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Abstract Background This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy. Methods We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Results Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality. Conclusions The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.

IntroductionThis study aimed to identify new clinical phenotypes of microscopic polyangiitis (MPA) using a principal components analysis (PCA)-based cluster analysis.MethodsA total of 189 patients with MPA between May 2005 and December 2021 were enrolled from a multicenter cohort in Japan (REVEAL cohort). Categorical PCA and cluster analysis were performed based on clinical, laboratory, and radiological findings. Clinical characteristics and outcomes, including all-cause mortality, respiratory-related mortality, end-stage renal disease (ESRD), and relapse were compared between each cluster.ResultsEleven clinical variables were transformed into four components using categorical PCA and synthetic variables were created. Additionally, a cluster analysis was performed using these variables to classify patients with MPA into subgroups. Four distinct clinical subgroups were identified: Cluster 1 included the renal involvements and diffuse alveolar hemorrhage (DAH)-dominant group (N=33). Cluster 2 comprised the elderly onset systemic inflammation group (N=75). Cluster 3 included patients in the younger-onset limited-organ disease group (N=45). Cluster 4 was comprised of an ILD-predominant group without kidney involvement (N=36). 61 patients died during follow-up, with 32 dying of respiratory-related causes. Additionally, 19 patients developed ESRD and 70 relapsed. Cluster 1 showed the worst ESRD-free survival and relapse rates, whereas Cluster 2 showed the worst overall survival and respiratory-related death-free survival rates among the four groups.ConclusionsOur study identified four unique subgroups with different MPA outcomes. Individualized treatments for each subgroup may be required to improve the prognosis of MPA.

Abstract Mesenchymal stem cells (MSCs) may be effective in treating connective tissue disease and associated organ damage, leveraging their anti-inflammatory and immunoregulatory effects. Moreover, MSCs may possess the ability to produce antiapoptotic, proliferative, growth, angiogenic, and antifibrotic factors. Among MSCs, adipose-derived MSCs (ASCs) stand out for their relative ease of harvesting and abundance. Additionally, studies have indicated that compared with bone marrow-derived MSCs, ASCs have superior immunomodulatory, proangiogenic, antiapoptotic, and antioxidative properties. However, relatively few reviews have focused on the efficacy of ASC therapy in treating connective tissue disease (CTD) and interstitial lung disease (ILD). Therefore, this review aims to evaluate evidence from preclinical studies that investigate the effectiveness of MSC therapy, specifically ASC therapy, in managing CTD and ILD. Moreover, we explore the outcomes of documented clinical trials. We also introduce an innovative approach involving the utilization of pharmacologically primed ASCs in the CTD model to address the current challenges associated with ASC therapy.

BackgroundMepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings.ObjectivesThis study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM).ResultsAfter PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012).ConclusionMepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.

IntroductionThis study aimed to identify useful clinical indicators for predicting the relapse of interstitial lung disease (ILD) complicated with anti-aminoacyl-tRNA synthetase (ARS) antibodies (anti-ARS-ILD), being treated with prednisolone and calcineurin inhibitors.MethodsFifty patients with anti-ARS-ILD were enrolled between October 2014 and August 2022. All patients were treated with prednisolone and calcineurin inhibitors as remission induction therapy and followed up for over a year with these combination therapies. We examined patients who experienced ILD relapse after immunosuppressive treatment. We explored the risk factors for predicting ILD relapse in these patients by comparing demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission.ResultsOf the 50 patients, 19 (38%) relapsed during a median follow-up of 4.8 years. Univariate and multivariate Cox regression analyses identified the presence of acute/subacute (A/S)-ILD, higher serum aldolase (ALD) and surfactant protein-D (SP-D) levels, and lower %forced vital capacity (FVC) as risk factors for relapse in patients with anti-ARS-ILD. Using the receiver operating curve analysis, ALD ≥6.3 U/L, SP-D ≥207 ng/mL, and %FVC ≤76.8% were determined as the cut-off levels for indicating a poor prognosis. The 5-year relapse rate was significantly higher in patients with A/S-ILD, serum ALD≥6.3 U/L, serum SP-D ≥207 ng/mL, or %FVC of ≤76.8% than in those without these parameters. (P=0.009, 0.0005, 0.0007, 0.0004, respectively) Serum ALD levels were significantly correlated with the disease activity indicators of anti-ARS-ILD.ConclusionThe presence of A/S-ILD, higher serum ALD and SP-D levels, and lower %FVC are useful indicators for predicting anti-ARS-ILD relapse.

Abstract Background To establish refined risk prediction models for mortality in patients with microscopic polyangiitis (MPA) by using comprehensive clinical characteristics. Methods Data from the multicentre Japanese registry of patients with vasculitis (REVEAL cohort) were used in our analysis. In total, 194 patients with newly diagnosed MPA were included, and baseline demographic, clinical, laboratory, and treatment details were collected. Univariate and multivariate analyses were conducted to identify the significant risk factors predictive of mortality. Results Over a median follow-up of 202.5 (84–352) weeks, 60 (30.9%) of 194 patients died. The causes of death included MPA-related vasculitis (18.3%), infection (50.0%), and others (31.7%). Deceased patients were older (median age 76.2 years) than survivors (72.3 years) (P < 0.0001). The death group had shorter observation periods (median 128.5 [35.3–248] weeks) than the survivor group (229 [112–392] weeks). Compared to survivors, the death group exhibited a higher smoking index, lower serum albumin levels, higher serum C-reactive protein levels, higher Birmingham Vasculitis Activity Score (BVAS), higher Five-Factor Score, and a more severe European Vasculitis Study Group (EUVAS) categorization system. Multivariate analysis revealed that higher BVAS and severe EUVAS independently predicted mortality. Kaplan–Meier survival curves demonstrated lower survival rates for BVAS ≥20 and severe EUVAS, and a risk prediction model (RPM) based on these stratified patients into low, moderate, and high-risk mortality groups. Conclusions The developed RPM is promising to predict mortality in patients with MPA and provides clinicians with a valuable tool for risk assessment and informed clinical decision-making.

Abstract Background Adipose-derived mesenchymal stem cells (ASCs) have gained attention as a new treatment for systemic sclerosis (SSc). Low-molecular-weight heparin (LMWH) enhances cell function and stimulates the production of hepatocyte growth factor (HGF) in a variety of cells. This study investigated the effects of LMWH on the functions of mouse ASCs (mASCs), and the therapeutic effects of mASCs activated with LMWH (hep-mASCs) in mouse models of SSc. Methods The cellular functions of mASCs cultured with different concentrations of LMWH were determined. Mice were divided into four groups: bleomycin (BLM)-induced SSc (BLM-alone), BLM-induced SSc administered with mASCs (BLM-mASC), and BLM-induced SSc administered with mASCs activated with 10 or 100 μg/mL LMWH (BLM-hep-mASC); there were 9 mice per group (n = 9). Skin inflammation and fibrosis were evaluated using histological and biochemical examinations and gene expression levels. Results In vitro assays showed that migration ability and HGF production were significantly higher in hep-mASCs than in mASCs alone. The mRNA expression levels of cell migration factors were significantly upregulated in hep-mASCs compared to those in mASCs alone. The hep-mASCs accumulated in the skin tissues more than mASCs alone. The thickness of skin and hydroxyproline content in BLM-hep-mASC groups were significantly decreased, and the skin mRNA expression levels of interleukin-2, α-smooth muscle actin, transforming growth factor β1, collagen type 1 alpha 1, and tissue inhibitor of metalloproteinase 2 were significantly downregulated compared to those in the BLM-alone group. Conclusions hep-mASCs showed higher anti-inflammatory and anti-fibrotic effects than mASCs alone and may be a promising candidate for SSc treatment.

Abstract The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, 28 controls, and 10 with Parkinson’s disease (PD) who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P

Abstract Background This study aimed to clarify predictors of preterm birth in pregnancy of women with systemic lupus erythematosus (SLE). We investigated the predictors of preterm birth before pregnancy from the perspective of the importance of preconception care. Methods We analysed fetal outcomes of 108 pregnancies in 74 SLE patients in a retrospective study. We compared pre-pregnancy clinical characteristics and disease activity in these women between the preterm birth and full-term birth groups to select predictive factors for preterm birth before pregnancy. Results Eighty-three of 108 pregnancies resulted in live births, of which 27 (25.0%) were preterm births. Pre-pregnancy serum complement 3 (C3) level was significantly lower in the preterm birth group (77.0 mg/dl) than the full-term birth group (87.5 mg/dl) (P = 0.029). Multivariate analysis identified history of lupus nephritis (odds ratio: 5.734, 95% CI 1.568–21.010, P = 0.008) and low C3 level (< 85 mg/dl) at pre-pregnancy (odds ratio 4.498, 95% CI 1.296–15.616, P = 0.018) as risk factors for preterm birth. The greater the number of these risk factors, the higher was the preterm birth rate (P = 0.0007). In the case of SLEDAI score ≤ 4, the preterm birth rate was higher in the pre-pregnancy low C3 group (< 85 mg/dl) (42.1%) than in the high C3 group (C3 ≥ 85 mg/dl) (14.7%) (P = 0.018). Conclusion For patients with a history of LN, treatment management focusing on pre-pregnancy serum complement levels is very important.

Abstract Background This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA). Methods Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model. Results Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59–0.86, p

Abstract The prognosis of microscopic polyangiitis (MPA) with interstitial lung disease (ILD) is significantly worse than that of MPA without ILD. However, the clinical characteristics in MPA-ILD, especially poor prognostic factors, are not elucidated. We evaluated demographic, clinical, laboratory, and radiological findings, treatments, and outcomes of 80 patients with MPA, and investigated prognostic factors of respiratory-related death in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive MPA-ILD. Ground-glass opacity and fibrosis were evaluated as scores on high-resolution computed tomography (HRCT). The presence of ILD was consistent with a high risk of respiratory-related death (hazard ratio, 4.8; P = 0.04). Multivariable logistic regression analyses using propensity scoring showed right or left lower lobe fibrosis score to be significantly associated with respiratory-related death (P = 0.0005 and 0.0045, respectively). A right or left lower lobe fibrosis score ≥ 2, indicating the presence of honeycombing at 1 cm above the diaphragm, was determined to be the best cut-off value indicating a poor prognosis. The 5-year survival rate was significantly lower in patients with right or left lower lobe fibrosis score ≥ 2 (survival rates: 37% and 19%, respectively) than those with a score

Background: Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 μg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment. Methods: We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 μg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients.Results: At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55–5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09–0.82 and HR 0.35, 95% CI: 0.04–0.48, respectively). Conclusions: The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient’s infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity.

BackgroundLupus nephritis is a life-threatening complication in systemic lupus erythematosus (SLE), but the efficiency of current therapies involving corticosteroids, immunosuppressants, and biological agents is limited. Adipose-derived mesenchymal stem cells (ASCs) are gaining attention as a novel treatment for inflammation in SLE. Low-molecular-weight heparin (LMWH) exhibits multiple functions including anti-inflammatory, anti-fibrotic, and cell function-promoting effects. LMWH stimulation is expected to increase the therapeutic effect of ASCs by promoting cellular functions. In this study, we investigated the effects of LMWH on ASC functions and the therapeutic effect of LMWH-activated human-ASCs (hep-hASCs) in an SLE mouse model.MethodsThe cellular functions of human-derived ASCs stimulated with different LMWH concentrations were observed, and the optimum LMWH dose was selected. The mice were assigned to control, human-ASC, and hep-hASC groups; treatments were performed on week 20. Twenty-six week-old mice were sacrificed, and urine protein score, serum blood urea nitrogen, creatinine (Cr), anti-ds DNA IgG antibody, and serum IL-6 levels were analyzed in each group. Mice kidneys were evaluated via histological examination, immunohistochemical staining, and gene expression levels.ResultsLMWH significantly promoted ASC migration and proliferation and hepatocyte growth factor production and upregulated immunomodulatory factors in vitro. Hep-hASC administration resulted in significant disease activity improvement including proteinuria, serum Cr and IL-6 levels, anti-ds DNA IgG antibody, glomerulonephritis, and immune complex in mice. Inflammation and fibrosis in kidneys was significantly suppressed in the hep-hASC group; the gene expression levels of TNF-alpha, TIMP-2, and MMP-2 was significantly downregulated in the hep-hASC group compared with the control group.ConclusionsHep-hASC exhibited higher anti-inflammatory and anti-fibrotic effects than hASCs and may be a candidate tool for SLE treatment in future.

Abstract Chemokines play an important role in the pathophysiology of dermatomyositis (DM) with interstitial pneumonia (IP). However, the relation between chemokines and the disease activity or prognosis of DM-IP has not been elucidated. We evaluated the serum C-C motif chemokine ligand (CCL) 2, Th1 chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11), and Th2 chemokine (CCL17) profiles of 30 patients, and examined the relation between these chemokines and the disease activity or prognosis of DM-IP. Initial serum CCL2 level was higher in the death group (P = 0.007). To determine the cut-off points effective as poor prognostic factors of DM-IP, ROC curve analysis was carried out on initial serum CCL2 level. The value that maximized the area under the ROC curve was 894 pg/mL (sensitivity: 100%, specificity: 70.8%). Serum CCL2, CXCL9, CXCL10, and CXCL11 levels were lower at 2 weeks after treatment initiation than before treatment. Serum CCL2, CXCL10, and CXCL11 levels at 2 weeks after treatment initiation were higher in the death group. Serum levels of chemokines such as CCL2, CXCL10, and CXCL11 may be possible biomarkers of disease activity and prognosis in DM-IP, and serum CCL2 level may be useful when deciding initial treatment.

OBJECTIVE:To investigate whether leucine-rich α2-glycoprotein (LRG) can be a biomarker for the disease activity, progression, and prognosis of interstitial pneumonia (IP) in patients with dermatomyositis (DM). METHODS:Correlations between the clinical findings and serum LRG levels were investigated in 46 patients with DM-IP (33 with acute/subacute IP [A/SIP] and 13 patients with chronic IP [CIP], including 10 fatal cases of IP). RESULTS:The median serum LRG level of 18.4 (14.6-25.2) μg/mL in DM-IP patients was higher than that in healthy control subjects. The median levels of serum LRG at baseline and at 2 and 4 weeks after the initiation of treatment in the patients who died were significantly higher than those in the surviving patients (P = 0.026, 0.029, and 0.008, respectively). The median level of serum LRG in the DM-A/SIP patients was significantly higher than that in the DM-CIP patients (P = 0.0004), and that in the anti-MDA5-Ab-positive group was slightly higher than that in the anti-ARS-Ab-positive group. The serum LRG levels correlated significantly with the serum levels of LDH, C-reactive protein, ferritin, AaDO2, %DLco, and total ground-glass opacity score. The survival rate after 24 weeks in patients with an initial LRG level ≥ 17.6 μg/mL (survival rate: 40%) was significantly lower than that in patients with an initial LRG level < 17.6 μg/mL (100%) (P = 0.0009). CONCLUSION:The serum LRG level may be a promising marker of disease activity, progression, and prognosis in patients with DM-IP.

[This corrects the article DOI: 10.1371/journal.pone.0202601.].

OBJECTIVE:The aim of this study was to clarify whether serum matrix metalloproteinase 3 (MMP-3) levels are associated with an effect of iguratimod as add-on therapy to biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA). METHODS:Forty three patients with RA were treated with iguratimod as add-on therapy to bDMARDs. They were classified into remission and non-remission groups at 24 weeks of iguratimod therapy. Remission was defined as a state with a disease activity score (DAS)

Matrix metalloproteinase 9 (MMP-9) is a risk factor for cardiovascular events. The serum MMP-9 levels were measured before and 2 weeks after treatment with infliximab (3 mg/kg) in 12 rheumatoid arthritis (RA) patients. The serum average MMP-9 level was 238.5 ng/ml before treatment with infliximab in RA patients (normal range: less than 43.8 ng/ml). Infliximab reduced the serum average MMP-9 level significantly (161.66 ng/ml, P = 0.0425). The serum MMP-9 level was high in the RA patients with active disease, and it was reduced by infliximab independently of the reduction in disease activity. Thus, infliximab may reduce the risk of cardiovascular events directly. Keywords:: rheumatoid arthritis, matrix metalloproteinase 9, acute coronary syndrome

It is difficult to differentiate polymyalgia rheumatica (PMR) from elderly-onset rheumatoid arthritis (EORA) in clinical practice. We compared FDG-PET/CT findings between patients with PMR and those with EORA and extracted factors useful for differentiating the two disorders.We compared abnormal FDG accumulation sites and maximum standardized uptake value (SUVmax) between 15 patients with PMR and 7 with EORA in whom FDG-PET/CT was performed.The proportion of patients in the PMR group with abnormal FDG accumulation at the following 9 sites on FDG-PET/CT was significantly higher than that in the EORA group: periarticular region of the scapulohumeral joint, enthesis of the pectineus muscle, vicinity of the enthesis of the rectus femoris muscle, lateral side of the greater trochanter, ischial tuberosity, hip joint, spinous process of the lower cervical vertebra, intervertebral joint of the lumbar vertebra, and spinous process of the lumbar vertebra. The PET/CT score was evaluated at 9 sites consisting of the abovementioned sites. The median score in the PMR group was 8, which was significantly higher than that of 0 in the EORA group (P = 0.0003). ROC curve analysis was performed with the PET/CT scores, and a score of 5 was shown to maximize the area under the ROC curve (sensitivity: 86.7%, specificity: 86.7%).FDG-PET/CT is useful for differentiating PMR from EORA. In patients with PMR, abnormal FDG accumulation was observed at the entheses, suggesting the presence of enthesitis in addition to bursitis and synovitis.

Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).The median serum LIGHT level was 119 (16-335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL-6 level was 14.7 (2.4-154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6-335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16-164.2] pg/ml) (P = 0.02). The serum IL-6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4-259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP.

BACKGROUND: Acute/subacute interstitial pneumonia in dermatomyositis (DM-A/SIP) is a disease associated with a poor prognosis that resists treatment with glucocorticosteroids (GC) and progresses rapidly in a period of weeks to months to death. We retrospectively studied outcomes, prognostic factors, and their relations with survival rate in patients with DM-A/SIP treated with early cyclosporine A (CSA)/GC combination therapy and 2-hour postdose blood concentration monitoring. METHODS: This study comprised 32 DM-A/SIP patients who were simultaneously treated with CSA and prednisolone. Clinical and laboratory findings were compared between those who died due to DM-A/SIP and those surviving 24 weeks after beginning of therapy. Prognostic factors were extracted, and their relations with the survival rate were evaluated. RESULTS: Of the 32 DM-A/SIP patients, 25 survived, 5 died of DM-A/SIP, and 2 died of infections. In those who died due to DM-A/SIP, ferritin level and the alveolar-arterial oxygen gradient were significantly increased compared with the survivors (P

For progressive interstitial pneumonia (progressive IP) that accompanies diffuse systemic sclerosis (diffuse SSc), no treatment guidelines have yet been established, and it is a complication with a poor prognosis. We herein report a case in which combination therapy of a low-dose corticosteroid and low-dose azathioprine was performed for progressive SSc-IP in a 64-year-old female whose respiratory function was severely damaged for a long period of time and for whom improvement was achieved. The beneficial effect has continued for 3 years with no side effects being observed during the course.