**4. Conclusion**

100 Rheumatoid Arthritis – Treatment

TACE plays a crucial role in post-translational regulation of TNF-α. Binding of soluble TNFα to TNF receptors activate various pathological events including the production of MMPs. TACE is a member of the ADAM (a disintegrin and metalloproteinase) family proteins, which possess characteristics of both cell surface adhesion molecules and proteinases. Some of the ADAM family proteins, including TACE, are considered to be responsible for the proteolytic processing of ectodomain of various cell surface molecules such as cytokines, cytokine receptors, adhesion molecules, and enzymes (Klein & Bischoff, 2011; Okada, 2005; Seals & Courtneidge, 2003). Several studies indicate that TACE levels are elevated in RA joints compared with osteoarthritis or normal articulations, suggesting that abnormal TACE activity contributes to TNF-α action in RA pathogenesis (Ohta et al, 2001). In the present case and in our previously reported case (Komiya et al., 2009), we demonstrated the expression of TNF-α, TACE and MMP-3 in SAPHO syndrome synovitis, thus it is speculated that TACE play roles in the pathogenesis of SAPHO syndrome synovitis through the processing of TNF-α, which triggers a cascade of pathological events through a mechanism

To our knowledge, 26 cases of SAPHO syndrome treated with anti-TNF-α agents (infliximab, etanercept or adalimumab) have been described, all of them showing a sustained response of osteoarticular manifestations (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), but not favorable for cutaneous manifestations in some cases (Ben Abdelghani et al., 2010; Massara et al., 2006). In the 26 previously reported cases in the literature, clinical response was rapid after within 2 infusions of anti-TNF-α agent in most of cases (24/26 cases, 92%). Clinical response was maintained in all cases, and clinical remission, which usually described as no recurrence of osteoarticular pain, was maintained with a follow up 8 to 42 months during treatment. Thus it is considered that the efficacy of anti-TNF-α agents on osteoarticular symptoms is reliable. Whereas, relapse or worsening of the skin lesion after anti-TNF-α therapy was observed in 5/26 cases (19%) (Ben Abdelghani et al., 2010; Massara et al., 2006). ACH, a skin lesion of this case, is a rare chronic pustular eruption of the distal portions of the hands and feet, characterized by sterlile pustules, paronychia and atrophic skin changes, onychodystrophy and osteolysis of the distal phalanges (Puig et al., 2010; Ryan et al., 2009). It is considered by many to be a localized variant of pustular psoriasis. (Kurooka et al., 2010; Yerushalmi et al., 2000). ACH is notoriously difficult to treat, with limited success with numerous agents including topical treatments, photochemotherapy, ciclosporin, methotrexate, retinoids, dapson and tetracyclines (Nikkels et al., 1999). Recently successful treatment of ACH with anti-TNF-α agents have been reported (Ahmad & Rogers, 2007; Bonish et al., 2006; Kazinski et al., 2005; Mang et al., 2004; Ryan et al., 2009). But in some cases of ACH, failed treatment with anti-TNF-α agents have been also reported (Adisen et al., 2007; Thielen et al., 2008; Ryan et al., 2009). In a recent review, 120 patients (with RA, ankylosing spondylitis, psoriasis, Crohn disease, SAPHO syndrome, psoriatic arthritis, and other diagnosis) from the literature who developed pustular lesions during treatment with anti-TNF-α agents were reported (Wollina et al., 2008). Psoriasis (except palmoplantar pustular type) was the most common adverse effect during anti-TNF-α agent treatment (n=73), followed by PPP (n=37). The reasons for these negative or paradoxical effects of anti-TNF-α agents on cutaneous

similar to RA.

We describe a rare case of SAPHO syndrome accompanied by marked knee synovitis and ACH as a skin manifestation. We demonstrated the expression of TNF-α, TACE and MMP-3 in SAPHO syndrome synovium and also shown the similarity between SAPHO syndrome

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