CANDLE syndrome [7 genes]

CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature), or Nakajo-Nishimura syndrome, is an autoinflammatory disease that occurs during b>first months of life with episodes of recurrent fever, along with the appearance of dermal lesions during childhood that are present during the disease, although they may be less apparent after puberty. During early childhood, lipodystrophy and joint damage (arthralgia, hypermobility of the phalanges, joint stiffness, chronic chondritis) usually appear in advanced adulthood. The morbidity of this disease is variable, and to date, there is no specific therapy. It is a genetically based disorder caused by mutations in the genes of the proteasome and the immunoproteasome system. Most of the cases described present a recessive inheritance pattern, although digenic forms have also been reported with the presence of heterozygous variants in the PSMB8 gene along with variants in other genes. such as PSMA3, pSMB9 or PSMB4.

1-9/1,000,000

• Diagnosis and genetic counseling
• Immunomodulatory therapy to control febrile episodes.
• JAK inhibitor therapy (under study)

The characteristics of the syndrome may be different depending on the age of the patient.
During the first months of life and early childhood:

• Febrile episodes in the first months of life
• Appearance of dermal lesions during childhood, present during the disease although they may be less apparent at puberty
• Athralgia
• Hypermobility
• Joint stiffness
• Chronic chondritis

Joint damage usually occurs in advanced adulthood. Typical dermal manifestations are:

• Perniotic lesions in acral regions
• Erythematous annular plaques
• Perioral and periocular edema
• Paniculitis

Accompanied by other manifestations such as:

• Hepatomegaly
• Conjunctivitis
• Macroglossia
• Development failure