Autosomic dominant familial Behçet disease and haploinsufficiency A20: A review of the literature

Autoimmun Rev. 2018 Aug;17(8):809-815. doi: 10.1016/j.autrev.2018.02.012. Epub 2018 Jun 8.


Introduction: Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the HLA B51 antigen. In rare and severe early onset cases, dominant Mendelian transmission has been linked to mutations in the TNFAIP3 gene encoding A20. Herein, we propose a systematic review of the literature about the haploinsufficiency A20 (HA20) published cases.

Systematic review: Our review of the 45 cases of HA20 from literature highlights the similarities and the differences between this genetic auto-inflammatory disease and classical BD. HA20 looks like BD if we consider recurrent oral (87%) and genital (67%) ulcers, arthralgia or arthritis (42%), skin involvement (53%) such as erythema nodosum or abdominal symptoms (60%) such as abdominal pain, digestive ulcers or diarrhea. However, HA20 differs from classical BD because its geographical distribution is ubiquitous, sex ratio is inversed (one man for two women), first symptoms occur in early childhood (median age = 5.5 years; interquartile range: 1-10) instead of adulthood, recurrent fever is common (62%) unlike classical BD, HLA B51 antigen is uncommon and abdominal symptoms are over-represented compared to classical BD. In addition, response to colchicine in HA20 is inconstant (24%) unlike classical BD.

Discussion/conclusion: High fever flares and digestive involvement starting in early childhood seem to be hallmarks of HA20 clinical features. Response to colchicine is unpredictable and biotherapies like anti-TNFα and anti IL1 appear to be treatments of choice, like for other auto-inflammatory diseases. Prospective description of larger cohort of HA20 cases is needed to understand better when this disease must be looked for and how to treat these patients.

Keywords: Auto-inflammatory disease; Behçet disease; Digestive ulcers; Haploinsufficiency A20; TNFAIP3.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Behcet Syndrome / genetics*
  • Behcet Syndrome / pathology*
  • Genes, Dominant*
  • Genetic Predisposition to Disease*
  • Haploinsufficiency*
  • Humans
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics*


  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3