Sm,—If the chronic inflammation of rheumatoid arthritis is to persistence of antigen in synovial tissue, additional


stimulation of the immune system may be beneficial. On the

hand, stimulation of

already aggressive, possibly aberrant, immunological response might prove harmful. Levamisole is a drug with immunostimulant properties and there are conflicting reports of its efficacy in rheumatoid arthritis. Schuennans1 and Basch et aI.2 reported benefit, but Dinai and Pras3 find it useless and possibly even harmful. We have treated 5 patients with undoubted rheumatoid



arthritis with levamisole for three months or more. Measureincluded pain, grip, strength, proximal interphalangeal joint circumference, duration of morning stiffness, and erythrocyte-sedimentation rate. Disease activity was reduced after three months’ treatment in all patients and no side-effects were observed. A large trial, preferably double-blind crossover (levamisole c placebo), will be required to assess the value of levamisole in rheumatoid arthritis.


atrophy at the injection site-a distressing effect, even though often slowly reversible. Straub Clinic, Honolulu, Hawaii 96813,




SIR,-Dr Toouli and his colleagues (Dec. 6, p. 1124) described the reduction of the lithogenic index of bile in gallstone patients treated for 6 months with 750 mg cholic acid plus 2250 mg purined soya-bean lecithin ("essential" phospholipid [E.P.L.]). The bile-acid profile changed during treatment, chenodeoxycholic acid (C.D.C.) falling from 40 to 12% and deoxycholic acid (D.C.) rising from 10 to 43% of total bile acids. BILIARY BILE ACIDS


Westwood Hospital.

Beverley, North Humberside HU17 8BU.


WITHDRAWAL OF CORTICOSTEROIDS Sm—Dr Herxheimer’s letter (Nov. 22, p. 1036) emphasises of the

major problems in the long-term use of oral steroids-namely, withdrawal-the other being, of course, the avoidance of hypercortisonism. For nearly 15 years, it has been my practice to avoid both problems by avoiding oral administration of steroids except where they are needed for only a few days. Triamcinolone acetonide (’Kenalog’) by intramuscular injection will maintain satisfactory suppression in nearly all steroid-responsive cutaneous disorders (to which my experience is largely limited) in doses of 40-60 mg at intervals of 4-6 weeks, or longer, without creating withdrawal problems-since virtually complete withdrawal occurs by the 4th or Sth week after each dose. Plasma-hydrocortisone levels by then have returned to 1030% above the normal in nearly all instances. It is, in effect, one

"alternate-month" schedule. Mikhail4 has shown that although the adrenal cortices are at rest 3 weeks after any dose, they are again responsive to stimulation by the end of the 6th week. Retreatment should as a rule be scheduled according to need, not-after the minimum 4-6 weeks-by the calendar. When the patient’s symptoms and skin lesions are not controllable by topical or other therapy, another dose of the steroid should be considered and (usually) given. I have not yet seen any instance of aggravation of diabetes, hypertension, peptic ulcer, infections (viral or bacterial), or pre-existing hypercortisonism already induced by oral steroid therapy; or of an abscess at the injection site. It should be noted that there is an ostrogenic effect which causes at least a 50% prevalence of hypermenorrhrea in premenopausal (and sometimes postmenopausal) women not taking birth-control pills. Caution is also required in children, lest growth be retarded. Our own findings do not suggest a significant risk of inducing either cataract or aseptic necrosis of the femur. We have suspected muscle wasting in only one patient, a man who was rather emaciated to begin with. Senile/actinic purpura of the dorsa of the forearms is often aggravated in residents of Hawaii; it should not be such a problem in Britain. Injection should be made only into the buttock, never the arm, and with a needle over 3.5cm long, in order to prevent







We have treated 5 patients cholecystectomised for gallstones by infusing E.P.L. alone (2 g intravenously for 5 days). Biliary bile acids were measured by liquid gas chromatography before and after treatment. The lithogenic index was unchanged and the biliary D.C. concentration was increased (see table). Since a rise in D.C. occurs in subjects with interrupted enterohepatic circulation, and after only a few days’ treatment, the hypothesis that the rise in D.C. may be due to dehydroxylation of cholic acid by bacteria in the gut is not supported by our experiment. Is D.C. present in the "essential" phospholipid preparation? Istituto di Clinica Medica, Via Del Pozzo 7, 41100 Modena, Italy.




SIR,-Dr Nicholson (Dec. 27, p. 1304) correctly cites our view’ that bumetanide and frusemide can be compared only under strictly controlled and "titrated" conditions. I pointed out (Nov. 29, p. 1093) that there may be advantages on occasion in "dropping a trusted friend" and in changing "old habits"-your editorial phrases (Nov. 1, p. 860)! Various factors, including the few that Dr Nicholson mentions, may influence response to diuretics on hospital admission, though we thought these on the whole unimportant in our patients’ circumstances. In 8, frusemide had failed during hospital inpatient treatment, and in the year or more since our study a further 15 inpatients whose oedema had not responded to oral frusemide when in hospital did so to oral bumetanide in equivalent or increased dosage. There was no change in any other feature of treatment. Conversely, in 4 patients bumetanide in higher dosage failed but systemic frusemide or ethacrynic acid was effective. Clearly bumetanide and frusemide are both highly effective "first treatment" diuretics. A direct comparison is required, but our experience suggests that bumetanide is sometimes more effective, especially in avoiding intramuscular and intravenous administration. East Herts


Stanstead Road, Hertford SG13 7HU.

Schuermans, Y. Lancet, 1975, i, 111. 2 Basch, M., Spitler, I. S., Engleman, E. P. Rheum. 1975, 18, 385. 3 Dinai, Y., Pras, M. Lancet, 1975, i, 556. 4 Mikhail, G. R. Ann. Allergy, 1973, 31, 337.



Pines, A., Streedharan, K. S., Nandi, A. R., Marsh, B. T. Br. J. clin. Pract. 1974, 28, 311.

Letter: Withdrawal of corticosteroids.

149 LEVAMISOLE IN RHEUMATOID ARTHRITIS Sm,—If the chronic inflammation of rheumatoid arthritis is to persistence of antigen in synovial tissue...
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