Abstract
CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature) is a rare, genetic autoinflammatory disease due to abnormal functioning of the multicatalytic system proteasome–immunoproteasome. Several recessive mutations in different protein subunits of this system, located in one single subunit (monogenic, homozygous, or compound heterozygous) or in two different ones (digenic and compound heterozygous), cause variable defects in catalytic activity of the proteasome–immunoproteasome. The final result is a sustained production of type 1 interferons (IFNs) that can be very much increased by banal triggers such as cold, stress, or viral infections. Patients start very early in infancy with recurrent or even daily fevers, characteristic skin lesions, wasting, and a typical fat loss, all conferring the patients a unique and unmistakable phenotype. So far, no treatment has been effective for the treatment of CANDLE syndrome; the JAK inhibitor baricitinib seems to be partially helpful. In this article, a review in depth all the pathophysiological, clinical, and laboratory features of CANDLE syndrome is provided.
Highlights
Specialty section: This article was submitted to Inflammation, a section of the journal Frontiers in Immunology
CANDLE is an acronym standing for Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature [1,2,3]
Mutations in different genes encoding protein subunits of the proteasome–immunoproteasome system are the cause of CANDLE syndrome
Summary
Reviewed by: Maryam Piram, CHU de Bicêtre, France Karoline Krause, Charité Universitätsmedizin Berlin, Germany. CANDLE syndrome is an autoinflammatory disease (AID) characterized by the appearance of recurrent fever in the first months of life, along with characteristic skin lesions, lipodystrophy, and manifestations of multisystem inflammation. Mutations in different genes encoding protein subunits of the proteasome–immunoproteasome system are the cause of CANDLE syndrome. The disease seemed to cause some general growth delay, and after more than 10 years of follow-up most patients looked wasted, with a striking loss of fat With all these features, the chronic eruption with skin neutrophilic and mononuclear immature infiltration, the fevers and the lipodystrophy, an acronym was coined. Accumulation of waste proteins within the cell causes cellular stress, which in turn stimulates type 1 IFN, and closes the circle of inflammation Common triggers, such as cold, physical or psychical stress, banal infections or others cause stimulation of type 1 IFN secretion, and provoke severe inflammatory attacks that can occur in any organ of the body. The immunoproteasome acts as a link between innate and adaptive immunity
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