Immunologic hypersensitivity to collagen, the major structural component of connective tissue, could explain both the systemic nature and chronicity of the inflammation occurring in rheumatoid arthritis. Recent demonstrations of antibodies to collagen in sera from patients with rheumatoid arthritis support this premise (1-8). Also consistent with this hypothesis is the distribution of collagen in structurally distinct types in various tissues. For example, types I and HI collagens are found in the skin and parenchyma of several organs, whereas type II exists in cartilage (9). Thus, an immune response to the cartilage type of collagen (type II) could explain the predilection of rheumatoid arthritis to involve diarthrodial joints.Native collagens consist of three polypeptide chains linked in triple helices. Terminal peptides (telopeptides) do not have a helical structure and are more variable in amino acid content (10). Type I collagen combines two al-type I chains with one a2-chain and is depicted as [al(I)]2a2. Types II and III collagens are comprised of three al-type II chains and three al-type HI chains, respectively. Thus, type II is depicted as [al(II)]3 and type III as [al(III)]3.Injection of heterologous type I and II collagen in complete Freund's adjuvant has been reported to elicit type-specific antibody responses in rats (11) and mice (12). This paper reports that approximately 40% of rats injected intradermally with native type H collagen, derived from human, chick, or rat cartilage, in either complete or incomplete Freund's adjuvant, develop an inflammatory arthritis. In contrast, type I and III collagen are not arthritogenic. This new animal model suggests that immune responses to type II collagen could play a role in inciting or perpetuating joint inflammation in other arthritides. Materials and MethodsRats. Outbred female Wistar, Sprague-Dawley and inbred Wistar-Lewis rats were obtained from Microbiological Associates (Bethesda, Md.), Harlan (Indianapolis, Ind.) or Charles River Breeding Laboratory (Wilmington, Mass.). These rats were housed in metal cages and given water

Relapsing polychondritis, an uncommon, chronic, multisystem disorder characterized by recurrent episodes of inflammation of cartilaginous tissues, can be life-threatening, debilitating, and difficult to diagnose. This review is based on the authors' experience with 36 patients with relapsing polychondritis who were followed from 1980 to 1997, 30 patients located elsewhere who completed a detailed questionnaire and interview, and a perusal of English-language textbooks and papers located by a systematic search of the MEDLINE database. Relapsing polychondritis can present in a highly ambiguous fashion; therefore, in the authors' series, the mean delay from the time medical attention was sought because of symptom onset until diagnosis was 2.9 years. Although prednisone was the main form of treatment, methotrexate seemed to be of additional value. Survival was much more favorable than previously thought. Greater awareness of relapsing polychondritis would probably lead to earlier diagnosis and better outcomes.

Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.

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