Intravenous Immunoglobulin Shows Efficacy Treating Hydroxychloroquine-Induced Myopathy

Treatment with intravenous immunoglobulin (IVIG) was found to improve biopsy-proven hydroxychloroquine-induced myopathy in a 35-year-old patient with systemic lupus erythematosus (SLE) in a case study published by Cureus.

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Limited reports have noted drug-induced myopathies as an adverse effect (AE) of treatment with hydroxychloroquine, which is underdiagnosed with unclear treatment interventions other than discontinuing the drug, according to the study authors. Drug-induced myopathy may be asymptomatic or manifested by myopathic symptoms and signs, with or without elevated creatine kinase level, among individuals who have not had prior primary muscular diseases following administration of a particular medication.

Hydroxychloroquine is among the most frequently used disease-modifying anti-rheumatic drug (DMARD), with use in all stages of SLE, and as a first-line DMARD for patients with mild rheumatoid arthritis.

“Hydroxychloroquine-induced myopathy has historically been a rare diagnosis, but recent publications show that it is an underdiagnosed and undertreated side effect,” the study authors wrote. “Apart from discontinuing the drug, there is no major intervention reported in the literature to reverse the myopathy.”

In the case study, the authors presented a 35-year-old Saudi female patient who had SLE for 13 years and whose disease was limited to musculoskeletal and hematological manifestations. She was administered 200 mg of hydroxychloroquine once daily and prednisolone 15 mg once daily following her diagnosis with SLE. In August 2020, the patient sought care at a rheumatology clinic for knee and hand joint pain bilaterally. An examination showed knee and wrist joint tenderness, without swelling, redness, or hotness.

Her laboratory results showed leukopenia of 2.0×10³/µL (normal count: 4.5-11×10³/µL), C-reactive protein (CRP) of 11 mg/L (normal count: <5 mg/L), erythrocyte sedimentation rate (ESR) of 23 mm/hour (normal range: 0-20 mm/hour), anti-double-stranded deoxyribonucleic acid (dsDNA) of 548 IU/ml (normal count: <27 IU/ml), low C3 of 0.65 g/L (normal count: 0.9-1.8 g/L), normal C4, and normal urinalysis and kidney function tests. The patient’s medication regimen was adjusted, with 50 mg azathioprine added, hydroxychloroquine was increased to 200 mg twice per day, and the prednisolone dose of 15 mg once daily was tapered with a 5 mg reduction each week.

At a follow-up visit 2 weeks later, the patient had worsened joint pain in the hand and tenderness in the hand joints. To treat this, naproxen 250 mg was added, azathioprine dose was increased to 100 mg per day, and there was no change in the tapered prednisolone dose.

Her arthritis symptoms were found to improve in subsequent follow-up visits; however, leukopenia worsened and reached 1.63×10³/µL. The dose of azathioprine was increased to 100 mg per day and alternated with 50 mg initially, before being discontinued. The patient’s symptoms then recurred, with laboratory results showing a persistent elevation of anti-dsDNA of >666 IU/ml.

IV belimumab was initiated at a dose of 10 mg/kg every 2 weeks for 3 doses and followed by a maintenance dose of 10 mg/kg every 4 weeks, and she was kept on 5 mg/day prednisolone and 200 mg of hydroxychloroquine twice daily. Following 2 doses of belimumab, the patient showed progressive proximal painless muscle weakness of the upper and lower limbs, which was subsequently discontinued with no diurnal variation.

“Despite the use of all these medications, she continued to have symptoms. It was a diagnostic predicament. Following the standard approaches in evaluating muscle weakness, we ultimately reached the diagnosis of [hydroxychloroquine]-induced myopathy based on histopathological findings,” the study authors wrote.

The care team then initiated treatment with IVIG, which was administered at a dose of 2 g/kg for 6 total doses per month. The patient showed what was deemed as an impressive clinical outcome as she completely regained muscle power and finished her IVIG course with no adverse effects.

“[Hydroxychloroquine]-induced myopathy reflects an underdiagnosed rather than rare side effect of the drug with serious consequences,” the study authors wrote. “In clinical practice, we still lack data for monitoring this side effect and, when encountered, how it should be treated. However, muscle biopsy is an essential step to diagnose it. Aside from stopping the offending drug, IVIG might be a treatment option. It is not easy to design studies to address these issues.”

Reference

Almoallim H, Samkari A, Fallata A, et al. (June 27, 2023) Hydroxychloroquine-Induced Myopathy Responding to Intravenous Immunoglobulin (IVIG). Cureus 15(6): e41016. doi:10.7759/cureus.41016.