A. Gustafson, B. Griswold, M.E. Burchett, S.H. Schurman, S. Ling, C.A. Francomano, N.B. McDonnell

Presented at the annual meeting of The American Society of Human Genetics, October 10, 2006,  New Orleans, Louisiana.

 ABSTRACT:
The Ehlers-Danlos syndromes (EDS) are characterized by joint, skin and vascular abnormalities. Non-inflammatory joint pain is a common feature in many patients with EDS. Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjogren's syndrome (SS) are inflammatory acquired rheumatologic conditions. Raynaud's phenomenon consists of vasospastic attacks in the digits, and may be found associated with an autoimmune disorder. We have found a high incidence of the above autoimmune disorders in a cohort of 72 consecutive EDS patients enrolled at the National Institute on Aging study 2003-086. In longitudinal follow-up 5/25 adults 40 years or older developed RA. One adult over 40 presented with a diagnosis of EDS and SLE. A 15-year-old girl had a positive ANA, joint swelling and unexplained fevers, and later met the diagnostic criteria for SLE. Another young girl, age 16, in whom a COL5A1 mutation was found, presented with Raynaud 's phenomenon and joint swelling at the time of initial visit, and was later diagnosed with Juvenile Rheumatoid Arthritis (JRA). The total number of patients who exhibited Raynaud's phenomenon in our cohort was 7/72. A 39-year-old woman was found to have SS, diagnosed by biopsy of the oral mucosa. In total, there were 12/72 patients in our cohort who either presented with a rheumatologic disorder in addition to EDS, or developed one during follow-up. The number of RA patients, 5/72 (7%) in the total cohort, and 5/25 (%20) in patients over 40, far exceeds the predicted co-occurrence of this disorder with EDS. The same is true, albeit to a lesser extent, for the number of patients with Raynaud ’s phenomenon, 7/72 (10%) and SLE, 2/72 (3%). This raises the possibility that abnormalities of the extracellular matrix might contribute to the development of autoimmunity in the presence of other environmental or genetic influences.