Corticosteroid-induced Myopathy Involving Respiratory Muscles in Patients with Chronic Obstructive Pulmonary Disease or Asthma 1 •2
MARC DECRAMER and KOENRAAD J. STAS
Introduction SUMMARY We made observations on two patients with asthma and one with COPO who developed Steroid-induced myopathy is a well-known steroid-Induced myopathy during prolonged treatment with high doses of corticosteroids. On adclinical entity in patients treated with high mission, quadriceps force was on the average reduced to 31% of predicted (range 16 to 46% of doses ofcorticosteroids (1). It remains unpredicted, nondomlnant leg), and urinary excretion of creatine In 24 h averaged 687 mg (range 275 clear, however, to what extent such treatment to 1,045 mg/24 hr). Respiratory muscle Involvement was evidenced by reductions In P1max and PEmax, might affect respiratory muscle function, albeing 38% (range 36 to 39) and 48% of predicted (range 36 to 68), respectively. Tapering of treatment though this question is of great potential relwith corticosteroids resulted In Important recovery of quadriceps force and respiratory muscle force. evance topatients with respiratory disorders In all three patients, a correlation between muscle forces and steroid dose was present during reduc(2). Recently, animal modelsdemonstrated retion of the dose. After 6 months quadriceps force averaged 62% of predicted (range 31 to 85), and spiratory muscle involvement in generalized P1max and PEmaxreached 74% (range 52 to 92) and 92% of predicted (range 80 to 106), respectively, muscle atrophy produced by high doses of after 3 months. Consequently, respiratory muscle force appeared to recover faster than quadriceps corticosteroids (3-6). Respiratory muscle inforce. The Implications of these observations for patients treated with the usual doses of corvolvement wasfurther suggested byJanssens ticosteroids for shorter periods require further Investigation. and Decramer (7) in two patients treated with AM REV RESPIR DIS 1992; 146:800-802 high doses of steroids for systemic disorders. Patients with asthma or chronic obstructive pulmonary disease (COPD) are frequently treated with corticosteroids for exacerbation of the disease. Whether this treatment can 1,045 to 159 mg124 hr.Within 3 wk, the maximal tronic transducer, however, instead of aneroid cause respiratory muscle dysfunction in these inspiratory pressure (PImax) rose from 39 to78070 gauges. PImax wasm easured after maximal expipatients has, to the bestof our knowledge, of predicted and the maximal expiratory pressure ration (near residual volume, RV)and PEmax was barely been studied (8, 9). We werefortunate (PEmax) increased from 68 to 89070 of predicted measured after maximal inspiration (near TLC). (figures 1and 2, upper panels). They were both related to the normal values of to make observations on three patients who Rochester and Arora (11). PEmax and PImax weremeasured according to developed steroid-induced muscle weakness the method of Black and Hyatt (10), with an elecThe increases in PImax a nd PEmax wereclearly involving the respiratory muscles, with a dosassociated with steroid dose reduction (figures 1 age regimenapplied for treatment of exacerand 2, lowerpanels) but not with the small variabation of disease. tions in FRC present during this period. His weight 100 Case Report Patient 1
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This 59-yr-old man worked for 26 yr,until 1981, eQ. 60 as acoal miner. He smoked 20 cigarettes a day un0 !! til 1989. Since April 1988 he usedbronchodilating .... 40 0 .... aerosols and was admitted to the hospital twice for til E bronchoconstriction episodes. InOctober 1989 he « 20 was admitted to another hospital because of an infectious COPD exacerbation. Despite intravenous antibiotic and bronchodilating therapy, with a daily 0 0 dose of 60 mg methylprednisolone, his clinical situation did not improve and he suffered from Time (monthsl progressive general weaknessand dyspnea. He was transferred to our hospital in December 1989 after 3 months of therapy with methylprednisolone, 60 mg/day. On admission the white cell count was 16,200/mI and a rightupper lobe infiltrate was present, treated with aminoxicillin. Blood gas analysis on admission showed Pco, 50 mm Hg, Po, 71 mm Hg, pH 7.48, with 1 LOs/min. Pco, normalized within 1 wk. Potassium, calcium, phoso phate, and albumin were within normal limits. His serum muscle enzyme levels were normal, with a normal nutritional status, 61 kg body weight, and 1.73 m height, that is, a 20.4 body mass index (BMI). Electromyogram of the four limbs revealed low volt60 age potentials and polyphasic tracings on contracsteroid dose lmg/day) tion and discrete denervation signs suggestive of Fig. 1. Upper panel. Maximal inspiratory pressure, steroid myopathy. P1max (Ofo of predicted) versus time (months). LowerpanOn admission, after gradual reduction of the steroid dose, the patient regained strength, the dysel. P1max (Ofo of predicted) versus steroid dose, expnea score (Borg scale) decreased from 7 to 2 within pressed in mg methylprednisolone per day. Patient 1 (open squares); patient 2 (triangles); patient 3 (solid 3 wk, FEV 1 increased from 0.60 to 1.28Land VC squares). from 77 to 110070, and creatinuria decreased from )(
800
•
•
•
increased to 66 kg, that is, 22.1 BMI. Lactic dehydrogenase (LDH) decreased from 341 to 181 lUlL in 1 month, as did urea from 90 to 43mg/dl and creatine from 1.2 to 0.6 mg/dl. The force inthe left, nondominant quadriceps, which was initially reduced to 11.5 kg or 35070 of the normal value, reached the normal range only after 5 months (figure 3, upper panel). This increase was clearly related to steroid dose reduction (figure 3, lower panel).
Patient 2 This 59-yr-old patient smoked some 40cigarettes per day for 37 yr,u ntil 1975. He wasknown to have asthma, requiring several hospitalizations. On each occasion he was treated with high doses of corticosteroids. Since 1986 he was on c ontinuous steroid treatment (average daily dose 10 mg prednisone). SinceDecember 1987 he was followed atour outpatient clinic. Histamine provocation testing was positive, PCzo 0.83 mg/ml, but no allergy wasfound and hyperventilation and exerciseprovocation were
(Received in original form June 5, 1991 and in revised form January 27, 1992) 1 From the Respiratory Muscle Research Unit, Laboratory for Pneumology, Department of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. 1 Correspondence and requests for reprints should be addressed to Dr. M. Decramer, Respiratory Division, University Hospital, Weligerveld 1, B-3212 Pellenberg, Belgium.
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MARC DECRAMER and KOENRAAD J. STAS
Introduction SUMMARY We made observations on two patients with asthma and one with COPO who developed Steroid-induced myopathy is a well-known steroid-Induced myopathy during prolonged treatment with high doses of corticosteroids. On adclinical entity in patients treated with high mission, quadriceps force was on the average reduced to 31% of predicted (range 16 to 46% of doses ofcorticosteroids (1). It remains unpredicted, nondomlnant leg), and urinary excretion of creatine In 24 h averaged 687 mg (range 275 clear, however, to what extent such treatment to 1,045 mg/24 hr). Respiratory muscle Involvement was evidenced by reductions In P1max and PEmax, might affect respiratory muscle function, albeing 38% (range 36 to 39) and 48% of predicted (range 36 to 68), respectively. Tapering of treatment though this question is of great potential relwith corticosteroids resulted In Important recovery of quadriceps force and respiratory muscle force. evance topatients with respiratory disorders In all three patients, a correlation between muscle forces and steroid dose was present during reduc(2). Recently, animal modelsdemonstrated retion of the dose. After 6 months quadriceps force averaged 62% of predicted (range 31 to 85), and spiratory muscle involvement in generalized P1max and PEmaxreached 74% (range 52 to 92) and 92% of predicted (range 80 to 106), respectively, muscle atrophy produced by high doses of after 3 months. Consequently, respiratory muscle force appeared to recover faster than quadriceps corticosteroids (3-6). Respiratory muscle inforce. The Implications of these observations for patients treated with the usual doses of corvolvement wasfurther suggested byJanssens ticosteroids for shorter periods require further Investigation. and Decramer (7) in two patients treated with AM REV RESPIR DIS 1992; 146:800-802 high doses of steroids for systemic disorders. Patients with asthma or chronic obstructive pulmonary disease (COPD) are frequently treated with corticosteroids for exacerbation of the disease. Whether this treatment can 1,045 to 159 mg124 hr.Within 3 wk, the maximal tronic transducer, however, instead of aneroid cause respiratory muscle dysfunction in these inspiratory pressure (PImax) rose from 39 to78070 gauges. PImax wasm easured after maximal expipatients has, to the bestof our knowledge, of predicted and the maximal expiratory pressure ration (near residual volume, RV)and PEmax was barely been studied (8, 9). We werefortunate (PEmax) increased from 68 to 89070 of predicted measured after maximal inspiration (near TLC). (figures 1and 2, upper panels). They were both related to the normal values of to make observations on three patients who Rochester and Arora (11). PEmax and PImax weremeasured according to developed steroid-induced muscle weakness the method of Black and Hyatt (10), with an elecThe increases in PImax a nd PEmax wereclearly involving the respiratory muscles, with a dosassociated with steroid dose reduction (figures 1 age regimenapplied for treatment of exacerand 2, lowerpanels) but not with the small variabation of disease. tions in FRC present during this period. His weight 100 Case Report Patient 1
• :0G) U
80
0
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•
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•
This 59-yr-old man worked for 26 yr,until 1981, eQ. 60 as acoal miner. He smoked 20 cigarettes a day un0 !! til 1989. Since April 1988 he usedbronchodilating .... 40 0 .... aerosols and was admitted to the hospital twice for til E bronchoconstriction episodes. InOctober 1989 he « 20 was admitted to another hospital because of an infectious COPD exacerbation. Despite intravenous antibiotic and bronchodilating therapy, with a daily 0 0 dose of 60 mg methylprednisolone, his clinical situation did not improve and he suffered from Time (monthsl progressive general weaknessand dyspnea. He was transferred to our hospital in December 1989 after 3 months of therapy with methylprednisolone, 60 mg/day. On admission the white cell count was 16,200/mI and a rightupper lobe infiltrate was present, treated with aminoxicillin. Blood gas analysis on admission showed Pco, 50 mm Hg, Po, 71 mm Hg, pH 7.48, with 1 LOs/min. Pco, normalized within 1 wk. Potassium, calcium, phoso phate, and albumin were within normal limits. His serum muscle enzyme levels were normal, with a normal nutritional status, 61 kg body weight, and 1.73 m height, that is, a 20.4 body mass index (BMI). Electromyogram of the four limbs revealed low volt60 age potentials and polyphasic tracings on contracsteroid dose lmg/day) tion and discrete denervation signs suggestive of Fig. 1. Upper panel. Maximal inspiratory pressure, steroid myopathy. P1max (Ofo of predicted) versus time (months). LowerpanOn admission, after gradual reduction of the steroid dose, the patient regained strength, the dysel. P1max (Ofo of predicted) versus steroid dose, expnea score (Borg scale) decreased from 7 to 2 within pressed in mg methylprednisolone per day. Patient 1 (open squares); patient 2 (triangles); patient 3 (solid 3 wk, FEV 1 increased from 0.60 to 1.28Land VC squares). from 77 to 110070, and creatinuria decreased from )(
800
•
•
•
increased to 66 kg, that is, 22.1 BMI. Lactic dehydrogenase (LDH) decreased from 341 to 181 lUlL in 1 month, as did urea from 90 to 43mg/dl and creatine from 1.2 to 0.6 mg/dl. The force inthe left, nondominant quadriceps, which was initially reduced to 11.5 kg or 35070 of the normal value, reached the normal range only after 5 months (figure 3, upper panel). This increase was clearly related to steroid dose reduction (figure 3, lower panel).
Patient 2 This 59-yr-old patient smoked some 40cigarettes per day for 37 yr,u ntil 1975. He wasknown to have asthma, requiring several hospitalizations. On each occasion he was treated with high doses of corticosteroids. Since 1986 he was on c ontinuous steroid treatment (average daily dose 10 mg prednisone). SinceDecember 1987 he was followed atour outpatient clinic. Histamine provocation testing was positive, PCzo 0.83 mg/ml, but no allergy wasfound and hyperventilation and exerciseprovocation were
(Received in original form June 5, 1991 and in revised form January 27, 1992) 1 From the Respiratory Muscle Research Unit, Laboratory for Pneumology, Department of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. 1 Correspondence and requests for reprints should be addressed to Dr. M. Decramer, Respiratory Division, University Hospital, Weligerveld 1, B-3212 Pellenberg, Belgium.
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CASE REPORT
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