Behcet-Like Familial Autoinflammatory Syndrome

Clinical Characteristics
Ocular Features: 

A minority of reported patients (3 of 14) have had Behcet-like uveitis with retinal vasculitis and chorioretinal lesions.  In two of the 3 patients with uveitis the inflammation was anterior but the authors reported significant visual loss.

Systemic Features: 

Fourteen patients in 6 unrelated families have been reported.  Onset usually occurs during the first or second decades of life.  Patients usually developed oral and genital ulcers.  Other features variably present were polyarthritis, a skin rash and inflammatory disease or ulcerations in the GI tract.  Several patients had periodic fevers and hemolytic anemia was present in one.  The majority of individuals have been female.

Three patients in a single family had lupus anticoagulant and three others had antinuclear antibodies.

Genetics

This syndrome results from heterozygous mutations in the TNFAIP3 gene (6q23.3) with loss of function leading to A20 haploinsufficiency.  Changes in the TNFAIP3 gene have also been identified in rheumatoid arthritis, systemic lupus erythematosis, and idiopathic juvenile arthritis.

Treatment
Treatment Options: 

Several patients have responded positively to treatment with tumor necrosis factor inhibitors or colchicine.

References
Article Title: 

Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y, Yang D, Demirkaya E, Takeuchi M, Tsai WL, Lyons JJ, Yu X, Ouyang C, Chen C, Chin DT, Zaal K, Chandrasekharappa SC, P Hanson E, Yu Z, Mullikin JC, Hasni SA, Wertz IE, Ombrello AK, Stone DL, Hoffmann P, Jones A, Barham BK, Leavis HL, van Royen-Kerkof A, Sibley C, Batu ED, Gul A, Siegel RM, Boehm M, Milner JD, Ozen S, Gadina M, Chae J, Laxer RM, Kastner DL, Aksentijevich I. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016 Jan;48(1):67-73.

PubMed ID: 
266422433

References

Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y, Yang D, Demirkaya E, Takeuchi M, Tsai WL, Lyons JJ, Yu X, Ouyang C, Chen C, Chin DT, Zaal K, Chandrasekharappa SC, P Hanson E, Yu Z, Mullikin JC, Hasni SA, Wertz IE, Ombrello AK, Stone DL, Hoffmann P, Jones A, Barham BK, Leavis HL, van Royen-Kerkof A, Sibley C, Batu ED, Gul A, Siegel RM, Boehm M, Milner JD, Ozen S, Gadina M, Chae J, Laxer RM, Kastner DL, Aksentijevich I. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016 Jan;48(1):67-73.

PubMedID: 266422433