Patients on antimalarials at risk for myopathy

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Patients on antimalarials at risk for myopathy

August 22, 2005 Janis

Barcelona, Spain - Antimalarials caused persistent muscle-enzyme

disturbances in 18.5% of rheumatic disease patients and clinical myopathy in

6.7% in a prospective study reported online August 11, 2005 in ls of the

Rheumatic Diseases [1].

The prevalence of antimalarial myopathy is higher than previously

recognized when the muscle-enzyme determination is used as a screening

method.

" 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

1. 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.