Akitomo Okada

The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM

OBJECTIVE Interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD), is a major poor prognostic factor in patients with DM. We investigated the association of anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with clinical characteristics and mortality in Japanese patients with DM. METHODS Seventy-nine DM patients, comprising 58 classic DM and 21 clinically amyopathic DM (CADM) patients, were enrolled. Serum Abs were screened by immunoprecipitation assays, and an immunosorbent assay (ELISA) was used for MDA5. The relationships of clinical characteristics and mortality with each Ab were investigated. RESULTS Anti-MDA5 Ab was detected in 17 patients. Anti-clinically amyopathic DM 140  kDa polypeptide Abs (anti-CADM-140 Abs) were found in 16 of the 17 anti-MDA5 Ab(+) patients. Skin ulcers, palmar papules, CADM, RPILD and mediastinal emphysema were widely distributed in anti-MDA5 Ab(+) patients. Mortality at 6 months as well as 5 years was also significantly higher in anti-MDA5 Ab(+) patients than in anti-MDA5 Ab(-) patients. In a multivariable Cox regression analysis, mortality was independently associated with anti-MDA5 Ab (relative hazard 6.33; 95% CI 1.43, 28.0). All of the deaths in anti-MDA5 Ab(+) patients were attributed to respiratory failure of RPILD; however, RPILD did not worsen in any of the anti-MDA5 Ab(+) patients who survived the first 6 months. CONCLUSION The presence of anti-MDA5 Ab identifies the characteristic skin, musculoskeletal, pulmonary and prognostic features in patients with DM. In addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated fatal RPILD.

The power Doppler ultrasonography score from 24 synovial sites or 6 simplified synovial sites, including the metacarpophalangeal joints, reflects the clinical disease activity and level of serum biomarkers in patients with rheumatoid arthritis

OBJECTIVE We evaluated the significance of the power Doppler ultrasonography (PDUS) score by comparing it with serum biomarkers and clinical disease activity. METHODS We measured the PDUS scores of 24 synovial sites in 12 joints in 22 RA patients. For convenience, the PDUS scores of six synovial sites in six joints were also examined. Each joint was scored for a power Doppler (PD) signal on a scale from 0 to 3. The PDUS scores are the sums of the PD signal scores for the 24 synovial sites or the 6 synovial sites. On the same day, serum variables as well as clinical disease activity were evaluated. RESULTS The PDUS scores from the 24 joint sites were significantly positively correlated with DAS of 28 joints (DAS-28), simplified disease activity index (SDAI), clinical disease activity index (CDAI) and serum biomarkers including MMP-3, VEGF and tissue inhibitor of metalloproteinases-1 (TIMP-1). Accordingly, the PDUS scores from the six synovial sites greatly correlated with those from the 24 joint sites. Clinical disease activities as well as serum variables were also clearly correlated with the PDUS scores from the six synovial sites. CONCLUSION The standard as well as the simplified PDUS scores well reflected clinical disease activity and serum variables, including angiogenic factors. Our data reaffirm the utility of ultrasonography for monitoring disease activity in patients with RA.

CD4+CD25(high)CD127(low/-) Treg cell frequency from peripheral blood correlates with disease activity in patients with rheumatoid arthritis.

Objective. To investigate whether the frequency of peripheral blood (PB) regulatory T cells (Treg) correlates with the clinical disease activity of rheumatoid arthritis (RA). Methods. PB Treg cells, defined as the CD4+CD25highCD127low/- population, were examined by flow cytometry in 48 patients with RA, including 13 who had never received disease-modifying antirheumatic drugs (DMARD), 19 with active disease who were receiving (n = 14) or had received (n = 5) DMARD, and 16 receiving DMARD whose disease was in remission. The clinical disease activity of the patients was defined by the 28-joint Disease Activity Score (DAS28). The association of DAS28, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) with the frequency of PB Treg cells was examined. Results. The frequency of PB Treg cells in patients with RA was significantly low compared with that of healthy controls (n = 14). Among the 3 populations of patients with RA, Treg cell frequency was lowest in patients with active RA. In contrast, the Treg cell frequency of patients with RA in remission was similar to that of healthy controls. Accordingly, the frequency of CD4+CD25highCD127low/- Treg cells negatively correlated with DAS28, CRP, and ESR in patients with RA. Conclusion. The data suggest that Treg cells, defined as the CD4+CD25highCD127low/- population, may contribute to the pathogenesis of RA and be an indicator of disease activity.

Anti-centromere antibody-seropositive Sjögren's syndrome differs from conventional subgroup in clinical and pathological study

BackgroundTo clarify the clinicopathological characteristics of primary Sjögrens syndrome (pSS) with anti-centromere antibody (ACA).MethodsCharacteristics of 14 patients of pSS with ACA were evaluated. All patients were anti-SS-A/Ro and SS-B/La antibodies negative (ACA+ group) without sclerodactyly. The prevalence of Raynauds phenomenon (RP), titer of IgG and focus score (FS) in the minor salivary glands (MSGs) were determined. Quantification analysis of Azan Mallory staining was performed to detect collagenous fiber. Forty eight patients in whom ACA was absent were chosen as the conventional (ACA-) pSS group.ResultsPrevalence of ACA+ SS patients was 14 out of 129 (10.85%) pSS patients. RP was observed in 61.5% of the patients with ACA. The level of IgG in the ACA+ group was significantly lower than that of the ACA- group (p = 0.018). Statistical difference was also found in the FS of MSGs from the ACA+ group (1.4 ± 1.0) as compared with the ACA- group (2.3 ± 1.6) (p = 0.035). In contrast, the amount of fibrous tissue was much higher in the ACA+ group (65052.2 ± 14520.6 μm2 versus 26251.3 ± 14249.8 μm2 ) (p = 1.3 × 10-12).ConclusionsLow cellular infiltration but with an increase in fibrous tissues may explain the clinical feature of a high prevalence of RP and normal IgG concentration in ACA+ pSS.

Comparative study of the detection of joint injury in early‐stage rheumatoid arthritis by magnetic resonance imaging of the wrist and finger joints and physical examination

To verify whether magnetic resonance imaging (MRI)–proven joint injury is sensitive as compared with joint injury determined by physical examination.

Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan

Background Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial. Objectives To investigate the incidence and risk factors for HBV reactivation in patients with RD. Methods We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded. Results Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3–182 months; median, 66 months). Conclusions The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

Early diagnosis and treatment for remission of clinically amyopathic dermatomyositis complicated by rapid progress interstitial lung disease: a report of two cases

We report two cases of clinically amyopathic dermatomyositis (CADM) complicated by rapid progress interstitial lung disease (RPILD). The diagnosis of CADM was based on Gottron’s papule and RPILD, and the absence of muscle weakness. The female patients were treated with early immunosuppressive therapies including steroid pulse therapy, resulting in significant improvement in respiratory symptoms, clinical data, and imaging. Measurement of anti-CADM-140/MDA5 antibody was useful for obtaining a definitive diagnosis of CADM in these cases.

Combination of MRI-detected bone marrow oedema with 2010 rheumatoid arthritis classification criteria improves the diagnostic probability of early rheumatoid arthritis

Efficient methods for distinguishing rheumatoid arthritis (RA) at an earlier phase from other diseases are strongly desired since early therapeutic intervention improves clinical and radiographic outcomes of RA.1–4 The clinical 2010 RA classification criteria was established based upon the consensus that RA is an inflammatory disease that develops persistent and/or erosive arthritis.2 ,3 Our series of studies as well as the article describing European League Against Rheumatism recommendations for the use of imaging for the clinical management of RA mention that MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria.5 ,6 The present study was undertaken to investigate whether MRI findings of wrist and finger joints improve the diagnostic performance of 2010 RA classification criteria. One hundred sixty-six patients with early arthritis, who do not fulfil the 1987 RA criteria or other international criteria for rheumatic disease at entry …

Takayasu arteritis developing during treatment of ulcerative colitis with infliximab

A 22-year-old female with ulcerative colitis that was successfully treated with infliximab (IFX), and remained stable following tapered discontinuation of prednisolone, developed anterior neck pain and elevation of C-reactive protein following her fourth administration of IFX. She was diagnosed with Takayasu arteritis (TA) based on neck ultrasound and computed tomography angiography. This is the first report describing the development of TA during treatment of UC with IFX.

Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis

A 47-year-old woman who had been treated for systemic lupus erythematosus (SLE) with myasthenia gravis (MG) was admitted to our hospital with acute onset of severe anemia after administration of isoniazid. Pure red cell aplasia (PRCA) was confirmed by elevated serum iron levels, reticulocytopenia and bone marrow aspiration showing a remarkable reduction of erythroblasts. Finally, cyclosporine A successfully improved PRCA. Although both SLE and MG have the potential complication of PRCA, we report here a case of isoniazid-triggered PRCA.