Rheumatic complaints in women taking aromatase inhibitors for treatment of hormone-dependent breast cancer.

BACKGROUND: The rheumatic adverse effects accompanying treatment with aromatase inhibitors (AIs) in hormone-dependent breast cancer represent an area of clinical relevance and emerging concern. This report describes these rheumatic complaints detailing their clinical pattern. METHODS: During 1-year period, 18 consecutive postmenopausal women (mean age, 58.33 years; range, 52-66 years) in treatment with AIs for hormone-dependent breast cancer (mean duration of therapy, 12.0 months; range, 9.1-17.7 months) were referred for evaluation in the outpatient clinic of the rheumatology unit in relation to rheumatic complaints. According to a routine protocol planned with oncologists, patient evaluations consisted of a complete clinical examination with careful assessment of rheumatic complaints and related physical symptoms, followed by laboratory testing and a bone scintiscan. In no cases were rheumatic complaints present before AI therapy. RESULTS: On the basis of clinical data and investigations and by applying accepted diagnostic criteria, a diagnosis of an undifferentiated spondyloarthropathy was reached in 10 (55.5%) of the 18 patients studied, and an oligoarthritis was shown in 2 more patients (11.1%), whereas a simple arthralgia was found in the remaining 6 patients (33.3%). In the patients meeting criteria as belonging to a spondyloarthritic subset, a family history positive for psoriasis and celiac disease was shown in 2 and 1 instance, respectively, whereas HLA-CW6 and HLA-B27 were detected in 3 and 1 case. A high serum level of anti-cyclic citrullinated peptide antibodies was shown in 1 patient with oligoarthritis. Most of the patients (16/18) were treated with nonsteroidal anti-inflammatory drugs or with corticosteroids. Methotrexate (10 mg weekly) was added in 3 of these patients, nonresponders. Aromatase inhibitor discontinuation was needed in the remaining 2 cases with spontaneous resolution of symptoms over time. CONCLUSIONS: Data from the present study emphasize a previously unsuspected high prevalence of defined arthritides underlying these rheumatic complaints. Therefore, investigative efforts should be addressed to better clarify the clinical and pathogenetic significance of these important consequences of AI therapy. An accurate monitoring of rheumatic complaints has to be suggested to patients taking AI therapy, with a rapid referral to a rheumatologist in the case of consistent suspicion of an inflammatory arthritis.

Effect of long-term L-thyroxine treatment on bone mineral density in young adults with congenital hypothyroidism.

OBJECTIVE: To evaluate whether long-term L-thyroxine therapy in young adults with congenital hypothyroidism may affect bone mineral density (BMD). DESIGN: Thirty-seven subjects with congenital hypothyroidism, detected by neonatal screening and longitudinally followed from the time of diagnosis and treatment (26+/-4 days) up to the age of 17.8+/-1.0 years, were studied. METHODS: Spinal (L2-L4) BMD, measured by dual-energy X-ray densitometry, and bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) by quantitative ultrasound, were evaluated. RESULTS: Z-score mean values (+/-s.d.) of BMD (-0.3+/-0.7) and Ad-SoS (-0.7+/-1. 1) were slightly below the average but within the normal range. Ad-SoS resulted in a z-score below -1 in 38% of patients as compared with BMD which resulted in a z-score below -1 in only 13.5% of subject. No significant differences were observed between males (BMD, -0.3+/-0.7; Ad-SoS, -0.9+/-1.0) and females (BMD, -0.3+/-0.7; Ad-SoS, -0.5+/-1.2) or when dividing patients on the basis of aetiological defects; ectopic gland (BMD, -0.3+/-0.6; Ad-SoS, -0.8+/-0.9), athyreosis (BMD, -0.3+/-0.9; Ad-SoS, -0.8+/-1.0) and eutopic gland (BMD, -0.3+/-0.8; Ad-SoS, -0.4+/-1.3). No significant relationships were observed between BMD or Ad-SoS z-score and hormonal status or L-thyroxine dosages at the time of the study or during the pubertal period. CONCLUSIONS: The careful monitoring of serum thyroid-stimulating hormone and adjustment of l-thyroxine dosage avoided the significant deleterious effects of prolonged L-thyroxine replacement therapy on bone tissue in adolescents and young adults with congenital hypothyroidism treated from the neonatal period.

Comparison of effectiveness and safety of infliximab, etanercept, and adalimumab in psoriatic arthritis patients who experienced an inadequate response to previous disease-modifying antirheumatic drugs.

The aim of this study is to compare effectiveness and safety of Infliximab (INF), Etanercept (ETN), and Adalimumab (ADA) in patients with psoriatic arthritis (PsA) with inadequate response to a previous disease-modifying antirheumatic drug (DMARD). One hundred consecutive PsA patients with inadequate response to a previous DMARD entered this study. Clinical and laboratory assessment at baseline (T0) and 12 (T12) months were performed and included physical examination, vital signs, global Psoriasis Area and Severity Index (PASI; extension of psoriasis), tender joints count (TJC), swollen joint count, health assessment questionnaire (HAQ; questionnaire for measuring disability), and monitoring of adverse events (AEs). After enrollment, all patients were randomly given INF 5 mg/Kg every 6-8 weeks, ETN 50 mg weekly, or ADA 40 mg every other week. Baseline therapy with DMARD remained unchanged. Effectiveness was defined as percentage of ACR20 responders and as clinical remission and/or minimal disease activity at 12 months treatment. INF, ETN, and ADA all effectively controlled signs and symptoms of PsA. All variables tested showed at T12 for each treatment a significant variation from the baseline value. In particular, patients on INF and ADA showed the greatest improvement in terms of PASI, while patients on ETN showed the greatest improvement on TJC and HAQ. ACR response rates were 72% of patients on ETN, 70% of those on ADA, and 75% of those patients on INF. Occurrence of AEs was reported in 15% of the cases. Only two AEs in patients on INF were considered drug related, pneumonitis and thrombocytopenia, respectively. All tumor necrosis factor-alpha blockers significantly controlled signs and symptoms of PsA. An increased knowledge of the different profiles of these agents may help in optimizing their use.