Herpes zoster in patients taking TNFalpha antagonists for chronic inflammatory joint disease.

OBJECTIVE: To assess the rate of occurrence and outcomes of herpes zoster in patients taking TNFalpha antagonists. METHODS: Retrospective review of the medical records of 300 patients who received TNFalpha antagonists to treat chronic inflammatory joint disease. RESULTS: We identified 9 (9/300, 3%) patients who experienced herpes zoster, 6 women and 3 men, with rheumatoid arthritis (n=7) or ankylosing spondylitis (n=2). The drug was infliximab in 4 patients, adalimumab in 2 patients, and etanercept in 3 patients, including 2 patients with a prior history of infliximab therapy (for 12 and 36 months, respectively). Mean treatment duration at the occurrence of herpes zoster was 27 months (range, 6-42 months). DISCUSSION: Glucocorticoid therapy (n=7) and methotrexate therapy (n=6) were the only risk factors identified in our study. Mean follow-up was 26 months. All 9 patients achieved a full recovery with antiviral treatment and interruption of the TNFalpha antagonist. One patient experienced a recurrence after resuming TNFalpha antagonist therapy. CONCLUSION: The scant data in the literature suggest a higher risk of herpes zoster with anti-TNFalpha antibodies than with the soluble receptor. The role for concomitant treatments (glucocorticoids and methotrexate) should be taken into account.

Pedicle stress fracture: an unusual complication of pycnodysostosis.

Pycnodysostosis is a rare dysplasia characterised by high bone density and susceptibility to long bone fractures caused by cathepsin K deficiency. Spinal abnormalities have rarely been described in this uncommon inherited bone dysplasia. A 28-year-old female, with a past history of pycnodysostosis and spontaneous leg fractures was hospitalized for a 2-month history of spontaneous low back pain. Physical examination revealed the typical facial and hand features of pycnodysostosis and local lumbar stiffness. No abnormalities were found in laboratory tests, particularly with regard to bone turnover markers. Fracture of the left pedicle of the third lumbar vertebra was suspected on lumbar radiographs and later confirmed by a computed tomography (CT) scan. A dramatic improvement in symptoms was achieved, thanks to a course of injectable calcitonin therapy and rest. To our knowledge, it is the first-ever reported case of pedicle stress fracture in a patient with pycnodysostosis, suggesting that spontaneous fractures resulting from this bone dysplasia do not only affect diaphysis of brittle long bones but could also affect the lumbar spine. Furthermore, the present case confirms previous observations in such patients of frequent spondylolysis, which could lead to abnormal lumbar pedicle stress. The dramatic improvement achieved by calcitonin therapy might be related to osteoclastic dysfunction in pycnodysostosis caused by a deficiency of cathepsin K, a cystein protease involved in bone matrix remodelling.

Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis.

Adipokines such as leptin and adiponectin are involved in the regulation of inflammation. Ghrelin, a gastric peptide playing a role in the appetite regulation, possesses anti-inflammatory properties. In this study, we evaluated the circulating levels of adipokines (leptin as potential proinflammatory and adiponectin as anti-inflammatory marker) and ghrelin and the fat mass in patients with ankylosing spondylitis (AS). Serum leptin, adiponectin, and ghrelin were evaluated in 53 AS patients with active disease (mean Bath Ankylosing Spondylitis Disease Activity Index >40) and 35 controls. Fat and lean masses were determined using dual-energy x-ray absorptiometry. Fat and lean masses did not differ between patients and controls. Ankylosing spondylitis patients had lower leptin levels compared with controls, even after adjustment for fat mass (AS vs controls: leptin, 7.6 +/- 1.3 ng/mL vs 10.3 +/- 1.5 ng/mL; leptin [in nanograms per milliliter]/fat mass [in kilograms], 0.28 +/- 0.04 vs 0.44 +/- 0.04; P = .006 and P = .0003, respectively). Serum adiponectin did not differ between patients and controls, whereas circulating ghrelin was higher in AS patients (1354.6 +/- 70.5 pg/mL vs 1008.0 +/- 82.5 pg/mL; P = .001). However, all these results were significant only for male patients. No correlation was found between leptin and adiponectin, and erythrocyte sedimentation rate, C-reactive protein levels, tumor necrosis factor alpha, or Bath Ankylosing Spondylitis Disease Activity Index. Ankylosing spondylitis patients had no changes in fat mass. Leptin production was reduced in contrast with normal levels of adiponectin. These adipokine results, together with high serum ghrelin levels, may influence the inflammatory response in AS.

The contribution of adipose tissue and adipokines to inflammation in joint diseases.

Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases.

Infectious complications with anti-TNFalpha therapy in rheumatic diseases: a review.

TNFalpha plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFalpha antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFalpha therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFalpha inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFalpha inhibitors related infections were described in the randomized clinical trials, and were then declared to post-marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFalpha antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFalpha inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

Imaging study scores for ankylosing spondylitis.

Scoring systems have been developed for radiographs and magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS). Radiographic scores focus on chronic structural alterations, which occur slowly and show little sensitivity to change in the short-term. Recent clinical studies used the modified Stoke ankylosing spondylitis spine score (mSASSS), which evaluates the cervical and lumbar spine. TNF antagonists were found to modify the mSASSS, indirectly supporting a structural effect of these agents. MRI using specific sequences is a potent tool for evaluating inflammation, most notably at the spine. MRI has proved sensitive to change in patients taking TNF antagonists. An outcome measures in rheumatology clinical trials (OMERACT) task force is working on standardizing MRI scores for the spine and sacroiliac joints.