Patients on antimalarials at risk for myopathy
Aug 22, 2005
Janis Kelly
"The prevalence of antimalarial myopathy is higher than previously recognized when the muscle-enzyme determination is used as a screening method. When a persistent muscle-enzyme disturbance is observed, a clinical and electromyographic study should be performed periodically to detect earlier the development of a clinical myopathy," say the researchers, led by Dr Enrique Casado (Parc Tauli University Hospital, Barcelona).
Muscle-enzyme changes in 18% of patients
This prospective study included all patients with rheumatic diseases taking antimalarials over a three-year period. Serum muscle enzymes were measured at inclusion and every six months thereafter. Patients who had muscle-enzyme disturbances at any point were further assessed with muscle strength electromyography (EMG) and muscle biopsy. The study included 111 patients taking chloroquine and eight taking hydroxychloroquine.
Antimalarial myopathy was defined as the presence of the specific ultrastructural microscopic findings associated with persistent muscle-enzyme disturbances, regardless of clinical symptoms.
Clinical antimalarial myopathy was defined as the presence of antimalarial myopathy associated with an objective muscle weakness, through direct examination of proximal and distal muscles of upper and lower limbs and neck flexor muscles.
Casado reported that 22 patients (18.5%) had persistent muscle-enzyme disturbances. These involved lactate dehydrogenase (LDH) in 19/22 patients, creatine kinase in 7/22 patients, and aldolase in 3/22 patients. Although LDH is not specific for muscle disease, levels normalized in all of the patients who stopped antimalarial drug therapy.
Fifteen patients were biopsied. Light microscopy showed antimalarial myopathy in 3/15. Electron microscopy showed antimalarial myopathy in all 15 patients.
Of these 15 patients, 11 had myopathy at the time they entered the study, and four developed myopathy during follow-up. Eight of 15 patients with biopsy-proven myopathy also had muscle weakness, for a prevalence rate of 6.7%, and all eight also had myopathy on electromyography.
"Antimalarial myopathy was demonstrated in 12.6% of the patients included in the study," Casado writes. Thirteen patients were being treated with chloroquine and two with hydroxychloroquine.
The authors note that the incidence of myopathy was much higher in their study than in previous studies, but they point out that this study was prospective and also used a sensitive screening test: muscle-enzyme changes. Earlier studies were smaller, retrospective, and uncontrolled, and no other prospective data on the incidence of antimalarial myopathy have been published, they add.
Casado emphasizes that antimalarial myopathy diagnosis should be confirmed by biopsy. "In these cases an ultrastructural examination is absolutely mandatory to detect the characteristic tissue deposits that confirm the diagnosis of an antimalarial myopathy, since light microscopy has numerous false negatives (80% in our series)."
May be masked by musculoskeletal symptoms
Myopathy is a recognized toxic effect of antimalarials, along with retinal problems. These toxicities occur with long-term administration of the drugs and stem from accumulation of intracellular deposits, mainly in the retina and muscle, the authors explain.
The muscle toxicity may be difficult to spot in patients who already have musculoskeletal symptoms, they comment. In this study, patients were being treated with antimalarials for rheumatoid arthritis (69 patients), palindromic rheumatism (14), Sjörgen's syndrome (11), systemic lupus erythematosus (9), undifferentiated connective tissue diseases (7), psoriatic arthritis (4), and other rheumatic conditions (5).
"Initial symptoms of muscular injury are characteristically mild. However, painless proximal weakness in both upper and lower extremities may become more severe in time," the authors write. "In many cases, this clinical feature is masked by the musculoskeletal manifestations of the underlying disease, which could explain why the diagnosis of antimalarial myopathy is usually difficult and often delayed."
Source
Casado E, Gratacos J, Tolosa C, et al. Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients. Ann Rheum Dis 2005; DOI:10.1136/ard.2004.023200. Available at: http://ard.bmjjournals.com.
Janis Kelly
"The prevalence of antimalarial myopathy is higher than previously recognized when the muscle-enzyme determination is used as a screening method. When a persistent muscle-enzyme disturbance is observed, a clinical and electromyographic study should be performed periodically to detect earlier the development of a clinical myopathy," say the researchers, led by Dr Enrique Casado (Parc Tauli University Hospital, Barcelona).
Muscle-enzyme changes in 18% of patients
This prospective study included all patients with rheumatic diseases taking antimalarials over a three-year period. Serum muscle enzymes were measured at inclusion and every six months thereafter. Patients who had muscle-enzyme disturbances at any point were further assessed with muscle strength electromyography (EMG) and muscle biopsy. The study included 111 patients taking chloroquine and eight taking hydroxychloroquine.
Antimalarial myopathy was defined as the presence of the specific ultrastructural microscopic findings associated with persistent muscle-enzyme disturbances, regardless of clinical symptoms.
Clinical antimalarial myopathy was defined as the presence of antimalarial myopathy associated with an objective muscle weakness, through direct examination of proximal and distal muscles of upper and lower limbs and neck flexor muscles.
Casado reported that 22 patients (18.5%) had persistent muscle-enzyme disturbances. These involved lactate dehydrogenase (LDH) in 19/22 patients, creatine kinase in 7/22 patients, and aldolase in 3/22 patients. Although LDH is not specific for muscle disease, levels normalized in all of the patients who stopped antimalarial drug therapy.
Fifteen patients were biopsied. Light microscopy showed antimalarial myopathy in 3/15. Electron microscopy showed antimalarial myopathy in all 15 patients.
Of these 15 patients, 11 had myopathy at the time they entered the study, and four developed myopathy during follow-up. Eight of 15 patients with biopsy-proven myopathy also had muscle weakness, for a prevalence rate of 6.7%, and all eight also had myopathy on electromyography.
"Antimalarial myopathy was demonstrated in 12.6% of the patients included in the study," Casado writes. Thirteen patients were being treated with chloroquine and two with hydroxychloroquine.
The authors note that the incidence of myopathy was much higher in their study than in previous studies, but they point out that this study was prospective and also used a sensitive screening test: muscle-enzyme changes. Earlier studies were smaller, retrospective, and uncontrolled, and no other prospective data on the incidence of antimalarial myopathy have been published, they add.
Casado emphasizes that antimalarial myopathy diagnosis should be confirmed by biopsy. "In these cases an ultrastructural examination is absolutely mandatory to detect the characteristic tissue deposits that confirm the diagnosis of an antimalarial myopathy, since light microscopy has numerous false negatives (80% in our series)."
May be masked by musculoskeletal symptoms
Myopathy is a recognized toxic effect of antimalarials, along with retinal problems. These toxicities occur with long-term administration of the drugs and stem from accumulation of intracellular deposits, mainly in the retina and muscle, the authors explain.
The muscle toxicity may be difficult to spot in patients who already have musculoskeletal symptoms, they comment. In this study, patients were being treated with antimalarials for rheumatoid arthritis (69 patients), palindromic rheumatism (14), Sjörgen's syndrome (11), systemic lupus erythematosus (9), undifferentiated connective tissue diseases (7), psoriatic arthritis (4), and other rheumatic conditions (5).
"Initial symptoms of muscular injury are characteristically mild. However, painless proximal weakness in both upper and lower extremities may become more severe in time," the authors write. "In many cases, this clinical feature is masked by the musculoskeletal manifestations of the underlying disease, which could explain why the diagnosis of antimalarial myopathy is usually difficult and often delayed."
Source
Casado E, Gratacos J, Tolosa C, et al. Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients. Ann Rheum Dis 2005; DOI:10.1136/ard.2004.023200. Available at: http://ard.bmjjournals.com.
posted by Ricardo Pocurull at 6:50 AM
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