**6. References**

86 Rheumatoid Arthritis – Treatment

During therapy with TNF-α inhibitors, patients should be regularly assessed to rule out active infections. With respect to NTM disease, repeated sputum cultures during therapy should be considered in the setting of chest symptoms or co-morbid pulmonary disease, as well as chest radiography or CT scans. Extrapulmonary disease should be thoroughly investigated, and biopsy specimens should be stained for acid-fast bacilli and cultured for

The TNF-α inhibitors, including the four currently available anti-TNF monoclonal antibodies and the soluble TNF receptor, have revolutionized the treatment of rheumatoid arthritis and other chronic inflammatory diseases since their introduction over a decade ago. However, their use is associated with an increased risk of granulomatous infections, including tuberculosis and NTM disease. The biological basis of this infection risk is the critical role played by TNF in the host response to mycobacterial infection, via its role in

The magnitude of the risk of tuberculosis associated with TNF-antagonist therapy appears to be between 1.5 and 30 times above the risk associated with rheumatoid arthritis alone. The risk of tuberculosis differs amongst the various TNF-α inhibitors; the monoclonal antibodies portend more risk and are associated with a shorter tuberculosis onset time than the soluble TNF receptor. These differences may be related to different pharmacokinetic properties of the drugs, differential binding of soluble and transmembrance receptors, and

All patients should be clinically evaluated for latent tuberculosis infection prior to the initiation of TNF-α inhibitor therapy. This evaluation should include a history, chest radiograph, and either a tuberculin skin test or an IGRA. IGRAs appear to be more specific for latent tuberculosis infection than tuberculin skin tests; they may also be more sensitive but this has not been definitively established. Most national guidelines recommend the tuberculin skin test as the diagnostic tool of choice for latent tuberculosis infection in this setting. The treatment of latent tuberculosis infection prior to the initiation of TNF-α inhibitors has proven benefit. Isoniazid therapy for a duration of 9 months is the most commonly recommended regimen, although some national guidelines recommend other regimens. The duration of

The presentation of active tuberculosis in patients on TNF-α inhibitors is different from classically described tuberculosis; it is more likely to be extra-pulmonary and more likely to be disseminated at presentation. Discontinuation of anti-TNF-α therapy may be associated with a paradoxical worsening of tuberculosis disease, but discontinuation of therapy is still

NTM disease is an under recognized but important complication of TNF-antagonist therapy. Some research has suggested that NTM disease may be more common than tuberculosis in the setting of TNF-α inhibitor therapy, however the magnitude of the risk of NTM disease in this setting is unknown. NTM disease is associated with a high level of morbidity and mortality when it develops on TNF-α inhibitor therapy and may have atypical presentations. The best approach to screening and prevention of NTM disease prior to

Future research should include prospective studies establishing the magnitude of the risk of NTM disease with TNF-α inhibitor therapy; such studies may guide development of

therapy required before starting anti-TNF-α therapy is not well established.

macrophage activation, cell recruitment, and granuloma formation and maintenance.

mycobacteria (van Ingen et al. 2008).

differential effects on immune cell function and death.

recommended in most guidelines.

initiation of TNF-α inhibitor therapy is unknown.

**5. Conclusion** 


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**5** 

*Japan* 

**Expression of Tumor Necrosis Factor-Alpha** 

**Metalloproteinase-3 in SAPHO Syndrome** 

**Synovium - A Rare Case Accompanied by** 

**Report and Review of Anti-TNF- Therapy** 

*1Department of Orthopaedic Surgery, Fujita Health University Second Hospital* 

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disorder characterized by osteoarticular and dermatological manifestations. The denotation was first proposed by Chamot et al. in 1987 after investigation of 85 cases (Chamot et al., 1987). The most common site of SAPHO syndrome is the upper anterior chest wall, characterized by predominantly osteosclerotic lesions and hyperostosis. The axial skeleton and peripheral bones can be involved. Peripheral synovitis is also common. Skin manifestations include

The pathogenesis of SAPHO syndrome has not been determined. Most of the reported series to date are anecdotal, small or uncontrolled, thus a variety of therapeutic approaches exist. Treatment remains empirical with several drugs including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibiotics, disease modifying anti-rheumatic drugs (DMARDs) and/or bisphosphonates (BPs), but results are inconsistent and usually variable. Recently, some successful experiences with anti-tumor necrosis factor-alpha (TNF-α) agents for refractory cases have been reported (Asmussen, 2003; Ben Abdelghani et al., 2010; Castellvi et al., 2010; Deutschmann et al., 2005; Iqbal & Kolodney, 2005; Kyriazis et al., 2004; Massara et al., 2006; Moll et al., 2008; Olivieri et al., 2002; Sabugo et al., 2008; Wagner et al., 2002; Widmer et al., 2003). The therapeutic strategy was largely originated from that for spondyloarthropathies, because accumulated arguments indicate that SAPHO syndrome can be classified with the inflammatory spondyloarthropathies (Takigawa et al., 2008) and treatment with anti-TNF-α agents is now well established in spondyloarthropathies or rheumatoid arthritis (RA). Chronic proliferative synovitis is one of the most important

palmoplantar pustulosis (PPP), severe acne and various patterns of psoriasis.

**1. Introduction** 

*2Department of Pathology, Fujita Health University Second Hospital 3Department of Orthopaedic Surgery, Fujita Health University* 

Koichiro Komiya1, Nobuki Terada1,

Yoshikazu Mizoguchi2 and Harumoto Yamada3

**(TNF- TNF- Converting Enzyme and Matrix** 

**Acrodermatitis Continua of Hallopeau: A Case** 

