Rheumatology Advance Access originally published online on August 27, 2007
Rheumatology 2007 46(10):1619-1621; doi:10.1093/rheumatology/kem213
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Severe disabling tendinopathy caused by anastrazole
Department of Rheumatology and Clinical Immunology, 1Department of Oncology, 2Department of Radiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Correspondence to: Henk A. Martens, MD, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB Groningen, The Netherlands. E-mail: h.a.martens{at}int.umcg.nl
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Introduction |
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SIR, Aromatase inhibitors are a group of drugs that are used in the adjuvant treatment of oestrogen receptor-positive breast cancer. Musculoskeletal symptoms are frequently observed during treatment with aromatase inhibitors [1]. Mostly, the complaints consist of arthralgias, muscle-weakness, morning stiffness and bone pain. Also osteoporosis and arthritis may occur. Recently, tenosynovitis occurring during treatment with aromatase inhibitors has been described [2].
In this case report, we describe a patient with severe, disabling tendinopathy during treatment with the aromatase inhibitor anastrozole (Arimidex®).
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Case report |
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A 55-yr-old woman was referred to our Department of Rheumatology for severe, disabling pain and swelling at the wrists. A year before she had started treatment with anastrozole because of oestrogen receptor-positive breast cancer. Since then, she experienced non-severe myalgias and morning stiffness. Pain and swelling at the radial side of the right wrist occurred after 5 months of treatment with anastrozole and had worsened since. In addition, she had pain in the Achilles tendons, but no pain or swelling of joints. She did not use drugs other than anastrozole. Non-steroid anti-inflammatory drugs and splintage had no effect. The week before presentation, pain and swelling also occurred in the left wrist.
At physical examination there was a tender swelling on the radial side of both wrists (Fig. 1A). Resisted extension and abduction of the thumbs was also very painful. Finkelstein's test was negative. Both Achilles tendons were tender. There were no signs of arthritis, and no further abnormalities at physical examination.
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Laboratory tests revealed a normal ESR (2 mm in first hour) and CRP (<5 mg/l). Blood count, renal function, liver enzymes and rheumatoid factor were normal. There were no anti-CCP antibodies. Thyroid function was normal. There was no hypercholesterolaemia. Radiographs of hands and wrists showed no abnormalities, neither did skeletal scintigraphy. Ultrasound showed a thickening and irregular aspect of the tendon of the abductor pollicis longus muscle on the right wrist (Fig. 1B). There were no signs of tenosynovitis such as a peri-tendinous fluid collection or swelling. Power Doppler revealed an increased vascularity of the tendon, confirming active inflammation. Based on these findings, the diagnosis of tendinopathy of the tendon of the abductor pollicis longus muscle was made. Treatment with anastrozole was discontinued. After this, the pain in the Achilles tendons resolved completely, but an additional local corticosteroid injection was needed for further improvement of the wrist symptoms.
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Discussion |
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TopIntroductionCase reportDiscussionReferences |
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Aromatase inhibitors are increasingly used as adjuvant hormonal therapy in post-menopausal patients with oestrogen-positive breast cancer. These drugs cause a depletion of oestrogen and thereby prevent progression of the disease. Musculoskeletal symptoms, especially arthralgias and myalgias, have been reported in up to 5.4–35.6% of patients during use of aromatase inhibitors [1]. Mostly, these complaints diminished in the first year after start of treatment, but, in some cases, the drugs had to be discontinued because of severe arthralgias [3]. Also carpal-tunnel syndrome has been reported [4]. It has been suggested that aromatase inhibitors inhibit the antinociceptive effects of oestrogen by depleting oestrogen levels, thereby decreasing the threshold for painful stimuli. Furthermore, oestrogen might exert effect on inflammation in the joint [5]. Recently, Morales et al. reported tenosynovitis in 12 patients treated with either letrozole or exemestane [2]. Six of these patients had to discontinue treatment because of disabling pain.
In our patient, a De Quervain's tenosynovitis appeared to be unlikely because there was no peri-tendinous fluid or swelling at ultrasound, as is often seen in the De Quervain's tenosynovitis [6]. The involvement of both wrists and the Achilles tendons suggest the presence of a (diffuse) tendinopathy.
Possible causes of tendinopathy were reviewed by Riley in 2004 [7]. Inherited disorders can lead to deficient or abnormal collagen or abnormal fibril structure. Endocrine and metabolic disorders may lead to altered collagen metabolism or deposits between fibrils. Finally, rheumatologic diseases may cause destruction of collagen by inflammation. Also other intrinsic factors, like age and joint laxity and extrinsic factors like occupation and sport may be implicated in chronic tendinopathy. Tendinopathy of the Achilles tendon is often associated with vigorous physical activity or use of drugs like fluoroquinolone antibiotics or steroids [8].
In our patient there were no signs of underlying systemic disease, there was no abnormal physical activity preceding the complaints and she used no other drugs beside anastrozole. Furthermore, the complaints improved after discontinuation of anastrozole. Therefore, the anastrozole is thought to be the cause of the tendinopathy in this patient.
To our knowledge, this is the first case describing a tendinopathy caused by an aromatase inhibitor. As complaints caused by tendinopathy can be severe and aromatase inhibitors are increasingly used in the treatment of breast cancer, one has to be aware of this possible side effect.
The authors have declared no conflicts of interest.
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References |
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TopIntroductionCase reportDiscussionReferences |
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- Pandya N, Morris GJ. Toxicity of aromatase inhibitors. Semin Oncol (2006) 33:688–95.[CrossRef][Web of Science][Medline]
- Morales L, Pans S, Paridaens R, et al. Debilitating musculoskeletal pain and stiffness with letrozole and exemestane: associated tenosynovial changes on magnetic resonance imaging. Breast Cancer Res Treat (2007) 104:87–91.[CrossRef][Web of Science][Medline]
- Donnellan PP, Douglas SL, Cameron DA, Leonard RC. Aromatase inhibitors and arthralgia. J Clin Oncol (2001) 19:2767.
[Free Full Text] - Buzdar A, Howell A, Cuzick J, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol (2006) 7:633–43.[CrossRef][Web of Science][Medline]
- Felson DT, Cummings SR. Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation. Arthritis Rheum (2005) 52:2594–8.[CrossRef][Web of Science][Medline]
- Giovagnorio F, Andreoli C, De Cicco ML. Ultrasonographic evaluation of de Quervain disease. J Ultrasound Med (1997) 16:685–9.[Abstract]
- Riley G. The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (2004) 43:131–42.
[Free Full Text] - Kowatari K, Nakashima K, Ono A, Yoshihara M, Amano M, Toh S. Levofloxacin-induced bilateral Achilles tendon rupture: a case report and review of the literature. J Orthop Sci (2004) 9:186–90.[CrossRef][Web of Science][Medline]
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