Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis.

OBJECTIVE: To investigate the occurrence and clinical correlation of the arg519-to-cys mutation in the type II procollagen gene in patients with osteoarthritis (OA). METHODS: Sixty-six subjects from 7 families with a strong family history of generalized OA and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction. RESULTS: The arg519-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA. CONCLUSION: The arg519-to-cys mutation defines a new pathogenic factor in generalized OA with characteristic clinical and radiologic features. The demonstration of a mutation in 3 of 8 families with OA studied thus far suggests a significant incidence of genetically related clinical OA.

Pneumatosis intestinalis and pneumoperitoneum complicating mixed connective tissue disease.

A case of a young woman with a 3-year history of mixed connective tissue disease who developed secondary pneumatosis intestinalis and pneumoperitoneum and died shortly after of rapidly progressive disease is reported. The pathogenesis, treatment and prognosis of this unusual complication in mixed connective tissue disease are discussed.

Leg ulcers in rheumatoid arthritis.

A retrospective study over an eight-year period of 33 episodes of leg ulceration in 26 patients with rheumatoid arthritis requiring inpatient management is reported. the aetiology of the ulcers was found to be multifactorial. The most common factors were venous insufficiency (45.5%), trauma or pressure (45.5%) and arterial insufficiency (36.4%). Vasculitis (18.2%) and Felty's syndrome (12.1%) were less frequent causes, and pyoderma gangrenosum was rare. Most patients had seropositive erosive disease with high rheumatoid factor titres and significant functional impairment; over half were on maintenance corticosteroids. Colonisation of the ulcers by organisms, predominantly Staphylococcus aureus, was common (69.7%). Skin grafting was required in 63.3%, but the rate of complete take was only 42.9% despite multiple attempts. Hospitalisation was prolonged (mean 47.9 days) and the recurrence rate requiring further hospitalisation was 26.9%. The diagnosis of vasculitis and the limited role of biopsy in establishing its presence are discussed.