Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

Other Names: CANDLE syndrome; Chronic atypical neutrophilic dermatosis-lipodystrophy-elevated temperature syndrome

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE syndrome) occurs when the immune system attacks the body by mistake

Symptoms usually develop within the first few months of life and may include recurrent fevers and purple colored spots on the skin particularly around the eyes. Loss of body fat, bone, and joint pain also usually occur. Since so few people have been reported with CANDLE syndrome, it is difficult to know how it affects people in the long term.

Cause

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome occurs when the PSMB8, PSMB4, PSMA3, or POMP gene is not working correctly. DNA changes known as pathogenic variants or mutations are responsible for making genes work incorrectly or sometimes, not at all.

Inheritance

Autosomal recessive inheritance, a 25% chance

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome usually inherited in an autosomal recessive pattern. All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

When CANDLE syndrome is associated with the POMP gene, it can be inherited in an autosomal dominant pattern.

Signs and symptoms

The following list includes the most common signs and symptoms in people with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms of CANDLE syndrome may include:

• Recurrent fever
• Muscle wasting
• Short stature
• Failure to thrive
• Loss of body fat (lipodystrophy)
• Enlarged liver (hepatomegaly)
• Bone pain
• Low blood iron (anemia)

The symptoms of CANDLE syndrome usually appear within the first months of life. Initial symptoms include recurrent fevers and skin lesions. Loss of body fat (lipodystrophy) typically begins in early childhood. Bone and joint pain may also occur over time. Very few people have been diagnosed with CANDLE syndrome, so it is not well understood how it changes over time.

Diagnosis

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is diagnosed through a clinical exam, the symptoms, and can be confirmed by genetic testing.

Treatment

Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment in order to stop the autoinflammatory response altogether. This suggests that the condition also involves IFN dysregulation.

NIH genetic and rare disease info

• NIH info on Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature is a rare disease.