Candle syndrome E88.1

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 29.10.2020

Dieser Artikel auf Deutsch

Synonym(s)

CANDLE Syndromes; Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; Japanese autoinflammatory syndrome with lipodystrophy; JASL; JMP syndrome; Nakajo-Nishimura Syndrome

Definition
This section has been translated automatically.

CANDLE syndrome (CANDLE is the acronym for "chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature") is a very rare, autosomal recessive inherited autoinflammatory syndrome that manifests itself in early childhood with abnormal, erythematous skin lesions, panniculitis-induced lipodystrophy, arthritis, joint contractures and recurrent fever attacks (Torrelo A et al. 2010). Some patients develop basal ganglion calcifications or antinuclear antibodies.

Occurrence/Epidemiology
This section has been translated automatically.

CANDLE is a very rare disease. So far about 60 cases have been described in the literature.

Etiopathogenesis
This section has been translated automatically.

CANDLE is caused by homozygous mutations in the PSMB8 (Proteasome subunit beta 8) gene, which encodes a subunit of the proteasome and is involved in the processing of MHC class I epitopes in antigen presenting cells. This causes variable defects in the catalytic activity of the proteasome immunoproteasome (Brehm A et al. 2015; Liu Y et al. 2012). The final result is a sustained elevated production of type 1 interferons, which can be significantly increased by banal triggers such as the common cold, stress or viral infections.

Manifestation
This section has been translated automatically.

Sickness onset between two weeks and six months after birth.

Clinical features
This section has been translated automatically.

Clinical symptoms are recurrent fever, anular erythema that can last from a few days to several weeks. Persistent purple eyelid edema and oedema of the lips. Progressive peripheral lipodystrophy occurs mainly on the face and upper limbs. Facial lipodystrophy gives patients a unique and unmistakable phenotype. Lipodystrophy is irreversible and is often accompanied by growth disorders of varying degrees. Further symptoms are arthralgias, sometimes considerable joint deformities, blepharitis, nodular episcleritis, chondritis of the ear and nose cartilages and relapses of aseptic meningitis.

Laboratory
This section has been translated automatically.

In the blood, a type I interferon signature with constitutive "signal transducers and activators of transcription" (STAT1) phosphorylation can be detected.

Internal therapy
This section has been translated automatically.

Trials with TNF-alpha antagonists have led to a temporary improvement in some patients, but in other patients they have induced relapse activities. Tocilizumab (imunosuppressive drug) showed only limited efficacy. The effects of tofacitinib and the JAK inhibitor baricitinib remain to be seen.

Progression/forecast
This section has been translated automatically.

CANDLE is a life-long disease with fluctuating disease activity.

Note(s)
This section has been translated automatically.

The CANDLE syndrome is classified as a type 1 interferonopathy. These represent a group of rare, genetically and phenotypically heterogeneous disease patterns caused by a malfunction of the innate immune system (Crow YJ 2011). With the exception of multifactorial SLE, these are very rare diseases. Pathogenetically, type 1 interferonopathies are based on disturbances in metabolism and in the immunological recognition of intracellular nucleic acids.

Literature
This section has been translated automatically.

  1. Brehm A et al (2015) Additives loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. Journal of Clinical Investigation. American Society for Clinical Investigation 125: 4196-4211.
  2. Cavalcante MP et al (2016) CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature-a rare case with a novel mutation". European Journal of Pediatrics. Springer Science+Business Media. 175: 735–740.
  3. Crow YJ (2011) Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 1238:91-98
  4. Crow YJ et al (2015) Aicardi-Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol 15:429-440
  5. Günther C et al (2016) Type I interferonopathies. Z Rheumatol 75: 134-140
  6. Liu Y et al (2012) Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis rheumatism 64:895-907
  7. Roberts T et al (2015) CANDLE SYNDROME: Orofacial manifestations and dental implications". Head & Face Medicine. BioMed Central 11: 38.
  8. Torrelo A et al (2010) Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. Journal of the American Academy of Dermatology 62: 489-495.

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020