Undifferentiated Connective Tissue Disease Research Articles

"Scleroderma" and "Scleroderma-like" Capillaroscopic Pattern-Differences and Similarities.

The "scleroderma" type capillaroscopic pattern is a reference pattern in rheumatology that is a diagnostic sign for systemic sclerosis (SSc) in an appropriate clinical context and is observed in more than 90% of scleroderma patients. Similar microvascular changes, the so-called "scleroderma-like", have been described albeit in a lower proportion of patients with other rheumatic diseases, such as dermatomyositis (DM), undifferentiated connective tissue diseases (UCTD), systemic lupus erythematosus (SLE), etc. Three distinct stages of "scleroderma" pattern have been suggested by Cutolo et al., i.e., "early", "active", and "late". However, disease duration is just one of the factors that contributes to the progression of microvascular changes, and in this regard, "active" or even "late" pattern could be observed in patients with shorter disease duration. In addition, stable microvascular changes could be found for long periods in other cases. The aim of the study was to assess the presence of differentiating features between "scleroderma" pattern in SSc and "scleroderma-like" pattern in other rheumatic diseases. 684 capillaroscopic images demonstrating a "scleroderma" and "scleroderma-like" pattern have been analysed in the current retrospective cross-sectional study. 479 capillaroscopic pictures were obtained from 50 SSc patients, 105 from 7 DM patients, 38 from 10 rheumatoid arthritis (RA) patients, 36 images from 5 patients with SLE, and 26 images from 9 patients with UCTD. All capillaroscopic images used in the current analysis have fulfilled the criteria for "sclerderma/scleroderma-like" pattern, as the pathological changes in the capillaroscopic parameters have also been confirmed by quantitative measurement of capillary diameters, capillary density, and intercapillary distance. All the images have been categorized into one of the following groups, i.e., "early", "active" and "late" phases (according to the definition of Cutolo et al.), or "other" findings, the latter being specifically described as they could not be attributed to one of the other three categories. 479 capillaroscopic pictures were obtained from 50 scleroderma patients. 31 of them showed an "early", 391 an "active" phase, and 57 a "late" phase "scleroderma" type microangiopathy. In 69 images assessed as an "active" pattern, neoangiogenesis was found. In 43 out of 105 capillaroscopic pictures from DM patients, an "active" phase was detected; in 2 of the images, a "late" pattern was found, and in 60 capillaroscopic pictures, neoangiogenesis in combination with giant capillary loops was observed. Early microangiopathy was not found in this group. Among capillaroscopic images from SLE patients, "late" phase microangiopathy was not found. "Early" phase was present in 3 images, "active" phase in 29, neoangiogenesis in "active" phase in 4 pictures. Early microangiopathy was detected in 11 capillaroscopic pictures from RA patients (8 out of 9 patients), an "active" phase in 4 images (3 patients), and in 23 capillaroscopic images, neoangiogenesis with mild capillary derangement and capillary loss and single giant capillaries ("rheumatoid neoangiogenic pattern") were observed. Classic "late" type microangiopathy was not found in RA patients as well as among patients with UCTD. The predominant capillaroscopic pattern in UCTD patients was early microangiopathy (n = 23). The rest images from UCTD exhibited features of the "active" phase. In conclusion, early microangiopathy was observed in RA, SLE, and UCTD patients, but not in patients with DM. An "active" phase "scleroderma" type capillaroscopic pattern was detected in all patient groups other than SSc, i.e., DM, SLE, RA, and UCTD. "Late" phase "scleroderma" type microangiopathy was present in patients with scleroderma and DM and was not observed in SLE, RA, and UCTD. Despite the fact that in some cases, microangiopathy in scleroderma and other rheumatic diseases may be indistinguishable, the results of the current research have shown the presence of some differentiating features between "scleroderma" and "scleroderma-like" microangiopathy that might be a morphological phenomenon associated with differences in the pathogenesis and the degree of microvascular pathology in various rheumatic diseases.

Successful Pregnancy and Delivery after Premature Ovarian Insufficiency Combined with Undifferentiated Connective Tissue Disease: A Case Report

Background:: Premature ovarian insufficiency (POI) is extremely rare in the early stage of undifferentiated connective tissue disease. Patients with POI find it difficult to achieve successful pregnancy and delivery. Case Presentation:: A 27-year-old female visited an outpatient department for premature ovarian insufficiency (POI) and infertility. She had regular menstrual periods since she was 14 years old and had no history of systemic disease. Laboratory tests showed low estrogen (15 ng/L, range 19.6-144.2 ng/L), elevated follicle-stimulating hormone (34 U/L), low anti-Mullerian hormone (0.1 μg/L), normal prolactin (11.48 ng/mL), and thyroid stimulating hormone (TSH) levels (0.97 mU/L). She demonstrated smaller bilateral ovarian volume and positivity to antinuclear and antiphospholipid antibodies. After the failure of conventional drug therapy and in vitro fertilization, the patient became pregnant naturally after treatment with glucocorticoids. Conclusion:: Immunosuppression could help improve ovarian function and pregnancy outcomes in POI patients, but the therapeutic mechanisms are not clear and should be elucidated with more clinical studies.

Diagnostic performance of classification criteria for systemic lupus erythematosus: A validation study from Singapore.

Classification criteria for systemic lupus erythematosus (SLE) include American College of Rheumatology (ACR) 1997, Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 and European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria. Their performance in an Asian childhood-onset SLE (cSLE) population remains unclear as the clinical manifestations differ. We aim to evaluate the diagnostic performance in a cSLE cohort in Singapore. Cases were physician-diagnosed cSLE, while controls were children with mixed and undifferentiated connective tissue disease that posed an initial diagnostic challenge. Data were retrospec-tively reviewed to establish the 3 criteria fulfilled at diagnosis and over time. The study population included 120 cSLE cases and 36 controls. At diagnosis, 102 (85%) patients fulfilled all criteria. SLICC-2012 had the highest sensitivity (97.5%, 95% confidence interval [CI] 92.3-99.5), while ACR-1997 had the highest specificity (91.7%, 95% CI 77.5-98.3). All criteria had diagnostic accuracies at more than 85%. Over time, 113 (94%) fulfilled all criteria. SLICC-2012 remained the criteria with the highest sensitivity (99.2%, 95% CI 95.4-99.9), while ACR-1997 had the highest specificity (75.0%, 95% CI 57.8-87.9). Only SLICC-2012 and ACR-1997 had more than 85% diagnostic accuracy over time. Using a cutoff score of ≥13 for EULAR/ACR-2019 criteria resulted in improved diagnostic performance. SLICC-2012 criteria had the highest sensitivity early in the disease course in this first study evaluating the SLE classification criteria performance in a Southeast Asian cSLE cohort, while the ACR-1997 criteria had the highest specificity. Using a cutoff score of ≥13 for EULAR/ACR-2019 improved the diagnostic performance.

Clinical trial eligibility of a real-world connective tissue disease cohort: Results from the LEAP cohort

IntroductionClassification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases (CTDs) represent a real-world cohort. MethodsA comprehensive review of all major published phase-III trials in CTDs was performed (clinicaltrials.gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort. ResultsThere were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials (N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our real-world CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjögren's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria. ConclusionIn an unselected, real-world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.

Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2 (PGI2) analog (IV-PGI2A). From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A. Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal). Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

The Value of Nailfold Capillaroscopy in the Classification and Differential Diagnosis of Raynaud's Phenomenon in Rheumatology.

Among instrumental techniques, nailfold capillaroscopy plays a leading role in the assessment of Raynaud's phenomenon (RP) patients because it is the only method that provides opportunities for morphological assessment of capillaroscopic findings in the nailfold area, with proven diagnostic and prognostic significance in rheumatology. The discussion about updating the classification of RP in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. The presence of dilation of the "true" capillary diameters in primary RP could be observed. There are some cases of primary RP where the capillaroscopic pattern is completely normal and there are no dilated capillaries present, which could be related to the duration and severity of the symptoms. It is possible that longer duration and greater severity are associated with the appearance of capillary dilations, but more research is needed to confirm it. Rarely, pathological capillaroscpic features of microangiopathy could be observed in RP patients in whom clinical, laboratory and immunological findings are compatible with the diagnosis "primary RP". These cases should be defined as "suspected secondary RP" and require closer follow-up for the assessment of symptom evolution. Abnormal "scleroderma" type capillaroscopic pattern has been established as a new classification criterion for systemic sclerosis (SSc) in 2013. Similar changes ("scleroderma-like" pattern) could be observed in other rheumatic diseases, i.e., undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, including without evidence of overlap with scleroderma. The appearance of such microvascular abnormalities at disease presentation is less well studied in diseases different from SSc. However, "scleroderma-like" microangiopathy has also been reported as an initial sign in some systemic rheumatic diseases, such as UCTD and systemic lupus erythematosus. Thus, interpretation of capillaroscopic findings is performed in overall context, including clinical findings and laboratory and immunological test results.

OA22 Pregnancy in connective tissue diseases: a 30 year follow-up study of 465 pregnancies from a Spanish monocentric registry

Abstract Background/Aims Pregnancy in patients with connective tissue diseases (CTDs) are known to be at high risk for the occurrence of adverse pregnancy outcomes. We aimed to evaluate pregnancy outcomes in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS) and undifferentiated connective tissue disease (UCTD). Methods A retrospective and descriptive study was conducted from 1990 to 2020. All data were collected from the medical records of women of childbearing age with SLE, SSc, SS and UTCD enrolled in our clinic at the time of their pregnancy and childbirth. The obstetric, maternal and fetal outcomes were collected and compared regarding diagnosis and adverse outcomes. Results The study group included 295 patients: 125 patients (42%) with SLE; 50 patients (17%) with SSc; 80 patients (27%) with pSS; 40 patients (14%) with UCTD. A total of 465 pregnancies were registered. The mean age at delivery was 31.5±8.5 years and the mean duration of disease was 7.2±5.6 years. Pregnancy loss occurred in 21% of patients, live births in 66% of pregnancies, preterm delivery in 8%, postpartum haemorrhage in 6%, preeclampsia in 5%, placental abnormalities in 4%, ectopic pregnancy in 3%, and premature rupture of membranes in 2%. Treatment with hydroxychloroquine (HCQ) was received in 115 pregnancies in SLE (59%), 21 pregnancies in SSc (24%) 62 pregnancies in pSS (52%) and 32 pregnancies in UCTD (49%). Exposure to corticosteroids and biologics during pregnancy was 23 (18.4%), 6 (12%), 15 (19%) and 3 (7.5%), respectively. Patients with SLE had a higher risk of fetal morbidity, including abortion (p = 0.03), mean abortion rate (p = 0.03), preeclampsia (p = 0.04), ectopic pregnancy (p = 0.03), preterm delivery (p = 0.02) and postpartum haemorrhage (p = 0.01) than patients without SLE. The multivariate model found an association between unfavourable pregnancy outcomes and disease activity (OR 2.4; 95% CI 1.3-7.2; p 0.003), whilst HCQ during pregnancy (OR 0.23; 95% CI 0.03-0.82) had a protective effect. Conclusion 66% of pregnancies in patients with autoimmune diseases resulted in live births. Patients with SLE had higher rates of fetal and maternal morbidity than SSc, pSS and UCTD. Disease activity was associated with unfavourable pregnancy outcomes. Exposure to HCQ had a protective effect during pregnancy. Disclosure C. Sieiro Santos: None. P. Pérez García: None. J. Ordas Martínez: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

E018 Prophylactic co-trimoxazole prescribing practice in patients who received rituximab therapy: comparison across indications and specialties

Abstract Background/Aims Rituximab is a chimeric anti-CD20 monoclonal antibody targeting B-cells used as part of treatment algorithms for malignancy and autoimmune diseases. As is the case of other immunosuppressive agents, rituximab increases the risk of infections. Primary prophylaxis with co-trimoxazole may be considered in high-risk cohort of patients to prevent opportunistic infection, particuarly Pneumocystis jerovecii pneumonia (PJP). To investigate the prescribing practice for prophylactic co-trimoxazole in patients who received rituximab infusion in a large tertiary referral centre. To compare practices between rheumatology and nephrology department. To compare the incidence of hospitalisation for infection (particularly PJP) between those prescribed prophylactic co-trimoxazole and those who did not. Methods This was a single centre retrospective observational study over a 3 year period assessing prophylactic co-trimoxazole prescribing practice in 185 patients attending rheumatology or renal services in Cork University Hospital (CUH) and receiving rituximab. Co-trimoxazole prophylactic treatment was defined as prophylaxis dose of co-trimoxazole (either 480mg daily or 960mg three times per week) received during rituximab treatment and at least 6 months post completion of treatment. Results 185 patients’ medical charts were reviewed. Only 28 patients received prophylaxis with co-trimoxazole. The majority of patients (n = 24, 85%) who received prophylaxis with co-trimoxazole had an underlying diagnosis of small vessel vasculitis (SVV). Co-trimoxazole was more commonly prescribed by nephrologists (n = 17, 71% primarily for SVV) as compared to rheumatologist (n = 7, 29% primarily for SVV). 156 patients were not prescribed prophylactic co-trimoxazole. The primary indication for rituximab in these patients was inflammatory arthropathy (IA) (n = 72,46%), SVV (n = 26, 16%), systemic lupus erythematosus (n = 19, 12%), with the remainder accounted for by scleroderma, undifferentiated connective tissue disease, membranous nephropathy (MN), myositis, focal segmental glomerulosclerosis and amyloid renal disease. No patient was admitted over the course of the study period with PJP. 59 patients required hospital admissions due to other infections, most commonly patients with SVV. The most common infections were respiratory tract and urinary tract infections. Overall infections requiring hospitalization were more common in the group receiving prophylaxis, perhaps highlighting the vulnerable nature and greater prednisolone prescribing in the SVV cohort. No difference was seen between groups in the prevalence of UTIs. Conclusion In this cohort co-trimoxazole prophylaxis was more commonly prescribed for patient with small vessel vasculitis and differences in prescribing patterns were seen between nephrologists and rheumatologists. With greater awareness of the heightened risk of PJP in patents receiving rituximab consideration should be given to use of antibiotic prophylaxis for other indications. Disclosure S. Tio: None. J. Morrow: None. S. Cowley: None. M. Clarkson: None. G. Murphy: None.

E012 Burden and risk factors for cardiovascular involvement in connective tissue disease

Abstract Background/Aims Connective tissue diseases (CTD) are associated with several cardiovascular manifestations. Cardiovascular diseases (CVD) are significant cause of morbidity and premature death. The pathogenesis of CVD in CTD patients is incompletely understood and likely multifactorial. Traditional risk factors for atherosclerosis are common among patients with CTD as well as metabolic syndrome. Furthermore, diabetes, dyslipidaemia, hypertension, and obesity may all be exacerbated by connective tissue disease itself or treatment with glucocorticoids. The aim of this study was to assess the burden of CVD and the risk factors for the development of cardiovascular disease in patients with CTD. Methods This was a retrospective study from a single centre. We reviewed clinical records of CTD patients as determined by treating rheumatologist. This CTD cohort included patients with systemic lupus erythematosus (SLE), myositis, systemic sclerosis, Sjogren’s syndrome, mixed and undifferentiated connective tissue diseases. Data on demographic, clinical, laboratory parameters, cardiac investigations, treatment and outcome were collected from electronic patient records. CVD and traditional risk factors were defined using standard criteria. Results A total of 298 patients with CTD were included in the analysis. Mean age of the cohort was 61±17.7 years and majority were females (n = 240, 80.5%). Of the 298 patients, 64 had CVD (21.5%). Most common CVD was ischaemic heart disease (17 patients) followed by hypertension (12), arrhythmia (9), pulmonary arterial hypertension (7), valvular diseases (5), pericardial disease (3), cardiomyopathy (3), myocarditis (2), thromboembolism (3), aortic dissection (2) and coronary spasm (1). Patient with CTD who had CVD were older (72.5±12.2 years) compared to CTD patients who did not develop CVD (non-CVD group, 57.7±17.6 years). The duration of CTD was shorter in patients with CVD (88.9±41.7 months), compared to 106±84.3 months in non-CVD group. The risk factors such as smoking, diabetes and dyslipidaemia was higher in the CVD group. Comparing CVD vs non-CVD patients respectively, systolic BP (147.1±23.0 vs 133.6±18.3mmHg), diastolic BP (83.2 ± 16.3 vs 78.2 ± 11.2mmHg) and serum uric acid (321.8±97.4 vs 292±83.9mg/dL) values were higher and statistically significant (p < 0.05) in CVD group. Patients with CVD had longer exposure to steroids (50%) compared to non-CVD patients (31.6%). They required high dose steroids (9.4% vs 5.6% in non-CVD patients). Current and previous DMARD use was also higher in patients who had CVD (51.6% vs 44.9%). Conclusion This study has demonstrated high burden of cardiovascular disease in CTD patients. Traditional risk factors were more prevalent in the CVD group. DMARD’s and steroid use was also higher in the CVD group. Screening for cardiovascular diseases and disease control in CTD patients is paramount for better outcomes. Further analysis will be carried out for risk factors and relevant outcomes. Disclosure K.K. Garg: None. S. Sampath: None. A. Erinjogunola: None. B. Ting: None. H. Noori: None. G.M. Koduri: None.

P150 Diagnostic utility of anti-cN1A autoantibody testing in sporadic inclusion body myositis

Abstract Background/Aims Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients aged over 50 years. Diagnostic criteria encompass clinical, biochemical, and myopathological features. Certain myopathological features possess high specificity but low sensitivity; reliance on such findings may lead to delayed or misdiagnoses. The discovery of autoantibodies against cytosolic 5'-Nucleotidase 1A (cN1A) in sIBM patients suggests an autoimmune component in pathogenesis, but the inclusion of this autoantibody in diagnostic criteria remains uncertain. Additionally, optimal testing methodology has not been established, with varying techniques (e.g., ELISA/line-blot) in use. We assessed antibody profiles in an sIBM cohort and reviewed diagnoses in anti-cN1A positive patients. Methods This study was based at the Northern Care Alliance NHS Foundation Trust which hosts a tertiary neuromuscular referral service for the North-West of England. Data sources included myositis clinic and immunology results databases. All patients tested using a validated myositis line-blot immunoassay (EUROLINE 16 Antigen et cN1A [EUROIMMUN]) November 2021-April 2023 were included. Diagnoses of all tested patients were identified through case-note review. Sensitivity and specificity metrics were calculated based on diagnosis and anti-cN1A antibody status. Results The total number of patients tested for anti-cN1A was 495. Of these, 10 patients had a diagnosis of sIBM. The true-positive and false-negative rates were both 50% (n = 5 each). Of the 485 patients who did not have sIBM, true-negativity was 97.52% (n = 473) and false-positivity 2.47% (n = 12). Overall, anti-cN1A had a sensitivity of 50%, specificity of 97.52%, positive predictive value of 29.41% and negative predictive value of 98.95% for sIBM (Table 1). Patients with a false-positive anti-cN1A antibody had diagnoses of: primary Raynaud’s (n = 5); undifferentiated CTD (n = 3); systemic sclerosis (n = 2); non-sIBM myositis (n = 2). Conclusion Anti-cN1A detected using the EUROLINE 16 Antigen assay has high specificity but lacks sensitivity for sIBM, consistent with previous literature. These findings suggest that this assay performs similarly to other cN1A detection methodologies and has utility in confirming the diagnosis of sIBM where there is clinical suspicion. Further real-world analysis of antibody data in larger cohorts is required to clarify the role of serological testing in sIBM diagnostic criteria, to improve diagnostic delays and misclassifications. Disclosure M. Al-Attar: None. T. Khoo: None. J.B. Lilleker: None. H. Chinoy: None.

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

BackgroundFemales 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. MethodsWe 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. ResultsThe mean age at pregnancy was 35 ± 7.0 years for patients with SLE and 35 ± 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). ConclusionOur 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.

Pruritic Erythema in a Child with Undifferentiated Connective Tissue Disease.

Pruritic Erythema in a Child with Undifferentiated Connective Tissue Disease.

The utility of USB microscope for assessment of Raynaud’s phenomenon patients in rheumatology practice

The aim of the study was to assess the utility of USB microscope (DinoLite) for evaluation of patients with primary and secondary Raynaud’s phenomenon (RP) in rheumatic diseases, , using magnification 200x.
 Methods: The study represents retrospective analysis of capillaroscopic images of 53 patients with RP – primary and secondary in the context of systemic sclerosis (SSc) or other rheumatic diseases i.e., undifferentiated connective tissue disease (UCTD), prescleroderma and systemic lupus erythematosus (SLE). Capillaroscopic images are obtained from 8 fingers (II÷V bilaterally) using USB microscope (DinoLite) at magnification 200x. Capillary diameters were measured (arterial, venous and apical loop) as well as the number of capillaries per millimeter and capillary length. The capillaroscopic images were categorized into the following groups i.e., 1. absence of microangiopathy: i) normal pattern, ii) nonspecific changes; 2. presence of microangiopathy i.e., “scleroderma/ scleroderma-like” pattern.
 Results: Images suitable for analysis with good visibility that permit analysis of the major capillaroscopic parameters were available in all patients (100%). Among 53 included patients, 14 patients were with SSc, 12 cases with primary RP, and 27 patients with secondary RP in other connective tissue diseases (22 patients with UCTD, 1 – with prescleroderma and 4 patients with SLE). „Scleroderma“ pattern was detected in 11 patients with SSc and in all these cases the capillaroscopic images were classifiable into one of the three distinct validated phases i.e., “early”, ”active” and ”late”. Presence of microvascular changes type “scleroderma-like” pattern was detected also in 17 among 27 patients with other connective tissue diseases. In primary RP patients, capillaroscopy revealed either normal pattern or nonspecific findings, but without features of microangiopathy.
 Conclusion: Capillaroscopic images of good quality, which could be analyzed and interpreted, are usually obtained using USB microscope. This permits evaluation of the major capillaroscopic parameters including quantitative measurement of the capillary diameters, capillary density and length. Assessment of the degree of microvascular changes i.e., staging of microangiopathy is also applicable and was possible in all cases with microangiopathy. The available software although less sophisticated vs those of videocapillaroscopes, providess the opportunity for adequate analysis of capillaroscopic parameters. The images obtained via USB microscope using magnification 200x are easily classified into “scleroderma”/“scleroderma-like” pattern, non-specific changes and normal findings using also the software of the device. Thus, USB microscopes using standard, 200x magnification could be suggested as an alternative of videocapillaroscopes in every day rheumatology practice especially in low-budget cases.

Effectiveness and safety of eltrombopag in connective tissue disease patients with refractory immune thrombocytopenia: a retrospective study.

We aimed to investigate the safety and effectiveness of eltrombopag for adult patients with refractory immune thrombocytopenia (ITP) secondary to connective tissue disease (CTD). This is a single-centre, retrospective cohort and propensity score-matched study. Data from CTD-ITP patients treated with eltrombopag between January 2019 and January 2023 were retrospectively analysed. Baseline characteristics and follow-up information were recorded. CTD patients without ITP were matched to identify the risk factors associated with CTD-ITP performed by Logistic regression analysis. Twenty patients were enrolled, including 5 systemic lupus erythematosus (SLE), 9 Sjögren's syndrome (SS) and 6 undifferentiated connective tissue disease (UCTD). Nineteen (95%) patients were female, and the median age was 59 years. Logistic regression analysis showed that anaemia (OR = 8.832, P = 0.007) was associated with increased risk of ITP, while non-erosive arthritis (OR = 0.045, P = 0.001) and interstitial lung disease (OR = 0.075, P = 0.031) were associated with reduced risk. Fourteen patients (70%) achieved a complete response (CR) and one (5%) achieved a partial response (PR). The median response time was 14 days. The median platelet count was 8.5 × 109/l at baseline of eltrombopag and increased to 122 × 109/l after 4 weeks. No adverse events were observed. Eltrombopag appears to be effective, safe and well-tolerated in refractory ITP patients with CTD; larger studies are needed to confirm the generalizability of these findings.

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.

Anisocoria after vitrectomy and scleral buckle surgery in a patient with undifferentiated connective tissue disease.

Anisocoria after vitrectomy and scleral buckle surgery in a patient with undifferentiated connective tissue disease.

Systemic Sclerosis in Individuals With Exposure to World Trade Center Ground Zero Rescue and Recovery Efforts: A Case Series.

The World Trade Center (WTC) attack in New York resulted in a dust plume containing silica, hydrocarbons, and asbestos. Autoimmune disorders have been reported among those with WTC site exposure. The characteristics of individuals developing systemic sclerosis (SSc) have not been previously described. The purpose of this study was to describe the features of patients with SSc with WTC exposure. Data were collected from 11 patients with SSc or SSc spectrum conditions who reported exposure to the WTC site. Seven patients completed an exposure assessment. Of the 11 patients, the majority (n = 8) were female. The median (range) for age at diagnosis was 46 (36-75) years, time between exposure and first non-Raynaud phenomenon SSc symptom was 8 (1-19) years, and time between exposure and diagnosis was 11 (2-18) years. Fifty-five percent had SSc onset > 5 years from WTC exposure. Five patients had limited cutaneous SSc, 3 patients had diffuse cutaneous SSc, 1 patient with SSc features met criteria for mixed connective tissue disease (CTD), and 2 patients had undifferentiated CTD with features of SSc. Four patients had overlapping features with other CTDs. Interstitial lung disease (ILD) was present in 10 patients. Five of 11 patients had a history of tobacco use. Seven of 7 patients who completed the questionnaire reported other hazardous exposures outside of WTC. Of these, only 2 patients reported personal protective equipment use. A high frequency of ILD and overlap features were observed among patients with SSc with WTC exposure. Future studies are needed to characterize this association.

Pulmonary Strongyloidiasis in a Patient with Newly Diagnosed Undifferentiated Connective Tissue Disease: Case Report

Pulmonary Strongyloidiasis in a Patient with Newly Diagnosed Undifferentiated Connective Tissue Disease: Case Report

Left ventricular longitudinal strain in patients with undifferentiated connective tissue disease and arrhythmia

Aim. To evaluate the left ventricular longitudinal strain in patients with arrhythmia and undifferentiated connective tissue disease (UCTD).Material and methods. This cross-sectional comparative study included young patients with arrhythmia and UCTD (43 men and 84 women; mean age, 30,82±8,17 years (group 1, n=127)). The control group included volunteers with single phenotypic characteristics of UCTD, comparable in age and sex (9 men and 21 women, mean age, 34,13±6,87 years (group 2, n=30)). A standard clinical examination, 72-hour electrocardiographic monitoring, and speckle-tracking echocardiography were performed.Results. Patients of group 1 were characterized by lower global systolic longitudinal myocardial strain compared to the control group: -22,96% [-24,56%; -21,50%] in group 1 vs -24,73% [-25,25%; -23,84%] in group 2 (p=0,016). A local decrease in longitudinal myocardial strain (in two or more segments) was noted in 62,2% of patients in group 1 and 13,3% of patients in group 2 (p=0,025). In group 1, a relationship was revealed between class I premature ventricular contractions (PVCs) and a longitudinal strain decrease in the medial anterior (r1=0,253, p=0,004) and apical anterior (r1=0,253, p=0,004) segments, as well as between class V PVCs and strain decrease in the basal lower (r1=0,215, p=0,021) and middle anterior (r1=0,211, p=0,023) segments. In addition, there was a moderate correlation between mitral valve prolapse (MVP) and a decrease in longitudinal systolic strain in the basal inferolateral (r1=0,405, p=0,041) and basal anterior (r1=0,519, p=0,003) segments.Conclusion. Local decrease in left ventricular longitudinal systolic strain in association with arrhythmia and MVP in patients with UCTD makes it possible to recommend speckle-tracking echocardiography for early non-invasive assessment of myocardial remodeling in this cohort of patients.

Matrix metalloproteinases system profile analysis and their endogenous inhibitors in children with periodontal diseases and various dysplasia phenotypes

Relevance. The search and development of modern non-invasive methods for early periodontal disease detection are of scientific and practical value for a personalized approach to disease course prognosis and explaining the choice of treatment tactics. Morphological immaturity, high intensity of anabolic processes, functional failure of neurohumoral, endocrine and immunological defence systems combined with an imbalance between the synthesis and degradation of extracellular matrix components in children with undifferentiated connective tissue disease (UCTD) significantly increases the risk of developing periodontal diseases. The available data on the activity of salivary matrix metalloproteinases (MMPs), which play a leading role in regulating connective tissue protein metabolism and bone remodelling mechanisms in children with UCTD of various degrees, are scarce and require further study.Purpose. The study aimed to explain the clinical, diagnostic and prognostic value of MMPs as markers of inflammatory periodontal diseases in children with UC TD and dysplastic disorders of various se verity.Material and methods. The study included 67 children with UCTD (main group) and 34 children of health groups I and II (comparison group) aged 12-17. The UCTD severity was established according to the diagnostic criteria by L. N. Abbakumova (2006) and a scale for assessing the significance of phenotypic and visceral signs. The main group was divided into two subgroups: Subgroup 1 (n = 38) – children with mild and moderate UCTD; Subgroup 2 (n=29) – children with severe UCTD. The studied groups had their periodontal status assessed, as well as the concentration of MMP-1, MMP-2, MMP-8, MMP-9 and their tissue inhibitors (TIMP-1, TIMP-2) in the oral fluid identified using the enzyme immunoassay, along with calculation done for the MMP ⁄ TIMP coefficients that set a balance between the degradation and synthesis of collagen.Results. The children with phenotypic signs of UCTD in the oral fluid appeared to show a statistically significant increase in the MMP-1, MMP-2, MMP-8, and MMP-9 levels and an imbalanced ratio in MMP-1⁄TIMP-1, MMP- 2⁄TIMP-2, MMP-8⁄TIMP-1, MMP-9⁄TIMP-1, compared with health groups I, II. An increase in the MMP-1, MMP-2, and MMP-8 concentrations, along with dominating expression of MMP-9 over TIMP-1 in the oral fluid of children of Subgroup 2, causes an increase in intensity and prevalence of periodontal diseases compared to the patients in Sub-group 1 and comparison group.Conclusion. Thus, when children with UCTD don’t demonstrate an increase in specific tissue inhibitors TIMP-1 and TIMP-2 in their oral fluid, along with an increase in the levels of the respective matrixins is the key pathogenetic factor in the degradation of extracellular matrix proteins, which causes a depressing impact on the proliferative activity in the periodontal set of tissues.