Musculoskeletal Manifestations in Sjogren's Syndrome: An Orthopedic Point of View.
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ABSTRACT:
SUBMITTER: Rozis M
PROVIDER: S-EPMC8068384 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In 9-20% of cases, Sjögren's syndrome is associated with various respiratory symptoms. The most typical manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The most common manifestation of ILD is nonspecific interstitial pneumonia in its fibrosing variant. Other types of ILD, such as organising pneumonia, usual interstitial pneumonia and lymphocytic interstitial pneumonitis, are rare. Their radiological presentation is less distinctive, and definitive diagnosis may require the use of transbronchial or surgical lung biopsy. Corticosteroid therapy is the mainstay of ILD treatment in Sjögren's syndrome, but the use of other immunosuppressive drugs needs to be determined. ILD is a significant cause of death in Sjögren's syndrome. Tracheobronchial disease is common in Sjögren's syndrome, characterised by diffuse lymphocytic infiltration of the airway. It is sometimes responsible for a crippling chronic cough. It can also present in the form of bronchial hyperresponsiveness, bronchiectasis, bronchiolitis or recurrent respiratory infections. The management of these manifestations may require treatment for dryness and/or inflammation of the airways. Airway disease has little effect on respiratory function and is rarely the cause of death in Sjögren's syndrome patients. Rare respiratory complications such as amyloidosis, lymphoma or pulmonary hypertension should not be disregarded in Sjögren's syndrome patients.
| S-EPMC9487244 | biostudies-literature
Project description:ObjectiveTo investigate the gene expression profile in patients with Sjögren's syndrome that is characterized by different clinical phenotypes.MethodsRNA from peripheral blood mononuclear cells was purified in 8 patients with glandular features (GFs) and widespread pain (WP) and 11 with extraglandular manifestations (EGMs) and then was analyzed by hybridization on a human gene chip exploring more than 40,000 human genes. Differentially expressed genes (DEGs) in the two subgroups (ie, those with false discovery rate-corrected P values ≤ 0.01) with respect to 20 healthy controls have been submitted to functional classification using a Gene Ontology database and were mapped to define the networks of protein to protein interactions (PPIs).ResultsThe enriched pathway analyses of DEGs and of the highly interconnected modules identified in the PPI networks showed that the pathological processes characterizing the two subgroups were substantially different. The predominant pathways in patients with EGMs are related to T- and B-cell activation, Toll-like receptor, interferon signaling, and apoptosis. Conversely, pathological processes related to pain transmission and modulation are preferentially operative in patients with GFs and WP. These data suggest that a neuroinflammatory pathway driven by cytokines and chemokines may play a central role in triggering WP features in this phenotype of patients.ConclusionThe present study supports the hypothesis that different biological pathways are operative in patients with primary Sjögren's syndrome with different clinical phenotypes. A better knowledge of these specific processes might help in tailoring more effective target therapies.
| S-EPMC6917337 | biostudies-literature
Project description:Pulmonary involvement in primary Sjögren's syndrome (pSS) is an understudied entity with important clinical implications. Its prevalence has been reported in up to 20% of pSS patients. Pulmonary manifestations of pSS are diverse with involvement of airway and/or lung parenchyma. Histopathology of lung lesions suggests a predominance of submucosal mononuclear cell infiltration consisting predominantly of CD4+ T cells. Current understanding of the pathophysiology of lung disease in pSS suggests a similar process driving the pulmonary process as those in the salivary glands, with epithelial cells playing a critical role in the initiation, maintenance, and symptomatology of the disease. Clinical manifestations of lung involvement in pSS are as varied as the underlying pathology and can be vague and non-specific, thus delaying diagnosis. Management options depend on the underlying pathology but are generally limited due to lack of systematic randomized controlled trials. This review helps summarize our current understanding of lung involvement in pSS.
| S-EPMC6583234 | biostudies-literature
Project description:This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet's Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0-4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021).
| S-EPMC10082129 | biostudies-literature
Project description:ObjectivesTo assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren's syndrome (SS) and non-Sjögren's sicca (non-SS sicca).MethodsCross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers.ResultsCurrent smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22-0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15-0.44, FDR q = 1.52x10E-06), focus score ?1 (OR 0.22, 95%CI 0.13-0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2-0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39-0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption.ConclusionsCurrent tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca.
| S-EPMC5293551 | biostudies-literature
Project description:IntroductionSjögren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.MethodsNondiabetic, nonobese diabetic (NOD) mice aged 21 weeks were evaluated for salivary gland function, salivary gland inflammation and extraglandular disease manifestations. The analytes, comprising chemokines, cytokines, growth factors, autoantibodies and other biomarkers, were quantified using multi-analyte profile technology and fluorescence-activated cell sorting. Age-matched and sex-matched Balb/c mice served as a reference.ResultsWe found NOD mice to exhibit impaired salivary flow, glandular inflammation and increased secretory SSB (anti-La) levels. Thirty-eight biomarkers in serum and 34 in saliva obtained from NOD mice were significantly different from those in Balb/c mice. Eighteen biomarkers in serum and three chemokines measured in saliva could predict strain membership with 80% to 100% accuracy. Factor analyses identified principal components mostly correlating with one clinical aspect of SS and having distinct associations with components extracted from other families of proteins.ConclusionAutoimmune manifestations of SS are greatly independent and associated with various immunological processes. However, CD40, CD40 ligand, IL-18, granulocyte chemotactic protein-2 and anti-muscarinic M3 receptor IgG3 may connect the different aspects of SS. Processes related to the adaptive immune system appear to promote SS with a strong involvement of T-helper-2 related proteins in hyposalivation. This approach further established saliva as an attractive biofluid for biomarker analyses in SS and provides a basis for the comparison and selection of potential drug targets and diagnostic markers.
| S-EPMC2374466 | biostudies-literature
Project description:BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM.MethodsBy utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma.ResultsA total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI.ConclusionCXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.
| S-EPMC10792874 | biostudies-literature
Project description:Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare, inherited disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. As a result of this deficiency, glycosaminoglycans accumulate in lysosomes in many tissues, leading to progressive multisystemic disease. The cardiopulmonary and neurological problems associated with MPS II have received considerable attention. Orthopedic manifestations are common but not as well characterized. This study aimed to characterize the prevalence and severity of orthopedic manifestations of MPS II and to determine the relationship of these signs and symptoms with cardiovascular, pulmonary and central nervous system involvement.Orthopedic manifestations of MPS II were studied using cross-sectional data from the Hunter Outcome Survey (HOS). The HOS is a global, physician-led, multicenter observational database that collects information on the natural history of MPS II and the long-term safety and effectiveness of enzyme replacement therapy.As of January 2009, the HOS contained baseline data on joint range of motion in 124 males with MPS II. In total, 79% of patients had skeletal manifestations (median onset, 3.5 years) and 25% had abnormal gait (median onset, 5.4 years). Joint range of motion was restricted for all joints assessed (elbow, shoulder, hip, knee and ankle). Extension was the most severely affected movement: the exception to this was the shoulder. Surgery for orthopedic problems was rare. The presence of orthopedic manifestations was associated with the presence of central nervous system and pulmonary involvement, but not so clearly with cardiovascular involvement.Orthopedic interventions should be considered on an individual-patient basis. Although some orthopedic manifestations associated with MPS II may be managed routinely, a good knowledge of other concurrent organ system involvement is essential. A multidisciplinary approach is required.
| S-EPMC3143973 | biostudies-literature
Project description:BackgroundCamurati-Engelmann disease (CED) is a rare genetic skeletal disorder characterized by limb pain, muscle emaciation and weakness, and cortical thickening of the diaphysis of long bones. It is caused by mutations in the transforming growth factor beta 1 (TGFB1) (type I) or other unknown gene(s) (type II). We present 8 consecutive patients with type I CED.MethodsWe retrospectively reviewed medical records and radiographs of type I CED patients with special reference to the mode of presentation, process of diagnostic work-up, and disease course. They were 4 sporadic patients, and two pairs of mother and son.ResultsWe categorized the mode of presentation into three groups. Group I had 4 patients who mainly presented with motor disturbances in young age. They drew medical attention for waddling gait, awkward ambulation or running, difficulty in going upstairs, or a positive Gower's sign at age 4 to 6 years. Subsequent development of limb pain and radiographic abnormality led to the diagnosis of CED at age 6 to 29 years. Group II had 3 patients who mainly presented with limb pain at age 15, 20, and 54 years, respectively. Radiographic evaluation and molecular genetic test led to the diagnosis of CED. The remaining 1 patient (group III) was asymptomatic until age 9 years when bony lesions at the tibiae were found incidentally. For the last 10 years, he intermittently complained of leg pain in the morning or after sports activities, which did not interfere with daily life. All the patients in group I showed a body mass index in the underweight range (< 18.4 kg/m2). At the latest follow-up, 4 patients in groups I and II required medication for the limb pain.ConclusionsCED presents with a wide range of severity. Awareness of this rare disease entity may be the key to timely correct diagnosis. This disease entity should be considered in the differential diagnosis of limb pain or motor disturbance in children to avoid unnecessary diagnostic work-up.
| S-EPMC5334020 | biostudies-literature
Project description:PurposeNeonatal nonketotic hyperglycinemia is an autosomal recessive inborn disorder of glycine metabolism in which large quantities of glycine accumulate in all body tissues. It is characterized by a progressive lethargy, hypotonia, myoclonic jerks, and early death secondary to respiratory problems. As a result of early diagnosis and treatment protocols, more patients survive the critical neonatal period with profound mental retardation, delayed developmental milestones, seizures, and spasticity. There are no reports about the orthopaedic manifestations of neonatal nonketotic hyperglycinemia. The purpose of this study is to evaluate the musculoskeletal findings of neonatal nonketotic hyperglycinemia.MethodsThis is a retrospective IRB-approved study of all patients in our Orthopaedic and Genetics Clinics with the diagnosis of neonatal nonketotic hyperglycinemia during a 10-year period. Demographic, clinical, and imaging data were analyzed.ResultsTwelve patients with neonatal nonketotic hyperglycinemia were evaluated, with a mean age of 7 years and 2 months (range: 5 months to 21 years). Seven were male and five were female. Eleven patients (92 %) have evidence of progressive early-onset neuromuscular scoliosis with a mean Cobb angle of 55° (range: 30-95°). Five children (42 %) presented evidence of progressive hip dislocation secondary to spasticity. All the patients have severe multiple joint contractures.ConclusionNeonatal nonketotic hyperglycinemia is a rare metabolic disorder presented in the past as a lethal condition. Recent advances in early diagnosis and neonatal care improve overall outcome. As pediatric orthopaedic surgeons, we need to establish treatment based on update information of the disease and probability to improve quality of life.
| S-EPMC3400000 | biostudies-literature