Departments of Orthopaedic Surgery, 1 Pathology and 2 Radiology, Royal Gwent Hospital, Cardiff Road, Newport, and 3 Department of Rheumatology, University of Wales College of Medicine, Heath Park, Cardiff, UK
Correspondence to: J. Bondeson, Department of Rheumatology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. E-mail: BondesonJ{at}cf.ac.uk
SIR, A previously healthy 30-yr-old man presented with a 4-day history of a tender and painful left thigh. He had no history of trauma, and had not performed any unaccustomed exercise. He had not felt generally unwell. Since the symptoms were progressive, he was referred to hospital by his GP. It was noted that these symptoms had presented 2 months after he had started venlafaxine (Efexor) for anxiety. Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor, used in the treatment of anxiety and depression, which has gained a considerable market share.
The patient had had a possible diagnosis of coeliac disease as a child, but his symptoms had settled many years earlier and he was no longer eating a restricted diet. Venlafaxine was his only medication. On examination he was generally well, apyrexial and able to walk unaided. His left leg showed no swelling or erythema. The posterior aspect of his left thigh was tender proximally and medially. He had a full range of movement of his hip and knee, but extension of the knee increased the pain. Reflexes and peripheral pulsations were normal. There were no cutaneous symptoms.
Blood investigations had been performed by his GP, and were repeated upon admission. The striking abnormality was a serum creatine kinase of 5286 IU/l (normal range 0180) on the day before admission; the day after, this had increased further to 7700. His other blood results on admission were normal, including an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and a full blood count. His urine tested negative for myoglobin. Further blood tests for rheumatoid factor, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), parietal cell antibodies, mitochondrial antibodies and smooth muscle antibodies gave negative results. A plain X-ray of his femur showed no abnormality. He was admitted to hospital and treated with diclofenac and codydramol. The venlafaxine was stopped on admission.
An MRI scan of the thigh demonstrated increased signal intensity within the hamstring compartment of the left thigh on T2-weighted images (Fig. 1A). Fat-suppressed axial images using the short inversion recovery method to achieve fat suppression clearly demonstrated hyperintensity within the left hamstring muscles (Fig. 1B), extending throughout the semimembranosus and semitendinosus muscles on a coronal image (Fig. 1C). These signal changes indicate considerable oedema in the hamstring musculature, and were considered to be consistent with myositis. A computed tomography (CT) guided biopsy of the abnormal tissue was performed (Fig. 2). The biopsy showed the muscle fibres to be largely intact, although there were changes in staining to suggest some may be undergoing regeneration. In one fragment, a modest sprinkling of mononuclear cells was seen. The appearances were considered to be consistent with a patchy myositis. The immunohistochemistry report showed CD45 positive, CD3 positive, CD79 negative cells; these T lymphocytes are non-specific, but consistent with a myositis.
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Drug-induced inflammatory muscle disease is not a rare phenomenon. Certain drugs like lipid-lowering agents, antibiotics and D-penicillamine may cause either a polymyositis-like picture or a disease resembling dermatomyositis, with typical skin changes [1, 2]. For some drugs, like simvastatin and other statins, myalgia is a common side-effect, while biopsy-proven myositis is less frequently seen. Antidepressive agents are uncommon causes of inflammatory muscle disease: the few cases upon record usually have a mixed picture of rash, eosinophilia, vasculitis and hepatitis [3, 4]. Both older antidepressants and new-generation drugs can cause arthralgia and myalgia, however. These symptoms are sometimes severe enough to cause the drug to be stopped, and can be verified upon reintroduction of the antidepressant [5, 6].
This is the first reported case of inflammatory muscle disease following treatment with venlafaxine, or indeed any new-generation antidepressant. The focal myositis was well verified by clinical symptoms, as well as by the markedly raised serum creatine kinase, the MRI findings and the biopsy showing inflammatory myositis. It should be noted that this biopsy was performed some time after the patient had started to recover; the histology would probably have reflected a much more aggressive picture of myositis had it been taken directly after admission. The patient recovered spontaneously after venlafaxine was stopped, and developed no further episode of myositis during a 15-month follow-up. Reintroduction of the drug was considered to be unethical due to the marked symptoms and very high creatine kinase upon admission.
A UK pharmacovigilance search performed by Wyeth Pharmaceuticals showed two previous cases of suspected venlafaxine-induced myositis. One of these concerned a 35-yr-old man who had been taken venlafaxine for 8 days when he experienced acute onset of muscle pain and tenderness, with a raised creatine kinase of 588 IU/l. Again, this patient recovered within 10 days of stopping venlafaxine. Along with the case presented here, this report would suggest that reversible myositis can be a side-effect of venlafaxine. Considering the number of people taking this and similar drugs, this is an important observation.
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This work was supported by ARC grant W0596 (to JB).
The authors have declared no conflicts of interest.
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