Detecting Drug-Induced Neuromuscular Disorders
Popular drugs used to treat rheumatologic diseases can have rare adverse effects
Two patients suffering from disabling, unexplained weakness and gait disorder owe their recovery to a neurologist who suspected that the problem lay in the treatment they received for autoimmune diseases. The first patient, a 49-year-old man with a five-year history of rheumatoid arthritis, was admitted to University Hospitals Case Medical Center with generalized weakness and gait imbalance. “He was on a small dose of prednisone and methotrexate, and because those two drugs didn’t have a strong enough effect, he had also been prescribed infliximab [Remicade®],” says Bashar Katirji, MD, Director, Neuromuscular Center and EMG Laboratory, Neurological Institute, University Hospitals Case Medical Center; and Professor, Neurology, Case Western Reserve University School of Medicine.
Infliximab, a biologic drug that is a tumor necrosis factor (TNF)-α antagonist, is commonly prescribed to treat rheumatoid arthritis and other autoimmune diseases. “About a year after starting infliximab, the patient began feeling numbness in both hands. He underwent an electromyogram [EMG] study, which was interpreted to indicate bilateral carpal tunnel syndromes,” Dr. Katirji says. “Then the numbness progressed to his legs. Two years after starting infliximab, he began having trouble walking and getting out of a chair. Finally, he was hospitalized here at UH Case Medical Center. At that point, he couldn’t walk; he had a steppage gait because of severe bilateralfoot drop.”
Identifying the Harmful Agent
Dr. Katirji administered another EMG study, which showed the patient had acquired demyelinating sensory and motor peripheral polyneuropathy. “This finding suggested chronic inflammatory demyelinating polyneuropathy [CIDP],” Dr. Katirji notes. Several possible causes of neuropathy were ruled out by further testing. Infliximab previously had been implicated in myelin disease of the central nervous system, which led Dr. Katirji to suspect that it had a role in peripheral nervous system demyelination as well. “We stopped infliximab but saw no improvement in the next two months,” Dr. Katirji explains. “We then gave him intravenous immunoglobulin [IVIG], and within three or four months he recovered completely. He still comes to the infusion center at University Hospitals Seidman Cancer Center to receive maintenance IVIG every four to five weeks.” If the infliximab had been stopped earlier, the patient’s neuropathy might have resolved on its own, Dr. Katirji says, “but he was on the drug for two years before we diagnosed the problem.”
The second patient, a 55-year-old woman with Sjögren’s syndrome, was seen regularly by both Dr.Katirji and an experienced rheumatologist. “I had been seeing her since 2008 because of discomfort in her feet due to a mild small fiber neuropathy. She came to a routine appointment last year complaining of weaknessin her hips and an abnormal gait for one to two months,” says Dr. Katirji. “She had significant bilateral weakness in her hip abductors and mild weakness of her hip flexors as well. As a result, she had a waddling gait, dropping her hip with each stride.”
Careful questioning about medications revealed that the patient had started taking the hydroxychloroquine (Plaquenil®) about six months prior. EMG revealed myopathic motor units with some fibrillation potentials in the glutei and iliacus muscles. A biopsy of the gluteus medius muscle showed “the classic finding of autophagic myopathy, which is what we see in toxic muscle disease such as commonly seen in patients taking chloroquine or hydroxychloroquine. We stopped the drug, her muscles improved significantly and she is now 70 to 80 percent better three months after stopping the drug.”
Early Recognition of Complications
Infliximab and hydroxychloroquine are highly effective against rheumatologic and autoimmune diseases, but neurologists, rheumatologists, internists and other physicians caring for these patients need to be aware that the drugs themselves may induce a variety of immunological disorders, Dr. Katirji warns. Treatment of these complications may require not just stopping the drug but also adding immunomodulating therapy. “The connection is not widely recognized. If a patient who is taking one of these drugs develops any sensory symptoms or weakness, that patient should be investigated carefully for the beginning of a problem affecting either the central or peripheral nervous system.”
Dr. Katirji’s report on the infliximab case, as well as a similar patient on etanercept (Enbrel®), was published in Muscle & Nerve (2010:May;41(5):723-7).
Bashar Katirji, MD
Director, Neuromuscular Center and EMG Laboratory
Neurological Institute
University Hospitals Case Medical Center
Professor, Neurology
Case Western Reserve University School of Medicine
Email Dr. Katirji for consultation.