It is one of a group of proteasome-associated autoinflammatory syndromes (PRAAS) that have in common recurrent fevers, variable rash, anemia, elevated acute phase reactants, and autoimmune manifestations. CANDLE syndrome is autosomal recessively inherited in patients with PSMB8 or PSMB4 gene mutations, and is autosomal dominantly inherited in patients with POMP gene mutations. Mutations in these proteosome genes lead to defective proteasome function and subsequent accumulation of modified and oxidized proteins that cause increased cellular stress, interferon signaling, and apoptosis.
CANDLE syndrome comprises the constellation of recurrent (often daily) fevers, a distinctive cutaneous eruption, lipodystrophy, internal organ involvement, and elevated acute phase reactants. More than 50 cases have been identified worldwide. Most patients are of Northern European or Hispanic descent. Cases have also been reported in Japan and South Africa.
Affected children present in the first 6 months of life with recurrent (often daily) fevers as well as recurrent edematous, erythematous plaques that occur in a periorbital location and elsewhere over the face and trunk. These plaques may become annular and violaceous and may leave purpuric macules or postinflammatory hyperpigmentation in their wake. Subsequently, delayed development, internal organ involvement, lipodystrophy, and elevated acute phase reactants become evident. Other characteristic facial features include edematous lips and loss of facial fat.
M04.8 – Other autoinflammatory syndromes
724834006 – Neutrophilic dermatosis
Differential Diagnosis & Pitfalls
- Nakajo-Nishimura syndrome (NNS)
- Japanese autoinflammatory syndrome with lipodystrophy (JASL)
- Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome