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ID PMID Title PublicationDate abstract
31691375 Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in 2020 Apr Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant-induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid-reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.
33392224 Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Diseas 2020 Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers. Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry. Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10(-11) and 7.09 × 10(-6), respectively), and glycerol was higher (Q = 1.20 × 10(-6)), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867-0.968, sensitivity 0.880, specificity 0.780). Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.
33310727 Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporoti 2020 Dec 11 BACKGROUND: Patients with rheumatoid arthritis (RA) commonly use oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), both associated with osteoporotic fractures. We investigated the association between concomitant use of oral GCs and PPIs and the risk of osteoporotic fractures among patients with RA. METHODS: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral GCs and PPIs was stratified by the most recent prescription as current use (<6 months), recent use (7-12 months) and past use (>1 year); average daily and cumulative dose; and duration of use. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications. RESULTS: Among 12 351 patients with RA (mean age of 68 years, 69% women), 1411 osteoporotic fractures occurred. Concomitant current use of oral GCs and PPIs was associated with a 1.6-fold increased risk of osteoporotic fractures compared with non-use (adjusted HR: 1.60, 95% CI: 1.35 to 1.89). This was statistically different from a 1.2-fold increased osteoporotic fracture risk associated with oral GC or PPI use alone. Most individual fracture sites were significantly associated with concomitant use of oral GCs and PPIs. Among concomitant users, fracture risk did not increase with higher daily dose or duration of PPI use. CONCLUSIONS: There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.
32982497 Risk Factors Associated with Methotrexate Intolerance in Rheumatoid Arthritis Patients. 2020 BACKGROUND: Methotrexate (MTX) Intolerance Severity Score (MISS) has been previously validated in the Arabic language and has helped to detect high levels of intolerance in rheumatoid arthritis (RA) patients. The aim of the current study was to evaluate patient and disease characteristics associated with a high risk of MTX intolerance. MATERIALS AND METHODS: A cross-sectional interview-based survey was conducted using adult RA patients as a study group, who were visiting a specialized rheumatology clinic at King Saud University Medical City. The Arabic MISS was used in this survey. Statistical analyses were performed to understand associations between MTX-intolerant and MTX-tolerant patients. RESULTS: A total of 117 patients were involved in this study. Of those, 101 (86.3%) were females with a mean (SD) disease duration of 6.6 (5.7) years. The median (interquartile range (IQR)) Disease Activity Score-28 (DAS28) was 3.6 (3.6-4.1). MTX intolerance was observed in 55 (47%) patients. The most predominant component in patients with a positive test was the behavioral component. Intolerant patients had a higher median of pain (47.3 vs. 50.0; P = 0.010) and patient global assessment (50.0 vs. 60.0; P = 0.004) scales compared to those in tolerant patients. Additionally, MTX intolerance was associated with the female gender (adjusted odds ratio (AOR) 6.724; 95% CI 1.420, 31.843, P = 0.016), marital status (AOR 2.549; 95% CI 1.037, 6.270, P = 0.042) and DAS28 (AOR 1.612; 95% CI 1.032, 2.517, P = 0.036). There was no significant difference between the two groups in the remaining disease activity parameters, background therapies, seropositivity, and smoking status (P > 0.05). CONCLUSION: Patient characteristics, rather than disease activity, significantly impact MTX intolerance. Behavioral component is the main driver of intolerance. Intolerant patients have higher patient-reported outcomes. Qualitative studies are needed to explore causes and potential solutions to MTX intolerance.
32612393 Rheumatoid Arthritis as a Risk Factor for Coronary Artery Calcification and Obstructive Co 2020 PURPOSE: To examine the occurrence and severity of coronary artery disease (CAD) in patients with rheumatoid arthritis (RA) compared to non-RA patients in a population referred for coronary computed tomography angiography (CTA) due to chest pain. PATIENTS AND METHODS: In this cross-sectional study, 46,210 patients from a national CTA database were included. Patients with RA were stratified on serology, treatment with conventional synthetic or biological disease-modifying antirheumatic drugs (DMARDs), and the need for relapse or flare treatment with intraarticular or -muscular glucocorticoid injections (GCIs). Primary outcomes were coronary artery calcium score (CACS) >0 and CACS ≥400, and secondary outcome was obstructive CAD. Associations between RA and outcomes were examined using logistic regression and results were adjusted for age, sex, cardiovascular risk factors and comorbidities. RESULTS: A total of 395 (0.9%) RA patients were identified. In overall RA, crude odds ratio (OR) for having CACS >0 was 1.48 (1.21-1.82) and 1.52 (1.15-2.01) for CACS ≥400, whereas adjusted ORs were 1.08 (0.86-1.36) and 1.21 (0.89-1.65), respectively. Seropositive RA patients had adjusted OR of 1.16 (0.89-1.50) for CACS >0 and 1.37 (0.98-1.90) for CACS ≥400. Patients who had received ≥1 GCI in the period of 3 years prior to the CTA had an adjusted OR of 1.37 (0.94-2.00) for having CACS >0 and 1.46 (0.92-2.31) for CACS ≥400. CONCLUSION: This is the first large-scale, CTA-based study examining the occurrence and severity of CAD in RA patients with symptoms suggestive of cardiovascular disease. A higher prevalence of coronary artery calcification was found in RA patients. After adjusting for age, sex, cardiovascular risk factors and comorbidities, the tendency was less pronounced. We found a trend for increased coronary calcification in RA patients being seropositive or needing treatment with GCI for a relapse or flare.
32506202 Treatment of refractory adult onset Still's disease with tocilizumab-a single centre exper 2020 Aug Adult-onset Still's disease (AOSD) is defined as a systemic inflammatory disorder of unknown aetiology and is classified as a multigene autoinflammatory disease. Treatment of AOSD still remains mostly empirical with nonsteroidal anti-inflammatory drugs, glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs or cyclosporin A. Inhibitors of tumour necrosis factor-alpha and interleukin-1 (IL-1) antagonists have shown efficacy in certain subsets of patients with AOSD. The IL-6 molecule is one of the potential targets in treating AOSD considering that its level is increased in both the systemic and chronic articular forms of the disease. We present a series of eight patients from our centre with refractory AOSD treated with tocilizumab (TCZ). The drug was administered intravenously (6-8 mg/kg every 3-4 weeks) or subcutaneously (162 mg weekly). One patient had a disease relapse during TCZ therapy, and the drug had to be withdrawn in one patient due to a severe infection, while five out of six patients currently treated are in stable remission.Many previous reports have suggested that TCZ is an efficacious option for the treatment of refractory AOSD and the cases presented herein support this finding. A literature search revealed two previous reports of subcutaneous TCZ administration TCZ in AOSD, and our experience supports subcutaneous TCZ as a promising option for treatment of refractory AOSD patients.
31424086 Cytometry by time of flight identifies distinct signatures in patients with systemic scler 2020 Jan Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs and 44 healty controls (HC) using mass-cytometry and assessed the diagnostic value of these results. Alterations in the frequency of immune-cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56(hi) NK-cells in SSc and IgM(+) Bcells in pSS, were disease specific; only a reduced frequency of plasmacytoid dendritic cells was common between all SADs Strikingly, hierarchical clustering of SSc patients identified 4 clusters associated with different clinical phenotypes, and 9 of the 12 cell subset-alterations in SSc were also present during the preclinical-phase of the disease. Additionally, we found a strong association between the use of prednisone and alterations in B-cell subsets. Although differences in immune-cell frequencies between these SADs are apparent, the discriminative value thereof is too low for diagnostic purposes. Within each disease, mass cytometry analyses revealed distinct patterns between endophenotypes. Given the lack of tools enabling early diagnosis of SSc, our results justify further research into the value of cellular phenotyping as a diagnostic aid.
30794472 Comparison of Meibomian Gland Imaging Findings and Lipid Layer Thickness between Primary S 2020 Purpose: To compare meibomian gland (MG) imaging findings and lipid layer thickness (LLT) between patients with primary Sjögren syndrome (SS) dry eyes (DE) and non-SS DE.Methods: A total of 60 patients-30 with SS DE and 30 with non-SS DE were evaluated. Infrared image findings of MGs and LLT were assessed using the LipiView II interferometer.Results: The maximum LLT was significantly lower in the SS DE group. SS DE exhibited significantly higher MG dropout compared to the non-SS DE. Average and maximal LLT showed significant negative correlations with MG dropout in both groups (p<0.05). Conjunctival staining scores showed significant correlations with average and maximum LLT and MG dropout values in the SS DE group (p<0.05).Conclusion: These findings suggest that the new interferometer will be useful in understanding the pathophysiology of SS DE.
32791244 Relationships between increased circulating YKL-40, IL-6 and TNF-α levels and phenotypes 2020 Nov BACKGROUND: There is now no single score or marker useful for evaluating disease activity of primary Sjögren's syndrome (pSS). This study was designed to explore the associations of circulating YKL-40, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with systemic activity and phenotypes of pSS. METHODS: This study included 58 pSS patients and 30 healthy controls (HC). The sera were measured by multiplex immunoassay for YKL-40, IL-6 and TNF-α concentrations. The disease activity of pSS patients was evaluated by European league against rheumatism (EULAR) SS disease activity index (ESSDAI). Local severity was assessed in accordance with the Tarpley score. RESULTS: Serum YKL-40, IL-6 and TNF-α levels significantly elevated in pSS patients compared with those in HC (all P < 0.001). These cytokines correlated with ESSDAI, ESR, CRP, and IgG (all P < 0.05). Serum YKL-40 level correlated markedly with age (r = 0.405, P = 0.002), neutrophil count (r = 0.399, P = 0.002) and neutrophil-to-lymphocyte ratio (NLR) (r = 0.401, P = 0.002), while IL-6 did weakly with NLR (r = 0.296, P = 0.024) and C3 (r = 0.288, 0.036). Serum levels of all three cytokines were substantially lower in patients with eye/mouth dryness vs. those without (all P < 0.05). Additionally, patients with pulmonary, renal involvement or anemia had remarkably higher concentrations of YKL-40 (all P < 0.05), while those with leukocytopenia had lower levels (P = 0.01). Fever or anemia patients showed higher serum concentrations of IL-6 (both P < 0.05), while serum levels of TNF-α were much higher in patients with presence of ANA, anti-SSA or anti-SSB antibodies (All P < 0.05). Serum IL-6 level correlated strongly with YKL-40 (r = 0.452, P < 0.001) and TNF-α (r = 0.743, P < 0.001) in pSS patients. A significant correlation was also found between YKL-40 and TNF-α (r = 0.308, P = 0.022) . CONCLUSION: The circulating YKL-40, IL-6 and TNF-α levels increase in pSS, and all of them are significantly correlated with indicators (ESSDAI, ESR, CRP, and IgG) for systemic inflammation of pSS. Each cytokine is separately associated with specific pSS phenotype.
32012291 Small fiber neuropathy in Sjögren syndrome: Comparison with other small fiber neuropathie 2020 Apr INTRODUCTION: We compared histological and clinical profiles of primary Sjögren syndrome (pSS) small fiber neuropathy (SFN; pSS-SFN) with idiopathic SFN (i-SFN) and hereditary transthyretin amyloidosis SFN (hATTR-SFN) and described the evolution of pSS-SFN. METHODS: All patients with pSS-SFN, i-SFN, and hATTR-SFN confirmed by reduced intraepidermal nerve fiber density on skin biopsy were retrospectively included, and their characteristics were compared. To analyze prognosis of pSS-SFN, patients prospectively underwent a second evaluation. RESULTS: Fifteen pSS-SFN, 17 hATTR-SFN, and 11 i-SFN were included. Time to diagnosis SFN was longer in pSS-SFN and i-SFN than in hATTR-SFN. Painful and non-length-dependent patterns were more frequent in pSS-SFN than in hATTR-SFN. Twelve (80%) patients with pSS-SFN had a non-length-dependent pattern. Ten patients with pSS were reassessed after 3.1 years (1.7-4.7); none developed large fiber neuropathy linked to pSS. DISCUSSION: Primary Sjögren syndrome SFN is characterized by a more frequent non-length-dependent pattern compared with i-SFN and hATTR-SFN. Primary Sjögren syndrome SFN did not evolve through large fiber neuropathy.
33266081 Mouse Models of Sjögren's Syndrome with Ocular Surface Disease. 2020 Nov 30 Sjögren's syndrome (SS) is a systemic rheumatic disease that predominantly affects salivary and lacrimal glands resulting in oral and ocular dryness, respectively, referred to as sicca symptoms. The clinical presentation of ocular dryness includes keratoconjunctivitis sicca (KCS), resulting from the inflammatory damage to the ocular surface tissues of cornea and conjunctiva. The diagnostic evaluation of KCS is a critical component of the classification criteria used by clinicians worldwide to confirm SS diagnosis. Therapeutic management of SS requires both topical and systemic treatments. Several mouse models of SS have contributed to our current understanding of immunopathologic mechanisms underlying the disease. This information also helps develop novel therapeutic interventions. Although these models address glandular aspects of SS pathology, their impact on ocular surface tissues is addressed only in a few models such as thrombospondin (TSP)-1 deficient, C57BL/6.NOD.Aec1Aec2, NOD.H2(b), NOD.Aire KO, and IL-2Rα (CD25) KO mice. While corneal and/or conjunctival damage is reported in most of these models, the characteristic SS specific autoantibodies are only reported in the TSP-1 deficient mouse model, which is also validated as a preclinical model. This review summarizes valuable insights provided by investigations on the ocular spectrum of the SS pathology in these models.
32943282 Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcome 2021 Jan OBJECTIVE: Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD. METHODS: We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated. RESULTS: We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade. CONCLUSION: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.
33246419 An elderly female with adult-onset Still's disease initially misdiagnosed as prosthetic jo 2020 Nov 27 BACKGROUND: High fever, knee swelling and pain after knee arthroplasty are often considered as symptoms of acute prosthetic joint infection. However, similar symptoms can also present as primary manifestations of adult-onset Still's disease, which creates some interference in differential diagnosis. To our knowledge, this is the first published case of misdiagnosis of adult Still's disease after total knee arthroplasty, who was initially misdiagnosed as an prosthetic joint infection due to the above-mentioned symptoms. The symptoms of the knee infection was not relieve after several revisions and continous antibiotic treatment. Finally, after several consultations and repeated evaluation it was diagnosed as adult-onset Still's disease. CASE PRESENTATION: A 77-year-old female who underwent bilateral total knee arthroplasty 6 years ago was admitted to our hospital with high fever, right knee effusion and painful knee. Based on the results of joint fluid aspiration and culture, we treated the right knee as acute hematogenous prosthetic joint infection. After three debridement and revision surgeries, the patient's symptoms continued to persist. Subsequent manifestations of other symptoms such as typical rash and sore throat and laboratory examination suggested the possibility of adult-onset Still's disease. So she underwent diagnostic steroid hormone therapy at the recommendation of a rheumatologist, and a final revision was performed after symptom was controlled. At the one-year follow-up, the patient's symptoms completely resolved and the knee revision was functioning well. CONCLUSIONS: When joint swelling and pain occurs after knee arthroplasty, the possibility of joint infection should not only be considered, but rheumatic autoimmune diseases should also be differentiated. Because the manifestations of joint infection and rheumatic immune disease sometimes overlap highly, when reasonable treatment over a period of time fails to relieve symptoms and signs, we should notice subtle differences in symptoms and laborotary tests and look for other diagnostic possibilities in time.
33150616 Employing immunohistochemical staining to labial minor salivary gland biopsies from patien 2021 Jan BACKGROUND: Sjogren's syndrome (SjS) is an autoimmune disease characterized clinically by dry eyes and dry mouth, and histopathologically by lymphocytic infiltrates in the salivary glands. Labial minor salivary gland biopsy (MSGB) is a major diagnostic test for SjS, deemed positive by a focus score of ≥1, meaning that ≥50 lymphocytes were found in 4 mm(2) tissue on hematoxylin and eosin (H&E)-stained slides. The diagnosis can be challenging, and the above diagnostic criteria has low and variable sensitivity. METHODS: We performed a retrospective study on MSGBs done for possible SjS. We compared the percent of MSGBs which met the histologic criteria by H&E stain alone and that with the addition of CD45, CD3, and CD20 immunohistochemical (IHC) staining for these patients. A total of 45 cases with complete data were analyzed. RESULTS: Thirty-five of the 45 patients had the diagnosis of Sjogren's syndrome (SjS+) based on ACR criteria. However, based on H&E staining alone, only 22/35 cases (63%) met the histologic criteria. After adding IHC staining with CD45, CD3, and CD20 to MSGBs of SjS + patients, 29/35 (83%) cases met the histological criteria for SjS. All MSGBs from patients without SjS had no significant lymphocyte infiltrate on either H&E or IHC stains. CONCLUSIONS: Immunohistochemical better identifies lymphocytic infiltrates in MSGB and increases diagnostic certainty. Due to high cost, their use should be restricted to cases where there is high clinical suspicion of SjS and negative H&E evaluation alone, or if the diagnosis is uncertain.
33095147 Total area of inflammatory infiltrate and percentage of inflammatory infiltrate identify d 2020 Jul OBJECTIVES: Recently, the total area of the inflammatory infiltrate and the percentage of inflammatory infiltrate have been proposed as novel histopathological parameters to improve the stratification of patients with Sjögren's syndrome (SS) in clinical trials. Both these parameters provide a more accurate assessment of the extent of the infiltrate in minor salivary gland biopsies (MSGBs) and may overcome the bias related to the Focus score (FS). To date, however, only few studies have investigated their clinical value and feasibility. In this study we revised consecutive MSGBs obtained routinely in a real-life clinical setting and correlated the total area of the inflammatory infiltrate and the percentage of inflammatory infiltrate both with the other MSGB histopathological parameters and with patients' clinical features in order to explore their usefulness in SS diagnostic work-up. METHODS: We assessed the area of the inflammatory infiltrate and the percentage of the inflammatory infiltrate in consecutive MSGBs and correlated these parameters with the number of foci, the FS and the presence of ectopic lymphoid structures (ELS). We also correlated these additional parameters with patients' clinical and biological data. RESULTS: We revised 69 MSGB samples: 46 from patients with a diagnosis of SS and 23 from subjects with no SS. The total area of inflammatory infiltrate and the percentage of inflammatory infiltrate appeared significantly higher in patients fulfilling the ACR/EULAR classification criteria for SS and correlated significantly with both the number of foci (p<0.001) and the FS (p<0.001). Particularly, they correlated better with the ELS in MSGBs than the number of foci and the FS. When we limited the analysis to the 32/69 patients with a FS<1, both the total area of the inflammatory infiltrate (p=0.02) and the percentage of the inflammatory infiltrate (p=0.03), but not the number of foci (p=0.12) remained significantly higher in the 10/32 anti-Ro/SSA positive patients fulfilling the ACR/EULAR classification criteria. Finally, the total area of inflammatory infiltrate and the percentage of inflammatory infiltrate correlated significantly with several biological and haematological SS-related abnormalities including hypergammaglobulinaemia, C4 levels, total number of white blood cells and the number of circulating lymphocytes. CONCLUSIONS: The total area of the inflammatory infiltrate and the percentage of the inflammatory infiltrate in SS referral centres, and particularly for selected cases, may maximise the information on disease activity at tissue level, ultimately improving SS patients' assessment.
32474638 [Severe polyneuropathy in primary Sjögren's syndrome : Sjögren's syndrome should be cons 2020 Sep A 64-year-old male patient developed over a period of 20 years a peripheral neuropathy symmetrically affecting the upper and lower limbs. The histological examination of a sural nerve biopsy revealed a severe axonal neuropathy. Despite extensive laboratory investigations including immunological and metabolic tests the origin could not be identified. Finally, a Schirmer test revealed xerophthalmia. A subsequent salivary gland biopsy from the lower lip revealed a grade III lymphocytic inflammation according to Chisholm and Mason and confirmed the diagnosis of Sjögren's syndrome.
33181702 Corticosteroid-induced exacerbation of cryptic miliary tuberculosis to acute respiratory d 2020 Nov 13 RATIONALE: Steroid is known to cause generalized immunosuppression, thereby increasing the risk of new infection or recurrence of tuberculosis. However, corticosteroid as a culprit for exacerbation of miliary tuberculosis-from a cryptic to an overt form-has rarely been described in the literature. Moreover, miliary tuberculosis is hardly diagnosed in a living patient as a primary cause of ARDS even in TB-endemic regions. To the best of our knowledge, this is the first case of a steroid-induced progression of cryptic miliary tuberculosis to ARDS, provided with clear depiction of its radiologic evolution. PATIENT CONCERNS: A 36-year-old male was treated with corticosteroid under suspicion of adult onset still's disease for six-week history of fever. Within 2 weeks since the initiation of corticosteroid therapy, the patient experienced acute exacerbation of cryptic miliary tuberculosis, which evolved to an overt form, appearing as miliary nodules on both chest radiograph and HRCT. Then, his condition suddenly deteriorated to severe acute respiratory distress syndrome in less than a day. DIAGNOSIS: The final diagnosis was miliary tuberculosis complicated by severe acute respiratory distress syndrome. INTERVENTIONS: The patient was placed on classic quadruple anti-TB treatment (isoniazide, ethambutol, rifampin, and pyrazinamide). OUTCOMES: His fever subsided in about 6 weeks and 3 consecutive sputum AFB smears collected on different days were confirmed negative. Diffuse infiltrates on his chest x-ray were completely resolved. LESSONS: The case described here draws a clinical and radiological picture of how an occult form of miliary TB evolved to an overt form with use of steroid, and then suddenly progressed to acute respiratory distress syndrome in an immunocompetent young male. This raises awareness on the potential risk of using corticosteroid in patients with cryptic miliary TB. There is formidable challenge in the diagnosis of miliary TB, especially in the early stages. Atypical or even normal outcomes of clinical, microbiochemical, and radiologic evaluation should not be overlooked and dedicated diagnostic work-up should be performed. For equivocal cases, active surveillance with serial radiographs can be helpful.
32691526 Value of labial salivary gland histopathology for diagnosis of Sjögren's syndrome in pati 2020 Aug AIM/INTRODUCTION: Although anti-centromere antibody (ACA)+ Sjögren's syndrome (SS) is considered a subtype of SS, it was not included in the recent American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) SS classification criteria. ACA+ patients without anti-SS-A/Ro antibodies require salivary gland histopathology to fulfill the ACR/EULAR criteria for diagnosis of SS. We reviewed salivary gland histology among ACA+ patients referred for the diagnosis of SS using the ACR/EULAR and Japanese criteria which does not require biopsy. METHOD: Data from 147 ACA+ patients with dry eyes and/or mouth who visited our department were retrospectively analyzed. Clinical, immunological, and histological data were collected and statistically analyzed. RESULT: Sixty-five patients (44%) had undergone labial salivary gland biopsy. The frequency of dry mouth was higher in ACA+ patients who had undergone labial salivary gland biopsy than in those who had not (P = .046), while there were no differences in biopsy rates between patients with and without sclerodactyly (P = .51). According to the current ACR/EULAR classification criteria, Greenspan grade of 3 or 4 for labial salivary gland histopathology is required in patients without anti-SS-A/Ro antibody for the diagnosis of SS. Four patients with Greenspan grades <3 and anti-SS-A/Ro antibody met the criteria for SS. In 54 patients in which the ACR/EULAR criteria were met, 53 patients were diagnosed with SS using the Japanese criteria. CONCLUSION: In ACA+/anti-SS-A/Ro- antibody patients, agreement between ACR/EULAR and Japanese criteria sets was excellent. For easily classifying ACA+ patients as SS cases, salivary gland biopsy should be performed in ACA+ patients with dry symptoms to identify ACA+ patients.
33089069 Ultrasound and multi-biomarker disease activity score for assessing and predicting clinica 2020 BACKGROUND: Musculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response. METHODS: Twenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy. RESULTS: MSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p < 0.0001). Baseline MSUS and MBDA score correlated with each other, and with 12-week changes in CDAI/DAS28 (r = 0.45-0.62, p < 0.05), except for GSUS with DAS28. Two-week change in MSUS correlated significantly with 12-week changes in CDAI/DAS28 (r = 0.42-0.57, p < 0.05), except for early change in PDUS with 12-week change in CDAI. Regression analysis demonstrated significant independent associations between baseline PDUS/MBDA score and 6-week change in CDAI/DAS28, with adjustment for baseline CDAI/DAS28 (all p < 0.05); and between baseline MBDA scores and 12-week change in DAS28 (p = 0.03). CONCLUSIONS: RA patients treated with tofacitinib for 12 weeks demonstrated improvement by clinical, imaging, and biomarker end-points. Baseline PDUS and MBDA score were predictive of CDAI and DAS28 responses. This is the first study to evaluate early measurements of MSUS and MBDA score as predictors of clinical response in RA patients treated with tofacitinib. TRIAL REGISTRATION: ClinicalTrials.gov NCT02321930 (registered 12/22/2014).
33062066 Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid 2020 BACKGROUND: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. METHODS: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. RESULTS: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR<3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to <5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA [odds ratio (OR) = 2.29 p < 0.001] whereas advanced age (OR = 0.98, p = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p < 0.001), use of GCs (OR = 0.75, p = 0.037) or ⩾2 bDMARDs (OR = 0.61, p = 0.002), high co-morbidity index (OR = 0.86, p = 0.011) and obesity (OR = 0.62, p = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR >3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. CONCLUSION: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors.