Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen.

OBJECTIVE: To determine whether oral tolerance to type I collagen (CI) could be induced in patients with systemic sclerosis (SSc). METHODS: Twenty adult patients with limited or diffuse SSc were enrolled in a study to receive 0.1 mg of solubilized native bovine CI daily for 1 month, followed by 0.5 mg daily for 11 months. Peripheral blood mononuclear cells (PBMC) were obtained from the patients and cultured with human alpha1(I) and alpha2(I) chains, before and after CI treatment. Culture supernatants were analyzed for levels of interferon-gamma (IFNgamma) and interleukin-10 (IL-10). Sera obtained before and after treatment were analyzed for levels of soluble IL-2 receptor (sIL-2R). Although this study was not intended to assess the clinical efficacy of oral CI administration in SSc, selected measures of disease severity and organ involvement were evaluated. RESULTS: Oral administration of CI to SSc patients induced significant reductions in levels of IFNgamma and IL-10 in alpha1(I)- and alpha2(I)-stimulated PBMC culture supernatants, indicating that T cell immunity to CI was decreased by this treatment. Serum levels of sIL-2R also decreased significantly after oral CI treatment, suggesting a reduction in T cell activation. Significant improvements occurred in the modified Rodnan skin thickness score and the modified Health Assessment Questionnaire after 12 months of oral CI in this open trial. The lung carbon monoxide diffusing capacity improved statistically and showed a trend toward clinically significant improvement. CONCLUSION: Oral administration of bovine CI to patients with diffuse or limited SSc induces a reduction in T cell reactivity to human CI, appears to be well tolerated, and does not worsen the disease. Further evaluation of oral tolerance to CI in patients with SSc is justified to determine whether it has therapeutic efficacy.

Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid arthritis.

OBJECTIVE: To investigate the efficacy of oral type II collagen (CII) in the treatment of rheumatoid arthritis (RA), when added to existing therapy. METHODS: Patients with active RA (n = 190) were randomized into a 6-month, double-blind, placebo-controlled trial. Patients continued to take their current arthritis medications. Patients received either placebo or bovine CII, 0.1 mg/day for 1 month, then 0.5 mg/day for 5 months. RESULTS: There were no significant differences between the baseline characteristics of either group. The primary response parameter was the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20). There was no statistically significant difference in the ACR 20 after 6 months (20.0% of placebo patients; 16.84% of bovine CII patients). There were significant differences in several clinical variables after treatment, all favoring the placebo group. CONCLUSION: Oral solubilized bovine CII, added to existing therapy, did not improve disease activity in patients with RA.

Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis.

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2-L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 +/- 0.08 g/cm2 versus 0.98 +/- 0.14 g/cm2, respectively; P = 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 +/- 0.08 g/cm2 versus 0.76 +/- 0.15 g/cm2, respectively; P = 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss.

Pseudothrombophlebitis in neuropathic arthropathy of the shoulder.

The syndrome of pseudothrombophlebitis is a well-known complication of popliteal cysts. We report the case of a patient with a neuropathic arthropathy of the shoulder in whom pseudothrombophlebitis of the upper extremity subsequently developed. To our knowledge, this is the first such case that has been reported.