Rheumatoid arthritis patients with low baseline Health Assessment Questionnaire scores have a risk of functional disability progression: a post hoc analysis of a nationwide longitudinal cohort in Japan.

OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.

Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

OBJECTIVES: To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice. METHODS: Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP. RESULTS: The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64-299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42). CONCLUSIONS: ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy.

To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.

An autopsy case of refractory vasculo-Behçet's disease.

Pulmonary vascular involvement in Behçet's disease is a rare complication with a poor prognosis. We present an autopsy case of vasculo-Behçet's disease complicated by pulmonary hemorrhage, possibly caused by rupture of pulmonary artery aneurysms. The patient was treated with a combination of high-dose steroids and pulse cyclophosphamide, but he died from massive hemoptysis. This case highlights the need for potent new therapies for patients with vasculo-Behçet's disease refractory to conventional immunosuppressive therapy, such as a combination of steroids and cyclophosphamide.

Successful treatment of rectal ulcers in a patient with systemic lupus erythematosus using corticosteroids and tacrolimus.

Systemic lupus erythematosus (SLE) is frequently accompanied by gastrointestinal symptoms. Although all parts of the gastrointestinal tract may be affected, colonic involvement is quite rare. Colonic ulceration, particularly in the rectum, is associated with a high mortality rate in patients with SLE, despite immunosuppressive therapy. While a standard regimen for treating rectal ulcers as a complication of SLE has not been established, combination therapy with steroids and immunosuppressive agents is necessary because of the associated high mortality rate. In this report, we describe a patient with SLE whose condition was complicated with ulcerative lesions in the rectum and sigmoid colon; the lesions were successfully treated with a combination of corticosteroids and tacrolimus therapy. Tacrolimus could be a useful additional or alternative modality for treating rectal involvement in SLE.

A case of late-onset systemic lupus erythematosus with severe anemia.

A 59-year-old woman was referred to our hospital because of severe anemia and leucopenia. Although she developed mild arthralgia without the typical symptoms of systemic lupus erythematosus (SLE), positivity for anti-Sm antibodies led us to a diagnosis of late-onset SLE. Autoimmune hemolytic anemia (AIHA) and suppression of reticulocyte production were considered to have been involved in the etiology of severe anemia. Administration of oral prednisolone (PSL) resulted in a marked improvement of the hematological abnormalities. As late-onset SLE is rare and patients tend to show the typical symptoms less frequently, close attention should be focused on latent symptoms and immunological findings.

The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.

BACKGROUND/AIMS: Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. METHODOLOGY/PRINCIPAL FINDINGS: In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1ß) gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1ß-511 (C/T) and IL-1 receptor antagonist (IL-1Ra) variable number of tandem repeat (VNTR) polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1ß -511 (C/T), IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%), and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5%) in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p=0.001) in FMF patients compared with healthy subjects. CONCLUSIONS/SIGNIFICANCE: Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5'-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms) of SAA1 gene, are associated with susceptibility to FMF in the Japanese population.

A case of rheumatoid arthritis improved from Steinbrocker classification class IV to class II after multi-joint surgery.

We report the case of a patient with rheumatoid arthritis (RA) who showed a reduction in disease severity (from class IV to class II) after multi-joint surgery. The patient was a 61-year-old man with a history of RA, type-2 diabetes, chronic obstructive pulmonary disease, and nephrotic syndrome. He had been undergoing treatment for RA for the past 10 years, but his condition could not be appropriately controlled. In addition to generalized edema, marked destruction of the left elbow joint and knees was observed, and he was unable to move in bed (Steinbrocker classification: stage IV, class IV). In March 2009, he developed suppurative arthritis of the left elbow (methicillin-sensitive Staphylococcus aureus [MSSA] infection) and was referred to our institution, where the infection subsided after cleaning of the wound and administration of antibiotics. In March 2010, he underwent artificial joint replacement arthroplasty of the left elbow, followed by replacement arthroplasty of the right knee in July that year and of the left knee in November. As of December 2011, the patient showed no signs of inflammatory reactions and was able to walk using crutches (Steinbrocker classification: stage IV, class II). Recent advancements in pharmacotherapy have made it possible to control the advancement of joint destruction in RA. However, in this patient, because of the advanced stage of joint destruction, surgical methods were required to aid the patient in recovering his ability to walk.

Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.

INTRODUCTION: There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor α (IL-18Rα). In this study, we evaluated the levels and characteristics of soluble IL-18Rα (sIL-18Rα) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. METHODS: The sIL-18Rα complex was isolated from pooled human blood serum using an anti-IL-18Rα monoclonal antibody affinity column. The purified sIL-18Rα was then examined using Western blot analysis and used in experiments to evaluate the effects on an IL-18-responsive natural killer (NK) human cell line, NK0. An enzyme-linked immunosorbent assay was developed, and sera from 145 patients with RA, 6 patients with adult-onset Still's disease, 31 patients with osteoarthritis (OA), 39 patients with systemic lupus erythematosus (SLE) and 67 controls were tested, along with levels of immunoglobulin M, rheumatoid factor, anticyclic citrullinated peptide antibody, IL-18, IL-13 and interferon (IFN)-γ. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18Rα complex. RESULTS: The isolated sIL-18Rα complex can be associated with IL-18 and the soluble form of the IL-18Rß chain. The sIL-18Rα complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2 on the NK0 cell line and inhibited IFN-γ production by the cells. The serum levels of sIL-18Rα complex in RA (186.0 ± 33.5 ng/mL, n = 145) and adult-onset Still's disease (98.2 ± 8.9 ng/mL, n = 6) were significantly (P < 0.001) higher than those in the healthy controls (52.3 ± 8.5 ng/mL, n = 67), OA (38.6 ± 5.4 ng/mL, n = 31), SLE (44.6 ± 3.2 ng/mL, n = 39). The serum level of sIL-18Rα complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-γ in the RA patients were significantly (P < 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18Rα indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (P < 0.0001) decreased levels of sIL-18Rα in the sera of 29 RA patients 6 months after treatment. CONCLUSIONS: The sIL-18Rα complex could be a potentially useful biomarker for the diagnosis of RA.

Recurrent thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus.

We encountered a 39-year-old female patient with systemic lupus erythematosus (SLE) in whom thrombotic thrombocytopenic purpura (TTP) recurred. The patient was successfully treated with corticosteroid in combination with immunosuppressive agents. Because TTP complicating SLE is more resistant to treatment than idiopathic TTP, prompt diagnosis and efficacious initial treatment are critical.

Bell-shaped sensory impairments of all modalities in a neurosarcoidosis patient.

We describe a 45-year-old man with neurosarcoidosis complaining of bell-shaped tightening and pain with sensory disturbance of superficial and deep sensations. The patient showed subacute progressive sensory impairment in bilateral C7-Th12 dermatomes. Triceps and patellar tendon reflexes were decreased. Chest X-ray revealed bilateral hilar lymphadenopathy without pleural effusion. There was abnormal accumulation of gallium in the bilateral hilar lymph nodes, parotid glands, and lacrimal glands on scintigraphy. Examination of bronchoalveolar lavage fluid showed an elevated CD4/CD8 ratio. Transbronchial lung biopsy showed non-caseating granulomas with many epitheloid cells and occasional Langhans giant cells without any necrotic lesion. The tuberculin reaction was negative, and elevation of serum lysozyme and IgG level were seen. These findings fulfilled the clinical criteria for sarcoidosis. Spine MRI demonstrated no abnormality. Studies of short-latency somatosensory evoked potentials showed delayed N13 latency and absent N19 and N28 potentials bilaterally. A nerve conduction study revealed no abnormality. The patient's muscle strength was normal through the entire clinical course. Therefore, we consider that his sensory impairment was caused by peripheral neuropathy, especially in the dorsal root region. Neurosarcoidosis is important for differentiating bell-shaped sensory impairments of all modalities.

Increased splenic fluorodeoxyglucose uptake in a patient with granulomatous angitis.

Although utility of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been rehearsed in large vessel vasculitides, it is not known if small vessel vasculitides are also associated with increased FDG uptake. Hereby described is a 64-year-old female patient with prolonged fever and splenomegaly, which was depicted as a hot area in FDG-PET. Splenectomy disclosed microaneurysms, giant cell granuloma, perivascular leukocytic infiltration with fibrinoid necrosis, consistent with granulomatous angitis. Serum myeloperoxidase-antineutrophil cytoplasmic antibody was positive. The present case illustrates that vasculitides affecting small vessels present increased FDG uptake as do those affecting large vessels.

[A case of bacterial pneumonia caused by Streptococcus dysgalactiae subsp. equisimilis, showing patchy consolidations resembling organizing pneumonia].

In December, 2001, a 67-year-old woman was given a diagnosis of having systemic sclerosis and organizing pneumonia. Steroid treatment improved her condition, and she received no further medication for approximately three years thereafter. In October 2005, she visited Kurume University Hospital because of cough and fever. Chest X-ray film and high-resolution computed tomography (HRCT) showed bilateral patchy consolidation with air-bronchogram sign and ground-glass opacities, predominantly in the right lower lung field, suggesting relapse of organizing pneumonia. However, bronchoalveolar lavage fluid (BALF) analysis showed an increase of neutrophils (79%) and the CD4/CD8 ratio (4.04). Streptococcus dysgalactiae subsp. equisimilis (beta-hemolytic, Lancefield group G) was detected by bacterial culture of the BALF. Treatment with sulbactam sodium/ampicillin sodium (SBT/ ABPC) rapidly improved her symptoms. The patchy consolidations on chest X-ray and HRCT also disappeared after the treatment. On the basis of these clinical and bacteriological findings, we diagnosed the patient as having bacterial pneumonia caused by Streptococcus dysgalactiae subsp. equisimilis.

Tacrolimus treatment for refractory lupus cystitis.

A 23-year-old woman presented with recurrence of lupus cystitis, which had been in remission under daily administration of a single corticosteroid over a period of 8 years. She was treated with increased doses of corticosteroid and immunosuppressants, i.e., cyclosporin, cyclophosphamide, azathioprine, and salazosulfapyridine, but the cystitis remained active. Since her condition became critical by the complication of intestinal pseudo-obstruction, tacrolimus was administered. This agent induced a remission promptly without significant adverse events in this patient, suggesting an efficacy to lupus cystitis refractory to corticosteroid and other immunosuppressants.

A case of polymyositis complicated with interstitial pneumonitis and pneumomediastinum.

Pneumomediastinum as a complication of interstitial pneumonia with leakage of air into the mediastinum or subcutaneous tissues is a rare complication of dermatomyositis (DM). Herein we report a case of pneumomediastinum complicating polymyositis (PM), which is usually associated with DM. A 61-year-old man was hospitalized in our department because of deterioration of interstitial pneumonia. Treatment with high-dose corticosteroid and cyclosporin A steadily improved his interstitial pneumonia. Two weeks later, he developed subcutaneous emphysema and chest X-ray showed pneumomediastinum. Both subcutaneous emphysema and pneumomediastinum improved gradually without any additional treatment.

Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells.

OBJECTIVE: To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression. CONCLUSION: Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.