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. PRAAS are autosomal recessively inherited. Mutations in the PSM8 gene are responsible. This leads to defective proteasome function and subsequent accumulation of modified and oxidized proteins that cause increased cellular stress, interferon (IFN) 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. Just over 50 cases have been identified worldwide. Most patients are of Northern European and Hispanic descent. Cases have also been reported in Japan and South Africa. PSM8 gene mutations have been identified in most patients with CANDLE syndrome.
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 may become annular and violaceous and may leave purpuric macules or post-inflammatory 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.
For more information, see OMIM.
M04.8 – Other autoinflammatory syndromes
724834006 – Neutrophilic dermatosis
- Nakajo-Nishimura syndrome (NNS)
- Japanese autoinflammatory syndrome with lipodystrophy (JASL)
- Joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome
Last Updated: 09/29/2017