Objective. Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD).Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development. Methods. We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age-and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset. Results. There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients. Conclusion. MTX is an independent risk factor for LPD onset in Japanese RA patients.

BackgroundRheumatoid arthritis is a systemic inflammatory disease characterized by synovitis and the destruction of articular structures in multiple joints. Methotrexate is recommended as an anchor drug for rheumatoid arthritis treatment to achieve the therapeutic goal of reducing damage to joints and improving clinical score. However, several studies have shown that methotrexate has been associated with the development of lymphoproliferative disorders, namely methotrexate-associated lymphoproliferative disorders. On the other hand, primary central nervous system lymphoma is an aggressive disease with poor prognosis. Both methotrexate-associated lymphoproliferative disorders and primary central nervous system lymphoma are reported to be associated with Epstein-Barr virus.Case presentationA Japanese female patient of between 60 and 70 years of age with rheumatoid arthritis was admitted to our hospital because of sudden convulsion and impaired consciousness. Just before admission, she was treated with adalimumab and methotrexate. Contrast-enhanced computed tomography scan showed a densely stained mass with surrounding edema in both frontal lobes and the left nucleus basalis, and enlarged lymph nodes in the right supraclavicular fossa. We performed a biopsy of the right cervical lymph node, but could not establish a histopathological diagnosis. In situ hybridization showed the presence of Epstein Barr virus, therefore we diagnosed this case as methotrexate-associated lymphoproliferative disorders mediated by Epstein Barr virus after considering the drug history of the patient. After we discontinued methotrexate, patient symptoms gradually improved. The masses at both frontal lobes and the left nucleus basalis were gradually regressed.ConclusionSince the frequency of methotrexate use and the maximum dosage has been increasing, particular attention should be paid to the development of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients who are treated with methotrexate.

BackgroundMESACUPTM test (enzyme-immunoassay assays; TIF1γ, MDA5, Jo-1, EJ, PL-7, PL-12, and KS; MBL) (MESA) is used for a diagnosis of idiopathic inflammatory myopathies (IIMs) in Japan. On the other hand, EUROLINE myositis Profile 3 (line blot; EUROIMMUN) (EURO) can analyze plural Myositis-specific autoantibodies (MSA: Mi-2, Jo-1, SRP, PL-7, PL-12, EJ, OJ) and Myositis-associated autoantibodies (MAA; Ku, PM-Scl) at the same time, which is used commercially in Western countries. However, the difference between utility of MESA and that of EURO haven't be disclosed.ObjectivesTo clarify difference between utility of EURO and MESA, and extract the problem of respective examination.MethodsWe enrolled 58 patients diagnosed DM/PM in our facility. Polymyositis (PM) and dermatomyositis (DM) were diagnosed according to Bohan and Peter's criteria.1) The MAA and MSA were analyzed using MESA and EURO. In case of MESA (+), MSA (anti-Jo1, anti-PL7, anti-PL12, anti-KS) were identified by specific ELISA. When those results were different, we analyzed by immunoprecipitation. And we analyzed the association between each autoantibody and clinical features.ResultsMSA and MAA were detected in 43/58 (74%) (anti-PL7: 12, anti-Jo1: 7, anti-EJ: 3, anti-PL12: 1, anti-OJ: 0, anti-Ro52: 27, anti-PM-Scl75: 7, anti-Ku: 6, anti-PM-Scl100: 1) by EURO. On the other hand, MSA and MAA were detected in 30/58 (52%) (anti-PL7: 9, anti-Jo1: 7, anti-EJ: 4, TIF1γ: 4, MDA5: 3, U1RNP: 3) by MESA. Five patients were MESA (-) and EURO (-). In the case of ARS positive patient, Two of EURO (-) patients was positive in MESA, respectively Jo1 and EJ. Three of MESA (-) patients was positive in EURO. Although MESA(-) and EURO(+) patients had plural MSA and MAA (PL7+Jo1, PL7+PL12, PL7+Ku), MSA and MAA weren't detected by immunoprecipitation in MESA(-) and EURO(+) patients. Two of patients that detected plural MSA or MAA had rapid progressive ILD.(Association between clinical manifestations and MSA, MAA)All patients with anti-ARS (anti-Jo-1, anti-PL-7, anti-PL-12 and anti-EJ) had ILD. In addition, anti-ARS were associated with arthritis and mechanic's hands. Anti-Mi-2 positive patients didn't have ILD. Patients detected anti-PM-Scl75, anti-PM-Scl100, anti-Ku were almost overlap syndrome. All of Anti-SRP positive patients was PM.ConclusionsEURO is a convenient and reliable method useful for detection of MSA and MAA. It was suggested the patients whom plural antibodies were detected by EURO have unique clinical course in others.References Bohan, A., Peter, J.B., 1975. Polymyositis and dermatomyositis (second of two parts). N. Engl. J. Med. 292, 403–407. Disclosure of InterestNone declared

BackgroundIgG4-RD shows relapses frequently. It is important to search to the factors to predict relapse. Recent research has shown the usefulness of FDG-PET/CT for IgG4-RD because it is more sensitive than conventional imaging to detect organ involvement of the disease. It has been suggested that FDG-PET/CT is also useful for monitoring therapeutic response of IgG4-RD.ObjectivesWe investigate the usefulness of FDG-PET/CT imaging and serological biomarkers to predict relapse in IgG4-RD.MethodsWe analyzed 24 patients with IgG4-RD treated for more than 1 year between 2008 and 2016 in our facility. The diagnosis for IgG4-RD was based on comprehensive diagnostic criteria for IgG4-RD. All cases underwent FDG-PET/CT at least once, and laboratory data were collected from their medical records retrospectively. Levels of serum C-reactive protein (CRP), eosinophil/leukocyte ratio, serum IgG, IgG4, IgA, IgM, IgE, sIL2-R and serum compliment were investigated.ResultsThe patients had a mean age of 67.9 years (range: 50–87 years). In the cases with high FDG uptake on FDG-PET/CT, they had a greater number of organ involvements, higher serum IgG and sIL-2R levels. Eight patients experienced relapses following treatment. Higher serum IgG predicted relapses of IgG4-RD. FDG-PET/CT findings at baseline were not associated with relapse. FDG-PET/CT was performed in 13 patients after initiation of treatment and 4 patients had a relapse. There were no significant reduction of abnormal FDG uptake in 6 patients, and 4 of 6 patients relapsed.ConclusionsIn this study, we examined the factors to predict relapse in IgG4-RD. Patients with higher serum IgG were regarded as a risk of relapse, but FDG-PET/CT findings at baseline were not associated with relapse. FDG-PET/CT reexamined after initiation of treatment is useful to predict relapse of IgG4-RD.References Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21–30.Nakatani K. Utility of FDG PET/CT in IgG4-related systemic disease Clin Radiol. 2012 Apr;67(4):297–305.Zhang J, Chen H, Ma Y, et al. Characterizing IgG4-related disease with 18F-FDG PET/CT: a prospective cohort study. Eur J. Nucl Med Mol Imaging. 2014;41:1624–1634. Disclosure of InterestNone declared

Background IgG4-related disease (IgG4-RD) is a systemic disease characterized by elevated levels of serum IgG4 (sG4) and mass-forming lesions infiltrated with IgG4-positive (IgG4+) plasma cell. To date in our facilities, IgG4-RD patients has been diagnosed as autoimmune pancreatitis (AIP), Mikulicz disease (MD) or IgG4-related kidney disease (IgG4-related KD) using the conventional organ-specific criteria respectively. However, in 2012, Umehara et al. proposed comprehensive diagnostic criteria for IgG4-RD (CDC IgG4-RD)1). Using this new comprehensive diagnostic criteria could diagnosed as IgG4-RD in some patient population that did not meet the conventional organ-specific criteria. On the other hand, there still exists important problem for the diagnosis of IgG4-RD about the requirement of histopathological evaluation. Histopathological proof is considered to need for the definitive diagnosis of IgG4-RD. Indeed clinically, there are some IgG4-RD patients diagnosed without histological findings. Additionally, pathological findings obtained from IgG4-RD patients diagnosed clinically could not reveal the typical findings with infiltration of IgG4+ plasma cell. Therefore, histopathological findings are quite important to meke a diagnosis of definitive IgG4-RD. Although the usefulness of fluorodeoxyglucose-psitron emission tomography (FDG-PET) is described in CDC IgG4-RD, it is unclear how to use FDG-PET for diagnosis of IgG4-RD. We focused on the usefulness of FDG-PET for diagnosis of definitive IgG4-RD at the point of making a biopsy-site decision. Objectives (1)To examine the diagnostic effectiveness of CDC IgG4-RD compared with conventional organ-specific criteria. (2)To determine the usefulness of FDG-PET for diagnosis of definitive IgG4-RD. Methods We examined suspected IgG4-RD patients that visited our facilities between August 2009 and November 2011 retrospectively. We obtained several information including physical findings, biochemical findings, sG4 level, and histopathological findings in each patients. These patients are analyzed using CDC IgG4-RD retrospectively. FDG-PET studies were performed in 10 IgG4-RD patients. For image evaluation, we used SUVmax that is the maximum value among the abnormal accumulation. In definitive IgG4-RD patients, we also investigated the relationship between FDG accumulation and histopathological findings in biopsy site. Results IgG4 levels were measured in 158 patients suspected for IgG4-RD, and 36 patients had high sG4 titers. Twelve cases were fulfilled to the conventional organ-specific criteria respectively (AIP, 2 cases; MD, 7 cases; IgG4-related KD, 3 cases; diagnostic rate, 7.6%). In contrast, 31 cases satisfied CDC IgG4-RD (definite, 12 cases; possible, 19 cases). FDG-PET was performed in 10 cases of IgG4-RD. In pathological examination in definitive IgG4-RD patients, IgG4+ plasma cell infiltration was demonstrated at the site of FDG accumulation. Conclusions CDC IgG4-RD might improve the diagnostic sensitivity for IgG4-RD. FDG-PET might be useful for determine th...