Placental Pathologic Features and Perinatal Outcomes in Pregnant Woman With Autoimmune Connective Tissue Disease.

INTRODUCTION: We aimed to investigate the association between perinatal outcomes and placental pathological features in pregnant women with ACTD, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and undifferentiated connective tissue disease (UCTD). MATERIALS AND METHODS: Placental tissue from SLE (n = 44), APS (n = 45), and UCTD (n = 45) were included, and contemporaneous deliveries of placenta were served as a control group (n = 46) between September 2015 and March 2021. The placental histopathology was evaluated using the Manual of Human Placental Pathology and classified according to the Amsterdam consensus framework. RESULTS: SLE pregnant women have a higher rate of cesarean section (61.40%), premature birth (24.56%), and SGA (26.32%) when compared to control group (p = 0.008, p = 0.005, and p = 0.000, respectively). The rate of vascular malperfusion, inflammatory-immune lesions, and other placental lesions in the SLE group was 47.73%, 56.82%, and 63.64%, which were higher than the control group (p = 0.000, p = 0.000, and p = 0.006, respectively). In the meantime, the incidence of inflammatory-immune lesions in the APS group (42.22%, p = 0.004) and vascular malperfusion in the UCTD group (37.78%, p = 0.007) were increased when compared to the control group. CONCLUSIONS: SLE appeared to confer increased risk for a wide range of adverse perinatal outcomes. We determined elevated placental histopathology risk for most women with ACTD, including vascular maldevelopment, vascular malperfusion, and inflammatory-immune lesions.

[Humoral Immunity Abnormalities in Advanced Maternal-Age Women With Recurrent Spontaneous Abortion: A Single Center Study]. / é«˜é¾„å¤å‘æ€§æµäº§æ‚£è€ ä½“æ¶²å ç–«å¼‚å¸¸çš„å•ä¸­å¿ƒç ”ç©¶.

Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein Ⅰ antibodies (ß2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.

Asthma in patients with the syndrome of undifferentiated dysplasia of connective tissue: peculiarities of the course or mutually aggravating mechanisms?

OBJECTIVE: Aim: To analyse laboratory and biochemical features of the severe persistent course of asthma in patients with undifferentiated connective tissue dysplasia (UCTD) syndrome, and their phenotypic and visceral stigmas of dysembryogenesis. PATIENTS AND METHODS: Materials and Methods: We enrolled 60 male patients with asthma, aged from 23 to 62 years (mean age (46.83 ±0.85) years): 30 patients with the background of UCTD, and 30 - without UCTD. We analysed clinical, somatometric, surveying (original questionnaire based on the phenotypic map of Glesby), instrumental (spirography, echocardiography, endoscopy, esophagofibrogastroduodenoscopy) and laboratory (including eosinophilic granulocytes and aldosterone levels) data. RESULTS: Results: Correlations were found in men with UCTD between the number of UCTD markers and rate of earlobe diagonal fold (r=+0.75; р<0.05), asthenic constitution (r=+0.72; р<0.05), easy bruising (r=+0.7; p<0.05) and straight abdominal line hernia (r=+0.52; p<0.05). Average aldosterone serum level in patients with UCTD (176,10 ±11,22) was significantly higher than in those without UCTD (142,77 ±9,43), (p<0.05), as well as average eosinophils levels (1.3 ±0.25 vs. 0.57 ±0.12, p<0.05). In the absolute majority of patients with UCTD (93.3%) asthma onset was confirmed after pneumonia, and their age of asthma manifestation was significantly higher (37.2 ±1.21) than in patients without UCTD (21.4 ±1.13). Also, in patients with UCTD there was a high number of severe exacerbations during the last year (2.7 ±0.12 per year) on the background of high doses of combined inhaled glucocorticosteroids use. CONCLUSION: Conclusions: Identified "phenotypic profile", clinical and biochemical features of patients with asthma on the background of UCTD syndrome, which determine the severe course and early formation of asthma complications, will further accelerate the diagnosis of this asthma phenotype and improve approaches to the selection of treatment regimens for these patients.

Comparing pregnancy outcomes in patients with Systemic Lupus Erythematosus (SLE) and Undifferentiated Connective Tissue Disease (UCTD): a descriptive cohort study.

BACKGROUND: Females diagnosed with systemic lupus erythematosus (SLE) face an elevated risk of adverse pregnancy outcomes (APOs). However, the evidence regarding whether a similar association exists in patients with undifferentiated connective tissue disease (UCTD) is inconclusive. METHODS: We conducted a retrospective review (2006-2019) of pregnancy outcomes among patients with SLE (n = 51) and UCTD (n = 20) within our institution. We examined the occurrence of various APOs, encompassing miscarriage, stillbirth, termination, preterm birth, pre-eclampsia, eclampsia, HELLP syndrome, intrauterine growth restriction, abruption placentae, congenital heart block, or other cardiac abnormalities. RESULTS: The mean age at pregnancy was 35 ±â€¯7.0 years for patients with SLE and 35 ±â€¯6.8 years for those with UCTD (p = 0.349). The proportion of Caucasian women was 47% in SLE and 80% in UCTD. Pregnancies in both groups were planned (81% in SLE and 77% in UCTD), and patients presented with inactive disease at conception (96% in SLE and 89% in UCTD). Hydroxychloroquine at conception was utilized by 86% of women with SLE, in contrast to 36% in the UCTD group. Both, SLE and UCTD cohorts exhibited low rates of disease flares during pregnancy and/or puerperium (14% vs. 10%). The incidence of APOs was 15.6% in SLE patients compared to 5% in those with UCTD (Risk difference 19.5%; 95% confidence interval: -3.9 to 43.1; p = 0.4237). CONCLUSION: Our study underscores the importance of strategic pregnancy planning and the maintenance of appropriate treatment throughout pregnancy to ensure optimal disease management and minimize adverse outcomes in both SLE and UCTD pregnancies.

Disease evolution and organ damage accrual in patients with stable UCTD: a long-term monocentric inception cohort.

OBJECTIVES: Undifferentiated connective tissue diseases (UCTDs) are systemic autoimmune conditions that cannot be diagnosed nor classified as defined CTD; the majority maintains an undifferentiated profile (stable UCTD, sUCTD) over time. Data on long-term outcomes of sUCTD are lacking. METHODS: Retrospective longitudinal analysis of an inception cohort of 141 patients with sUCTD.Disease evolution and damage accrual were evaluated at 1, 5 and 10 years. Partial least square (PLS) regression was used to identify the basal variables contributing to damage accrual at 1, 5 and 10 years of follow-up. Trend of damage over time was compared with a cohort of age-matched and sex-matched patients with systemic lupus erythematosus (SLE) by means of Nelson-Aalen analysis. RESULTS: 11.3% of patients evolved to a definite CTD after a median 11 years (IQR 6-25) from the first symptom. At last visit, 10% were on glucocorticoids and 6% on immunosuppressive therapy. In 27.3%, at least one item of organ damage was recorded according to the SLICC/DI score (mean score 1.19±0.46). At PLS analysis, age at diagnosis and age at first symptoms were related to damage at 1 year, not taking antimalarials and taking immunosuppressants were associated with damage at 5 years.The mean survival without damage was 9.3 years in sUCTD and 8.4 years in SLE. The 10-year probability without damage was 62% and 23% in SLE and sUCTD, respectively (p=0.015). CONCLUSIONS: Although less significantly impacted than in patients with SLE, in the long-term UCTDs can accumulate organ damage and evolve into defined connective tissue diseases.

Clinical features of patients with connective tissue disease with anti-human upstream binding factor antibodies: A single-center retrospective study.

Anti-human upstream-binding factor (anti-hUBF) antibodies have been reported predominantly in patients with connective tissue diseases (CTDs); these have also been reported in patients without CTDs such as hepatocellular carcinoma. Because of the low frequency of expression and few case reports, there is no consensus on the clinical significance of these antibodies. Thus, we aimed to examine the clinical features of patients with anti-hUBF antibodies and analyzed 1042 patients with clinically suspected CTDs. The presence of anti-hUBF antibodies was screened using immunoprecipitation assays. Of the 1042 patients, 19 (1.82%) tested positive for anti-hUBF antibodies; among them, 10 (56%) were diagnosed with undifferentiated CTD (UCTD), six with systemic sclerosis (SSc) and three with other diseases. Five of the 10 patients with UCTD were referred to our hospital with suspected SSc. None of the five patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria, but three scored seven points, a relatively high score. Six anti-hUBF-positive patients with SSc had a significantly lower modified Rodnan skin score (mRSS) than that of anti-hUBF-negative patients with SSc (2 [0-2] vs 7 [0-49], p < 0.01). Compared with anti-topoisomerase I-positive patients, anti-hUBF-positive patients had a significantly lower mRSS (2 [0-2] vs 13 [0-42], p < 0.01) and lower incidence of scleroderma renal crisis (0 of 6 vs 8 of 184, p < 0.01). Compared with anti-centromere-positive patients, anti-hUBF-positive patients had a higher incidence of interstitial lung disease (ILD), but the difference was not statistically significant (4 of 6 vs 19 of 239). In conclusion, anti-hUBF antibodies were predominantly detected in patients with CTDs and UCTD. In patients with CTDs, SSc exhibited a high ratio, displaying a lower mRSS and higher incidence of ILD. In patients with UCTD, careful follow-up is recommended as they may develop CTDs in the future.

[Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease].

OBJECTIVE: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). METHODS: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. RESULTS: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. CONCLUSION: Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Epipericardial fat necrosis in chest CT and MRI: a case report of an unusual cause of chest pain associated with the initial diagnosis of undifferentiated connective tissue disease.

BACKGROUND: Epipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients. Clinically, it presents with severe acute left pleuritic chest pain, often leading the patient to the Emergency Room (ER). CASE PRESENTATION: A 23-year-old male, smoker (5 pack-years), was evaluated in the ER due to left pleuritic chest pain, worsening with deep breathing and Valsalva maneuver. It was not associated with trauma and did not present other symptoms. The physical examination was unremarkable. The arterial blood gases while breathing room air and the laboratory tests, including D-dimers and high-sensitivity cardiac Troponin T, were normal. The chest radiograph, electrocardiogram, and transthoracic echocardiogram showed no abnormalities. A computed tomography (CT) pulmonary angiogram showed no signs of pulmonary embolism but depicted at the left cardiophrenic angle a focal 3 cm ovoid-shaped fat lesion with stranding and thin soft tissue margins, consistent with necrosis of the epicardial fat, which was confirmed by magnetic resonance (MRI) of the chest. The patient was medicated with ibuprofen and pantoprazole, with clinical improvement in four weeks. At a two-month follow-up, he was asymptomatic and presented radiologic resolution of the inflammatory changes of the epicardial fat of the left cardiophrenic angle on chest CT. Laboratory tests revealed positive antinuclear antibodies, positive anti-RNP antibody, and positive lupus anticoagulant. The patient complained of biphasic Raynaud's phenomenon initiated five years ago, and a diagnosis of undifferentiated connective tissue disease (UCTD) was made. CONCLUSIONS: This case report highlights the diagnosis of EFN as a rare and frequently unknown clinical condition, which should be considered in the differential diagnosis of acute chest pain. It can mimic emergent conditions such as pulmonary embolism, acute coronary syndrome, or acute pericarditis. The diagnosis is confirmed by CT of the thorax or MRI. The treatment is supportive and usually includes non-steroidal anti-inflammatory drugs. The association of EFN with UCTD has not been previously described in the medical literature.

Anti-ganglioside antibody positive neuromyelitis optica spectrum disorders with peripheral neuropathy: a case report.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is a group of autoimmune-mediated disorders of the central nervous system primarily involving the optic nerve and spinal cord. There are limited reports of NMOSD associated with peripheral nerve damage. CASE PRESENTATION: We report a 57-year-old female patient who met the diagnostic criteria for aquaporin 4 (AQP4)-IgG positive NMOSD with undifferentiated connective tissue disease and multiple peripheral neuropathy. In addition, the patient was positive for multiple anti-ganglioside antibodies (anti-GD1a IgG antibodies and anti-GD3 IgM antibodies) and anti-sulfatide IgG antibodies in serum and cerebrospinal fluid. After treatment with methylprednisolone, gamma globulin, plasma exchange, and rituximab, the patient's status improved and was subsequently discharged from our hospital. CONCLUSIONS: The neurologist should be aware of the unusual association between NMOSD and immune-mediated peripheral neuropathy undifferentiated connective tissue disease and nerve damage mediated by multiple antibodies may have combined to cause peripheral nerve damage in this patient.

Undifferentiated Connective Tissue Disease: Comprehensive Review.

PURPOSE OF REVIEW: Undifferentiated connective tissue disease (UCTD) is characterized by the presence of clinical symptoms of a systemic autoimmune disease in addition to laboratory evidence of autoimmunity with the patients not fulfilling any of the widely used classification criteria for classic autoimmune diseases. The presence of UCTD as a separate entity versus an early stage of such diseases as systemic lupus erythematosus (SLE) or scleroderma has long been debated. Given the uncertainty regarding this condition, we performed a systematic review on the topic. RECENT FINDINGS: UCTD can be subcategorized as evolving (eUCTD) or stable UCTD (sUCTD) based on its evolution towards a definable autoimmune syndrome. Analyzing the data from six UCTD cohorts published in the literature, we found that 28% of patients have an evolving course with the majority developing SLE or rheumatoid arthritis within 5-6 years of the UCTD diagnosis. From the remaining patients, 18% do achieve remission. Published treatment regimens were similar to other mild autoimmune diseases with low-dose prednisone, hydroxychloroquine, and NSAID. One-third of patients did need immune suppressive medications. Importantly, the reported outcomes were excellent with survival rates of more than 90% over 10 years. It has to be noted though that as data on patient related outcomes are not available to date, the exact impact of this condition on quality of life is unclear. UCTD is a mild autoimmune condition with generally good outcomes. There is still great uncertainty though regarding diagnosis and management. Going forward, consistent classification criteria are needed to advance UCTD research and eventually provide authoritative guidance on the management of the condition.

[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.

Frequency of ANA/DFS70 autoantibodies in Colombian patients with undifferentiated connective tissue disease.

The objective was to describe the clinical characteristics and the frequency of the ANA/DFS70 autoantibodies in patients affected by undifferentiated connective tissue disease (UCTD) in a tertiary hospital in Colombia. This descriptive cross-sectional study enrolled patients who fulfilled the classification criteria for UCTD. ANAHEp- 2 test and the modified assay for ANA/DFS70 autoantibodies were performed through the indirect immunofluorescence technique. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and the antibodies to anti-extractable nuclear antigens, DNA, phospholipids (IgG, IgM, IgA), and cyclic citrullinated peptide were also evaluated. Fifty-three patients were studied; 42/53 (79%) tested positive for ANA and 5/42 (11.9%) for ANA/DFS70 antibodies with a dense fine speckled fluorescent pattern (AC-2) in ANA HEp-2 test that was confirmed by a modified HEp-2-DFS70 assay. Patients had arthralgia (87%, n=47), non-erosive arthritis (66%, n=34), xerostomia (64%, n=34), xerophthalmia (42%, n=22), and Raynaud's phenomenon (17%, n=9). Arthralgia, xerophthalmia, xeroderma, and absence of disease evolution to a specific disease over five years were more frequent in patients with a positive result for the anti-DFS70 antibodies. The ANA/DFS70 autoantibodies were more frequent in patients with UCTD compared to other rheumatic diseases for which they were initially evaluated. More studies are required to support the predictive role of this antibody to the absence of progression to a well-defined connective tissue disease.