Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

The CIRAS Study: A Case Control Study To Define the Clinical, Immunologic and Radiographic Features of the Aromatase Inhibitor Arthralgia Syndrome.

Shanmugam3,  Victoria K., McCloskey1,  James, Elston4,  Elizabeth, Allison2,  Sandra J., Isaacs5,  Claudine, Eng-Wong5,  Jennifer

Department of Internal Medicine, Georgetown University Medical Center, Washington, DC
Department of Radiology, Georgetown University Medical Center, Washington, DC
Division of Rheumatology, Immunology and Allergy, Georgetown University Medical Center, Washington, DC
Georgetown University
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC


Aromatase inhibitors (AIs) reduce recurrence in post-menopausal hormone-receptor positive breast cancer. However, development of joint pains (Arthralgia Syndrome) limits compliance. The pathophysiology of this syndrome is unknown, but morning stiffness suggests an inflammatory etiology. Associations have been reported with tenosynovitis and autoimmune diseases. The CIRAS study was designed to determine the evidence for an inflammatory etiology.


Postmenopausal breast cancer patients followed at Lombardi Cancer Center with hand pain but without known autoimmune disease were recruited. Subjects receiving AIs were cases (n=25) while those not receiving AIs were controls (n=23).

Subjects were evaluated after abstaining from non-steroidal anti-inflammatory drugs for 48 hours. They completed a health assessment questionnaire (PROMIS-HAQ). The rheumatologist completed a history and physical, and disease activity score (DAS-28). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), vitamin D and cytokine levels were tested. Bilateral hand radiographs and ultrasound were performed. The hand ultrasound was scored for presence of flexor tenosynovitis, fluid in the metacarpophalangeal joints, tissue edema, and tendon sheath enhancement for each digit on both hands, and a total ultrasound score was computed. The rheumatologist and radiologist were blinded as to study group. Data was analyzed using t-test and Fisher's exact test.


Patients in both groups were predominantly Caucasian and of similar age. Neither the DAS-28 nor the ESR was significantly different between cases and controls.

Table 1. Results of the CIRAS study

 CASE (n = 25)CONTROL (N = 23)p value 
Symptoms:PROMIS-HAQ (mean ± SEM)9.700 ± 1.83210.05 ± 2.5290.5091
 PROMIS-HAQ Global (mean ± SEM)51.04 ± 7.14154.43 ± 7.7140.7478
 Pain score (mean ± SEM)34.88 ± 5.45142.83 ± 5.5060.3111
 Duration of morning stiffness/hours (mean ± SEM)2.400 ± 0.42031.435 ± 0.29370.0704
Inflammatory indices:DAS-28 (mean ± SEM)2.311 ± 0.14692.29 ± 0.13930.9182
 ESR mm hr (mean ± SEM)17.08 ± 3.03618.50 ± 2.9360.7399
Vitamin DVitamin D ng/ml (mean ± SEM)30.17 ± 2.53733.35 ± 2.5760.3848
Autoimmune featuresANA positive (n)460.3900
 Autoimmune disease (n)460.3900
X-rayDegenerative joint disease (n)15140.9509
Other medication:Bisphosphonate (n)1180.5661
 Tamoxifen (n)7 current use9 prior use 
Ultrasound findings:Total ultrasound score (mean ± SEM)6.600 ± 1.0494.909 ± 1.0400.2606
 Tendon nodules (n)300.2354
 DeQuervain's tenosynovitis (n)420.6681
 Ganglion cysts (n)881.0000
 Flesor tenosynovitis (n)14100.5639

Hypovitaminosis D was found in 1 case and 5 controls (p 0.06).There was no significant difference in mean vitamin D. In each group two subjects had previously undiagnosed autoimmune disease (8.3%). A positive ANA was identified in 6 controls and 4 cases (20.8%). While cases experienced more prolonged morning stiffness, this did not reach statistical significance (p= 0.07). PROMIS-HAQ, global-HAQ and mean pain scores were not significantly different. There was no difference in ultrasound score or tendon nodules, Dequervain's tenosynovitis, ganglion cysts or flexor tenosynovitis. Several patients in the control arm had a similar constellation of symptoms to those receiving AIs.


The arthralgia syndrome may not be unique to patients receiving AIs. This syndrome warrants further investigation since development affects compliance with AI therapy.

To cite this abstract, please use the following information:
Shanmugam, Victoria K., McCloskey, James, Elston, Elizabeth, Allison, Sandra J., Isaacs, Claudine, Eng-Wong, Jennifer; The CIRAS Study: A Case Control Study To Define the Clinical, Immunologic and Radiographic Features of the Aromatase Inhibitor Arthralgia Syndrome. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :912
DOI: 10.1002/art.28680

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