Ibuprofen Would Be the First-Line Nonsteroidal Anti-inflammatory Drug for Polymyalgia Rheumatica: A Case Series of Five Patients.

The primary treatment of choice for polymyalgia rheumatica (PMR) is corticosteroids, which are better avoided for elderly patients susceptible to PMR. The cases of five patients cured with only a small dosage of 600 mg/day ibuprofen without steroids or methotrexate are reported. Their clinical features were compared with those of the 26 PMR patients who had steroids and/or methotrexate in addition to ibuprofen. PMR was diagnosed based on the 2015 EULAR/ACR criteria. They were all females aged 73-80. They all had no giant cell arteritis or autoantibodies. Nonsteroidal anti-inflammatory drugs (NSAIDs) other than ibuprofen had not worked in four cases; for the one, ibuprofen was the first NSAID. Their serum CRP levels were 1.57-12.8 mg/dL at ibuprofen introduction. Colchicine was co-administered in two patients. At the next visit three to seven days after ibuprofen introduction, they all showed a clear recovery with a CRP level decrease. Ibuprofen tapering was started within three months, and no relapse was until two to five years' follow-up. Comparison with the 26 patients who had additional steroid and/or methotrexate showed that the disease duration until ibuprofen introduction was statistically significantly shorter in the five patients (1.40±0.65 vs 3.28±2.98 months). Ibuprofen would be the first-line drug for PMR, and its earliest use would be beneficial.

Cure of Fingertip Necrosis after Median Nerve Block Application in Two Cases of Definite and Probable Systemic Sclerosis.

One patient with systemic sclerosis with index fingertip necrosis and another with probable systemic sclerosis with index and middle fingertip impending necrosis were successfully treated with ultrasound-guided median nerve block application on the affected side. The nailfold temperatures of the affected fingers measured using thermography were below 25°C. Immediately after application, the temperature increased substantially. After repeated applications, the mean basal temperature on the affected side increased by 3.6°C in Case 1 and by 5.9°C in Case 2. Peripheral nerve block can be a basic treatment for fingertip necrosis. The thermographical observation of the extent and region in which the temperature increased is novel.

Habitual Hot-Tub Bathing and Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Several studies suggested that heat therapy, including sauna or hot-tub bathing, was associated with improved glycemia and other risk factors for cardiovascular diseases. This study aimed to assess the influences of the habit of hot-tub bathing on cardiovascular risk factors in patients with type 2 diabetes in a real-world setting. Methods: In this cross-sectional study, we enrolled the patients with type 2 diabetes who regularly visited the outpatient clinic between October 2018 and March 2019. We obtained the information on the habit of hot-tub bathing by using a self-reported questionnaire. The results of anthropometric measurements, blood tests and medications were obtained from the medical charts. We divided the patients into three groups according to the frequency of hot-tub bathing as follows; group 1: ≥ 4 times a week, group 2: < 4 times a week, ≥ 1 time a week, group 3: < 1 time a week. The biomarkers were compared among the groups by one-way analysis of variance. Multiple linear regression analyses were performed to adjust for confounding variables. Results: We enrolled 1,297 patients. There were significant differences in body mass index (group1: 25.5 ± 5.0, group 2: 26.0 ± 5.4, group 3: 26.7 ± 6.0, P = 0.025), diastolic blood pressure (73 ± 12, 75 ± 12, 77 ± 13, P = 0.001) and hemoglobin A1c (7.10 ± 0.97, 7.20 ± 1.11, 7.36 ± 1.67, P = 0.012). Multiple regression analysis revealed that the frequency of hot-tub bathing was a significant determinant of hemoglobin A1c, body mass index and diastolic blood pressure. Conclusions: In this real-world study, habitual hot-tub bathing was associated with slight improvements in glycemia, obesity and diastolic blood pressure, and thus, can be a possible lifestyle intervention in patients with type 2 diabetes.

Search of official nationwide database in Japan for adverse events associated with disease-modifying antirheumatic drug therapies: focus on therapies in combination with methotrexate.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are essential for rheumatoid arthritis (RA) therapy. The adverse events (AEs) evaluation should focus on that methotrexate (MTX) is frequently prescribed in combination with others (combination MTX). METHODS: A search of the website of the official Japanese Agency for AEs, including lymphoproliferative disease (LPD), cytopenia, interstitial pneumonia, infectious pneumonia other than Pneumocystis jirovecii pneumonia (PCP) (i-Pn), and PCP, associated with MTX, tacrolimus, adalimumab, tocilizumab, and abatacept therapies reported from 2014 to 2016 was performed. Number of each AE cases and its ratio to total number of AEs cases were examined. Combination MTX was checked for RA cases. RESULTS: A total of 8874 cases were listed. In 3955 MTX cases, LPD was most frequent (36.4%). In any of the other four DMARDs cases, i-Pn was most frequent (4.2 ~ 15.3%); PCP cases showed most frequent combination MTX (94.4%). In total, including cases reported for MTX therapy, 98.2% of LPD and 97.6% of PCP cases had MTX, and less than 90% of the other AEs cases had MTX. CONCLUSION: LPD was by far the most frequent AE associated with MTX therapy. PCP was strongly associated with combination MTX. For any of the other four DMARDs, i-Pn was most frequent.

Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital.

BACKGROUND: The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. METHODS: HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. RESULTS: Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive < 2.1 log copies/mL during the observation period. We designed the following scoring system: HBV reactivation risk score = 1 × (age > 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. CONCLUSIONS: Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

Safety and effectiveness of abatacept in Japanese non-elderly and elderly patients with rheumatoid arthritis in an all-cases post-marketing surveillance.

Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis patients. Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2. Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p = .021) and infections (4.8% vs. 7.2%, p = .002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline. Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.

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.

Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals: Post Hoc Analysis of Japanese Patients (MELODY Study).

INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose. RESULTS: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. CONCLUSION: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01076959. FUNDING: AbbVie and Eisai Co., Ltd.

Thermal Disparity between Fingers after Cold-water Immersion of Hands: A Useful Indicator of Disturbed Peripheral Circulation in Raynaud Phenomenon Patients.

OBJECTIVE: To devise an effective method to assess the peripheral circulation using an infrared thermographic analysis. METHODS: Sequential measurements of the skin temperature before and after cold-water immersion of the hands were analyzed by a thermographic examination in healthy controls and patients diagnosed to have Raynaud phenomenon (RP). The skin temperatures of the dorsum of all fingernail folds and the metacarpophalangeal (MCP) joints were measured at baseline. Then the hands were immersed in 10°C water for 10 s, and the skin temperatures were measured at 0, 3, 5, 10, 15, 20 and 30 min after immersion. The mean temperature, recovery rate and disparity (coefficient of variation) of the nail fold temperatures were calculated. The distal-dorsal difference (DDD) was calculated by subtracting the mean MCP temperature from the mean nail fold temperature. Receiver operating characteristic (ROC) curves were generated to compare these parameters in terms of their capability to differentiate patients with RP. RESULTS: Thirty-one RP patients and 25 controls were included in the study. The baseline nail fold temperature was significantly lower in RP patients than in the controls. The RP patients had a lower recovery rate, lower DDD and higher disparity than the controls. The disparity and DDD were negatively correlated (r=-0.63, p<0.01), whereas the recovery rate and DDD were positively correlated (r=0.91, p<0.01). The ROC curve analysis revealed that the disparity in nail fold temperature effectively differentiated RP patients from controls (area under the curve: recovery rate 0.72; disparity 0.88; DDD 0.79). CONCLUSION: The temperature disparity between fingers is a useful thermographic parameter for evaluating disturbed peripheral circulation in patients with Raynaud phenomenon.

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Postmarketing surveillance of the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis.

OBJECTIVE: To perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA). METHODS: Safety and effectiveness data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations. RESULTS: Overall, 3882 and 3016 abatacept-naïve RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept. CONCLUSIONS: Abatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected.

Atypical Subacute Recurrence of Catastrophic Antiphospholipid Syndrome in a Japanese Female Patient.

Catastrophic antiphospholipid syndrome (CAPS) survivors rarely relapse. We herein report a case of a second CAPS episode with an unusual subacute course and no microangiopathic hemolytic anemia (MAHA), a common CAPS symptom. During the first episode, the 69-year-old woman responded well to high-dose glucocorticoids and plasma exchange. On relapse, these treatments plus rituximab were ineffective and she died of multi-organ failure and bacterial cholangitis. The absence of MAHA and a subacute course do not exclude a CAPS recurrence.

Eosinophilic granulomatosis with polyangiitis demonstrating IgE-immune complexes and the possible involvement of IgE autoantibodies.

We herein report a case of female eosinophilic granulomatosis with polyangiitis (EGPA) in which polyethylene glycol (PEG) precipitation was used to evaluate the patient's levels IgE-immune complexes (IC). Her serum IgE (7,110 IU/mL) and IgE-IC (1,880 IU/mL) levels were observed with an IgE PEG precipitated index of 26.4%. We speculate that the circulating IgE-IC were formed by anti-neutrophil IgE autoantibodies. Therefore, the large amount of IgE autoantibodies in the patient's serum appears to have induced a constant allergic pathology. This pathology may have resulted in a marked infiltration of eosinophils into the tissues, as well as intensified the EGPA pathology.

Trend of patient characteristics and its impact on the response to adalimumab in patients with rheumatoid arthritis: post hoc time-course analysis of an all-case PMS in Japan.

OBJECTIVES: To investigate the relationship between changes in patient characteristics over time and the effectiveness and safety of adalimumab in the treatment of rheumatoid arthritis (RA) in clinical practice. METHODS: Patients enrolled in the post-marketing registry study in Japan were divided into 5 subgroups based on the time adalimumab treatment was initiated. Demographic and baseline characteristics and responses to adalimumab were compared among the 5 subgroups to detect any time-course trend. Multiple logistic regression analysis was performed to identify characteristics that were significantly associated with the effectiveness or safety of adalimumab and to estimate response rates and the incidence of adverse drug reactions in individual subgroups. RESULTS: During the study period, patient characteristics changed significantly over time, in particular with regard to prior biologic use and concomitant methotrexate therapy. There was a significant trend toward higher response rates and lower incidence of infections and injection-site reactions in patients initiating adalimumab later in the study. Patient characteristics, such as concomitant methotrexate therapy and early stage RA, were significant predictors of the effectiveness and safety of adalimumab. CONCLUSIONS: Patient characteristics have changed since adalimumab became available for the treatment of RA; several of these characteristics were significant predictors of adalimumab effectiveness and safety.

Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of 7740 patients.

OBJECTIVES: To confirm the safety and effectiveness of adalimumab and to evaluate the influence of the concomitant use of methotrexate (MTX). METHODS: Postmarketing surveillance of 7740 Japanese rheumatoid arthritis (RA) patients was performed. All patients who received adalimumab in the registration period were followed for 28 weeks after starting treatment for safety and 24 weeks for effectiveness. Effectiveness was measured by duration of morning stiffness, swollen and tender joint counts (28 joints), patient global assessment of disease activity, erythrocyte sedimentation rate and serum C-reactive protein. RESULTS: Comparable rates of adverse drug reactions (ADRs) were reported in this study and in the interim analysis. Age, pulmonary disease history or comorbidity, co-existing diabetes mellitus, concomitant MTX at doses of > 8 mg/week and concomitant glucocorticoids at doses of > 5 mg/day were risk factors for infections. All mean values of effectiveness measurements improved. Relatively lower disease activity at baseline, biologic-naïve, concomitant MTX use and early RA stage/low functional class were background factors contributing to the effectiveness. The combination of adalimumab with MTX improved the response to adalimumab treatment. CONCLUSION: Adalimumab, especially with concomitant use of MTX, provided significant improvement in disease activity, without any unexpected ADRs in Japanese RA patients.

Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan.

OBJECTIVE: An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan. METHODS: Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness. RESULTS: A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score-erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously. CONCLUSION: These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.

Safety and effectiveness of 6 months' etanercept monotherapy and combination therapy in Japanese patients with rheumatoid arthritis: effect of concomitant disease-modifying antirheumatic drugs.

OBJECTIVE: To assess real-world safety, tolerability, and effectiveness of etanercept monotherapy, etanercept plus methotrexate (MTX), or etanercept plus other disease-modifying antirheumatic drugs (DMARD) in Japanese patients with active rheumatoid arthritis (RA) despite previous treatment with DMARD. METHODS: In this 24-week, all-cases postmarketing surveillance study, adverse events (AE) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was assessed every 4 weeks using the 28-joint Disease Activity Score and the European League Against Rheumatism response criteria. RESULTS: Of 13,861 patients (81% women) in the analysis, 3616, 2506, and 7739, respectively, were classified into etanercept monotherapy (ETN-mono), etanercept plus DMARD other than MTX (ETN + DMARD), and etanercept plus MTX (ETN + MTX) groups. Rates of AE and serious AE (SAE) in the ETN + MTX group were lower than in other groups. Risk of SAE or serious infections was not significantly increased with higher versus lower MTX doses at baseline or with concomitant use of salazosulfapyridine or bucillamine in ETN + DMARD versus ETN-mono groups. A greater likelihood of achieving clinical remission was seen with ETN + MTX versus ETN-mono (OR 1.36; 95% CI, 1.16-1.60; p < 0.001). Higher MTX dose at baseline was associated with a higher remission rate (> 8 mg vs 0 to ≤ 4 mg, OR 1.47, 95% CI 1.07-2.00, p = 0.016; 6 to ≤ 8 mg vs 0 to ≤ 4 mg, OR 1.27, 95% CI 1.01-1.60, p = 0.038). CONCLUSION: Combination therapies with etanercept plus MTX or other DMARD were reasonably well tolerated, and ETN + MTX at higher doses was more effective than ETN-mono in Japanese patients with RA.

Cut-off levels of salivary beta2-microglobulin and sodium differentiating patients with Sjögren's syndrome from those without it and healthy controls.

OBJECTIVES: For the diagnosis of Sjögren's syndrome (SS), cut-off levels of ß2-microglobulin (ß2MG) and sodium (Na+) in unstimulated whole saliva have not yet been shown. We aimed to determine the cut-off levels of salivary ß2MG and Na+ which differentiate SS patients from non-SS patients and healthy controls. METHODS: Seventy-one patients of primary SS (pSS, 69 females/2 males, 60.0±16.8 years old), 50 of secondary SS (sSS, 49/1, 55.8±17.4), 54 of connective tissue diseases other than SS (non-SS-CTD, 43/11, 60.0±16.0), and 75 healthy volunteers (HC, 43/32, 50.7±15.6) were included. Unstimulated whole saliva were examined for levels of ß2MG, Na+, potassium (K+), and chloride (Cl-). Receiver-operating characteristic curve analysis was carried out. RESULTS: ß2MG, Na+, and Cl- levels in the SS group (pSS and sSS) were significantly higher than those in the non-SS group (non-SS-CTD and HC). The salivary ß2MG level was 5.3±4.6 mg/L in pSS, 5.1±2.0 in sSS, 2.5±2.1 in non-SS-CTD, and 1.2±0.7 in HC, respectively. The Na+ level was 39.2±25.2 mEq/L, 36.4±26.1, 19.6±16.8, and 16.5±7.3, and the Cl- level was 51.1±25.0, 47.8±24.3, 32.1±16.6, and 27.0±7.9 in the same order. The K+ level in the SS group was significantly higher than that in HC. The optimal cut-off ß2 MG and Na+ levels that differentiate the SS group from the non-SS group were 2.3 mg/L and 23 mEq/L. CONCLUSIONS: Salivary ß2MG and Na+ levels are useful markers for differentiating SS patients from non-SS-CTD patients and HC.

Serum ß2-microglobulin level is a useful indicator of disease activity and hemophagocytic syndrome complication in systemic lupus erythematosus and adult-onset Still's disease.

This study demonstrates whether serum ß2-microglobulin (ß2-MG) level can be an indicator of the status of systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and development of hemophagocytic syndrome (HPS) complication. Serum ß2-MG level was compared between the active and inactive statuses of SLE and AOSD in hospitalized patients. Active status was defined as a state for which a therapy was introduced. Serum ß2-MG level was also compared between patients with and without HPS complication. HPS was diagnosed on the basis of clinical and pathological findings. Laboratory markers of HPS including peripheral blood cell counts and levels of serum lactate dehydrogenase (LDH), serum ferritin, plasma fibrin/fibrinogen degradation product (FDP), and plasma D-dimer were examined to determine their correlations with serum ß2-MG level. Sixteen SLE and seven AOSD patients (all females, aged 39.0 ± 16.4) were included. The serum ß2-MG level was high in the active status of underlying diseases and decreased significantly after the therapy (3.5 ± 1.4 vs. 2.1 ± 0.8 mg/L, p < 0.001). Among patients with active status, the ß2-MG level was higher in patients with HPS (two with SLE and three with AOSD) than in patients without HPS (4.9 ± 1.8 vs. 3.3 ± 1.4 mg/L, p < 0.05). Serum ß2-MG level significantly correlated with the levels of serum LDH (r(s) = 0.42, p < 0.05), plasma FDP (r(s) = 0.58, p < 0.05), and plasma D-dimer (r(s) = 0.77, p < 0.01). Serum ß2-MG level would be a useful indicator of disease activity and development of HPS complication in patients with SLE and AOSD.