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A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis. We suspected familial Mediterranean fever (FMF) based on his history and administered colchicine; his symptoms subsequently improved. Thus, he was diagnosed with atypical FMF. After tocilizumab administration, the amyloid deposits disappeared. This case suggests that physicians should consider FMF even in cases with atypical symptoms in order to prevent the progression of amyloidosis and that amyloid deposits can be eliminated by interleukin (IL)-6 inhibition., Internal Medicine, 58(12), pp.1781-1785; 2019

A 70-year-old woman presented with a fever and pain in both lower extremities and the right shoulder and right upper arm continuously for approximately 3 months. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG/PET-CT) revealed the accumulation of FDG in the right shoulder, lumbar spinous processes, both ischial tuberosities, and both hips and greater trochanters, indicating polymyalgia rheumatica (PMR). In addition, upper gastrointestinal endoscopy revealed esophageal carcinoma. After endoscopic submucosal dissection was performed, her musculoskeletal symptoms spontaneously improved, and the 18F-FDG/PET-CT findings decreased. In light of these findings, she was diagnosed with paraneoplastic syndrome. When atypical features of PMR, such as asymmetric symptoms occur, we should search for malignancies.

BackgroundLupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE).MethodsWe retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993–2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares.ResultsOf the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5–154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44–0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06–0.74, p = 0.00098) levels.ConclusionsAmong LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

Background The antimalarial drug hydroxychloroquine (HCQ) is used worldwide to control the disease activity of systemic lupus erythematosus (SLE). In Japan, HCQ was not approved until September 2015 due to the problem of retinopathy induced by chloroquine. There is insufficient evidence of the effects of HCQ or adverse events linked to HCQ treatment. Objectives Here, we evaluated adverse events and the relapse risk of SLE during HCQ treatment. Methods We retrospectively analyzed the data of 109 patients diagnosed with SLE and treated with HCQ for ≥12 months at Nagasaki University Hospital and community hospitals. The demographic data included the patient‘s age at the onset of SLE, gender, the disease duration of SLE (the time from the diagnosis of SLE until the renal biopsy), comorbidities of Sjogren syndrome (SS)/anti-phospholipid syndrome (APS), and the treatment for induction. We identified the risk of adverse events and relapse at 12 months after the introduction of HCQ. Decision tree models predicting relapse were built with the Classification and Regression Trees (CART) algorithm. The data of the length of time between a patient‘s HCQ induction to the first observation of relapse was analyzed by the Kaplan-Meier method with a log-rank test. Results Most of the patients were female (88.1%). The median age at the introduction of HCQ was 40.0 years (interquartile range [IQR] 30.5–50.0 years), and the SLE disease duration was 95 months (IQR 38.0–184.5 months). The mean observation period after HCQ introduction was 12 months. The comorbidity rates of SS and APS were 25.7% and 20.2%, respectively. The SELENA-SLEDAI scores were significantly decreased at 3 months post-HCQ introduction. The dose of oral prednisolone was significantly decreased at 6 months post-HCQ introduction. Eighty-six patients (78.9%) were continuing HCQ at 12 months post-introduction. Adverse events occurred in 27 patients (24.8%), including skin rashes (n=11, 10.1%) and gastrointestinal symptoms (n=6, 5.5%). The sole predictive factor for adverse events was the white blood cell (WBC) count at baseline (odds ratio: 0.9997, 95%CI: 0.9994–0.9999, p=0.0285). Twelve of 86 patients (14.0%) experienced relapse that required the start of prednisolone or an immunosuppressant or an increased prednisolone dose. The multivariate analysis revealed that the C4 value at baseline was a predictive factor of relapse (odds ratio: 0.841, 95%CI: 0.718–0.984, p=0.0097). The cut-off point determined by the CART algorithm showed that C4 ≥9.3 mg/dl at baseline provides the best performance for predicting relapse. The Kaplan-Meier analysis showed that compared to C4 Conclusion A lower C4 value at HCQ introduction was a predictive factor for the relapse of SLE, and a lower WBC count was a predictive factor for adverse events. References [1] Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017 Mar;16(3):411-419. doi: 10.1080/14740338.2017.1269168. Disclosure of Interests None declared

Background Systemic lupus erythematosus (SLE) is multisystem disorder that is caused by tissue damage resulting from antibody and complement-fixing immune complex deposition. Lupus nephritis (LN) is frequent complication and one of the most serious manifestations of SLE. The expression of nephrin, as podocyte marker, is reduced in various renal diseases that develop into nephrotic syndrome1). The alteration of the structural protein in podocytes is known as a mechanism of proteinuria in LN. Objectives The signaling lymphocyte activation molecule family (the SLAM family) of type I transmembrane receptors consists of nine related members of the immunoglobulin superfamily and has been reported to mediate important regulatory signals between immune cells through their homophilic and heterophilic interactions2).The 1q23 region (Sle1b region in mouse) on human chromosome 1 including the SLAMF cluster of genes, containing SLAMF6 has been identified as a lupus susceptibility locus3).It has been shown that the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) is enhanced in CD4+T cells of SLE patients and is involved in IL-17 production4). We sought to examine the functional role of SLAMF6 in lupus podocytes. Methods We evaluated the co-expression of nephrin, a podocyte marker and SLAMF6 in kidney of normal controls and LN patients, also in B6 and MRL/lpr mice at the age of 8wk and 16wk by immunofluorescence analysis. We also examined nephrin positive SLAMF6 expression in isolated podocytes from B6 and MRL/lpr kidneys. Then, we analyzed the expression of SLAMF6 in CD4+T cells of isolated kidney and spleen in B6 and MRL/lpr mice. We treated human podocytes with IgG from healthy individuals and LN patients for 24 h and 48h and analyzed the expression of SLAMF6 by real-time PCR. Results In the histopathology, the expression of SLAMF6 was increased in nephrin positive area in LN patients and MRL/lpr mice compared to each control groups. Although the expression of nephrin in MRL/lpr mice kidney at 16 wk old decreased compared to B6 mice at same age, the expression of SLAMF6 in podocytes increased in diseased MRL/lpr mice compared to B6 mice. Similarly, the expression of SLAMF6 in CD4+ T cells increased in diseased MRL/lpr mice kidney and spleen compared to B6 mice. The level of SLAMF6 mRNA elevated in human podocytes exposed to LN-derived IgG compared to healthy individuals-derived IgG. Conclusion The expression of SLAMF6 is enhanced in LN podocytes, suggesting that the possibility of cooperating with CD4+T cells contributing to its dysfunction. Further examination is needed to investigate in detail how SLAMF6 is involved in the development of LN in the future. References [1] J Am Soc Nephrol. 2003Aug;14(8):2063-71., [2] Nat Rev Immunol. 2003Oct;3(10):813-21., [3] Nat Rev Rheumatol. 2010Jun;6(6):348-57., [4] J Immunol2012; 188:1206-1212. Disclosure of Interests Takashi Igawa: None declared, Kunihiro Ichinose: None declared, Mizuna Eguchi: None declared, Momoko Okamoto: None declared, Yushiro Endo: None declared, Sousuke Tsuji: None declared, Ayuko Takatani: None declared, Toshimasa Shimizu: None declared, Remi Sumiyoshi: None declared, Tomohiro Koga: None declared, Shin-ya Kawashiri: None declared, Naoki Iwamoto: None declared, Mami Tamai: None declared, Hideki Nakamura: None declared, Tomoki Origuchi: None declared, Atsushi Kawakami Grant/research support from: Astellas Pharma, Consultant for: Astellas Pharma, Speakers bureau: Astellas Pharma

We report a female in her twenties who developed generalized edema. She was diagnosed as systemic lupus erythematous (SLE) and Sjögren's syndrome (SS) based on her physical manifestations and positive findings for antinuclear antibody and anti-SS-A/SS-B-antibody. Although she manifested hypoproteinemia, a possibility of lupus nephritis was denied due to a lack of significant abnormality in kidney function tests and urinalysis. The nature of hypoproteinemia and related symptoms was identified as protein losing gastroenteropathy (PLGE) based on α 1-antitrypsin clearance and histopathology findings. Physicians should be aware that PLGE may develop as an underlying cause of edema in SLE and SS.

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment. Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation. Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months. Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

RATIONALE: Power Doppler ultrasonography (PDUS) in musculoskeletal ultrasound (MSUS) is a sensitive and reliable method for the assessment of rheumatoid arthritis (RA). The association between ultrasound-detectable forefoot bursae and the development of RA has gained attention. However, a few studies have evaluated the utility of PDUS for examining forefoot bursae in early RA. We report the case of an RA patient who developed reduced foot mobility and had detectable intermetatarsal bursitis with remarkable power Doppler (PD) signals in MSUS at the onset of RA. PATIENT CONCERNS: A 40-year-old Japanese woman diagnosed with palindromic rheumatism visited our department due to sustained forefoot pain and difficulty walking. The levels of both rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA) were high. She had opening toes with swelling in metatarsophalangeal (MTP) joints. PDUS showed intermetatarsal bursitis with mild MTP synovitis. DIAGNOSES: We diagnosed RA by comprehensive judgment based on the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. INTERVENTIONS:We administered 6.0?mg/wk of methotrexate (MTX) and 2.0?mg/d of prednisolone (PSL) followed by an increase of MTX to 10?mg/wk. OUTCOMES: After those treatments, the patient's symptoms showed improvement. As of this writing,the patient's remission has been maintained for >2 months. LESSONS: Her case suggests that PDUS is useful for the detection of forefoot bursitis, and the detection of forefoot bursitis by PDUS may provide the opportunity to make an early diagnosis of RA., Medicine, 97(51), e13295; 2018