Connective Tissue Disease Screening Research Articles

Pericardial infiltration and constriction due to cardiac actinomycosis—case report

Abstract Background Constrictive pericarditis associated with actinomycosis infection is a rare and challenging diagnosis due to its insidious manifestation. We describe the successful treatment of pericardial infiltration and constriction due to actinomycosis. Case summary A 50-year-old Aboriginal man presented with insidious onset of fatigue, dyspnoea, pleuritic chest pain, fever, drenching sweats, severe exercise intolerance to 50 m, and recurrent itchy skin lesions over 8 months. Prior investigations, including serial fluorodeoxyglucose (FDG)-Positron emission tomography scans, found a progressively enlarging, metabolically active anterior mediastinal mass with two biopsies on separate occasions showing no malignancy, granulomas, tuberculosis, or other pathology. Screening for infective, autoimmune, and connective tissue disease was negative. A transthoracic echocardiogram (TTE) showed fibrinous pericarditis with extensive myocardial tethering and constrictive physiology confirmed on heart catheterization. A pericardial biopsy showed inflammatory tissue only. Biopsy of a skin lesion on the buttock showed abscess formation with Splendore Hoeppli phenomenon with Gram-positive and Grocott-positive filamentous bacteria suggestive of actinomyces, confirmed by 16S rRNA gene sequencing. He was diagnosed with cardiac actinomycosis, likely due to mediastinal infiltration from a lung infection, with haematogenous spread and treated with Penicillin G with adjunctive high-dose steroid therapy with resolution of symptoms and marked improvement in TTE features of constriction after 6 weeks. Discussion Actinomycosis is an extremely rare cause of pericardial infiltration and constriction yet highly sensitive to penicillin, highlighting the importance of accurate diagnosis. Corticosteroids are a useful adjunct to prevent chronic constrictive pericarditis and to avoid the high morbidity and mortality associated with pericardiectomy.

P45 Lyme-associated uveitis: Panuveitis and positive Lyme results – is it a masquerade or the real deal?

P45 Lyme-associated uveitis: Panuveitis and positive Lyme results – is it a masquerade or the real deal?

Remote self-collection of capillary blood using upper arm devices for autoantibody analysis in patients with immune-mediated inflammatory rheumatic diseases

ObjectivesTo evaluate the feasibility, accuracy, usability and acceptability of two upper arm self-sampling devices for measurement of autoantibodies and C reactive protein (CRP) levels in patients with immune-mediated rheumatic diseases...

Acute fibrinous and organizing pneumonia following the COVID-19 mRNA-1273 vaccine

A 57-year-old man developed respiratory symptoms 72 hours after receiving his third dose of the COVID-19 mRNA-1273 vaccine and underwent computed tomography (CT) chest imaging. This showed new diffuse subpleural and peribronchovascular nodular opacities with reverse halo sign. Laboratory investigations demonstrated an eosinophil count of 0.8 x 10E9/L and unremarkable connective tissue disease screen. Bronchoscopy with lavage and transbronchial biopsies demonstrated lymphocytic alveolitis without evidence of infection and histopathology consistent with acute fibrinous and organizing pneumonia (AFOP). He was treated with corticosteroids resulting in resolution of symptoms and CT findings. We present radiographic and histopathologic findings of AFOP following COVID-19 mRNA-1273 vaccination.

Transverse myelitis and coronavirus disease 2019 vaccine: A temporal association

AbstractBackgroundTransverse myelitis (TM) is most often triggered by an autoimmune reaction due to infections and perhaps vaccines. During the current coronavirus disease 2019 (COVID‐19) pandemic, some case reports have shown a temporal association between TM and COVID‐19 vaccine. We aimed to report a case of TM with a temporal association with ChAdOx1 nCoV‐19 (AZD1222, Oxford/AstraZeneca) vaccine in a Brazilian public hospital.Case PresentationA 27‐year‐old woman experienced fever, low back pain and urinary retention 3 weeks after the first dose of the ChAdOx1 nCoV‐19 vaccine. Two days later, she experienced decreased strength of the lower limbs associated with paresthesia of the distal extremities. At the hospital, there was progression of weakness associated with anesthesia in T4‐L1. Magnetic resonance imaging findings were suggestive of demyelination and acute inflammation. Cerebrospinal fluid analysis showed monomorphonuclear pleocytosis, increased protein and decreased glucose. Gram stain, oligoclonal bands, anti‐aquaporin‐4 antibody, and screening for infectious agents and connective tissue disease were all negative. During treatment, the patient received 5‐day pulse therapy with methylprednisolone, acyclovir and 7‐day plasmapheresis. Despite all treatments, she persisted with lower limb plegia, areflexia and anesthesia at the level of T4. She was discharged with a monthly cyclophosphamide plan and outpatient follow up.ConclusionsIn the absence of other causes, the diagnosis of TM was made with evidence of a possible temporal association with ChAdOx1 nCoV‐19 vaccine. It is important to emphasize that it is a temporal association only and the benefits of vaccination continue to outweigh the risk of TM.

Prevalence of systemic lupus erythematosus-related symptoms assessed by using the Connective Tissue Disease Screening Questionnaire in a large population-based cohort

BackgroundTo assess the prevalence of self-reported SLE-related symptoms associated with demographic and biochemical data and connective tissue disease (CTD)-related autoantibodies in a large population-based cohort.MethodsParticipants of the Dutch Lifelines population...

P19 Total visual loss in connective tissue disease – an unusual presentation of optic peri-neuritis

Case report - IntroductionSince the discovery of aquaporin-4 antibody in 2004, the association between visual loss and auto-immune disease has become increasingly apparent. Certainly, neuro-myelitis optica spectrum disorders (NMOSD) can co-exist with connective tissue disease (CTD). The complexity comes in trying to differentiate the two diagnoses. NMOSD feels like the tip of an iceberg with regards to autoimmune eye disease. When no specific antibody can be found, the clinical syndrome can only be described.Case report - Case descriptionA 22-year-old female, with a history of childhood ITP presented with 4 months of myalgia, arthralgia, raised inflammatory markers (ESR 81, CRP 49) and weight loss. She had no clinical features suggestive of CTD. PET-CT demonstrated abnormal uptake associated with large joints. Small joint musculoskeletal ultrasound was normal. Initial ANA was borderline positive. 3 months later she presented with right-sided retro-orbital pain of 3 weeks' duration, followed by abrupt onset total visual loss in the right eye. The visual acuity in the left eye was also reduced. Ophthalmological examination revealed brilliant white optic atrophy of the right disc, with only perception of light. On the left, the disc and acuity were normal. MRI coronal STIR images of the orbits demonstrated inflammatory change in the peri-optic structures and signal change in the optic nerve anteriorly. Post-contrast images confirmed abnormal enhancement affecting the right optic nerve sheath and surrounding fat, some intrinsic enhancement of the optic nerve and some ill-defined enhancement of the left optic nerve sheath. Saggital T2 imaging of the spine confirmed no cord lesions.All disease-specific antibodies were negative (rheumatoid factor, CCP, connective tissue disease screen, dsDNA, ENA panel, anti-phospholipid, centromere, MOG, Aquaporin-4). HLA-B27 was negative. Complements were normal. HIV, syphilis and Lyme serology were all negative. She was initially treated with oral prednisolone and hydroxychloroquine with poor recovery of vision in the right eye.2 years later, she developed a small deep left thalamic infarct, and was switched to azathioprine. Following a further episode of right eye pain associated with a rise in ESR, treatment was changed to injectable methotrexate resulting in resolution of arthralgia and normalisation of inflammatory markers.Surveillance MRI this year has identified a subtle area of high FLAIR signal in the right pons, with further interval scan awaited.Case report - DiscussionInflammatory eye disease is a developing field, with the relatively recent identification of aquaporin-4 and MOG antibodies in the context of neuromyelitis optica spectrum disorders.Case report - Key learning pointsThis patient initially presented with an inflammatory arthritis, and then went on to develop abrupt onset visual loss. The rheumatologist should remain vigilant for development of optic peri-neuritis in CTD, and consider investigation if eye pain or discomfort develops.In NMOSD, aquaporin-4 (AQP4) antibodies are directed against the AQP4 channels on astrocytes. It is possible that optic peri-neuritis in this case may be due to inflammation in the optic nerve sheath caused by an as-yet unidentified antigen/antibody-mediated process.In patients presenting with CTD who develop optic neuritis or peri-neuritis, further evaluation for NMOSD is essential. AQP4 and MOG antibodies are now readily available and easily checked in routine practice.There appears to be an emerging association between NMOSD and CTD, and the rheumatologist should remain vigilant for the presence of dual pathology.

Visual loss after long-haul flight.

Deep cerebral venous sinus thrombosis is a reversible yet potentially serious thromboembolic event. A number of reports suggest a relationship between long-haul flights and thromboembolic events, mainly deep venous thrombosis (DVT) and pulmonary embolism (PE). It is rarely reported to cause deep cerebral venous sinus thrombosis. We report a case of a bilateral papilledema after long-haul flight secondary to deep cerebral venous sinus thrombosis with subsequent complete recovery post corticosteroid and anticoagulant therapy. A case of a 21-year-old woman with no known medical illness who presented with gradual painless bilateral visual loss is described. She had a history of travelling on a long-haul flight 3 weeks prior to presentation. Examination showed presence of bilateral papilloedema, no vitritis, choroiditis and retinitis. Blood investigations showed raised international normalised ratio (INR). Otherwise, workup for infectious causes of optic disc swelling, connective tissue disease screening were normal. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain showed loss of flow signal in the right transverse sinus and the left sigmoid sinus. Blood workup for preexisting hypercoagulable state was normal. She was diagnosed with deep cerebral venous sinus thrombosis and showed complete recovery with oral corticosteroid and anticoagulant therapy. Deep cerebral venous sinus thrombosis is a potentially serious consequence of long-haul flights. A high index of suspicion along with radiological techniques is needed for early detection and initiation of anticoagulation for this reversible condition.

Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

ObjectivesTo assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA.MethodsIn the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up.ResultsOf 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia.ConclusionsACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

Cross-cultural adaptation of the connective tissue disease screening questionnaire and development of a Chinese version in a multi-ethnic Asian population.

To cross-culturally adapt the Connective Tissue Disease (CTD) Screening Questionnaire (CSQ) in a multi-ethnic Asian population in Singapore. An expert panel of accredited rheumatologists evaluated the content validity of the original CSQ. Consenting participants newly referred from primary care to a rheumatology specialist outpatient clinic for evaluation of possible CTDs were studied. Cognitive debriefing interviews (CDIs) using the original CSQ were conducted with English-speaking participants, with modifications made based on their inputs and in discussion with a second expert panel (rheumatologists and the CSQ developers). Forward and back translations of the adapted English version were reviewed by the second expert panel. The common translation produced was tested in CDIs with Chinese-speaking participants. Adapted English and Chinese versions were pilot tested in a separate group of newly referred patients. Content validity of the original CSQ was confirmed by the expert panel. A total of 30 and 15 participants were recruited for English and Chinese CDIs, respectively. Alternative terms and explanatory notes were added to difficult medical terms in the adapted English CSQ. A further explanatory note was added to one difficult item, and English medical terms were retained in the Chinese version. Pilot testing of the adapted CSQ was performed on 116 participants, which exhibited an overall sensitivity and specificity of 71% and 58%, respectively, in identifying CTDs. The adapted CSQ demonstrated satisfactory sensitivity in the pilot testing and appears to be a promising tool for facilitating early identification of CTDs in the multi-ethnic Asian population. • Early identification and management of patients with CTDs is crucial given their high disease burden and short "windows of opportunity." • High reliability and validity of original CSQ and its cross-culturally adapted versions have been reported; however, the CSQ has not been validated in Southeast Asia where CTDs are associated with higher morbidity and mortality compared to other countries. • Our cross-culturally adapted CSQ demonstrated satisfactory sensitivity in identifying CTDs in the multi-ethnic Asian population.

Screening characteristics for enrichment of individuals at higher risk for transitioning to classified SLE.

Further prospective study is needed to elucidate the etiology and natural history of systemic lupus erythematosus development. The clinical complexity of this heterogeneous disease makes study design challenging. Our objective was to ascertain useful screening factors for identifying at-risk individuals for follow-up rheumatologic assessment or inclusion in prospective studies. We attempted to re-contact 3823 subjects with a family history of systemic lupus erythematosus, who did not meet American College of Rheumatology systemic lupus erythematosus classification at a baseline study visit; 436 agreed to follow-up participation an average of 6.3 years after baseline. In total, 56 of these individuals had transitioned to classified systemic lupus erythematosus (≥ 4 cumulative American College of Rheumatology criteria, verified by medical record review) by the time of follow up. Generalized estimating equations assessed associations between our dichotomous outcome of transitioning to systemic lupus erythematosus with baseline characteristics, including ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score, and number of American College of Rheumatology criteria. We analyzed predictive accuracy of characteristics on transitioning. ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus, and greater number of American College of Rheumatology criteria at baseline were each associated with transitioning to systemic lupus erythematosus classification. Being ANA positive and having confirmed immunologic criteria at baseline had the highest positive predictive value and specificity for transitioning to systemic lupus erythematosus. American College of Rheumatology Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus had a better positive predictive value, negative predictive value, sensitivity, and specificity than ANA positivity. Given limited resources, identifying individuals for follow up based on the systemic lupus erythematosus portion of the Connective Tissue Disease Screening questionnaire could be an efficient way to identify family members at highest risk of disease transition.

Screening for Myositis Antibodies in Idiopathic Interstitial Lung Disease.

International guidelines recommend screening for connective tissue disease (CTD) with autoantibodies when evaluating patients with idiopathic interstitial lung disease (ILD). Idiopathic inflammatory myositis comprises of a subgroup of CTD diagnosed with myositis antibodies (MA), often presenting with ILD. Our aim was to evaluate the utility of MA screening in patients with idiopathic ILD. A retrospective analysis was conducted on patients referred with idiopathic ILD to a tertiary centre ILD clinic who were screened for MA. Patients with known or suspected CTD were excluded. Descriptive statistics, univariate analysis and multivariable logistic regression were used to detect associations between MA and patient characteristics. Of 360 patients, 165 met inclusion criteria and 44 (26.7%) were identified to have MA. Fourteen patients (8.5%) had a change in diagnosis as a result of MA screening. Multivariable logistic regression identified the presence of MA to be associated with current smoking [OR 6.87 (1.65-28.64), p = 0.008] and a diffusing capacity of < 70% predicted [OR 2.55 (1.09-5.97), p = 0.03]. In patients with a change in diagnosis due to MA screening, 3 (1.8%) underwent a surgical lung biopsy and 2 (1.2%) were previously treated with antifibrotic therapy. Screening for MA in patients with idiopathic ILD can contribute to a change in patient diagnosis, and may prevent invasive testing and unproven use of antifibrotic therapy. These results support the addition of MA to CTD screening panels during the initial evaluation of idiopathic ILD.

Screening for connective tissue disease-associated antibodies by automated immunoassay.

Antinuclear antibodies (ANAs) are useful for the diagnosis of ANA-associated systemic rheumatic disease (AASRD). The objective of this study was the evaluation of an immunoassay that detects antibodies to a mixture of 17 antigens as an alternative to indirect immunofluorescence (IIF). Nine thousand eight hundred and fifty-six consecutive patients tested for ANAs were tested by IIF and EliA connective tissue disease screen (Thermo-Fisher). Medical records were reviewed for 2475 patients, including all patients that tested positive/equivocal by either test and a selection of 500 patients that tested negative. Concordance between IIF and EliA was 83.1%. AASRD was found in 12.8% of IIF-positive patients, 30.2% of EliA-positive patients and 0.4%, 46.6%, 5.8% and 3.0% of patients that tested, respectively, double negative, double positive, single positive for EliA and single positive for IIF. The association with AASRD increased with increasing antibody level. IIF and EliA were positive in, respectively, 90.4% and 69.9% of systemic lupus erythematosus (n=83), 100% and 84.1% of systemic sclerosis (n=63), 86.7% and 93.3% of Sjögren's syndrome (n=45), 88.2% and 52.9% of polymyositis/dermatomyositis (n=17), and in all cases of mixed connective tissue disease (n=8). The specificity was projected to be 94%-96% for EliA and 86% for IIF. When all AASRDs were taken together, the areas under the curve of receiver operator curves were similar between IIF and EliA. The positive predictive value for AASRD was higher for EliA than for IIF, but, depending on the disease, EliA might fail to detect antibodies that are detected by IIF. Combining immunoassay with IIF adds value.

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features.

Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Of the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

Soluble mediators and clinical features predict transition to systemic lupus erythematosus classification in previously unaffected relatives of SLE patients (HUM3P.243)

Abstract Healthy relatives of lupus patients have an increased risk of developing SLE, but predictors and mechanisms of disease transition are unknown. Unaffected relatives of SLE patients (n=409) were enrolled in this follow-up study to identify factors associated with transition to SLE. Participants provided detailed demographic and clinical information, including the Connective Tissue Disease Screening Questionnaire (CSQ). Medical records were reviewed for ACR classification criteria. Plasma samples were tested for the presence of autoantibodies and soluble mediators. Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time = 6.4 years) who had more autoantibodies (p&amp;lt;0.0001) and higher pre-classification (baseline) CSQ scores (p&amp;lt;0.0001). Relatives who transitioned also had elevated baseline levels of inflammatory mediators, including BLyS, SCF, and IFN-associated chemokines (p&amp;lt;0.05), with concurrent decreased regulatory mediators, including TGF-β and IL-10 (p&amp;lt;0.05). Logistic regression analysis revealed that baseline ACR and CSQ scores (but not autoantibodies), and baseline plasma levels of SCF and TGF-β were significant and independent predictors of SLE transition. Thus, perturbations in immune-mediated processes precede SLE clinical classification and can help identify unaffected relatives at highest risk of future SLE classification for early intervention studies.

Altered soluble mediator levels and systemic lupus erythematosus-specific Connective Tissue Disease Screening Questionnaire (CSQ) scores differentiate unaffected relatives of lupus patients from healthy individuals with no family history of SLE (CCR4P.214)

Abstract Identifying populations at risk of SLE who remain unaffected would provide insights for potential disease prevention. Using a unique resource of SLE patient family members, first degree relatives (FDRs) of SLE patients (n = 154) with plasma samples available from previous genetic studies and who remained unaffected at follow-up evaluation (mean time = 6.8 years) were matched to healthy individuals unrelated to SLE patients (Controls). FDRs and Controls provided clinical and demographic information, and completed screening questionairres at baseline (BL) and follow-up (FU). BL and FU plasma samples were assessed for autoantibody production and soluble mediators. FDRs had significantly higher BL and FU CSQ scores (p&amp;lt;0.0001), but no difference in the number of positive autoantibodies compared to Controls. FDRs had significant (p &amp;lt; 0.01) increases in 38 (of 52) soluble mediators at BL and FU, including IFN-associated chemokines, TNFR ligands, and regulatory mediators (p&amp;lt;0.002). Levels of MIP-1α (p=0.008), MIG (p=0.019), GROα (p=0.001), ICAM-1 (p=0.007), and VEGF (p=0.004), along with CSQ scores (p=0.010), best distinguished FDRs from Controls in logistic regression models. These alterations are present despite lack of progression to classified SLE, suggesting that multiple perturbations in immune-mediated inflammatory processes present in FDRs of SLE patients may be offset by inhibitory factors.

Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective study.

To evaluate the association of alcohol consumption with the risk of rheumatoid arthritis (RA) in 2 large prospective cohorts, the Nurses' Health Study (NHS) and NHSII. The NHS was established in 1976 and enrolled 121,701 female registered nurses in the US. The NHSII began in 1989, enrolling 116,430 female nurses. Lifestyle and environmental exposures were collected through biennial questionnaires. Alcohol consumption was assessed with a food frequency questionnaire, which was completed every 4 years. Incident RA cases were identified using a connective tissue disease screening questionnaire and a medical record review. Separate Cox proportional hazards models were used to estimate hazard ratios (HRs) after adjusting for potential confounders in the NHS and NHSII. The pooled HR from 2 cohorts was estimated using a DerSimonian and Laird random-effects model. Among 1.90 million person-years from 1980 to 2008, 580 incident cases of RA were diagnosed in the NHS cohort, and among 1.78 million person-years from 1989 to 2009, 323 incident cases of RA were diagnosed in the NHSII cohort. Compared to no use, the pooled multivariable adjusted HR for alcohol use of 5.0-9.9 gm/day was 0.78 (95% confidence interval [95% CI] 0.61-1.00). For seropositive RA cases, the association appeared stronger (HR 0.69 [95% CI 0.50-0.95]). In addition, women who drank beer 2-4 times a week had a 31% decreased risk compared to women who never drank beer. We found a modest association between long-term moderate alcohol drinking and reduced risk of RA. Future studies are needed to confirm our findings in other populations.

Implementation of the Connective Tissue Screening Questionnaire in Northeast Pennsylvania to Identify Comorbidities of Connective Tissue Diseases in Subjects With Systemic Lupus Erythematosus

Previous studies have described an increased risk of developing an additional connective tissue disease (CTD) when one such ailment is present. We examine here the likelihood that individuals with systemic lupus erythematosus (SLE) screen positive for one or more of the following five autoimmune CTDs: Sjögren's syndrome, scleroderma, rheumatoid arthritis, dermatomyositis/polymyositis, and mixed connective tissue disorder. Five hundred SLE-diagnosed subjects were asked to complete a CTD screening questionnaire (CSQ). The results were analyzed according to the set of diagnostic criteria given by the American College of Rheumatology to identify probable cases of each CTD. Significant standardized prevalence ratios and comorbidities indicate an increased risk for the other autoimmune CTDs. In all, 96% of the subjects screened positive for at least one additional CTD, and 13% screened positive for at least two additional CTDs. We see that the SLE-diagnosed population may benefit from further attention regarding the presence of additional CTDs, which may further inform treatment strategies. We also see the application of the CSQ as a potentially important tool for clinical practice, and we describe the present study's limitations along with possible ways that these can be addressed.

Contemporary Trends in the Diagnosis and Management of Pulmonary Arterial Hypertension: An Initiative to Close the Care Gap

The Pulmonary Arterial Hypertension-Quality Enhancement Research Initiative (PAHQuERI) was created to help clinicians to implement a guidelines-based approach to the diagnosis and management of pulmonary arterial hypertension (PAH). Patients with PAH represent a heterogeneous population, and physician evaluation and treatment paradigms may vary considerably.Using an electronic data management system, participating physicians recorded data on diagnostic workup, disease management, and outcomes of patients with PAH. Queries were generated automatically following each follow-up visit if the tests recommended by the American College of Chest Physicians (ACCP) were not performed at least once.Of 791 patients enrolled in PAH-QuERI, 77% were women; 64% received a diagnosis . 3 months prior to enrollment; 9% were in New York Heart Association functional class I, 39% in II, 48% in III, and 5% in IV; and the median age was 55 years (interquartile range, 45-66 years). At enrollment, all ACCP-recommended tests had been performed in only 6% of patients. The automated program generated 1,530 reminders for 642 patients (81%) with validated enrollment data. The proportion of recommended tests performed was 91% for CBC count, 91% for liver function test, 50% for connective tissue disease screen, 29% for HIV screen, 88% for chest radiograph, 82% for ECG, 97% for two-dimensional echocardiogram, 83% for pulmonary function tests, 41% for oximetry, 57% for ventilation/perfusion scan, 79% for 6-min walk distance, and 90% for right-sided heart catheterization. Regarding management, 78% of patients were on disease specific therapy, and the use of these therapies tended to increase with the functional disability of the patient. One hundred seventy patients were taking calcium channel blockers, 91 specifically for PAH. Only six of 91 patients (7%) who received calcium channel blockers specifically for PAH had met the current guideline for acute vasoreactivity.When comparing reported clinical practice with ACCP guidelines-recommended strategies, a diagnostic care gap is apparent such that certain essential and recommended diagnostic tests may be underused despite the availability of detailed guidelines and reminders.