SULPHASALAZINE THERAPY IN RHEUMATOID ARTHRITIS: QUALITATIVE CHANGES IN LYMPHOCYTES AND CORRELATION WITH CLINICAL RESPONSE

Clinical and immunological parameters in 14 patients with rheumatoidarthritis (RA) receiving sulphasalazine (SASP) were evaluated,to determine whether their clinical response was reflected byany quantitative changes in their peripheral blood lymphocytesafter 12 weeks. Whilst disease activity markers fell significantly,no such changes were noted in the percentage or absolute numbersof lymphocytes or their subsets. The lymphocytes of a further 21 patients before and after receivingSASP for 12 weeks were then studied qualitatively. The suppressionmediated by in vitro SASP on ex vivo PHA stimulated lymphocytesshowed a decrease at 12 weeks. This change was more marked andreached statistical significance only in those patients whoshowed a good clinical response. It is postulated that thismay in some way be related to expression of activation markersand concomitant SASP binding. KEY WORDS: Lymphocyte transformation, Mitogen, Rheumatoid arthritis, Sulphasalazine     

RENAL AND PANCREATIC CALCIFICATION IN RHEUMATOID ARTHRITIS WITH SJOGREN'S SYNDROME

We describe a female patient who developed seropositive rheumatoidarthritis (RA) at the age of 12 years. After 10 years her diseasewas complicated by Sjogren's syndrome (SS) and distal (type1) renal tubular acidosis (RTA). Seven years later she was notedto have nephrocalcinosis. At the age of 32, investigation ofa short history of weight loss and abdominal pain revealed abenign gastric ulcer and chronic calcific pancreatitis. We believe she is the first patient with RA and SS in whom complicatingrenal and pancreatic calcification have been reported. Her caseemphasizes the good prognosis of type 1 RTA in SS and suggeststhat pancreatic involvement may be more common than clinicallyapparent. KEY WORDS: Rheumatoid arthritis, Sjögren's syndrome, Renal tubular acidosis, Pancreatic calcification     

EFFECT OF SULPHASALAZINE AND ITS METABOLITES ON MITOGEN INDUCED TRANSFORMATION OF LYMPHOCYTES--CLUES TO ITS CLINICAL ACTION?

The effects of sulphasalazine (SASP), sulphapyridinc (SP), and5-aminosalicylic acid (5-ASA) have been studied on mouse spleencells cultured in the presence of phytohaemagglutmin (PHA),concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide(LPS). SASP exhibited a significant degree of suppression, at dosesin the range 25–100 .µg/ml (p < 0.01), this suppressionbeing >50% at 50 µg/ml. SP exhibited only a minor degreeof suppression (10% at 75 µg/ml. p < 0.01). Coadministrationof a non-steroidal anti-inflammatory drug (NSAID), indomethacin,produced no evidence of further suppression in the presenceof SASP or SP. Administration of SP plus 5-ASA to parallel culturesthat were profoundly suppressed by the molecular equivalentamount of SASP resulted in no suppression. This implied requirementof the intact parent molecule (SASP) to produce this effect,at these concentrations. The concentration of SASP required to produce more than 50%suppression was higher than that ever attained in the peripheralblood of humans receiving therapeutic doses of the drug. Humanlymphocytes are similarly suppressed by SASP, but only at higherconcentrations than are required for murine cells. Thus, ifthe parent drug is the active moiety and requires these concentrationsto be effective in vivo, it follows that the site where theseeffects may be mediated is likely to be the intestinal tract.The effects described would suggest the gut associated lymphoidtissue as a likely target. KEY WORDS: 5-Aminosalicylic acid, Small intestine, Rheumatoid arthritis, Reactive arthritis, Ankylosing spondylitis     

Anti-rheumatic Drugs and Joint Damage in Rheumatoid Arthritis

The effect of second-line anti-rheumatic drugs such as goldon the course and progression of joint damage has been the subjectof considerable controversy. We have evaluated the effects ofsecond-line anti-rheumatic drugs in three studies of 46–84patients with rheumatoid arthritis given a second-line drugcontinuously for 12 months. Using two different methods of radiographicassessment we found that there was significant progression overthe 12-month period when the mean changes in the groups of patientswere examined, and there was similar indications of continuingdisease activity shown by mean values of acute phase proteinsand ESR which were above the normal range at both six and 12months. But there were subgroups of patients who showed a reductionin ESR and joint tenderness with a related slowing of the rateof radiographic progression in the second six months of treatment.There was no direct relationship between changes in the ESRand radiographic progression in individual patients. Althoughanti-rheumatic drugs are not ideal and therapy does not causeremission in many patients, some patients respond well. Rheumatoidarthritis may represent a heterogeneous collection of patientswho respond individually to different drugs.     

SERUM AMYLOID A PROTEIN DURING THE TREATMENT OF RHEUMATOID ARTHRITIS WITH SECOND-LINE DRUGS

Serum amyloid A protein (SAA), serum C-reactive protein (CRP)and the ESR were measured in 19 patients with rheumatoid arthritisbefore treatment and during therapy with gold, penicillamineor sulphasalazine for a mean period of 148 months (range 6—23months). All three measurements decreased significantly; however,only 7% of SAA values fell to within the normal range (18—44mg/l). compared to 38% measurements of serum CRP (>10 mg/l)and 32% of the ESR (>25 mm/h). In 8 (42%) of the 19 patients,SAA remained high (>400 mg/l) for 3 months or more whilstserum CRP was depressed below 20 mg/l; this discrepancy wasnot related to particular drugs We conclude that during treatment of rheumatoid arthritis withgold, penicillamine or sulphasalazine. SAA concentrations canbe high when serum CRP and ESR are suppressed SAA may be a moresensitive index of disease activity KEY WORDS: Rheumatoid arthritis, Serum amyloid A protein, C–reactive protein, Erythrocyte sedimentation rate