Recurrent Optic Perineuritis With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Complicated With Granulomatous Polyangiitis.

Optic perineuritis (OPN) is an intraorbital inflammatory disease that targets the optic nerve sheath, which can cause severe vision loss. OPN has been recently reported to be sometimes caused by myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). MOGAD is rarely reported to be complicated with other autoimmune diseases. We report the first rare case of MOG-associated OPN complicated with granulomatous with polyangiitis (GPA). The vision loss, in this case, was initially considered to be caused by cavernous sinusitis in GPA. However, she was diagnosed with MOGAD with serial MRI findings and positive MOG antibody and had been successfully treated with glucocorticoid and tocilizumab for one and half years. This case emphasized the importance of evaluating the MOG antibody in a patient with recurrent OPN, complicated with vasculitis.

Accuracy of Anti-GBM Antibodies in Diagnosing Anti-Glomerular Basement Membrane Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The sensitivity and specificity of anti-glomerular basement membrane (GBM) antibodies have not been systematically analyzed. In this systematic review, we aimed to evaluate the diagnostic accuracy of anti-GBM antibodies for anti-GBM disease. SUMMARY: Potential studies were searched using MEDLINE, Embase, the Cochrane Library, and the International Clinical Trials Registry Platform based on the index test and target condition. The inclusion criteria were prospective or retrospective cohort studies or case-control studies assessing the sensitivity and specificity of anti-GBM antibodies, and the reference standard was clinical diagnosis including biopsy results. The exclusion criteria were review articles, case reports, animal studies, and in vitro studies. Quality assessment was conducted based on the Quality Assessment of Diagnostic Accuracy Studies-2. The pooled estimates of sensitivity and specificity were calculated using a bivariate random-effects model. The overall quality was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation. Six studies (1,691 patients) and 11 index tests were included in our systematic review. A high risk of bias and concerns regarding the applicability of patient selection were noted because of the case-control design in 67% of the included studies. The pooled sensitivity and specificity were 93% (95% CI: 84-97%) and 97% (95% CI: 94-99%), respectively. The certainty of evidence was low because of the high risk of bias and indirectness. Key Messages: Anti-GBM antibodies may exhibit high sensitivity and specificity in the diagnosis of anti-GBM disease. Further cohort studies are needed to confirm their precise diagnostic accuracy and compare diagnostic accuracies among different immunoassays.

Infection with capsular genotype K1-ST23 hypervirulent Klebsiella pneumoniae isolates in Japan after a stay in East Asia: Two cases and a literature review.

Disseminated community-acquired infections caused by the hypervirulent Klebsiella pneumoniae (hvKp) among relatively healthy individuals in East Asia have been reported in recent years. Isolate of the capsular genotype K1, belonging to sequence type (ST) 23, is the most common causative agent of this disease. We experienced two cases of K1-ST23 infection with a travel history in East Asia, and hvKp infection was diagnosed after entering or returning to Japan. Case 1 was a 45-year-old Myanmar seaman with a history of ischemic heart disease who developed a fever on board and was transported to Japan via Shanghai and Taiwan. He had multiple disseminated lesions due to K. pneumoniae; other symptoms included liver abscess, intraocular inflammation, intraventricular thrombosis, brain abscess, and bloodstream infection. Along with antimicrobial treatment, drainage of liver abscesses and surgery for intraocular inflammation and intraventricular thrombosis were required. The patient was discharged 93 days after admission, with little improvement in the visual acuity. Case 2: A 29-year-old Japanese man with no underlying disease developed a prostate abscess and bloodstream infection caused by K. pneumoniae after a trip to Korea. However, he improved only with antimicrobial treatment. K. pneumoniae in both cases were identified to have the rmpA gene, with capsular genotypes K1 and ST23. Further, both cases were considered to have been infected with hvKp during their stay in East Asia. In conclusion, it is important to suspect disseminated disease and perform a systemic search, taking into account that hvKp may be present in cases of Klebsiella infection acquired from East Asia.

Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: To provide evidence for the revision of clinical practice guideline (CPG) for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society were searched for articles published between January 1994 and January 2015 to conduct systematic review (SR), and the quality of evidence was assessed with GRADE approach. RESULTS: Nine randomized controlled trials (RCTs) and two non-RCTs were adopted for remission induction therapy, three RCTs and two non-RCTs for plasma exchange, and five RCTs and one non-RCT for remission maintenance therapy. A significant difference was found in efficacy and safety for the following comparisons. In the non-RCT adopted for remission induction therapy, glucocorticoid (GC) + cyclophosphamide (CY) was significantly superior to GC monotherapy regarding remission. GC + intravenous CY for remission induction therapy was superior to GC + oral CY regarding death at one year, serious adverse events, and serious infection. Concomitant use of plasma exchange for remission induction therapy of AAV with severe renal dysfunction reduced risk of end-stage renal disease versus non-users at month 3. CONCLUSION: This SR provided necessary evidence for developing CPG for the management of ANCA-associated vasculitis.

Dermatomyositis with Rapidly Progressive Interstitial Lung Disease Treated with Rituximab: A Report of 3 Cases in Japan.

We performed a retrospective chart review of three patients with hypomyopathic dermatomyositis and rapidly progressive interstitial lung disease. The patients were Japanese women of 71, 69, and 65 years of age. Two patients were anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive and 1 was anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive. Their respiratory statuses deteriorated despite the administration of glucocorticoid, calcineurin inhibitors, and intravenous cyclophosphamide therapy. We subsequently administered rituximab. The anti-ARS antibody-positive patient survived, while 2 anti-MDA5 antibody-positive patients died.

Skin ulcer is a predictive and prognostic factor of acute or subacute interstitial lung disease in dermatomyositis.

The aim of this study was to determine whether skin ulcer can be used as a predictive and prognostic factor of acute/subacute interstitial lung disease (ILD) in Japanese patients with dermatomyositis (DM). We reviewed the medical records of 39 consecutive DM patients who were admitted to Tokyo Metropolitan Komagome Hospital from January 2000 to December 2009. The mean follow-up period was 63.9 ± 51.6 months. Fifteen patients had acute/subacute ILD and 11 patients had chronic ILD. Seven out of 15 acute/subacute ILD led to respiratory failure and 3 of them died due to ILD. Skin ulcers were observed in 5 out of 15 patients with acute/subacute ILD (33.3 %) and in 2 out of 24 patients without acute/subacute ILD (8.3 %). The presence of skin ulcers was revealed to be a significant predictive factor for acute/subacute ILD among various parameters by multivariate analysis. In the 15 patients with acute/subacute ILD, the presence of skin ulcers was a significant poor prognostic factor (p = 0.0231) and the cumulative survival rate of patients with skin ulcers was 53.3 % for 12 months. Skin ulcer is a significant predictive and prognostic factor of acute/subacute ILD in patients with DM.

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules.

OBJECTIVE: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). METHOD: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. RESULTS: The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. CONCLUSIONS: Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.

Time-dependent increased risk for serious infection from continuous use of tumor necrosis factor antagonists over three years in patients with rheumatoid arthritis.

OBJECTIVE: To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database. METHODS: We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.1 PY) at the time of enrollment in the REAL. We assessed the occurrence of SIs within a 3-year observation period, including the period after switching to other TNF antagonists, and all SIs, unlimited to the first one in each patient as reported in other studies, to evaluate the real safety of TNF antagonists in daily practice. RESULTS: The incidence rate of SIs per 100 PY was 5.54 (95% confidence interval [95% CI] 4.44-6.84) in the anti-TNF group and 2.72 (95% CI 1.87-3.83) in the unexposed group. Poisson regression analysis revealed that the relative risk (RR) of continuous use of TNF antagonists for SIs after adjusting for baseline and time-dependent covariates was significantly elevated both overall (1.97, 95% CI 1.25-3.19) and for the first year (2.40, 95% CI 1.20-5.03), but not for the second and third years combined (1.38, 95% CI 0.80-2.43). The adjusted RR for SIs of etanercept compared to infliximab was not significantly elevated. CONCLUSION: Continuous anti-TNF therapy was significantly associated with increased risks for developing SIs during, but not after, the first year.

Inflammatory pseudotumors in multiple organs associated with elevated serum IgG4 level: recovery by only a small replacement dose of steroid.

A 62-year-old man developed a fever, fatigue, anorexia and arthralgia. Central hypocorticoidism and central hypothyroidism were observed, and a low serum antidiuretic hormon level without symptoms of diabetes insipidus, as well. Images showed swelling of pituitary stalk, mediastinal and hilar lymphnodes and pancreas, pulmonary infiltrates and retroperitoneal mass. Serum CRP level was 20.6 mg/dL, and IgG4 level was 292 mg/dL. Lung biopsy revealed pseudotumor containing IgG4-positive plasmacytes, and obliterative vasculitis both in arterioles and venules. These features were similar to those of reported IgG4-related autoimmune disease. However, replacement steroid therapy for hypocorticoidism brought about almost complete recovery except that diabetes insipidus got apparent. This is the first report on the efficacy of only a small dose of steroid, and on features of pituitary stalk involvement and central hypocorcicoidism.