CANDLE syndrome
Autoinflammatory disorder with skin lesions, fever, and lipodystrophy.
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is an autosomal recessive disorder characterized by autoinflammatory responses, multiple types of skin lesions, and recurrent long-term fever symptoms. The syndrome was first named and classified in March 2010 after four patients were reviewed with similar symptoms. As of 2015, approximately 30 cases had been reported in the scientific literature.
- First named
- March 2010
- Inheritance
- Autosomal recessive
- Known cause
- Mutation in PSMB8 gene or related genes
- Reported cases as of 2015
- Approximately 30
- Category
- Proteasome-associated autoinflammatory syndromes (PRAAS)
Lore & Background
CANDLE syndrome presents with outwardly visible conditions including facies not matching other known disorders, contracture of the joints, and skin lesions across any part of the body. Internal inflammatory developments include nonspecific lymphadenopathy, hepatosplenomegaly, and autoimmune hemolytic anemia. Other possible conditions are hypertriglyceridemia and lipodystrophy. A 2015 case also described dental symptoms such as microdontia and osteopenia of the jaw, along with diabetes mellitus.
Reader's Guide
The most common known cause of CANDLE syndrome is a mutation in the PSMB8 gene, which codes for proteasomes that break down other proteins. The mutated gene results in proteins not being degraded and oxidative proteins building up in cellular tissues, leading to apoptosis, especially in muscle and fat cells. A study by Brehm et al. in November 2015 discovered additional mutations in PSMA3, PSMB4, PSMB9, and the proteasome maturation protein (POMP), with 8 mutations in total between them. Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment, suggesting the condition also involves IFN dysregulation. The syndrome is part of the broader category of proteasome-associated autoinflammatory syndromes (PRAAS), which includes Nakajo-Nishimura syndrome and Joint contractures, Muscular Atrophy, Microcytic anemia, and Panniculitis-induced Lipodystrophy (JMP) syndrome. It has been proposed that these syndromes are clinical phenotypic variations of the same syndrome based around different mutations of the PSMB8 gene.
Did You Know?
- The syndrome does not respond to IL-1 inhibition treatment, suggesting IFN dysregulation.
- A 2015 case reported dental symptoms including microdontia and osteopenia of the jaw.
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