Treatment Of Connective Tissue Diseases Research Articles

Connective Tissue and Autoimmune Diseases Associated With Postsurgical Breast Augmentation: An Updated Review.

This review provides an updated overview of the association between breast augmentation and connective tissue diseases (CTDs). A narrative review of recent literature was conducted. Various autoimmune disorders, such as Raynaud's syndrome, rheumatoid arthritis (RA), and Sjögren's syndrome, have been reported in association with breast implants, particularly silicone implants. Symptoms can be diverse and systemic, including fatigue, joint stiffness, muscle pain, skin rashes, and neurological and gastrointestinal issues. Explantation has shown promise in alleviating symptoms, but the exact pathogenesis remains unclear. Recent studies emphasize the need for informed consent, vigilant monitoring, and multidisciplinary management. The association between breast implants and CTDs remains contentious. While advancements in implant technology have improved patient outcomes, concerns about long-term health implications persist. Continuous research is necessary to elucidate the mechanisms underlying these potential risks and to develop informed patient care guidelines. In this narrative review, we discuss the history of breast implants, illness associated with breast augmentation, and treatment of CTDs and autoimmune diseases associated with breast augmentation.

Manifestations of systemic connective tissue diseases on the oral mucosa: a literature review

Annotation. Despite the modern high level of medical care, autoimmune connective tissue diseases cause a lot of questions among scientists and are a significant problem for society. At the same time, in the scientific works available today, little attention is paid to the manifestations of connective tissue diseases in the oral cavity and modern diagnostics of the main types of dental pathology in such patients, which would have great scientific and practical importance. Therefore, the purpose of the review article was to perform an analysis of the scientific literature regarding orofacial manifestations of autoimmune connective tissue diseases. When using the following databases: PubMed, Google Scholar, Scopus, Web of Science and various combinations of keywords and subject headings of MESH such as “oral manifestations”, “oral mucosal lesions”, “autoimmune diseases”, “rheumatic diseases”, “connective tissue diseases”, “systemic lupus erythematosus”, “rheumatoid arthritis”, “systemic sclerosis”, “Sjögren’s syndrome”, “dermatomyositis”, 40 articles were chosen, which corresponded to the purpose of the study. The search results indicate that there is a direct correlation between the duration of the main disease and the severity of oral symptoms. Pronounced hyposalivation and dryness of oral mucosa are the most similar common signs of autoimmune diseases, which contributes to functional disorders and diseases of oral cavity. Oral manifestations are quite often a side effect of the treatment of connective tissue diseases. The pathology of oral mucosa in autoimmune diseases remains not well-understood, so makes it difficult to clarify its pathogenesis in detail, that would allow for the development of justified measures of prevention and treatment.

Real world experience with nintedanib in connective tissue disease-related interstitial lung disease: a retrospective cohort study.

Various connective tissue diseases tend to affect specific organs, lungs being the organ with the most serious repercussions and consequences. The diagnosis of interstitial lung disease makes the treatment more difficult and worsens long-term prognosis and overall survival. Positive results from the registration studies of nintedanib led to approval of the drug for the treatment of idiopathic pulmonary fibrosis and chronic fibrosing interstitial lung diseases in connective tissue diseases. After registration, real-world data on the use of nintedanib are being collected in everyday clinical practise.The objective of the study was to collect and analyse real world experience gathered after the registration of nintedanib for the treatment of CTD-ILD and to show if the positive results collected from a homogeneous and "representative" study population can be applied to everyday clinical practice.We are presenting a retrospective observational case-series study of patients treated with nintedanib from the three largest Croatian centers specialised in the treatment of connective tissue diseases with interstitial lung diseases.Stabilisation or improved of lung function tests was reported in 68% of patients when changes in predicted FVC were observed and in 72% of patients when changes in DLco were analysed. Almost all of the reported patients (98%) were treated with nintedanib as an add-on drug to immunosuppressants. The most common side-effects were gastrointestinal symptoms and abnormal liver function tests in less extent.Our real-world data confirm the tolerability, efficacy and similar side-effects of nintedanib as reported in pivotal trials. Key Points • Interstitial lung disease is a common manifestation of several connective tissue diseases and its progressive fibrosing phenotype contributes to high mortality rate and many unmet needs regarding the treatment remain. • Registration studies of nintedanib obtained sufficient data and positive results to support approval of the drug. • Real-world evidence from our CTD-ILD centres confirm the clinical trial data regarding efficacy, tolerability and safety of nintedanib.

Mesenchymal stem cells and connective tissue diseases: From bench to bedside.

The pathogenesis of connective tissue diseases (CTDs), represented by systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), primary Sjögren's syndrome (pSS), and idiopathic inflammatory myopathies (IIM), includes various immune cells involved in both innate and adaptive immunity. The mesenchymal stem cells (MSCs) are unique due to their regulatory effect on immunity. This makes them a promising therapeutic approach for patients with immune-mediated disorders such as CTD. The safety and clinical efficacy of MSC treatment in CTD have been tested in a growing number of preclinical and clinical studies. Administration of MSCs has consistently shown benefits with both symptomatic and histologic improvement in CTD animal models. MSC therapies in severe and drug-resistant CTD patients have shown promise in a number of the pilot studies, cohort studies, and randomized controlled trials in SLE, RA, and SSc, but some problems still need to be resolved in the transition from the bench to the bedside. The relevant studies in pSS and IIM are still in their infancy, but have displayed encouraging outcomes. Considerable efficacy variations have been observed in terms of the route of delivery, time of MSC injection, origin of the MSCs and dosage. Furthermore, the optimization of conventional drugs combined with MSC therapies and the applications of novel cell engineering approaches requires additional research. In this review, we summarize the current evidence about the immunoregulatory mechanism of MSCs, as well as the preclinical and clinical studies of MSC-based therapy for the treatment of CTDs.

Recommendations for the diagnosis and treatment of connective tissue disease associated pulmonary arterial hypertension in China

Pulmonary arterial hypertension (PAH) is a clinicopathological syndrome caused by the increase of pulmonary artery, and it is the most serious complication of connective tissue disease (CTD). In recent years, a lot of progress has been made in the diagnosis, treatment and evaluation of PAH. Chinese Rheumatology Association formulated this recommendation on the basis of current experience and guidelines, in order to promote early screening, early diagnosis and early intervention of CTD-PAH, as well as patient follow-up and management, to improve the prognosis of CTD-PAH patients.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P<0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

Congenital malformations of the urinary system as visceral markers of undifferentiated connective tissue dysplasia

ABSTRACT Objective The relevance of this study is conditioned by the need for urgent search and implementation of effective methods of treatment of urinary system diseases in people of different ages, as well as addressing issues of quality treatment of connective tissue diseases in general and its dysplasia in particular. The aim of the article is to identify congenital defects as visceral markers of connective tissue dysplasia. Methods The methodology of this study includes a survey of a group of children with considerable problems in the development and functioning of the urinary system at the age of 2 weeks to 3 years, in order to qualitatively select and determine the most effective methods of treatment. Children who took part in this study had a set of phenotypic and clinical properties of undifferentiated connective tissue dysplasia. Results The considerable prevalence of undifferentiated connective tissue dysplasia in young children with congenital malformations of the urinary system, especially in children with abnormal development and functioning of kidney tissue, which substantially influences the course of the disease was determined. Also, treatment of undifferentiated connective tissue dysplasia was predicted. Conclusions It was concluded that the presence of a malformation of the urinary system, which is acquired by a child from birth, can be considered as a visceral manifestation of undifferentiated connective tissue dysplasia.

Standardized diagnosis and treatment of undifferentiated connective tissue disease and mixed connective tissue disease

Undifferentiated connective tissue disease (CTD) usually refers to patients who are presented with certain symptoms and signs related to CTD, and positive serological evidence of autoimmune diseases but don't fulfill any of the classification criteria for a certain CTD. Mixed CTD refers to patients who are presented with one or more clinical manifestations such as hand swelling, synovitis, myositis, Raynaud's phenomenon, and acrosclerosis. Patients with mixed CTD always have high-titer anti-nuclear antibodies (ANA) of speckled pattern and high-titer anti-U1 ribonuclear protein (RNP) antibody in serum, while with negative anti-Sm antibody. The update of diagnosis and treatment of undifferentiated CTD and mixed CTD lags behind other established CTD. There is a lack of evidence from randomized controlled trials or guidelines/recommendations on the treatment of undifferentiated CTD or mixed CTD. At present, the conventional therapy is mainly adopted according to the specific clinical manifestations of the disease. The standardized diagnosis and treatment of undifferentiated CTD and mixed CTD were drafted by the Chinese Rheumatology Association based on the previous guidelines and the progress of available evidence, so as to improve the management of these patients in China.

How toxic is an old friend? A review of the safety of hydroxychloroquine in clinical practice.

Hydroxychloroquine (HCQ) and its close relative chloroquine (CQ) were initially used as antimalarial agents but are now widely prescribed in rheumatology, dermatology and immunology for the management of autoimmune diseases. HCQ is considered to have a better long-term safety profile than CQ and is therefore more commonly used. HCQ has a key role in the treatment of connective tissue diseases including systemic lupus erythematosus (SLE), where it provides beneficial immunomodulation without clinically significant immunosuppression. HCQ can also assist in managing inflammatory arthritis, including rheumatoid arthritis (RA). Debate around toxicity of HCQ in COVID-19 has challenged those who regularly prescribe HCQ to discuss its potential toxicities. Accordingly, we have reviewed the adverse effect profile of HCQ to provide guidance about this therapeutic agent in clinical practice.

Treatment of Connective Tissue Disease-Related Intractable Disease with Biological Therapeutics.

The treatment of connective tissue disease (CTD) and CTD-related intractable diseases (CTD-IDs) currently depends on the use of steroid therapy. Approximately 20 years have passed since the approval of infliximab for rheumatoid arthritis in 2003. Since then, several biological therapeutics have been marketed and adapted for many CTDs and CTD-IDs other than rheumatoid arthritis. Although conventional treatment for patients with these diseases is rarely used because of their poor prognosis, these cases may benefit from biological therapeutics. However, choosing biological therapeutics is difficult because they have different target molecules compared with conventional therapeutics. In this review, we address the current situation of biological therapeutics for CTD-IDs including Behcet’s disease, psoriatic arthritis, ankylosing spondylitis, anti-neutrophil cytoplasmic antibody-related arthritis, and adult Still’s disease, as well as the choice of biological therapeutics in clinical practice.

Cholinergic anti-inflammatory pathway and connective tissue diseases

Connective tissue diseases (CTDs) consist of an extensive range of heterogeneous medical conditions, which are caused by immune-mediated chronic inflammation and influences the various connective tissues of the body. They include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, Sjögren's syndrome, Behcet's disease, and many other autoimmune CTDs. To date, several anti-inflammatory approaches have been developed to reduce the severity of inflammation or its subsequent organ manifestations. As a logical mechanism to harnesses the undesired inflammation, some studies investigated the role of the intrinsic cholinergic anti-inflammatory pathway (CAP) in the modulation of chronic inflammation. Many different experimental and clinical models have been developed to evaluate the therapeutic significance of the CAP in CTDs. On the other hand, an issue that is less emphasized in this regard is the presence of autonomic neuropathy in CTDs, which influences the efficiency of CAP in such clinical settings. This condition occurs during CTDs and is a well-known complication of patients suffering from them. The advantages and limitations of CAP in the control of inflammatory responses and its possible therapeutic benefits in the treatment of CTDs are the main subjects of the current study. Therefore, this narrative review article is provided based on the recent findings of the complicated role of CAP in CTDs which were retrieved by searching Science Direct, PubMed, Google Scholar, and Web of Science. It seems that delineating the complex influences of CAP would be of great interest in designing novel surgical or pharmacological therapeutic strategies for CTDs therapy.

2020 Chinese Expert-based Consensus on the Diagnosis and Treatment of Connective Tissue Disease Associated Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD) and is one of the leading causes of morbidity and mortality among patients with this condition. To establish an expert-based consensus on the diagnosis and treatment of CTD-associated PAH, a multidisciplinary consensus development panel was established. The consensus panel is composed of 45 experts in rheumatology, cardiology, pulmonology, and radiology, most of whom are members of the Group of Pulmonary Vascular and Interstitial Lung Diseases (ILD) Associated with Rheumatic Diseases. The consensus development panel compiled 9 recommendations for the diagnosis and treatment of CTD-associated PAH. It covers screening, diagnosis, disease evaluation, risk assessment, the use of immunosuppressive agents, and PAH-specific therapy with a treat-to-target approach. The consensus is intended to facilitate decision-making and standardize the care of CTD-associated PAH in China.

2020 Chinese expert-based consensus statement regarding the diagnosis and treatment of connective tissue disease associated pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease(CTD),being one of the leading causes of morbidity and mortality for patients with this condition. To establish the expert-based consensus on diagnosis and treatment of CTD-associated PAH, a multidisciplinary consensus development panel was established. The panel of consensus was composed of 45 experts in rheumatology, cardiology, pulmonology, radiology, most of whom were members of Group of Pulmonary Vascular and Interstitial Diseases Associated with Rheumatic Diseases. The consensus development panel developed 9 recommendations for the diagnosis and treatment of CTD-associated PAH. The consensus covers the early screening, diagnosis, disease evaluation and risk assessment, immunosuppressive and PAH-specific therapy with a treat-to-target approach. This consensus is intended to facilitate the decision-making and standardize the care of CTD-associated PAH in China.

To accumulate clinical evidence and improve the diagnosis and treatment of connective tissue disease associated pulmonary hypertension in China

第一大类肺动脉高压（pulmonary arterial hypertension，PAH）是影响结缔组织病（CTD）远期预后的决定性因素，需要风湿免疫科、心脏科、呼吸科、影像科、重症医学科和康复科等多学科紧密协作，才能及时、准确及有效的诊治。目前各相关专科医师急需可供遵循的符合我国国情的CTD相关PAH诊疗指南，以提高CTD相关PAH患者的规范化诊治水平。中国医师协会风湿免疫科医师分会风湿病相关肺血管/间质病学组、国家风湿病数据中心和国家皮肤与免疫疾病临床医学研究中心组织制定“2020中国结缔组织病相关肺动脉高压诊治专家共识”，纳入了更多我国的循证医学证据，充分反映了近年来的学术进展，有助于提高我国CTD相关PAH的诊疗水平，改善患者预后。.

Safety and efficacy of rituximab in connective tissue disease-associated interstitial lung disease: A systematic review and meta-analysis

ObjectiveRituximab (RTX) is widely used in the treatment of connective tissue disease (CTD) because it can target and eliminate pathogenic B cells. Interstitial lung disease (ILD) is one of the common complications of CTD; however, the clinical benefits of RTX in connective tissue disease-associated interstitial lung disease (CTD-ILD) are still controversial. This meta-analysis was performed to systematically evaluate the efficacy and safety of RTX in CTD-ILD patients. MethodsWe performed a systematic online query in PubMed, Cochrane, and Embase up to February 2020. Randomized controlled trials and observational studies on the use of RTX and conventional treatment in CTD-ILD patients were comprehensively reviewed and investigated. ResultsIn total, 6 studies, including 242 participants, were analysed. The pooled results showed that RTX is superior to conventional treatment methods in improving forced vital capacity and modified Rodnan skin scores (MRSS) in patients with systemic sclerosis (P＜0. 05), but there was no statistically significant difference between RTX and conventional treatment method in the improvement of lung diffusion function. The risk of adverse effects declined in the RTX therapy groups compared with the conventional therapy groups in terms of infection and the blood system. ConclusionThe pooled results of this meta-analysis indicated that RTX is well tolerated, and RTX is able to improve or stabilize pulmonary function in CTD-ILD patients.

JAK Inhibitors: Prospects in Connective Tissue Diseases.

The dysregulation of the JAK-STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK-STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

Immunosuppressive Treatment of Connective Tissue Disease and Occurrence of Tuberculosis

Introduction: The occurrence of tuberculosis (TB) during the follow-up of Connective tissue diseases (CTD) is a particular situation often posing real diagnostic problems. This is an association described in the literature. Patients and methods: We conducted a retrospective and descriptive study at the internal medicine department of Aristide Le Dantec Hospital. The purpose of this study was to determine the treatment that patients followed for CTD and suffering from TB took before the occurrence of this one. Results: During a study period of 11 years and 6 months, 21 cases of TB were diagnosed in 602 cases of CTD (0.03%). The predominance was female with a sex ratio (H/F) of 0.6. The median age was 42 years old. The majority of cases originated from the Dakar region (13 patients or 61.9%) and 85.7% had previous follow-up exclusively in modern medicine and 21 cases (95%) received the CTD’s treatment. This consisted of prednisone (90.5%) combined with methotrexate (52.4%), azathioprine (23.8%) or cyclophosphamide (19.4%). The respective medians doses of these drugs were 12.5 mg per day for prednisone, 13.5 mg per week for methotrexate and 100 mg per day for azathioprine. The median duration of patient follow-up was 36 months. The cumulative dose of prednisone during this period was 23.6 g and that of methotrexate 2.25 g. CTD were dominated by rheumatoid arthritis (RA) (57.1%), and systemic lupus (19%). Isolated cases of systemic scleroderma, primary Sjögren, SHARP syndrom, mixed connective tissue disease, and multiple autoimmune syndrom were noted. TB was localized in 95% of cases, readily bilateral and poorly disseminated. The respective medians diagnostic delays for systemic disease and TB were 21 months and 5 months. Tuberculin intradermal reaction was performed in 16 cases and was positive in 9 cases, sputum bacilli was performed in 19 cases and was positive in 15 cases. Conclusion: The association of TB and CTD was characterized by its rarity, its poorly disseminated character and its frequency on RA field.

Current and EmergingDrug Therapies for Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD).

Interstitial lung disease (ILD) can be associated with all connective tissue diseases and is an important cause of morbidity and mortality. The management of connective tissue disease-interstitial lung disease (CTD-ILD) is challenging due substantial heterogeneity in disease behaviour and paucity of controlled clinical trials to guide treating clinicians. Not all patients require treatment, and the decision to treat needs to be individualised based on a patient's observed disease behaviour, baseline and longitudinal lung function measurements, extent of lung involvement on radiology and patient factors including age, co-morbidities and personal preference. If indicated, treatment of the CTD-ILD is largely with immunomodulation, with the aim to prevent progression of the ILD before further irreversible lung injury and disability occurs. Corticosteroids, cyclophosphamide, mycophenolate mofetil and azathioprine are the most common immunosuppressive agents currently used to treat CTD-ILD, demonstrating stability of lung function in case series and a small number of randomised controlled trials in ILDassociated with systemic sclerosis. Biological and non-biological disease-modifying anti-rheumatic drugs, and the anti-fibrotics nintedanib and pirfenidone, have revolutionised the treatment of connective tissue diseases and idiopathic ILD, respectively. Furthermore, anti-fibrotics have recently demonstrated safety and efficacy in ILD associated with systemic sclerosis. There remains a critical unmet need to clarify when and in whom to initiate treatment, and which agent(s) to utilise to achieve optimal outcomes for CTD-ILD patients whilst minimising harms through prospective multicentre trials. This review highlights the challenges faced when treating patients with CTD-ILD and summarises available evidence for current, emerging and novel therapies.

Load transfer, damage, and failure in ligaments and tendons.

The function of ligaments and tendons is to support and transmit loads applied to the musculoskeletal system. These tissues are often able to perform their function for many decades; however, connective tissue disease and injury can compromise ligament and tendon integrity. A range of protein and non-protein constituents, combined in a complex structural hierarchy from the collagen molecule to the tissue and covering nanometer to centimeter length scales, govern tissue function, and impart characteristic non-linear material behavior. This review summarizes the structure of ligaments and tendons, the roles of their constituent components for load transfer across the hierarchy of structure, and the current understanding of how damage occurs in these tissues. Disease and injury can alter the constituent make-up and structural organization of ligaments and tendons, affecting tissue function, while also providing insight to the role and interactions of individual constituents. The studies and techniques presented here have helped to understand the relationship between tissue constituents and the physical mechanisms (e.g., stretching, sliding) that govern material behavior at and between length scales. In recent years, new techniques have been developed to probe ever smaller length scales and may help to elucidate mechanisms of load transfer and damage and the molecular constituents involved in the in the earliest stages of ligament and tendon damage. A detailed understanding of load transfer and damage from the molecular to the tissue level may elucidate targets for the treatment of connective tissue diseases and inform practice to prevent and rehabilitate ligament and tendon injuries. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3093-3104, 2018.

5. Recent Progress of Diagnosis and Treatment in Connective Tissue Diseases

5. Recent Progress of Diagnosis and Treatment in Connective Tissue Diseases