Objective Body fat is an important source of hormones and cytokines (adipokines) that not only regulate the energy balance, but also regulate the inflammatory and immune responses. This study investigated the association of clinical conditions with serum levels of adipokines in patients with rheumatoid arthritis. Methods Serum levels of resistin, leptin, and adiponectin were measured by enzyme-linked immunosorbent assay in 141 patients (110 women) who fulfilled the 1987 revised criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis and in 146 normal controls (124 women). Then the correlations between adipokine levels and clinical parameters were evaluated. Results The serum resistin level did not differ between the patients and controls. However, serum leptin levels were significantly higher in male and female rheumatoid arthritis patients than in the corresponding controls, while the serum adiponectin level was significantly higher in female patients than in female controls. Multivariate analysis revealed that predictors of an elevated resistin level were female sex and Creactive protein (CRP), while the leptin level was related to the body mass index and CRP. Predictors of an elevated adiponectin level were the use of prednisolone and CRP, however, CRP was negatively associated with adiponectin in patients with rheumatoid arthritis. Conclusion The serum levels of resistin and leptin were positively associated with CRP level in patients with rheumatoid arthritis, suggesting that these adipokines may act as pro-inflammatory cytokines in this disease. The serum adiponectin level was elevated in the patients, however, it was negatively associated with CRP level. In addition, the serum levels of resistin, leptin, and adiponectin were also associated with female sex, BMI and the use of prednisolone, respectively.

We assessed the safety of tacrolimus therapy for rheumatoid arthritis. Forty-two patients who started tacrolimus therapy between April 2005 and July 2006 were investigated retrospectively using data from their medical records up to June 2007. The cumulative treatment continuation rate was assessed by the Kaplan-Meier method. Fisher's exact test was used to compare gastrointestinal symptoms between different tacrolimus doses and between the presence and absence of each concomitant medication. The mean (+/-SD) observation period was 288 +/- 238 days. The cumulative treatment continuation rate was, respectively, 59.5% and 38.1% at 6 months and 1 year after the patients started treatment. Tacrolimus was discontinued in 28 patients, and was discontinued because of adverse reactions in 21 patients. Gastrointestinal symptoms were the most common adverse reactions (45.2% = 19/42 patients), followed by infections and hyperglycemia. Tacrolimus was discontinued in 9/19 patients with gastrointestinal symptoms, and was discontinued within 60 days of starting treatment in seven of them. Nausea and vomiting led to discontinuation in seven patients (within 60 days of starting treatment in six of them). The incidence of gastrointestinal symptoms was higher in patients receiving a daily dose >or=2 mg than in those receiving <2 mg/day. During treatment of rheumatoid arthritis by oral tacrolimus therapy, gastrointestinal symptoms were common, early, and dose-dependent. However, these symptoms were not severe and did not cause any serious safety problems.

We conducted a pilot study to investigate whether tacrolimus was effective for treating patients with systemic lupus erythematosus (SLE) without renal involvement. Ten SLE patients with symptoms such as arthritis and erythema, but no active nephritis, were treated with tacrolimus. They included 8 women and 2 men aged from 24 to 62 years [mean +/- standard deviation (SD): 42.1 +/- 11.3 years]. Tacrolimus was administered at doses of 1-3 mg daily, and efficacy was assessed from the SLE Disease Activity Index (SLEDAI) after 1 year. Two patients ceased treatment due to adverse reactions (after 4 days for chest pain and 7 months for recurrent infections). The other 8 patients completed 1 year of treatment, and significant improvement of disease activity was observed in 6 of them. The mean (+/-SD) SLEDAI showed a significant decrease after 1 year of tacrolimus therapy, from 6.8 +/- 3.1 to 3.4 +/- 0.9; p < 0.05 by Student's paired t test. The mean (+/-SD) dose of prednisolone also decreased significantly, from 16.8 +/- 8.6 to 9.3 +/- 4.6 mg/day; p < 0.05. Although a prospective controlled study will be necessary to confirm, tacrolimus might be a treatment option for active SLE without renal involvement.

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcgamma receptor (FcgammaR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcgammaRIIA) and 176F/F (FcgammaRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcgammaRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcgammaR polymorphisms.

Pneumothorax is a rare pleuropulmonary manifestation of systemic lupus erythematosus. We encountered a 37-year-old Japanese woman who had systemic lupus erythematosus complicated by recurrent pneumothorax during treatment for recurrent serositis with glucocorticoid therapy. She was admitted for the third episode of lupus peritonitis in December 2005. Intravenous cyclophoshamide and increased dose of oral prednisolone were administered. In early January 2006, hemoptysis was observed and bronchofiberscopy revealed hemorrhage from the left lower lobe. After intravenous methylprednisolone pulse therapy and oral cyclosporine therapy were added, pleurisy and pulmonary hemorrhage improved. On February 22nd, she suddenly developed pneumothorax on the right side, followed by pneumothorax on the left side after 2 days. This pneumothorax on the left side did not improve despite chest tube drainage for over one month. She underwent thoracoscopic partial lobectomy of lower lobe of the left lung, and her symptoms improved. Review of the literature identified 10 case reports of systemic lupus erythematosus complicated by pneumothorax. All of the patients including our case had underlying pulmonary lesions, and 9/11 patients had pleurisy. Besides 10/11 patients received glucocorticoid therapy before the occurrence of pneumothorax. Tissue fragility caused by these factors might contribute to the complication of pneumothorax in patients with systemic lupus erythematosus.