PNEUMOCYSTIS CARINII INFECTION COMPLICATING CYTOTOXIC THERAPY IN TWO PATIENTS WITH LYMPHOPENIA, BUT A NORMAL TOTAL WHITE CELL COUNT

Two cases of Pneumocystis carinii pneumonia in patients whodeveloped lymphopenia secondary to immunosuppression with cytotoxictherapy but with a normal total white cell count, and neutrophilcount are reported. KEY WORDS: Pneumocystispneumonia, Opportunistic infection     

AN ACUTE ARTHRITIS CLINIC--ONE YEAR'S EXPERIENCE

Over a 12-month period, 150 patients were seen at an acute arthritisclinic to assess the type of case not usually seen in our chronicservice, where delays of up to 24 weeks may occur before patientscan be investigated. The majority of patients in whom the diagnosiscould confidently be made had either gout or reactive arthritis,and, while the former diagnosis was unlikely to be missed, manypractitioners seemed unaware of the type of presentation andvariety of organisms that can cause reactive arthritis. Despiteintensive investigation, a diagnosis could not be made in somecases. Those with septic arthritis had a better prognosis thanpatients in a previous series from this centre. Early referralleading to prompt diagnosis of this serious complication mayhave been an important factor in the improved outcome. KEY WORDS: Acute arthritis, Clinic, Gout, Reactive arthritis, Septic arthritis     

Clinical and Laboratory Studies of Levamisole in Patients with Rheumatoid Arthritis

Two studies with levamisole in rheumatoid arthritis are reported.In the first study of 30 patients levamisole was superior toplacebo in terms of pain relief, reduction in articular tenderness,duration of morning stiffness, erythrocyte sedimentation rate(ESR), and radioisotope uptake in knee and wrist joints. Therewere no consistent differences in lymphocyte function, immunoglobinor complement concentration, or polymorphonuclear granulocyticfunction. In the second study forty patients were commenced on treatmentwith either gold or levamisole. At the end of one year therewere significant improvements with both regimens in pain score,joint tenderness and ESR. The patients on levamisole showedsignificant improvement of duration of morning stiffness, whilethe patients on gold showed significant improvement of rheumatoidfactor titre and left hand grip, but there were no significantdifferences between the two regimens.     

SULPHASALAZINE IN THE TREATMENT OF RHEUMATOID ARTHRITIS: RELATIONSHIP OF DOSE AND SERUM LEVELS TO EFFICACY

Previous studies of sulphasalazine in rheumatoid arthritis havechosen an empirical dose based upon its use in ulcerative colitis.In this study we compare the efficacy and toxicity of two doses(1.5 g/day and 3 g/day, 30 patients per group), and attemptto relate efficacy to serum levels of sulphasalazine and itsmetabolites. After six months 24 of the low-dose group and 20 of the high-dosegroup remained on treatment. Greater improvement was seen inthe high-dose group. When dose was expressed as mg/kg, the doseefficacy ratio became more apparent and a dose of >40 mg/kg/dayappears to confer greater benefit. No relationship was demonstrated between serum levels of sulphasalazineor its measured metabolites, and efficacy.We conclude that responseto sulphasalazine in rheumatoid arthritis is dose dependentbut does not relate to serum levels of sulphasalazine, sulphapyridine,or acetyl sulphapyridine. KEY WORDS: Rheumatoid arthritis, Sulphasalazine     

UNUSUAL COMPLICATIONS OF CERVICAL SPINE SURGERY FOR CERVICAL MYELOPATHY IN RHEUMATOID ARTHRITIS

Cervical myelopathy is a recognized complication of rheumatoidarthritis and other inflammatory arthropathies. In a significantproportion of patients, surgical stabilization of the cervicalspine offers the best opportunity for improvement of symptomsand long-term survival. We report two cases that illustratesome potential complications of cervical spine surgery and whichalso emphasize the need for vigilance when caring for patientsin this group. KEY WORDS: Cervical myelopathy, Surgery     

SELECTION OF SUITABLE PATIENTS FOR SECONDLINE THERAPY IN RHEUMATOID ARTHRITIS

Investigators studying second-line drugs often try to enrol‘ideal’ patients with a high ESR, short diseaseduration and who have received no previous second-line therapy.In this paper we investigate the influence of gender, diseaseduration, previous second-line therapy, and initial ESR in 150rheumatoid patients with clinically-active disease treated withsulphasalazine. Clinical improvement was seen in all subgroupsand no difference in toxicity could be demonstrated. Haematologicalresponse was absent in patients with an initial low ESR althoughthese patients improved clinically. Thus, patients with clinically-active disease suggesting a needfor second-line drugs should benefit from sulphasalazine therapyirrespective of any of the above variables. The implicationsfor clinical trial design regarding patients with low ESR, however,may be more complex. KEY WORDS: Rheumatoid arthritis, Sulphasalazine, Disease activity, Previous treatment, ESR     

THE 'NATURAL' HISTORY OF ACTIVE RHEUMATOID ARTHRITIS OVER 3-6 MONTHS--AN ANALYSIS OF PATIENTS ENROLLED INTO TRIALS OF POTENTIAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS, AND TREATED WITH PLACEBO

The natural history of RA over a period of 6 months is not known,but this is of central importance to the design and interpretationof drug trials of possible DMARDs. We analysed the disease activityof 142 rheumatoid patients who were randomized to receive placeboin five double blind, placebo-controlled trials of possibledisease-modifying drugs conducted in a single unit. There wasno significant change in ESR, duration of morning stiffnessor platelet count over a period of 6 months; the mean changein ESR at 3 months was an increase of 2 mm/h (99% C.I. –3,+7), and only 5% of patients more than halved their ESR over6 months. There was a small significant fall in articular indexover 6 months of placebo treatment. There is no measurable placeboeffect on ESR, morning stiffness or platelet count when theseare used as measures of disease activity in trials of drug therapyin RA. ESR is an informative, stable measure of disease activity;the duration of morning stiffness may be more useful than thearticular index. The use of these results as the basis of ahistorical cohort to help design future placebo-controlled trials,and to interpret uncontrolled trials of putative anti-rheumaticdrugs is discussed. KEY WORDS: Rheumatoid arthritis, Placebo effect     

PRODUCTION OF INTERLEUKIN-6 BY MONOCYTES ISOLATED FROM RHEUMATOID ARTHRITIS PATIENTS RECEIVING SECOND-LINE DRUG THERAPY

IL-6 production by peripheral blood monocytes isolated fromRA patients receiving the second-line drugs auranofin (AUR),sulphasalazine (SASP) or gold sodium aurothiomalate (GST) wasinvestigated. In patients receiving AUR a significant reductionin both basal and lipopolysaccharide (LPS) stimulated IL-6 productionby isolated cells was observed. Similarly, SASP significantlyreduced basal IL-6 production. In contrast, monocytes isolatedfrom individuals receiving GST had no significant change eitherin basal or LPS stimulated IL-6 production. We suggest an effectby AUR and SASP either on pre-monocytic cells in the bone marrowor on monocytes in the periphery may subsequently result ina reduction in IL-6 production by these cells once they haveinfiltrated the RA joint. This may be one way by which thesetherapies contribute to the beneficial effects seen in patientsreceiving these treatments. KEY WORDS: Interleukin-6, Second-line drugs, Rheumatoid arthritis     

SULPHASALAZINE: A 'NEW' ANTIRHEUMATIC DRUG

Sulphasalazine was first introduced for the treatment of rheumatoidarthritis in 1942. Following initial enthusiasm, interest waneduntil 1978 when a large open study suggested that it might havea ‘second-line effect’. Since then further studieshave confirmed this effect and once again rheumatologists arestarting to use sulphasalazine in the treatment of rheumatoidarthritis. In this review we examine the pharmacology of sulphasalazineand its metabolites, comment upon the possible modes of actionand review the recent literature pertaining to its use in rheumatoidarthritis. KEY WORDS: Rheumatoid arthritis, Sulphasalazine