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Objective: This study assessed the efficacy and safety of combination (COMB) of cyclosporine (CSA) and leflunomide (LEF) versus each drug alone, in the treatment of severe rheumatoid arthritis (RA)., Methods: One hundred six patients with active RA refractory to at least one disease modifying antirheumatic drug (methotrexate obligatorily) were entered into a 12-month open, prospective trial and were randomly allocated to receive either CSA 2.5 to 5 mg/kg/day, or LEF 20 mg/day, or the combination of both at the same initiating dose., Results: The American College of Rheumatology 50% (ACR50) response rates for the 3 groups were COMB 80%, CSA 40%, and LEF 42% (p = 0.001). Combination therapy was also significantly better than CSA and LEF at the more stringent 70% response rate (69% vs 34% vs 30%, respectively; p = 0.001). Comparable Disease Activity Score 28 reduction rates were noted at trial termination for all 3 treatment arms: COMB -2.74 vs CSA -2.53 vs LEF -2.28 (p nonsignificant). Discontinuation rates were more common in LEF vs CSA arm (p = 0.046). No unexpected or serious adverse drug effects were identified in the combination group during the 12-month period., Conclusion: The combination of CSA and LEF in patients with refractory RA provided statistically significant benefit in ACR50 and ACR70. Adverse events were not substantially increased.

Circulating levels of P- and L-selectins and the degree of T-lymphocyte activation were assessed by enzyme-linked immunosorbent assays in 75 selected patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood donors matched for age and gender. Mean levels of P-selectin were significantly higher than normal in RA (lower in patients with clinical remission) and SSc (higher in patients with early-onset diffuse disease), but not in SLE. In contrast, mean L-selectin levels were significantly higher than normal in SLE (no correlation to the degree of disease activity), but not in RA or SSc. Mean levels of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte activation, in patients with active RA, SSc and SLE were almost double the normal level; however, correlations between individual levels of circulating P- or L-selectins and sIL-2R within groups revealed a strong positive correlation only between L-selectin and sIL-2R (r = 0.66, p<0.001), and only in patients with SLE. Given the different expression of P- and L-selectins, these findings indicate a distinct pattern of immune cell activation in chronic diseases that share an overactivation of T-lymphocytes. The possible clinical value of quantitation of circulating P-selectin in patients with RA and SSc on the one hand, and L-selectin in patients with SLE on the other, should be investigated by prospective studies.

Cold panniculitis is a form of physical panniculitis due to exposure of skin to severe cold. It usually appears on the cheeks of infants and children. It has also been reported on the thighs and buttocks of young females. Its clinical manifestations include red, cold, indurated plaques or nodules which appear one to three days after exposure to low temperatures and resolve spontaneously within several weeks without scarring. The histopathological picture shows a perivascular infiltrate of lymphoid and histiocytic cells at the dermal-subcutaneous junction in the early phase of the reaction (1). After 48 to 72 hours, a well developed panniculitis appears. We report an unusual case of an adult female patient with recurrent panniculitis on her legs appearing in the winter but without any preceding repeated or prolonged exposure to cold. She responded dramatically to oral tetracycline. This drug was successful as a prophylactic agent as well.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell-cell adhesive interactions of the immune system. The levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation were studied in the sera of patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay. Serum concentrations of s-ICAM-1 were significantly increased in 61 patients with SLE compared to 51 controls (mean +/- SEM: 564 +/- 30 versus 348 +/- 17 ng/ml, p < 0.0001) and 41% of patients had higher serum levels than the normal cut off value of 584 ng/ml. Among the various clinical manifestations, skin involvement was significantly associated with high serum levels of s-ICAM-1. Individual values of serum s-ICAM-1 concentrations in patients with SLE correlated significantly with two different disease activity indices, as well as with the erythrocyte sedimentation rate and serum levels of soluble interleukin-2 receptors, but not with serum levels of anti-dsDNA antibodies or C4. No significant differences in s-ICAM-1 levels were found between patients receiving immunomodulatory treatment and those who were not. These findings suggest that s-ICAM-1 measurement may serve as an additional serologic marker of disease activity in patients with SLE. Further studies to determine whether increased s-ICAM-1 shedding has any pathogenetic significance or biological role in SLE are warranted.