Fatal exacerbation of systemic lupus erythematosus after treatment with griseofulvin

R Madhok, A Zoma, H Capell
1985 BMJ (Clinical Research Edition)  
Sixteen children aged 8 to 15 (mean 10.9) years with perennial asthma were selected on the basis of >20% decrease in lung function after exercise. None had received corticosteroids within the past three months. Sodium cromoglycate was stopped 24 hours before the study and inhaled B2 agonists eight hours before visits. The study consisted of two three week treatment periods separated by a fortnight's wash out; during each treatment period participants received 200 jLg budesonide aerosol twice
more » ... ly through a 750 ml cone spacer or a placebo with a double blind randomised crossover protocol. Immediately before and at the end of each treatment period the children performed an exercise test and delivered a 24 hour urinary sample for analysis of cortisol. The exercise challenge consisted of five or six minutes of continuous running on a treadmill at individually adjusted, submaximal workloads. Heart rate was measured by radiotelemetry, and all subjects wore a nose clip during exercise. The absolute humidity was recorded. Forced expiratory volume in one second was recorded on a dry spirometer (Vitalograph) before exercise (baseline) and three or five, 10, and 20 minutes after exercise. Results were expressed as the maximal percentage fall from the baseline value. Urinary cortisol was measured by radioimmunoassay. Two Placebo Budesonide 80 Forced 60expiratory volume in one second 40 (%fall from baseline) 20-01 NS p<0001 Individual percentage falls in forced expiratory volume in one second induced by exercise before and after three weeks' treatment with budesonide aerosol and its placebo. Means (SD) are shown. way analysis of variance and t tests for paired comparisons (two tailed, 50" level) were performed. Fourteen children completed the study. Mean (SD) baseline forced expiratory volume in one second (%O predicted) improved from 84 (17)0' to 94 (16)0% (p<002) during treatment; placebo showed no effect. Budesonide reduced the mean fall in forced expiratory volume in one second from 45 (16) o' to 17 (14)0¾ (p< 0-001) (figure). No carryover effect from the treatment was detected after wash out. No significant changes occurred in the test conditions (absolute humidity, final heart rate, and workload). The mean 24 hour urinary free cortisol excretion was 94 (55) nmol/l (3 4 (2 0) ug/100 ml) and 116 (55) nmol/l (4-2 (2 0) Ag/100 ml) before treatment and 96 (34) nmol/} (3-5 (1.2) ,g/100 ml) and 85 (34) nmol/l (3-1 (12, /igilO0 ml) after placebo and budesonide, respectively (F=-1-64; df 3-44, NS). One case of hoarseness during budesonide treatment was the only side effect reported. Comment Budesonide given by inhalation for three weeks afforded significant protection against exercise induced asthma in most children without appreciable suppression of adrenal function. Improvement in baseline airway function cannot explain the effect of budesonide on exercise induced asthma.4 Normal 24 hour urinary free cortisol excretion cannot exclude more subtle degrees of adrenal suppression. The present results and the finding that the immediate reaction induced by allergen was blocked after a week's treatment with predni-sone5 show that regular steroid treatment attenuates some immediate asthmatic reactions. The pathogenesis of exercise induced asthma and the precise modes of action of steroids, however, are incompletely understood. It is generally accepted that the airway cooling that occurs during exercise initiates the bronchoconstriction, but the mechanism is unknown. The decrease in bronchial reactivity during steroid treatment might result from decreased mucosal inflammation, reflex activity, or mediator release. Inhaled B, agonists are the most effective drugs against exercise induced asthma, though the duration of action of bronchodilators is short and the effect sometimes insufficient, especially in severe cases. Additionally, children often forget to use or refrain from using prophylactic medicine when necessary. The present results suggest inhaled steroids may be valuable in managing troublesome exercise induced asthma. I thank Anders Holst Andersen for statistical help and A B Draco (Sweden) for the budesonide, placebo medihalers, and cone spacers. I Konig P, Jaffe P, Godfrey S. Effects of corticosteroids on exercise-induced asthmna. J7 Allergy ClGn Immunol 1974;54:14-9. 2 Smith J. Inhaled steroids in the management of childhood asthma. In: Clark TJH, ed. Steroids in asthma. Auckland: Adis Press, 1983. 3 Hartley JPR, Charles TJ, Seaton A. Betamethasone valerate inhalation and exercise-induced asthma in adults. Br 7 Dis Chest 1977 ;71 :253-8. 4 Henriksen JM, Dahl R. Effects of inhaled budesonide alone and in combination with low-dose terbutaline in children with exercise-induced asthma. Am Rev Respir Dis 1983;128:993-7. 5 Martin GL, Atkins PC, Dunsky EH, Zweiman B. Effect of theophylline, terbutaline and prednisone on antigen-induced bronchospasm and mediator release. J Fatal exacerbation of systemic lupus erythematosus after treatment with griseofulvin Most cases of systemic lupus erythematosus pursue a chronic relapsing course. Some drugs that are, commonly prescribed and considered to be fairly safe can exacerbate existing disease, unmask a lupus diathesis, or produce a drug induced lupus syndrome. Awareness that drugs can adversely alter the course of systemic lupus erythematosus could prevent morbidity and death. We report a fatal exacerbation of systemic lupus erythematosus presumed to be due to griseofulvin. Case report A 22 year old woman with a six year history of systemic lupus erythematosus was admitted after one month of malaise, sweating, and fever. The diagnosis had initially been made on the basis of fever, lymphadenopathy, Raynaud's phenomenon, digital vasculitis, photosensitivity, and butterfly rash. Antinuclear and native double stranded deoxyribonucleic acid (DNA) antibodies were present in considerable but varying titres. She subsequently developed proteinuria. Renal biopsy showed focal proliferative glomerulonephritis: cerebral lupus was presumed to be present because of changes in personality and an electroencephelogram showed diffuse slow wave activity. She was given maintenance treatment of prednisolone 7 mg on alternate days. Over the month before admission her genera' practitioner had prescribed ampicillin and erythromicin for a presumed respiratory tract infection. Griseofulvin had been prescribed seven days before admission; although the precise amount was unknown, the total dose could not have exceeded g. On admission she looked unwell and had a fever of 38 7'C, pulse rate 110 beats/min regular, and blood pressure (supine) 120/100 mm Hg. Results of examination were otherwise normal with no cutaneous signs of systemic lupus erythematosus and no obvious source of sepsis. White cell count was 3.9 X 109/1, haemoglobin concentration 105 g/dl, and erythrocyte sedimentation rate 121 mm in the first hour; C reactive protein was absent, and blood, sputum, and urine cultures yielded negative results. Renal function, electrolyte concentrations, and results of a shorz Synacthen test were normal. Liver enzyme activity (aspartate transaminase, alanine transaminase, and y glutamyl transferase) and bilirubin concentrations were normal, as was a chest x ray film. DNA binding was 41% (normal < 30%). She was presumed to have an exacerbation of her disease rather than infection, and prednisolone was increased. On the second day in hospital she developed symptoms of a peripheral, sensory polyneuropathy and left lateral popliteal nerve palsy. Examination of cerebrospinal fluid showed a normal cell count and protein concentration. Results of gram staining and culture were negative. An intravenous bolus of methylprednisolone 1 g was given with symptomatic benefit. Further neurological signs did not develop, but nausea and a low intake of fluid necessitated intravenous fluids. On the fourth day a further 1 g methylprednisolone was given for weakness. Objective and biochemical evidence of myositis was absent. Urea and creatinine concentrations had risen to 16 mmol/l (96 mg/100 ml) (normal 2-5-8-0 mmol/l (15-48 mg/100 ml)) and 180 bAmol/l (2-0 mg/100 ml) (normal 40-130 itmol/l (0-5-1-5 mg/100 ml)) respectively. Intravenous fluids were increased to maintain a positive fluid balance.
doi:10.1136/bmj.291.6490.249 fatcat:q7eelyx2kjfaxc5c6axu42wriu