Cardiovascular risk and inflammation in a population with autoimmune diseases: a narrative review.

Juvenile Systemic Connective Tissue Diseases (JSCTD) are a heterogeneous group of chronic autoimmune diseases, associated with dyslipidemia and increased cardiovascular risk are related. Studies from the last 10 years, from 2013 to 2022, on lipid profiles in JSCTD were collected. Different studies on lipid profiles in children affected by JSCTD were selected, because the aim is to analyze the cardiovascular risk and the possibility of atherosclerosis in these patients in whom, sometimes, corticosteroid therapies and immunosuppressants increase the state of dyslipidemia. Several studies have shown that autoimmune diseases with an inflammatory substrate also share abnormalities in lipid profile and increased cardiovascular risk. Specifically, associations have been found between Juvenile Systemic Connective Tissue Diseases and elevated triglycerides, TC-C (Total Cholesterol), LDL-C (Low-Density Lipoprotein), low HDL-C (High-Density Lipoprotein), and increased risk of developing diseases such as myocardial infarction, peripheral vascular disease, pulmonary and arterial hypertension, and atrial fibrillation. Supplementation with alpha-linolenic acid (ALA) on the other hand has also been analyzed with positive results in reducing inflammatory parameters, such as IL-6 (Interleukin-6), CRP (C-reactive protein), and fasting glucose, in subjects with dyslipidemia. These observations suggest that supplementation with ALA, an omega-3 precursor, may positively modulate both the inflammatory status and dyslipidemic conditions in patients with autoimmune disorders.

Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

De novo Connective Tissue Disorders as Immune-related Adverse Events.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment through blocking immunoregulatory pathways, resulting in augmented antitumor responses. However, ICIs can cause inflammatory autoimmune toxicities, known as immune-related adverse events (irAEs). Common rheumatic irAEs include inflammatory arthritis, polymyalgia rheumatica-like symptoms, and myositis. Fewer cases of de novo connective tissue disease as irAEs have been described and have mainly presented with cutaneous manifestations of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Treatments include glucocorticoids and steroid-sparing agents such as hydroxychloroquine, mycophenolate mofetil, and methotrexate with improvement of symptoms. In this review, the authors discuss immune-related SLE and SSc and their management.

Relationship between idiopathic interstitial pneumonias (IIPs) and connective tissue disease-related interstitial lung disease (CTD-ILD): A narrative review.

While idiopathic interstitial pneumonia (IIP) centering on idiopathic pulmonary fibrosis (IPF) is the most prevalent interstitial lung disease (ILD), especially in the older adult population, connective tissue disease (CTD)-related ILD is the second most prevalent ILD. The pathogenesis of IPF is primarily fibrosis, whereas that of other ILDs, particularly CTD-ILD, is mainly inflammation. Therefore, a precise diagnosis is crucial for selecting appropriate treatments, such as antifibrotic or immunosuppressive agents. In addition, some patients with IIP have CTD-related features, such as arthritis and skin eruption, but do not meet the criteria for any CTD, this is referred to as interstitial pneumonia with autoimmune features (IPAF). IPAF is closely associated with idiopathic nonspecific interstitial pneumonia (iNSIP) and cryptogenic organizing pneumonia (COP). Furthermore, patients with iNSIP or those with NSIP with OP overlap frequently develop polymyositis/dermatomyositis after the diagnosis of IIP. Acute exacerbation of ILD, the most common cause of death, occurs more frequently in patients with IPF than in those with other ILDs. Although acute exacerbation of CTD-ILD occurs at a low rate of incidence, patients with rheumatoid arthritis, microscopic polyangiitis, or systemic sclerosis experience more acute exacerbation of CTD-ILD than those with other CTD. In this review, the features of each IIP, focusing on CTD-related signatures, are summarized, and the pathogenesis and appropriate treatments to improve the prognoses of patients with various ILDs are discussed.

[Long-term result of aortic root remodeling using the Florida sleeve technique in a patient with connective tissue dysplasia and aortic root aneurysm without aortic insufficiency]. / Otdalennyi rezul'tat ekzoprotezirovaniya kornya aorty po metodike Florida Sleeve u bol'nogo s soedinitel'notkannoi displaziei i anevrizmoi kornya aorty bez aortal'noi nedostatochnosti.

Aortic root remodeling using the Florida sleeve technique was proposed as a simpler alternative to classical reconstructive interventions in patients with aortic root aneurysm without aortic insufficiency. We present a 10-year result of valve-sparing surgical treatment using the Florida sleeve technique in a patient with connective tissue dysplasia and aortic root aneurysm.

[Factors influencing the occurrence of small for gestational age at different degrees]. / ä¸åŒç¨‹åº¦å°äºŽèƒŽé¾„å„¿å‘ç”Ÿçš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

[Interstitial Lung Disease associated with Connective Tissue Diseases]. / Interstitielle Pneumopathien bei Konnektivitiden.

INTRODUCTION: Interstitial Lung Disease associated with Connective Tissue Diseases Abstract: Interstitial lung diseases (ILD) are in up to one-third of cases associated with connective tissue diseases (CTD). In systemic sclerosis, rheumatoid arthritis, polymyositis/dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease, an associated ILD significantly increases morbidity and mortality. The diagnostic workup for suspected CTD-ILD includes a range of functional, radiological, laboratory, and, if necessary, invasive tests. A thorough medical history and physical examination with targeted rheumatological diagnosis is particularly important. Also, patients with unclassified ILDs should be evaluated thoroughly for any underlying CTD. Pharmacological treatment options for CTD-ILD differ significantly from those for other ILDs. In addition to short-term glucocorticoids, antimetabolites and biological agents are often used. Antifibrotic drugs have also been successfully used in CTD-ILDs. The decision on whether and which immunosuppressive and/or antifibrotic therapy is indicated depends on the underlying disease, disease activity, extrapulmonary manifestations, severity of organ involvement, ILD progression, comorbidities, and patient preferences. Complex treatment decisions are ideally made in multidisciplinary expert teams.

Unraveling the genetic collagen connection: clinical and therapeutic insights on genetic connective tissue disorders.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

Clinical characteristics of patients with connective tissue disease-related interstitial lung disease: a retrospective analysis.

INTRODUCTION: Interstitial lung disease is one of the most critical manifestations of connective tissue diseases that may cause morbidity and mortality. This study aimed to evaluate the clinical and demographic characteristics and treatment of the patients with connective tissue disease-related interstitial lung disease. METHOD: This retrospective observational study included patients from the Gulhane Rheumatology Interstitial Lung Disease cohort between October 2016 and June 2023. The patients were assessed retrospectively. RESULTS: A total of 173 patients were included in the study with a mean age of 63.4 ± 11.9 years. The frequencies of CTD were 34.1% Sjogren's syndrome, 30.1% rheumatoid arthritis, 25.4% systemic sclerosis, 5.8% undifferentiated connective tissue disease, 2.9% idiopathic inflammatory myositis, 1.2% mixt connective tissue disease, and 0.6% systemic lupus erythematosus in decreasing frequencies. Nonspecific interstitial pneumonia, which was the most common interstitial lung disease pattern in 103 (59.5%) patients, was most frequent among patients with SS and SSc (p < 0.001 vs. p < 0.001). Usual interstitial pneumonia was most frequent among patients with RA (p < 0.001). All patients received immunosuppressive treatment, most commonly azathioprine. 57.2% were using immunosuppressives for ILD. Six patients had mortality, and infections were the leading cause. CONCLUSIONS: As a critical manifestation of connective tissue diseases, immunosuppressive treatment is indispensable in the management of interstitial lung diseases especially those at an increased risk for progression. The treatment approaches should be assessed in a patient-based way. The patients under immunosuppressive treatment should be cautiously followed for infections. Key Points • Interstitial lung disease is a noteworthy manifestation of connective tissue diseases. • The clinical findings, treatment requirements, and progression vary according to the severity of the disease. • Immunosuppressive treatment may be essential in patients with worsening symptoms, impaired pulmonary function tests, and radiological findings.

Unusual overlap of systemic sclerosis with Takayasu arteritis.

Overlap syndromes are diseases that meet the criteria of two or more rheumatic diseases. In this case report, a woman in her 20s presented with a constellation of symptoms, including skin thickening, Raynaud's phenomenon, hypertension, absent pulse in both lower limbs with bilateral renal artery bruit. The antinuclear antibody profile revealed Scl-70 positivity. CT thorax identified early interstitial lung disease, and nailfold capillaroscopy showed severe capillary loss. CT angiogram features were suggestive of Takayasu arteritis. Notably, there have been only four documented cases of systemic sclerosis coexisting with Takayasu arteritis, highlighting the rarity of this overlap syndrome. The diagnosis of overlap syndrome was made after a thorough history recording and clinical examination. In the presence of bilateral renal artery stenosis, managing the scleroderma renal crisis may be challenging . This patient received treatment with mycophenolate mofetil and oral corticosteroids, aiming to address both systemic sclerosis and Takayasu arteritis effectively.

Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2.

We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough examination was necessary. We compared rates of disease severity, death, and PASC in connective tissue diseases versus the entire cohort as well as in diabetes and hypertension to determine if connective tissue disease was a risk factor. Of the 15,676 patients in the database, 63 (0.40%) had a connective tissue disease, which is elevated relative to the distribution in the population, suggesting a higher risk of severe disease. Within these 63 patients, 9.52% developed PASC compared to 2.54% in the entire cohort (p < 0.005). Elucidation of populations at high risk for severe disease and development of PASC is integral to improving treatment approaches. Further, no other study to date has examined the risk in those with connective tissue diseases and these data support a need for enhanced awareness among physicians, patients, and the community.

Connective tissue disease-associated interstitial lung disease.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Relative incidence of interstitial lung diseases in Brazil.

OBJECTIVE: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. METHODS: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. RESULTS: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). CONCLUSIONS: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

[5 cases of silicosis complicated with connective tissue diseases].

Long-term inhalation of silica dust can cause silicosis, but also may induce autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, anti-histidyl tRNA synthetase antibody (JO-1 antibody) syndrome. These two diseases can be isolated or combined. In this paper, the clinical characteristics of 5 cases of silicosis complicated with connective tissue diseases were analyzed and summarized to strengthen the clinical understanding of silicosis complicated with connective tissue diseases, so as to reduce its misdiagnosis and missed diagnosis, and provide reference for clinicians in diagnosis and treatment.

Rheumatic diseases in migrant patients resident in Tuscany: epidemiological data analysis and single-center experience.

OBJECTIVE: In the last decades, the number of foreigners in Tuscany has considerably increased with a multiethnic distribution. We reviewed the main rheumatic diseases in the foreign population resident in Tuscany and also reported the experience at the Rheumatology Division of the University Hospital of Careggi, Florence, in order to identify the areas of origin of these patients and the main rheumatic diseases observed in them. METHODS: The collaboration with the Tuscan Region provided data about foreign patients residing in Tuscany on January 1, 2021 (country of origin, chronic diseases). Moreover, we conducted a retrospective review of the clinical charts of our Rheumatologic Division from January 1, 2019, to December 31, 2020. RESULTS: In Tuscany, on January 1, 2021, there were 61,373 patients with chronic inflammatory rheumatic diseases, and 3994 of them (6.51%) were foreigners. Most patients were born in Europe (39.03%), followed by the Balkans (15%), South America (11.27%), and North Africa (10.31%). Inflammatory joint diseases, Sjögren syndrome, and systemic lupus erythematosus were the most frequent diseases. In the period 2019-2020, 511 foreign patients visited our Rheumatology Division and mainly originated from the Balkans (34.64%), South America (18%), and European countries (16.44%). In these patients, chronic inflammatory joint diseases and connective tissue diseases (systemic sclerosis, Sjögren syndrome, and systemic lupus erythematosus) were the most prevalent diseases. CONCLUSIONS: This study provides a picture of the rheumatic diseases affecting foreign patients residing in Tuscany that are in agreement with the epidemiological data previously provided.

Patient interest in the development of a center for Ehlers-Danlos syndrome/hypermobility spectrum disorder in the Chicagoland region.

BACKGROUND: The Ehlers-Danlos Syndromes (EDS) are a group of connective tissue disorders that are hereditary in nature and characterized by joint hypermobility and tissue fragility. The complex nature of this unique patient population requires multidisciplinary care, but appropriate centers for such care do not exist in large portions of the country. Need for more integrated services has been identified in Chicagoland, or Chicago and its suburbs. In order to explore and begin to address barriers to seeking appropriate care facing EDS patients in this region, we developed an online survey which we circulated through EDS social media groups for Chicagoland patients. RESULTS: Three hundred and nine unique respondents participated. We found that there exists a strong medical need for and interest in the development of a center in the region, and participants reported that, if made available to them, they would make extensive and regular use of such a facility. CONCLUSIONS: We conclude that the establishment of a collaborative medical center specializing in the diagnosis and treatment of EDS, Hypermobility Spectrum Disorder, and related disorders in the Chicagoland area would greatly benefit patients by providing comprehensive care, alleviate the burden on overworked healthcare providers, and contribute to the sustainability of medical facilities.

Loeys-Dietz syndrome with a novel in-frame SMAD3 deletion diagnosed as a result of postpartum aortic dissection: A case report.

OBJECTIVE: Loeys-Dietz syndrome (LDS) is a rare, autosomal dominant connective tissue disorder which can aggressively affect the aortic vasculature. Limited information is available regarding its impact on pregnancy and postpartum outcomes. CASE REPORT: A pregnant 38-year-old nulliparous woman with mild aortic regurgitation and family history of aortic aneurysms presented with an aortic root measuring 49 mm. Despite concerns of an underlying connective tissue disorder, a definitive diagnosis was not reached. She delivered under strict blood pressure control, developed intractable uterine atony, and underwent uterine artery embolization. On the second postpartum day, aortic dissection was incidentally diagnosed, and aortic root replacement surgery was performed. Genetic testing revealed a novel in-frame SMAD3 deletion [NM_005902.4: c.703_708del, (p.Ile235_Ser236del)], leading to a diagnosis of LDS type 3. CONCLUSION: This case highlights the high postpartum aortic dissection risk in women with LDS, emphasizing the importance of early diagnosis in pregnant women with few clinical symptoms.

Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.