Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27741237 Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Comp 2016 OBJECTIVE: Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis. METHODS: We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages. RESULTS: MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo. CONCLUSION: The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for chronic inflammatory arthritis, thus providing reliable evidence for a MMP-2-cleavable mechanism as a tissue-targeted strategy for treatment of RA.
27287704 ApoE deficiency exacerbates the development and sustainment of a semi-chronic K/BxN serum 2016 Jun 10 BACKGROUND: The risk for developing cardiovascular disease is greater in patients with rheumatoid arthritis (RA) than in the general population. While patients with RA also have dyslipidemia, the impact of dyslipidemia on the severity of inflammatory arthritis and associated cardiovascular disease is unclear. Currently, there are conflicting results regarding arthritis incidence in apolipoprotein E (ApoE) deficient mice, which spontaneously exhibit both hyperlipidemia and atherosclerosis. Here, we utilize a distinct approach to investigate the contribution of a hyperlipidemic environment on the development of arthritis and atherosclerosis in mice lacking ApoE. METHODS: K/BxN serum transfer-induced arthritis (STIA) was assessed in C57BL/6 (control) and ApoE(-/-) mice using clinical indices and immunohistochemical staining. Ankle synoviums were processed for flow cytometry. Aortic atherosclerosis was quantitated using Sudan IV staining. Serum cholesterol and cytokine levels were determined via enzymatic and luminex bead-based assays, respectively. RESULTS: ApoE(-/-) mice developed a sustained and enhanced semi-chronic inflammatory arthritis as compared to control mice. ApoE(-/-) mice had increased numbers of foamy macrophages, enhanced joint inflammation and amplified collagen deposition versus controls. The presence of arthritis did not exacerbate serum cholesterol levels or significantly augment the level of atherosclerosis in ApoE(-/-) mice. However, arthritic ApoE(-/-) mice exhibited a marked elevation of IL-6 as compared to non-arthritic ApoE(-/-) mice and arthritic C57BL/6 mice. CONCLUSIONS: Loss of ApoE potentiates a semi-chronic inflammatory arthritis. This heightened inflammatory response was associated with an increase in circulating IL-6 and in the number of foamy macrophages within the joint. Moreover, the foamy macrophages within the arthritic joint are reminiscent of those within unstable atherosclerotic lesions and suggest a pathologic role for foamy macrophages in propagating arthritis.
25963626 CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. 2015 May 12 Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag(-/-) mice. The CD8α(+) DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4(+) T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4(+) T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α(+) DCs and other cells of the immune system.
25186344 Validation of the rheumatic disease comorbidity index. 2015 May OBJECTIVE: There is no consensus on which comorbidity index is optimal for rheumatic health outcomes research. We compared a new Rheumatic Disease Comorbidity Index (RDCI) with the Charlson-Deyo Index (CDI), Functional Comorbidity Index (FCI), Elixhauser Total Score (ETS), Elixhauser Point System (EPS), and a simple comorbidity count (COUNT) using a US cohort of rheumatoid arthritis (RA) patients. METHODS: Using administrative diagnostic codes and patient self-reporting, we tested predictive values of the RDCI, CDI, FCI, ETS, EPS, and COUNT for 2 outcomes: all-cause mortality and physical functioning. Indices were compared using 3 models: bare (consisting of age, sex, and race), administrative (bare plus visit frequency, body mass index, and treatments), and clinic (administrative plus erythrocyte sedimentation rate, nodules, rheumatoid factor positivity, and patient activity scale). RESULTS: The ETS and RDCI best predicted death, with FCI performing the worst. The FCI best predicted function, with ETS and RDCI performing nearly as well. CDI predicted function poorly. The order of indices remained relatively unchanged in the different models, though the magnitude of improvement in Akaike's information criterion decreased in the administrative and clinic models. CONCLUSION: The RDCI and ETS are excellent indices as a means of accounting for comorbid illness when the RA-related outcomes of death and physical functioning are studied using administrative data. The RDCI is a versatile index and appears to perform well with self-report data as well as administrative data. Further studies are warranted to compare these indices using other outcomes in diverse study populations.
26171269 Mineral Oil Aspiration Related Juvenile Idiopathic Arthritis. 2015 We describe the development of rheumatoid factor-positive migratory polyarthritis in a 5-year-old male who had been administered bidaily oral mineral oil as a laxative since birth. Minor respiratory symptoms, radiographic and bronchoscopic findings were consistent with chronic lipoid pneumonia. We speculate that immune sensitization to mineral oil promoted the clinical syndrome of juvenile idiopathic arthritis.
28027754 Correlation between intravoxel incoherent motion MR parameters and MR nodular grade of par 2017 Jan PURPOSE: To explore the correlation between intravoxel incoherent motion (IVIM) magnetic resonance (MR) parameters and MR nodular grade of parotid glands in patients with Sjögren's syndrome (SS). MATERIALS AND METHODS: A total of 31 consecutive patients with SS and 28 gender- and age-matched healthy volunteers underwent bilateral parotid 3.0T MR examination including the IVIM sequence (9 b values, 0-800s/mm(2)). The apparent diffusion coefficient (ADC), diffusion coefficient D, pseudo-diffusion coefficient D(*), and perfusion fraction f of bilateral parotid glands were obtained, and the nodular grade of each parotid gland was evaluated according to the MR morphological appearance. RESULTS: Sixty-two parotid glands in 31 patients with SS consisted of 32, 14, 8, and 8 parotid glands at MR nodular grades 0, 1, 2, and 3, respectively. In parotid glands of grade 0, 1, 2, 3 and healthy volunteers, the ADC values were (1.13±0.25, 1.11±0.17, 1.05±0.24, 0.89±0.04 and 1.00±0.21)×10(-3)mm(2)/s, D values were (0.92±0.13, 0.90±0.19, 0.90±0.03, 0.67±0.03, 0.81±0.03)×10(-3)mm(2)/s, f values were 0.20±0.04, 0.18±0.02, 0.15±0.01, 0.11±0.01, 0.15±0.06, and D(*)values were (53.89±28.26, 41.78±16.35, 51.24±18.69, 31.83±18.03, 36.83±16.14)×10(-3)mm(2)/s respectively. The ADC, D, f, and D(*) values of parotid glands in patients with SS at grade 0 were significantly higher than those in healthy volunteers (all P<0.05). Significant differences were observed in the D and f values of parotid glands in patients with SS among different grades (P=0.003,<0.001, respectively). The IVIM parameters (D, f) of parotid glands at early (grades 0-1) and advanced (grades 2-3) stages in patients with SS were significantly higher and lower, respectively, than those in healthy volunteers (all P<0.05). The D and f values inversely correlated with MR nodular grades significantly (r=- 0.297, P=0.019; r=- 0.653, P<0.001, respectively) CONCLUSION: The parotid glands with different MR nodular grades in patients with SS showed different IVIM parameters, reflecting different pathophysiological characteristics of parotid glands at different stages.
27644591 Association of Dry Eye Tests With Extraocular Signs Among 3514 Participants in the Sjögre 2016 Dec PURPOSE: To identify a screening strategy for dry eye patients with a high likelihood of having Sjogren syndrome (SS) through the evaluation of the association of ocular surface tests with the extraocular signs used for the diagnosis of SS. DESIGN: Multicenter cross-sectional study. METHODS: The Sjogren's International Clinical Collaborative Alliance (SICCA) registry enrolled 3514 participants with SS or possible SS from 9 international academic sites. Ocular surface evaluation included Schirmer I testing, tear breakup time (TBUT), and staining of the cornea (0-6 points) and conjunctiva (0-6 points). Multivariate logistic regression analysis was performed to identify predictive factors for (1) histopathologic changes on labial salivary gland (LSG) biopsies (positive = focus score of ≥1 focus/4 mm(2)) and (2) positive anti-SSA/B serology. RESULTS: The adjusted odds of having a positive LSG biopsy were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.26, 95% CI 1.05-1.51, P = .014) and positive conjunctival staining (for each additional unit of staining 1.46; 95% CI 1.39-1.53, P < .001) or corneal staining (for each additional unit of staining 1.14; 95% CI 1.08-1.21, P < .001). The odds of having a positive serology were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.3; 95% CI 1.09-1.54, P = .004) and conjunctival staining (adjusted OR = 1.51; 95% CI 1.43-1.58, P < .001). CONCLUSIONS: In addition to corneal staining, which was associated with a higher likelihood of having a positive LSG biopsy, conjunctival staining and abnormal Schirmer I testing are of critical importance to include when screening dry eye patients for possible SS, as they were associated with a higher likelihood of having a positive LSG biopsy and serology.
27180164 Identification of definitive serum biomarkers associated with disease activity in primary 2016 May 14 BACKGROUND: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sjögren's syndrome (pSS). METHODS: Serum protein concentrations in pSS patients and healthy controls (HCs) were comprehensively screened using high-throughput proteomic analysis, and differentially expressed proteins were extracted. Correlation between differentially expressed proteins and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores was analyzed and disease activity-associated biomarkers were identified. These biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) in a separate pSS cohort. RESULTS: The serum concentrations of 1100 proteins were compared between 30 pSS patients and 30 HCs, with 82 differentially expressed proteins identified as pSS-associated proteins. Of these 82 proteins, 9 were identified as disease activity-associated biomarkers. These nine biomarkers underwent validation by ELISA in a separate pSS validation cohort (n = 58), with five proteins (CXCL13, TNF-R2, CD48, B-cell activating factor (BAFF), and PD-L2) subsequently being confirmed as candidate biomarkers. Of these five candidate biomarkers, CXCL13 exhibited the most significant correlation with the lymphadenopathy, glandular, and pulmonary domains of the ESSDAI. CXCL13, TNF-R2 and CD48 exhibited a positive correlation with the biological domain of the ESSDAI. TNF-R2 exhibited the most negative correlation with uptake in the submandibular gland on technetium 99m-pertechnetate salivary gland scintigraphy. CONCLUSIONS: Our approach successfully identified serum biomarkers associated with disease activity in pSS patients. These markers might be potential therapeutic targets in pSS patients.
26608250 [Clinical usefulness of salivary gland ultrasonography in Sjögren's syndrome: Where are w 2016 Mar Salivary gland ultrasonography is a simple, noninvasive and inexpensive procedure, which provides valuable information for the diagnosis of primary Sjögren's syndrome (pSS). The main sonographic characteristic of the major salivary glands (parotid and submandibular) in pSS patients is the heterogeneity of the parenchyma, with the appearance of hypoechoic areas. Numerous studies published over the past 20 years report a sensitivity of 70% and a specificity of more than 90% for the diagnosis of pSS. Before the widespread use of this procedure in daily practice and its integration into classification criteria of the disease, it has yet to be validated in terms of reproducibility and a consensus score should be established. This work is being conducted by an international group of experts. Other ultrasound techniques such as elastography could also be of interest to objectively quantify changes in the glandular tissue that occur during the disease.
25986268 Successful Detection of Renal Involvement in Sjögren's Syndrome Secondary to Systemic Lup 2015 An 80-year-old man presented with a mildly decreased renal function and increased anti-double-stranded-DNA (anti-dsDNA) antibody levels, and met the diagnostic criteria of the American College of Rheumatology for systemic lupus erythematosus (SLE). However, the incremental increase in creatinine levels and the mild proteinuria were inconsistent with lupus nephritis. We performed a renal biopsy, which revealed interstitial nephritis and minor glomerular abnormalities. Further examinations determined that the renal lesion was due to Sjögren's syndrome secondary to SLE. Following treatment with oral prednisolone, the patient's renal function improved as his anti-dsDNA antibody levels decreased. This case report indicates that renal biopsy should be considered even in elderly individuals when it may assist in the diagnosis, treatment, and prognosis of the patient.
25340658 A case of HIV-associated diffuse infiltrative lymphocytosis syndrome simulating primary Sj 2015 Jan Diffuse infiltrative lymphocytic syndrome is a clinical identity that can be part of the spectrum of Human Immunodeficiency Virus infection. It is characterized by sicca symptoms, parotid and lachrymal enlargement and extra-articular manifestations. We report the case of a 60 years old woman with clinical sicca syndrome in association with leukopenia, positive anti-nuclear antibody (ANA) and polyclonal hypergammaglobulinemia. In the follow up the patient developed a mucosa-associated lymphoid tissue pulmonary neoplasm. Furthermore, the clinical surveys revealed human immunodeficiency virus (HIV) positive markers. In this particular case report, we must underline the clinical presentation of a sicca syndrome as a manifestation of the HIV infection, bearing in mind that, frequently, the differential diagnosis from other diseases, namely the Sjögren's syndrome, is a real challenge.
26809203 Ultrasound and magnetic resonance imaging assessment of joint disease in symptomatic patie 2016 Jul OBJECTIVES: Cystic fibrosis arthropathy (CFA) is a term commonly used for joint pain with and without swelling seen in some patients with CF. Early studies into CFA focused on the presence of rheumatoid factor and immunological changes on synovial biopsy, with parallels drawn between respiratory and joint activity. Identification of anti-cyclic citrullinated peptide antibodies (anti-CCP) as a marker of rheumatoid arthritis (RA), along with increased access to sensitive imaging techniques including ultrasound (US) and magnetic resonance imaging (MRI), offer great potential to investigate and more accurately understand the type(s) of inflammatory arthritis that may underlie CFA. The aim of this study was to phenotype an active CFA cohort using serology and imaging, as a basis for further work in this understudied area. METHODS: This was a prospective observational cohort study of symptomatic CFA patients presenting with joint pain. Participants underwent serological testing, clinical and US joint and entheseal assessment, as well as MRI of the most symptomatic joint/joint area. RESULTS: Ten symptomatic patients were studied with 9/10 having positive clinical findings. Inflammatory changes on US were seen in 8/10 cases. Five patients had positive findings on MRI (3 of whom had received IV gadolinium contrast). This included patients with significant erosive changes. One patient was anti-CCP positive suggestive of RA, and two were anti-nuclear antibody positive. CONCLUSION: Imaging, and to a lesser extent serology, identified inflammatory joint pathology in a proportion of cases, providing important data to explore in a large CFA cohort examining the clinical and imaging phenotype of this group.
28343613 Effects of the use of growth hormone in children and adolescents with juvenile idiopathic 2017 Mar INTRODUCTION: Children with juvenile idiopathic arthritis (JIA) often have impaired growth and short stature. There is evidence that the therapeutic use of growth hormone (GH) is useful and safe in these patients. OBJECTIVE: To analyze the effects of GH use in patients with JIA. METHOD: A systematic review of the literature over the last 18 years in Medline and Embase databases. The criteria were analyzed independently by the researchers. We used the following keywords: "growth hormone", "arthritis, juvenile", "arthritis, rheumatoid", "child" and "adolescent". RESULTS: Among the 192 identified articles, 20 corresponded to the inclusion criteria. Seventeen longitudinal studies and 3 case reports were found. Most studies analyzed observed increased growth, muscle mass and bone mass using GH. Adverse effects observed were glucose intolerance, diabetes, bone deformities, osteonecrosis, reactivation of the disease and low final height. CONCLUSION: The majority of studies reported positive effects after the therapeutic use of GH, but some variability in response to treatment was observed. The combination of growth hormone with other drugs seems to be a good option.
26535145 Cardiovascular and selected comorbidities in early arthritis and early spondyloarthritis, 2015 OBJECTIVES: To investigate the prevalence of comorbidities in early rheumatoid arthritis (ERA) and early axial spondyloarthritis (ESpA) versus the general population. METHODS: Baseline data of 689 patients with ERA from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (age 48.2±12.1 years, symptoms duration 14.2±14.5 weeks) and 645 patients with ESpA from Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; age 32.8±8.4 years, axial symptoms duration 79.0±45.7 weeks) were analysed. Metabolic and cardiovascular diseases (CVD), infections and neoplasia were determined in each cohort. The prevalence (95% CI) of several comorbidities was compared with that in the French general population. For patients without CVD, the 10-year risk of developing CVD was calculated using the Framingham and SCORE equations. The heart age was calculated using the 2008 Framingham points system. RESULTS: 42% of patients with ERA and 20.3% of patients with ESpA had at least 1 comorbidity; the most common were arterial hypertension (AHT) and dyslipidaemia. AHT prevalence (95% CI) in ERA (18.2% (15.5% to 21.3%)), but not in ESpA (5.08% (3.57% to 7.14%)), was significantly increased (p<0.05) compared with the general population (7.58%). Prevalence of tuberculosis history was higher in ERA (4.7% (3.3% to 6.6%)), and ESpA (0.99% (0.4% to 2.3%)) than in the general population (0.02%; both p<0.05). No differences were observed in malignancies, coronary heart disease or diabetes. In ERA, among patients without a history of CVD, an intermediate to high CVD risk was found. The heart age exceeded the real age by 4.1±9.6 years in ERA and by 2.1±7.0 years in ESpA (p<0.001). CONCLUSIONS: We found an increased prevalence of AHT and tuberculosis history in ERA and ESpA, and an increased CVD risk. These results should prompt rheumatologists to check these comorbidities early in the disease.
26921255 Heat shock proteins and chronic fatigue in primary Sjögren's syndrome. 2016 Apr Fatigue occurs frequently in patients with cancer, neurological diseases and chronic inflammatory diseases, but the biological mechanisms that lead to and regulate fatigue are largely unknown. When the innate immune system is activated, heat shock proteins (HSPs) are produced to protect cells. Some extracellular HSPs appear to recognize cellular targets in the brain, and we hypothesize that fatigue may be generated by specific HSPs signalling through neuronal or glial cells in the central nervous system. From a cohort of patients with primary Sjögren's syndrome, 20 patients with high and 20 patients with low fatigue were selected. Fatigue was evaluated with a fatigue visual analogue scale. Plasma concentrations of HSP32, HSP60, HSP72 and HSP90α were measured and analysed to determine if there were associations with the level of fatigue. Plasma concentrations of HSP90α were significantly higher in patients with high fatigue compared with those with low fatigue, and there was a tendency to higher concentrations of HSP72 in patients with high fatigue compared with patients with low fatigue. There were no differences in concentrations of HSP32 and HSP60 between the high- and low-fatigue groups. Thus, extracellular HSPs, particularly HSP90α, may signal fatigue in chronic inflammation. This supports the hypothesis that fatigue is generated by cellular defence mechanisms.
26753209 [Evaluation of usefulness of Polycheck method in the detection autoantibodies in patients 2015 INTRODUCTION: To recognize the connective tissue diseases (CTD), which include lupus erythematosus (SLE), Sjögren's syndrome (SS) and Systemic sclerosis (SSc) it is necessary to determine the presence of autoantibodies (Ab). There is still work going on to find effective and equivocal detection methods. THE AIM OF STUDY: To evaluate the usefulness, clinical value and innovativeness of the Polycheck method in the detection of autoantibodies in patients with connective tissue diseases. MATERIALS AND METHODS: The study involved 178 people: 153 patients of the Department of Rheumatology and 25 healthy people. According to the main diagnosis the patients were divided into 3 groups: SLE-59, ZS-45, SSc-49. The presence and concentrations of Ab were determined by using multiparametric enzyme-linked immunosorbent assay Polycheck Rheuma (Biocheck, GmbH, Münster, Germany). Statistical data analysis was performed using Statistica v10.0. RESULTS: In our study we found thatthe frequency of antibodies characteristic of the SS: anti-SS-A/Ro 52, anti-SS-A Ro 60 and anti-SS-B/La was significantly higher in patients with SS group compared to TRU, TU, and GK (p <0.05); concentrations of Ab were lower in TRU and in SSc group. Marker Ab for SLE anti-dsDNA were only present in patients with SLE. Anti-Sm antibodies were more common in this patient population too. Antibodies associated with diagnosis of SSc anti-SCL-70 and anti-CENP B were significantly more often observed in patients with SSc in higher concentrations compared to the other groups examined (anti-SCL-70 p<0,0005). The Ab concentration analysis performed with use of this analysis help us to confirm diagnosis in particular patients. CONCLUSIONS: The multiparametric enzyme-linked immunosorbent assay Polycheck Rheuma is helpful in making a quick and comprehensive identification of autoantibodies in pts with suspected CTD. The concentration analysis performed with use of this method enables an accurate diagnosis despite the ambiguous clinical picture.
26164595 New insights into B cell biology in systemic lupus erythematosus and Sjögren's syndrome. 2015 Sep PURPOSE OF REVIEW: Our understanding of the physiological and pathogenic functions of B cells in systemic lupus erythematosus (SLE) and Primary Sjögren's syndrome (pSS) continues to expand. In this review, we discuss novel insights published in the last 18 months into the roles of B cells in systemic autoimmunity. RECENT FINDINGS: Data have continued to expand regarding the diverse mechanisms by which innate immune signals including Toll-like receptors (TLRs) regulate the B cell compartment. Localized B cells and long-lived plasma cells have been identified as playing an important role in target tissue including the development of ectopic lymphoid structures in kidney and salivary gland. In addition to pathogenic roles for B cells, there is mounting evidence for regulatory B cell subsets that play a protective role and new insights into the signals that regulate their development. SUMMARY: The past few years have provided insights into the multiple paths by which innate immune signals can lead to B cell activation in SLE and pSS and the increasingly diverse ways in which B cells contribute to disease expression. Further understanding the imbalance between protective and pathogenic functions for B cells in disease including in understudied target tissue should yield new treatment approaches.
25929927 The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult 2015 May Adult-onset Still disease (AOSD) is characterized by fever, skin rash, and lymphadenopathy with leukocytosis and anemia as common laboratory findings. We investigated the characteristic pathologic findings of skin, lymph node, liver, and bone marrow to assist in proper diagnosis of AOSD.Forty AOSD patients were included in the study. The skin (26 patients), lymph node (8 patients), liver (8 patients), or bone marrow biopsies (22 patients) between 1998 and 2013 were retrospectively analyzed. AOSD patients were diagnosed according to the Yamaguchi criteria after excluding common infections, hematological and autoimmune diseases. Immunohistochemistry, immunofluorescence, and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were performed.Most skin biopsies revealed mild lymphocytic or histiocytic infiltration in the upper dermis. Nuclear debris was frequently found in the dermis in 14 cases (53.8%). More than half of the cases (n = 14, 53.8%) showed interstitial mucin deposition. Some cases showed interface dermatitis with keratinocyte necrosis or basal vacuolization (n = 10; 38.5%). The lymph node biopsies showed a paracortical or diffuse hyperplasia pattern with immunoblastic and vascular proliferation. The liver biopsies showed sparse portal and sinusoidal inflammatory cell infiltration. All cases showed various degrees of Kupffer cell hyperplasia. The cellularity of bone marrow varied from 20% to 80%. Myeloid cell hyperplasia was found in 14 out of the 22 cases (63.6%). On immunohistochemistry, the number of CD8-positive lymphocytes was greater than that of CD4-positive lymphocytes in the skin, liver, and bone marrow, but the number of CD4-positive lymphocytes was greater than that of CD8-positive lymphocytes in the lymph nodes.The relatively specific findings with respect to the cutaneous manifestation of AOSD were mild inflammatory cell infiltration in the upper dermis, basal vacuolization, keratinocyte necrosis, presence of karyorrhexis, and mucin in the dermis. In all cases, pathologic findings in the lymph nodes included paracortical hyperplasia with vascular and immunoblastic proliferation. Skin and lymph node pathology in addition to clinical findings can aid in the diagnosis of AOSD.
27564390 Comorbidities in Patients With Primary Sjögren's Syndrome and Systemic Lupus Erythematosu 2017 Jan OBJECTIVE: To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases. METHODS: This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate. RESULTS: A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P < 0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P < 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P < 0.001). CONCLUSION: Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.
27421224 Primary Sjögren's syndrome. 2016 Feb Primary Sjögren's syndrome (pSS) is a relatively common autoimmune systemic rheumatic disease. In addition to sicca syndrome and swollen salivary glands, systemic features manifest in the majority of patients, and are severe in 15%, particularly affecting the joints, skin, lungs, and peripheral nervous system. A recent meta-analysis estimated a pooled relative risk of 13.76 for the development of non-Hodgkin lymphoma, particularly in pSS patients who have parotid enlargement, vasculitis, cryoglobulinemia, and antibodies to Ro and La. pSS is the underlying diagnosis in one-third of mothers of neonates affected by congenital heart block. The diagnosis of pSS is complex and requires a stepwise approach to evaluate symptoms of ocular and oral dryness, objective measures of lacrimal and salivary gland dysfunction, and evidence of autoimmunity with Ro/La autoantibodies and labial salivary gland biopsy. It is essential to eliminate other autoimmune diseases, as well as non-autoimmune causes of sicca syndrome, such as menopause, endocrine diseases, anticholinergic effects of drugs, and fibromyalgia, to delineate pSS patients who are at risk of systemic complications. Recent major advances in the diagnosis of pSS have been the development of classification criteria, which serve as a template for clinical diagnosis, and outcome measures for use in clinical trials and prospective patient cohorts. Clinical data and biological samples from longitudinal cohorts, embedded into clinical practice, will be essential to further improve the diagnosis and management of pSS, increase knowledge about the natural history of the disease, gain insights into its pathogenesis, and stratify patients according to their risk of systemic disease and NHL. At present, there is a gap in evidence regarding the role of structured protocols in the management of pSS. Recent recommendations for the management of sicca symptoms and clinical trials of disease-modifying therapy are discussed.