Determinants of health-related quality of life across the spectrum of connective tissue diseases using latent profile analysis: results from the LEAP cohort.

OBJECTIVES: Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. METHODS: Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. RESULTS: A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. CONCLUSION: Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.

Causes of Raynaud's phenomenon and the predictive laboratory and capillaroscopy features for the evolution to a definite connective tissue disease.

OBJECTIVE: In patients with RP, capillaroscopy is useful for discriminating primary from secondary causes. There are certain capillaroscopy and lab values as predictive factors leading to a known CTD. We conducted the present study to evaluate the causes of RP in our area and followed the studied subjects to find prognostic factors indicating a definite CTD or remaining a UCTD. METHODS: In this retrospective cohort study we included all adult patients with RP who were referred for capillaroscopy from 2010 to 2019. All the patients with primary and secondary RP with follow-up were evaluated for demography, laboratory results and capillaroscopy to find the risk factors of their progression to a CTD. RESULTS: A total of 760 of 776 patients were included, with 679 being female (89.3%) and 81 (10.7%) male. There were 660 subjects (90.8%) with secondary RP [mostly UCTD (48.2%) and then SSc (16.4%)] and 67 (9.2%) with primary RP; 109 patients were followed up and 42 (42%) of those with secondary RP developed a definite CTD. The scleroderma pattern and some capillary changes on capillaroscopy and/or positive ANA had statistically significant differences for CTD transition. CONCLUSION: We had a small number of patients with primary RP. The most prevalent causes of secondary RP in our patients were UCTD and SSc. Some capillaroscopy and laboratory results alone or in combination could be used as a predictive marker for the transition of patients with UCTD to CTD.

Performance of the systemic lupus erythematosus risk probability index in a cohort of undifferentiated connective tissue disease.

OBJECTIVES: We sought to evaluate the performance of the SLE Risk Probability Index (SLERPI) for identification of SLE in a large cohort of patients with UCTD. METHODS: The SLERPI was applied in a cohort of patients who met classification criteria for UCTD and did not fulfil any classification criteria for other defined CTD including SLE. Patients with a SLERPI score of >7 were 'diagnosed' as SLE. Patients diagnosed with SLE and those not were compared in terms of disease characteristics and index parameters. RESULTS: A total of 422 patients with UCTD were included in the study. Median (interquartile range) SLERPI was 4.25 (2.5) points, while 39 (9.2%) patients had a SLERPI score >7 and were diagnosed as SLE. Patients with younger age (P = 0.026) and presence of malar rash (P < 0.0001), mucosal ulcer (P < 0.0001), alopecia (P < 0.0001), ANA positivity (P < 0.0001), low C3 and C4 (P = 0.002), proteinuria >500 mg/24 h (P = 0.001), thrombocytopenia (P = 0.009) or autoimmune haemolytic anaemia (P < 0.0001) were more likely to fulfil criteria for SLE by the SLERPI. CONCLUSION: SLERPI enabled a significant proportion of patients to be identified as SLE in our UCTD cohort. This new probability index may be useful for early identification of SLE among patients with signs of CTD without fulfilling any definite criteria set.

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report.

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder. Ultrastructural analysis of the kidney biopsy specimen revealed unusual subepithelial aggregates of microspherules admixed with few microtubules alongside extensive infolding of podocyte foot processes into the underlying GBMs. Characteristic clustering of these microparticles near the invaginated tips of podocyte foot processes in the GBM was observed on transmission electron microscopy. The patient's clinical condition responded favorably to immunosuppressive therapy. The clinical, light microscopic, and diagnostic electron microscopic features of this condition are highlighted in this report in an attempt to contribute some insights into the possible pathogenetic mechanisms of this obscure entity.

Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: analysis of a large monocentric cohort with a long-term follow-up.

Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD.

Assessment of rehabilitation potential in patients with vascular dysfunction caused by undifferentiated connective tissue dysplasia.

INTRODUCTION: Degradation of collagen, inherent to undifferentiated connective tissue dysplasia (UCTD) syndrome, also influences the changes in the structure of vascular walls. This contributes to the development of configured vascular anomalies, which are an independent predictor of vascular accident risk. Such diversity of UCTD manifestations requires development of prognostic criteria for rehabilitation potential, correction of which may contribute to recovery process in case of development of vascular catastrophe. Study aim is to evaluate the rehabilitation potential in patients with vascular dysfunction and underlying UCTD. MATERIALS AND METHODS: The study involved 150 male patients with confirmed diagnosis of UCTD (average age - 26.4 ± 0.6 years). All patients had a complex clinical and instrumental examination. Phenotypic and UCTD visceral stigmas, UCTD biochemical markers were analyzed, followed by statistical processing of the results by method of variotional statistics. RESULTS: We revealed the high degree of direct correlation between the presence of vascular dysfunction and myxomatous degeneration of the mitral valve (r = + 0.76, p.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

Hyperviscosity Syndrome in Undifferentiated Connective Tissue Disease: A Diagnostic and Therapeutic Challenge.

Hyperviscosity is an uncommon manifestation of various underlying diseases. Rapid diagnosis and management of the underlying disease is crucial to prevent significant complications, including hypertension, cerebral vascular accidents, pulmonary embolism, bowel ischemia, and ophthalmologic pathologies. Although the acute management of complications arising from hyperviscosity is relatively straightforward, identifying and treating the underlying cause can prove difficult. This case highlights the difficulties of establishing a diagnosis and initiating appropriate management for a patient with hyperviscosity syndrome in a suspected rheumatologic disorder.

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

INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Predicting progression from undifferentiated connective tissue disease to definite connective tissue disease: A systematic review and meta-analysis.

PURPOSE: Undifferentiated connective tissue disease (UCTD) encapsulates a broad range of conditions including incomplete forms of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), some of whom progress to a formal clinical diagnosis over time. This systematic review (SR) and meta-analysis aimed to identify clinical and laboratory features and biomarkers that can predict progression of UCTD. METHODS: A systematic literature search was carried out on MEDLINE, EMBASE and the Cochrane Central Register of Randomized Controlled Trials. Abstracts and full-text manuscripts were screened by two reviewers. Publications were included if they included at least 20 UCTD patients, a minimum of six months of follow up, and provided data on at least one risk factor for developing a defined CTD. The QUIPS tool was used to assess risk of bias (RoB) and GRADE for grading the quality of the evidence. The study is registered with PROSPERO (ID: CRD42021237725). RESULTS: Fifty-nine studies were included in the SR, and forty-one in the meta-analysis. The predictors for progression to SLE with the highest certainty of evidence included those with younger age (MD -5.96 [-11.05-0.87 years]), serositis (RR 2.69 [1.61-4.51]), or the presence of anti-dsDNA antibodies (RR 4.27 [1.92-9.51]). For SSc, the highest certainty of evidence included puffy fingers (RR [3.09 [1.48-6.43]), abnormal nailfold changes (NFC) (avascular areas [RR 5.71 (3.03-10.8)] or active or late SSc pattern [RR 2.24 (1.25-4.01)] and anti-topoisomerase-I (RR 1.83 [1.45-2.30]). No novel biomarkers were included in the meta-analysis; however HLA molecules, regulatory T cell shift, pro-inflammatory cytokines and complement activation products were identified as potential predictors for evolution of disease. CONCLUSIONS: Clinical and immunological parameters may predict which patients with UCTD progress to definitive disease; however, the heterogeneous nature and RoB in most studies limits the ability to apply these results in routine clinical practice. Limited data suggest that some novel biomarkers may provide additional predictive value but these will need larger well designed studies to fully delineate their clinical utility.

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.

Diagnosis of Undifferentiated Connective Tissue Disease in a Patient With Digital Gangrene and Positive Antinuclear Antibodies.

The occurrence of ischemia of the digits or digital gangrene is a well-known complication of systemic autoimmune diseases, such as systemic sclerosis, systemic lupus erythematosus, and anti-phospholipid syndrome, among others. The pathophysiological mechanisms are small vessel vasculitis, vasospasm of Raynaud's phenomenon, microthrombi due to antiphospholipid syndrome, and/or accompanying accelerated atherosclerosis. Digital ischemia can also occur in the context of disseminated bacterial infections and sepsis. We present here the case of a patient who had digital ischemia and positive antinuclear antibodies but without well-defined clinical features of a connective tissue disease. A diagnosis of undifferentiated connective tissue disease was made.

Peroxidative degradation of proteins and lipids in undifferentiated connective tissue dysplasia in children, Ukraine.

The aim of the study was to assess the state of lipid and protein peroxidation in children with undifferentiated connective tissue dysplasia (UCTD). In this study, 63 children (33 children with UCTD and 30 children without UCTD were recruited and the indicators of lipid and protein peroxidation were measured. The enzymatic, colorimetric method was used to measure the level of total cholesterol (TC). The phospholipids were analyzed by liquid chromatography/mass spectrometry using electrospray ionization. Lipid peroxidation was studied by assessing the change of index and the end product of lipid peroxidation, malondialdehyde (MDA), using spectrophotometric method. Protein peroxidation - by the content of carbonylated protein based on 2,4 dinitrophenyl-hydrazones derivatization. The activity of the antioxidant defense system enzymes was assessed by measuring catalase (CAT) and superoxide dismutase (SOD). Our study revealed a significant increase of PPO products in the venous blood plasma and LPO products in erythrocytes in children with UCTD. Furthermore, an imbalance of the antioxidant defense system was observed in both blood plasma and erythrocytes membrane.

Association of Adult-Onset Bartter Syndrome With Undifferentiated Connective Tissue Disorder.

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. We are reporting a case of 21 years old patient, who presented with lower limb weakness, marked hypokalemia, proteinuria, and renal impairment detected on laboratory evaluation. The diagnosis of Bartter syndrome was suspected by marked hypokalemia and was supported by renal biopsy which showed evidence of Juxtaglomerular (JG) hyperplasia. This is the first case report about clinicopathological features of the patient with acquired Bartter syndrome and associated undifferentiated connective tissue disorder manifesting as hypokalemia with paralysis.

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

The connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren's syndrome (SS), and mixed connective tissue disease (MCTD). In RA patients in particular, interstitial lung abnormality (ILA) (of varying degrees; severe vs. mild) is reported to occur in approximately 20-60 % of individuals and CT disease progression occurs in approximately 35-45 % of them. The ILAs have been associated with a spectrum of functional and physiologic decrement. The identification of progressive ILA may enable appropriate surveillance and the commencement of treatment with the goal of improving morbidity and mortality rates of established RA-ILD. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with disease progression. At histopathologic analysis, connective tissue disease-related interstitial lung diseases (CTD-ILDs) are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP). Even though proportions of ILDs vary, NSIP pattern accounts for a large proportion, especially in PSS, DM/PM and MCTD, followed by UIP pattern. Evidence has been published that treatment of subclinical CT lung abnormalities showing a tendency to progress to ILD may stabilize the CT alterations. The identification of subclinical lung abnormalities can be appropriate in the management of the disease and CT appears to be the gold standard for the evaluation of lung parenchyma.

An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases.

High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction.

Medically explained symptoms: a mixed methods study of diagnostic, symptom and support experiences of patients with lupus and related systemic autoimmune diseases.

OBJECTIVES: The aim was to explore patient experiences and views of their symptoms, delays in diagnosis, misdiagnoses and medical support, to identify common experiences, preferences and unmet needs. METHODS: Following a review of LUPUS UK's online forum, a questionnaire was posted online during December 2018. This was an exploratory mixed methods study, with qualitative data analysed thematically and combined with descriptive and statistically analysed quantitative data. RESULTS: There were 233 eligible respondents. The mean time to diagnosis from first experiencing symptoms was 6 years 11 months. Seventy-six per cent reported at least one misdiagnosis for symptoms subsequently attributed to their systemic autoimmune rheumatic disease. Mental health/non-organic misdiagnoses constituted 47% of reported misdiagnoses and were indicated to have reduced trust in physicians and to have changed future health-care-seeking behaviour. Perceptions of physician knowledge and listening skills were highly correlated with patient ratings of trust. The symptom burden was high. Fatigue had the greatest impact on activities of daily living, yet the majority reported receiving no support or poor support in managing it. Assessing and treating patients holistically and with empathy was strongly felt to increase diagnostic accuracy and improve medical relationships. CONCLUSION: Patient responses indicated that timely diagnosis could be facilitated if physicians had greater knowledge of lupus/related systemic autoimmune diseases and were more amenable to listening to and believing patient reports of their symptoms. Patient priorities included physicians viewing them holistically, with more emotional support and assistance in improving quality of life, especially in relation to fatigue.

Necessity of brain imaging in COVID-19 infected patients presenting with acute neurological deficits.

BACKGROUND: Patients undergoing cardiopulmonary stabilization in the intensive care unit for novel coronavirus (COVID-19) are often sedated, placing timely assessment of a neurological decline at risk. CASE DESCRIPTION: Here, we present two cases of COVID-19 infected young patients transferred to our facility in a cardio-pulmonary crisis, with a poor neurological exam. While there was significant delay in obtaining brain imaging in the first patient, the second patient had timely recognition of her ischemic infarct, underwent emergent surgery, and is now doing well. CONCLUSIONS: These cases highlight the importance of early head imaging in COVID-19 patients with a poor neurological exam. While lungs remain the primary target of COVID-19, these cases alert the medical community to suspect involvement of the central nervous system, since there may be life-saving surgical interventions available.

Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early-early systemic sclerosis): a TDI study.

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E t 14 ± 3 vs. 16 ± 2, p = 0.02; E t/A t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S m 13 ± 3 vs. 15 ± 2 cm/s, p < 0.0003; S t 14 ± 2 vs. 16 ± 3 cm/s, p < 0.0001) and increased estimated pulmonary artery wedge pressure (9 ± 2 vs. 8 ± 1, p = 0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A't, (71% of UCTD-risk-SSc patients vs. 19% of controls; p < 0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.