previously known acceptable treatment. They also offer insights into the role of interleukin 1beta in more common inflammatory diseases.
Acute Disease↗