Lupus

Ann. rheum. Dis. (1970), 29, 673

Cyclophosphamide in systemic lupus erythematosus
T. HADIDI From the Rheumatology Department, Maadi Hospital, Cairo, U.A.R.

Cyclophosphamide has been used in systemic lupus erythematosus (SLE) (Seah, Wong, Chew, and Jayaratnam, 1966) and beneficial results have been claimed. In experimental studies, cyclophosphamide prevents the occurrence of autoimmunedisease in NZB mice which are unique in that they uniformly have a form of glomerulonephritis resembling human lupus nephritis (Schwartz, 1969). The drug is known to affect both lymphocytic and plasmocytic cell lines in their pathological forms and it also prevents the proliferation of immunoblasts (Turk, 1967). It consistently appears to depress the white blood count before any damage occurs toplatelets or red blood cells. It can be administered orally since its absorption is very predictable (Dubois, 1966). The controlled trial of a drug in a chronic but sometimes lethal disease such as SLE presents obvious difficulties and no such trial has ever been attempted. The author has nevertheless acquired considerable experience in the use of this drug during the past 5 years and a description ofthis experience is now presented.
Selection of patients During the past 5 years 35 patients suffering from SLE have been admitted to hospital for assessment and treatment of their disease. All fulfilled the criteria for the diagnosis of SLE of Dubois (1966) and also the criteria proposed by Winslow, Ploss, and Loitman (1958) and modified by Willkens, Decker, and Wilske (1968).
All 35 patientswere treated initially with prednisolone 40-60 mg. daily (Pollak, Pirani, and Kark, 1961) with subsequent reduction in dosage as indicated by their clinical condition. Eight patients failed to respond to treatment, and in another four patients steroid administration was complicated by the development of posterior subcapsular cataract, duodenal ulcer, diabetes mellitus, and aseptic necrosis of thefemoral heads. These twelve patients had a severe, active, and continuing form of the disease and are referred to as 'Group A'. There were eleven females

and one male and their ages at onset ranged from 16 to 38 years. They initially had very high erythrocyte sedimentation rates (over 90 mm./hr Westergren). The duration of illness on admission ranged from 1 to 9 years and all had renalinvolvement (proteinuria greater than 100 mg./litre of urine and granular casts). The treatment of the remaining 23 patients was easier to manage and they thus constituted a more benign group. For purposes of comparison, twelve patients with renal involvement were selected from these 23 patients to form 'Group B'. These twelve patients were roughly comparable to those in Group A in terms of age, diseaseduration, and the presence of renal involvement, but their symptoms had been readily controlled with prednisolone and there were no complications of treatment.

Method All the patients were assessed clinically on admission and at weekly intervals during their hospital stay. The following investigations were carried out routinely: chest radiograph, blood count, blood urea, creatinine clearance,erythrocyte sedimentation rate (Westergren method), LE-cell tests, urine microscopy and quantitative estimation of albuminurea, serum protein electrophoresis, serological tests for syphilis, Waaler-Rose test, and electrocardiographs. On discharge our patients were followed up for 2 years at 4-weekly intervals. They were advised to avoid pregnancy, an intrauterine device being recommended in preferenceto the oral contraceptive pill. Use of cyclophosphamide Cyclophosphamide was added to prednisolone for the patients in Group A, while the patients of Group B
continued to take the steroid alone. Long-term therapy with relatively small doses was preferred to short intensive courses because such a plan is probably safer, produces fewer side-effects, and may be expected to produce more favourable...