Mixed Connective Tissue Disease Research Articles

578VP Recurrent rhabdomyolysis as the presenting feature of mixed connective tissue disease

578VP Recurrent rhabdomyolysis as the presenting feature of mixed connective tissue disease

A Complicated Case of Recurrent Visceral Leishmaniasis in an HIV-Negative Immunodepressed Patient

Background: Visceral leishmaniasis (VL) has a lower relapse rate in immunocompetent patients and a higher rate in immunosuppressed patients particularly in patients affected by HIV, but also in other immunosuppressive conditions [1, 2]. Case History A 74-year-old woman with mixed connective tissue disease on steroid therapy had previously treated visceral leishmaniasis with liposomal amphotericin B (L-AmB). She admitted to Emergency Department for progressive asthenia and periodic low-grade fever. Exams showed pancytopenia, hypergammaglobulinemia and hepatosplenomegaly. Patient admitted to the Infectious Diseases ward and underwent a first bone marrow biopsy (BOM) negative for amastigotes. She developed fever and respiratory failure, requiring transfer to Emergency Medicine. Lung CT showed severe bilateral interstitial and parenchymal pneumonia with positive PCR nasal swab for Influenza A and positive blood culture for carbapenem resistant Acinetobacter Baumannii (CRAB). Patient was treated with Oseltamivir, Cefiderocol, and NIV; her condition resolved and she was retransferred to Infectious Diseases ward. A second BOM was positive for Leishmania PCR. She was successfully treated with L-AmB and Miltefosine. Discussion: We describe a case report of a recurrence VL in an immunodepressed rheumatology patient receiving chronic steroid treatment. Immunosuppressive treatments due to rheumatologic diseases are considered at the highest risk of occurrence and recurrence of VL.

Quality of life in patients with mixed connective tissue disease

Quality of life in patients with mixed connective tissue disease

Detection and differentiation of antinuclear antibodies in serum of dengue suspected patients with or without systemic autoimmune disease in Kolkata, India

ABSTRACT The pathophysiology of dengue may be influenced by antibodies released during infection. Several autoimmune diseases are accompanied by antinuclear antibodies (ANAs) but 8–10% of the general population have positive ANA tests. To test the hypothesis that an ANA-positive test indicates an immune dysregulated state that modifies the risk for certain clinical disorders in people with or without an autoimmune disease, we examined the various ANA profiles and their relationships to various autoimmune disorders, as well as the severity of these relationships, in patients infected with dengue fever. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. Indirect immunofluorescence assay (IIFA) and line immunoassay (LIA) were performed to detect and differentiate the ANAs among dengue infected patients. Out of 135 dengue virus-positive patients, 94.07% were positive by ELISA and 5.93% positive by RT-PCR method. ANAs by IIFA and LIA were detected in 54.8% and 18.5% of the dengue positive patients, respectively, and 10.3% and 7.1% of the 126 dengue negative patients, respectively. This study showed that dengue was associated with an increased risk of autoimmune myositis and mixed connective tissue disease (MCTD), a rare complication of dengue. The risk of other autoimmune diseases did not seem to increase after DENV infection.

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

Antinuclear Antibodies in Systemic Lupus Erythematous – Their Complex Role and Clinical Significance in Diagnosis

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice.In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study

BackgroundAn association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis.MethodsThe genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran’s Q value, respectively.ResultsPBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method.ConclusionsOur research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.

Heart Full of Autoimmunity: A Case Report and Review of Literature

Pericardial disorders in connective tissue diseases (CTD) are common and may present as acute or chronic pericarditis. Their presentation as cardiac tamponade is rare. The availability of echocardiography has enhanced the ability to make a early diagnosis of pericardial effusion and tamponade. We report a case of mixed connective tissue disease (MCTD) manifesting as cardiac tamponade at presentation and review of the literature.

Delayed diagnosis of TAFRO syndrome: A case report.

TAFRO syndrome is a systemic inflammatory disorder, manifesting as thrombocytopenia (t), anasarca (a), fever (f), reticulin myelofibrosis/renal insufficiency (r), and organomegaly (o), and considered as a unique clinical subtype of idiopathic multicentric Castleman disease (iMCD). Such syndrome gave rise to a clinical picture similar to that of either a connective tissue disease or an autoimmune disease. A Chinese young female initially presenting with arthralgia, Raynaud phenomenon, generalized edema, and a positive anti-small nuclear ribonucleoprotein particle antibody was diagnosed as mixed connective tissue disease. The kidney biopsy showed thrombotic microangiopathy. Bone marrow smear showed bone marrow hyperplasia and biopsy revealed suspected light chain restricted expression, megakaryocyte proliferation, and moderate to severe bone marrow fibrosis. A lymph node biopsy was conducted and the histopathological findings were consistent with the subtype of mixed Castleman disease. The clinical symptoms were relieved after regular chemotherapy. After above examination results and clinical manifestations, the final diagnoses was TAFRO syndrome. The she was started on chemotherapy with bortezomib, cyclophosphamide, and dexamethasone. After chemotherapy, symptoms such as thrombocytopenia, hematuria and proteinuria disappeared, lymphadenopathy and VEGF level decreased, and bone marrow fibrosis relieved. Our case illustrated the first cases of shared characteristics of mixed connective tissue disease and iMCD-TAFRO syndrome. Cytokines may play a role in the shared pathogenicity of the iMCD-TAFRO syndrome and systemic autoimmune diseases. Therapy directly against inflammatory factors such as corticosteroids or chemotherapy have an important therapeutic implication.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.

Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Assessing Patient Values and Preferences to Inform the 2023 American College of Rheumatology/American College of Chest Physicians Interstitial Lung Disease Guidelines.

Patient engagement is critical to clinical practice guideline (CPG) development. This work presents our approach to ascertaining patients' values and preferences to inform the American College of Rheumatology guidelines for screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs). We conducted a cross-sectional qualitative study of a purposefully sampled Patient Panel using a modified content analytic approach. The study team reviewed text transcripts from the Patient Panel discussion to identify themes and develop a clustered thematic schema. Twenty-one patients (75% women) participated, with a mean age of 53 years (range 33-73). Patients had one or more SARDs: systemic sclerosis (38%), Sjögren disease (38%), idiopathic inflammatory myopathy (33%), rheumatoid arthritis (24%), and mixed connective tissue disease (10%). We identified 10 themes in 4 thematic clusters: communication, screening and monitoring, treatment goals, and treatment adverse effects. Patients prioritized recognizing ILD symptoms, importance of ILD screening and close monitoring, goals of survival and improving quality of life, and willingness to accept treatment risks provided that there is close communication with providers. Patient representatives shared patients' priorities and insight at the Voting Panel meeting, influencing multiple guideline recommendations. Patient engagement fosters a holistic approach to CPG development, leading to recommendations aiming for the best clinical outcomes while prioritizing outcomes important for patients. The patient-identified themes played a critical role in ILD guideline development and provide core elements for shared decision-making as clinicians make management and therapeutic decisions with patients with SARD-associated ILD.

Common presentations of an uncommon disease: A report of two pediatric cases with mixed connective tissue disease

Mixed connective tissue disease (MCTD) is one of the rarest connective tissue diseases. Incidence is around 2–3 cases per 100,000 people. The diagnosis is often difficult due to multiple diagnostic criteria and overlapping features with other connective tissue diseases such as systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis (JIA). An accurate diagnosis is important for proper treatment and follow-up. We report two pediatric cases, who initially presented with common diseases such as nephrotic syndrome and JIA, but later turned out to have MCTD after completing the workup. Both patients had strongly positive anti-U1-ribonucleoprotein (RNP) antibodies. The first patient had features of Raynaud’s phenomenon as supportive evidence of MCTD. The second patient had hand edema, aseptic meningitis, and myositis as the supporting evidence in addition to clinical features and strongly positive anti-U1-RNP antibodies. Both patients showed good improvement after proper treatment and are under our follow-up.

Autoimmunity in Type 2 Diabetes: When the Only Effective Therapy Becomes Immunosuppressive.

Type B insulin resistance syndrome is a rare form of diabetes due to the presence of anti-insulin receptor antibodies [1, 2], which causes glycemic decompensation and antidiabetic therapy failure and instead responds to immunosuppressive therapy. A 67-year-old patient was admitted to the hospital due to autoimmune hemolytic anemia and glycemic decompensation. We first prescribed subcutaneous basal-bolus insulin and then intravenous insulin without improvement in blood sugar levels (between 300 and 500 mg/dL). Considering the non-response to therapy and the autoimmune diathesis of the patient (hemolytic anemia and mixed connective tissue disease), we suspected an autoimmune etiopathogenesis of glycemic decompensation; we excluded type 1 diabetes mellitus (specific antibodies were negative), and we considered the anti-insulin-antibodies-(-assayed and negative) and anti-insulin receptor antibodies (not assayed due to the lack of a center specialized in this assay in the area). Therefore, we decided to start Rituximab. After 2 weeks from the infusion, the patient improved glycemic compensation, reducing insulin requirement. Further, 2 months after the first infusion, the patient stopped insulin, returning to oral therapy with Metformin. To date, the patient has completed 3 cycles of Rituximab with the benefit of glycemic control (HbA1c 6.7%). The brilliant response to Rituximab supports the hypothesis of an autoimmune pathogenesis. The anti-insulin receptor antibodies (in the type B insulin resistance syndrome) affect mostly middle-aged adults, especially women, in the context of other autoimmune diseases. Hence, it is necessary to consider the diagnosis of this rare disease in order to perform timely and effective treatment.

Raynaud's phenomenon in a patient with silicone implants: How far is ASIA syndrome and not mixed connective tissue disease?

Raynaud's phenomenon represents a harbinger of polyautoimmunity and although it is usually associated with systemic sclerosis, the discussion surrounding its classification in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. We present the case of a young woman who presented with biphasic Raynaud's phenomenon (pallor, cyanosis) associated with polyarthralgia affecting small joints of hands and feet in the context of immunological profile suggestive of undifferentiated connective tissue disease (ANA -anti-nuclear antibodies- 1:1280, mottled pattern and anti-RNP -anti-U1 ribonucleoprotein- at high titers: >200). Considering personal history of cohesive silicone buttock implants in 2012, a probable case of ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome was considered, given the presence of one major and two minor criteria. However, a debate arises regarding the clinical spectrum of mixed connective tissue disease and the controversial ASIA syndrome.

COVID-19 and autoimmune rheumatic disease: behavioural changes adopted by patients amid the pandemic.

Amid concerns about severe COVID-19 in patients with autoimmune rheumatic disease (AIRD) during the outbreak, it is crucial to explore behavioural changes, whether healthy or unhealthy, arising from this patient population in response to the changing healthcare environment. To investigate COVID-19-driven behavioural changes in patients with AIRD. This observational study invited patients who attended the rheumatology clinic of the Korle Bu Teaching Hospital from 1 August 2020 to 1 July 2021, to respond to a survey questionnaire distributed on the patient's WhatsApp platform. Variables observed were changes in patient behaviour and decision-making related to medication, healthcare service utilisation and clinical advice. Results for 233 patients were analysed in the study, the majority (89.7%) of whom were women. The most significant behavioural changes were a reduction in hydroxychloroquine (HCQ) dosage, adoption of telemedicine for clinical consultation and keen adherence to protective/preventive health measures. Patients also expressed anxiety regarding the risk of contracting COVID-19 (52.5%), infecting their families (66.5%) and losing income (50.2%) due to the pandemic. Women and students were more likely to engage in self-isolation/shielding behaviour. Employed participants practised social distancing more, reduced HCQ dosage and had more fear of losing income. Having mixed connective tissue disease is associated with being anxious about the risk of COVID-19 infection. The COVID-19 pandemic has resulted in behaviour changes among patients with AIRD. Despite the perceived risk, most of these patients continue to adhere to their prescribed medication regimens, especially maintaining the dosage of traditional immunosuppressive agents.

Lung ultrasound in the assessment of interstitial lung disease in patients with connective tissue disease: Performance in comparison with high-resolution computed tomography.

To investigate clinical relevance of performing lung ultrasound (LUS) in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) in comparison with high-resolution computed tomography (HRCT). This single-centre study enrolled eligible patients with CTD-ILD from the prospective LUS registry. Total B-lines were detected by assessment at 14 sites via LUS. Forced vital capacity, diffusing lung capacity for carbon monoxide (DLCO), DLCO/alveolar volume, 6-minute walking distance, and the ILD-GAP index were used as ILD prognostic parameters. Correlations were examined using single and multiple regression analyses. Sixty-seven patients were enrolled, including 29 with idiopathic inflammatory myopathy or anti-synthetase syndrome, 25 with systemic sclerosis (SSc), 10 with rheumatoid arthritis, and 3 with mixed connective tissue disease. The total number of B-lines correlated with ILD extent on HRCT in patients with CTD-ILD (r = 0.66; P < 0.001), particularly in patients with SSc-ILD (r = 0.78; P < 0.001). Total B-lines and ILD extent on HRCT showed comparable correlations with prognostic parameters, while multiple regression analysis revealed the limited benefit of performing LUS in addition to HRCT in predicting correlations with prognostic factors. LUS serves as an alternative tool for assessing the severity and prognosis of patients with CTD-ILD.

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.