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Ann Rheum Dis. 2007 April; 66(4): 557–558.
PMCID: PMC1856055

Will steroidal aromatase inhibitors induce rheumatoid arthritis?

Aromatase inhibitors are used in advanced breast cancer treatment to cause an oestrogen deprivation. Such treatment can induce benign arthralgias.1,2 We describe a case of rheumatoid arthritis after treatment with aromatase inhibitors. A 64‐year‐old Caucasian woman, with a 3‐year history of advanced right breast cancer (infiltrative ductal carcinoma classified as oestrogen‐receptor positive; progesterone‐receptor negative with positive lymph nodes; pT2pN1bM0) received treatment with tamoxifen (20 mg/day) for about 3 years. Cancer follow‐up was normal and no side effects were reported. In November 2004, tamoxifen was switched to exemestane (25 mg/day) in accordance with studies showing better efficacy and good safety. A few days later, she developed arthralgias affecting the hips, shoulders, knees, wrists and hands associated with morning joint stiffness for 2 h. Treatment with non‐steroidal anti‐inflammatory drugs did not improve her condition. About 4 weeks later, she developed symmetric and active arthritis, with swelling affecting the wrists, metacarpophalangeal joints and proximal interphalangeal joints. Erythrocyte sedimentation rate and C reactive protein concentration were raised (30 mm/h and 15 mg/l, respectively). After 4 months, exemestane treatment was stopped and tamoxifen restarted. However, this switch did not induce a regression of joint symptoms. At this stage, we examined the patient. She had active and symmetric arthritis with synovitis affecting both wrists, metacarpophalangeal joints and proximal interphalangeal joints. In addition, she had flexor tenosynovitis and ulnar deviation of fingers. Erythrocyte sedimentation rate was 14 mm/h and C reactive protein concentration 13.2 mg/l. Tests for rheumatoid factor and anti‐anticyclic citrullinated peptide antibodies were negative. The shared epitope was present with the human leucocyte antigen DRB1* 0101 allele. x Rays already showed erosions of the first and second metacarpophalangeal joints and joint space narrowing of other metacarpophalangeal joints. A magnetic resonance image of the right hand showed synovitis and erosions affecting the wrists and metacapophalangeal joints (fig 11).). The patient fulfilled the American College of Rheumatology criteria for rheumatoid arthritis and had an active disease with a Disease Activity Score including 28‐joint count of 4.77. Methotrexate was started at 15 mg/week, inducing an improvement of the Disease Activity Score, including 28‐joint count at 2.30 after 4 months.

figure ar66159.f1
Figure 1 (A) Coronal T1‐weighted magnetic resonance imaging (MRI) scan of the right wrist and metacarpophalangeal joints showing small erosions of the first metacarpal head near the proximal synovial insertion as well as defined areas ...

This case suggests the role of aromatase inhibitors in the induction of rheumatoid arthritis. Many arguments favour the role of hormones in the induction and expression of rheumatoid arthritis. Its highest incidence and prevalence are observed in women after menopause. Moreover, symptoms are reduced during pregnancy and increased in the postpartum period,3 as observed in the case of a 36‐year‐old woman who developed both rheumatoid arthritis and ulcerative colitis 2 weeks after a normal delivery.4

Accordingly, this case suggests the contribution of the anti‐aromatase treatment. In this case, additional factors such as the presence of the shared epitope could explain the switch from common benign arthralgias to active destructive rheumatoid arthritis. At the late stage, cessation of treatment had no effect on arthritis. The presence of erosions suggests that the patient had rheumatoid arthritis with low disease activity, which became worse when aromatase inhibitors were used. Accordingly, arthralgias in women receiving aromatase inhibitors should be better evaluated to estimate the incidence of rheumatoid arthritis.

Footnotes

Competing interests: None declared.

References

1. Felson D T, Cummings S R. Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation. Arthritis Rheum 2005. 522594–2598.2598 [PubMed]
2. Coombes R C, Hall E, Gibson L J, Paridaens R, Jassem J, Delozier T. et al A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004. 3501081–1092.1092 [PubMed]
3. Lansink M, de Boer A, Dijkmans B A, Vandenbroucke J P, Hazes J M. The onset of rheumatoid arthritis in relation to pregnancy and childbirth. Clin Exp Rheumatol 1993. 11171–174.174 [PubMed]
4. Boyer F, Fontanges E, Miossec P. Rheumatoid arthritis associated with ulcerative colitis: a case with severe flare of both diseases after delivery. Ann Rheum Dis 2001. 60901

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