Features Of Connective Tissue Disease Research Articles

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome

Primary Sjögren’s Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with “idiopathic” interstitial lung disease

BackgroundAutoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. Methods499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. Results2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. ConclusionSpecific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

As Milky as It Can Get; Chyluria: A Case Report and Review of Literature

Abstract Filariasis is an important public health problem in India. Extralymphatic manifestation of filariasis includes chyluria or passage of intestinal lymph or chyle into urine imparting a milky-white color, is an important manifestation of renal involvement. A young woman residing in a filaria endemic region, presented with persistent chyluria of 3-month duration. She did not have any features of nephrotic or nephritic syndrome or features of connective tissue disease. After routine hematological, biochemical, serological, and urinalysis, nephrotic range proteinuria and lipiduria were confirmed, and kidney biopsy was performed. Kidney biopsy showed an elongated parasitic sheathed structure with multiple basophilic nuclei spread along the length of the tail, suggestive of microfilaria, in capillaries of a single glomerulus; immunofluorescence was negative for immunoglobulin (Ig) A, IgM, IgG, C3, C1q, kappa, and lambda. She was given antifilarial drug and chyluria promptly subsided. The complex evaluation and management of chyluria have been discussed.

Health prevention intervention for chronic tissue fibrosis: Based on the specific expression of CCL19/21 + mast cell

Chronic tissue fibrosis is a common pathological feature of connective tissue diseases and malignant tumors, and its prevention has been a major focus of relevant research.However, the details of the mechanism of action of tissue-colonizing immune cells in fibroblast migration are unclear. In this study, connective tissue disease tissue specimens and solid tumor specimens were selected to observe the relationship between mast cells and interstitial fibrosis and the expression characteristics of mast cells. Our findings suggest that the number of mast cells in the tissue correlates with the degree of pathological fibrosis and that mast cells specifically express the chemokines CCL19 and CCL21, especially CCL19. CCR7+ fibroblasts are highly expressed in mast cell clusters. The mast cell line HMC-1 regulates CD14+ monocyte-derived fibroblasts via CCL19. In disease tissue fibrosis, mast cell activation may increase the expression of chemokines, especially CCL19, in the tissue, thereby inducing a large number of CCR7-positive fibroblasts to migrate to specific tissues. This study lays a foundation for the mechanism of tissue fibrosis and provides evidence for the mechanism by which mast cells induce fibroblast migration.Through the experimental results of this paper, we can combine the induction factors of chronic tissue fibrosis and put forward targeted health prevention strategies.

E030 Rheumatologists beware! Digital ischaemia as a presenting feature in metastatic ovarian cancer

Abstract Background/Aims Digital ischaemia is an umbrella term to describe the spectrum of acral vascular phenomena irrespective of aetiology, ranging from temporary (as in Raynaud’s phenomenon) to permanent (necrosis). It can be the presenting feature in multiple cancer types, and can be present with or without other features of connective tissue disease. Methods A 54-year-old woman was referred to Rheumatology with a four-day history of acute pain and ischaemic discolouration of all her fingertips bilaterally. There was no history of Raynaud’s phenomenon and no other clinical features of connective tissue disease. She had never smoked. There was a family history of breast cancer in her maternal aunt. She was admitted under vascular surgery for urgent review. All ten fingertips were ischaemic, with a capillary refill time of greater than five seconds. The history was otherwise significant for abdominal bloating, altered bowel habit and fatigue. Examination revealed normal peripheral pulses with no bruits, normal heart sounds and chest sounds. Her abdomen was soft with a mildly enlarged liver. Results FBC, U&amp;E, and LFTs showed no abnormalities. CRP, ESR, ANA, serum protein electrophoresis and complement levels were all normal. Blood tests for ANCA, rheumatoid factor and anti-CCP were also negative. Lupus anticoagulant, anti-cardiolipin and anti-B2-glycoprotein were all negative. The tumour marker CA125 was markedly elevated at 837kU/L (0.0-35.0kU/L). A CT abdomen &amp; pelvis showed a large right-sided adnexal mass with multiple enhancing peritoneal and omental nodules and moderate ascites. Biopsy of a metastatic deposit in the omentum revealed high grade serous ovarian adenocarcinoma. Partial improvement in digital ischaemia was achieved with iloprost and maintenance apixaban and sildenafil. Four cycles of carboplatin and paclitaxel chemotherapy produced near-complete resolution of digital ischaemia symptoms, corresponding to a fall in her CA125 level and reduction in the size of the ovarian mass and intra-abdominal metastases on CT. Ten cases of digital ischaemia associated with ovarian cancer have been described prior to this. The age of onset ranged from 45 to 71, with a median age of 56. Most patients had digital ischaemia without features of connective tissue disease. Four had no blood test abnormalities other than a raised tumour marker CA125. The time from onset of digital ischaemia to diagnosis of ovarian cancer ranged from less than one week to 2 years, with a median time of four months. Conclusion This case study supports previous findings that patients with digital ischaemia associated with ovarian cancer may have normal markers of inflammatory or rheumatological disease. Marked therapeutic responses can be achieved with systemic anti-cancer therapies. Therefore, underlying cancer should be suspected in patients with new-onset or worsening digital ischaemia over the age of 45. A high index of suspicion is required - rheumatologists beware! Disclosure J.H. Miller: None. P. Merry: None.

Clinical significance of anti-rheumatoid arthritis 33 antibody in patients with systemic lupus erythematosus.

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587-0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE.

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

Phenotype of COL3A1/COL5A2 deletion patients

IntroductionThe diagnosis of Ehlers-Danlos syndrome is usually based on well-defined diagnostic criteria and the result of DNA investigation. Classical (cEDS) and vascular type (vEDS) are the most prevalent subtypes and are caused by heterozygous pathogenic variants in COL5A1, COL5A2, COL1A1 or, respectively, in COL3A1. We describe 3 cases with contiguous deletions resulting in haploinsufficiency of both genes with relative mild features of connective tissue disease. Patients and methodsInformation on medical history, physical information, genetic results (CNV-analysis) and imaging were obtained from the medical file. ResultsThe first patient was a 31 yr old female, diagnosed during pregnancy after the NIPT result showed an interstitial deletion of 2.3 Mb on chromosome 2q32.2, confirmed by XON array. She had normal aortic diameters. She had no signs of cEDS or vEDS except for a relatively thin skin with increased visibility of the veins. Her father died suddenly of a type A/B dissection at the age of 62 years. The second patient was diagnosed at the age of 10 years after she was referred because of her intellectual disability, autism and constipation. She was known with a thin and vulnerable skin and had a bleeding after tooth extraction. Array showed a 14,5 Mb deletion of 2q31.3q32.3 (de novo). Imaging (latest age 17 years) did not show any abnormalities. The third patient, aged 28 years, was diagnosed during pregnancy with an interstitial deletion of circa 6 Mb on chromosome 2q31.1q32.2 3, previously shown in the fetus with bilateral club feet and hydronephrosis. She had no vEDS facial features and the skin was relatively thin. She has thoracolumbar scoliosis and dural ectasia. Imaging did not reveal any vascular abnormalities. Her son, born at 37 weeks 3 days. had club feet but not other clinical signs suggestive of classical or vascular EDS. DiscussionThree patients are described with a contiguous deletion of varying size encompassing the COL3A1 and COL5A2 gene. Due to the mild phenotype a diagnosis of EDS was not suspected and was found coincidental. Since two of the patients were pregnant without major complications these patients may require a less defensive, approach to pregnancy/delivery.

P239 Are patients with acute pericardial syndromes adequately screened for connective tissue diseases? Results from a single-centre study and comparison to European Society of Cardiology Guidelines

Abstract Background/Aims Pericardial syndromes (PS) comprising pericarditis, pericardial effusions, cardiac tamponade, and constrictive pericarditis, can be presenting features of connective tissue disease (CTD) including lupus (SLE) and rheumatoid arthritis (RA). PS comprise 0.1% of all hospital admissions and 5% of acute non-cardiac chest pain. PS occur as single episodes but recur in 30% of patients within 18 months after the first episode. The 2015 European Society of Cardiology (ESC) pericardial disease guidelines recommend assessment of NSAID response with follow-up and tests in those who are NSAID non-responders or who have recurrent PS. We audited the management of patients presenting with PS in a tertiary referral centre, using the 2015 ESC guideline standards to determine if investigations to uncover autoimmune diseases as a cause of PS were performed. Methods We obtained data on all patients coded with PS presenting to St George’s Hospital Emergency Department between Jan 1st, 2019, and October 31st, 2020. We also searched data including patients’ length of stay, test results including blood tests, imaging (X-ray, ultrasound, CT and MRI), initial management, outpatient follow-up, recurrence numbers and identifiable cause. Data were compared to the 2015 ESC guidelines. Results We identified 132 PS cases, of which 37 (28%) had recurrent pericardial disease. Of these, 15 (41%) were screened for connective tissue disease with antinuclear antibody (ANA) testing. Of those tested, nine (60%) had a positive ANA (titre 1/80 or greater), with three (33%) positive for extractable nuclear antigens (anti-Ro, anti-Sm and anti-RNP). Only 14 patients (38%) with recurrent disease had rheumatoid factor (RhF) tested, with four of these (29%) positive, while one of eight (12.5%) patients tested was anti-CCP antibody positive. Only 13 of 37 recurrent cases (35%) had both ANA and RhF tested. Furthermore, 37 of all PS cases (28%) were not followed up after initial presentation, while only five (14%) of recurrent cases received any follow up. By contrast, presumed infection tested serologically was found in only 7.8% of all cases tested, most commonly Mycoplasma or raised ASOT. Conclusion A high proportion of recurrent PS patients screened in our study had a positive ANA, ENA or RhF suggesting screening can identify new potential CTD, including SLE or RA. These patients require different treatment strategies to infectious PS. We demonstrated screening was inconsistent despite the absence of obvious infective causes in most cases and limited to 41% of patients with recurrent disease, which present the highest risk of association with CTD. ESC guidelines recommend all patients be followed up after 1 week, yet few high-risk patients received any outpatient review, from any speciality. There is a pressing need to ensure potential cases of CTD presenting as PS are not missed as doing so may prolong symptoms and worsen outcome. Disclosure D. Srikantharajah: None. V. Joseph: None. A. Kaul: None.

P054 Vascular Ehlers-Danlos syndrome: a life-altering diagnosis not to be missed

Abstract Background/Aims A 41-year-old lady underwent a laparotomy and small bowel resection for small bowel obstruction due to adhesions after presenting with a three-day history of abdominal pain. The surgery was complicated by significant bleeding from multiple points of the mesentery and a laceration of the uterine fundus, the repair of which was complicated due to extremely friable tissue. Post-operative ileus, fever, tachycardia, and raised inflammatory markers led to antibiotic therapy and further investigation with computed tomograph angiography (CTA) abdomen which identified a retroperitoneal haematoma due to a herald bleed from an adrenal artery pseudoaneurysm and multiple further true aneurysms in the coeliac, splenic, and right posterior hepatic arteries. The right adrenal artery aneurysm was treated by right renal artery stent graft as targeted embolisation was not possible due to extremely friable arterial intima that dissected and bled on instrumentation. The rheumatology team was consulted to advise on the possibility of vasculitis and whether treatment with immunosuppressives was indicated. Methods Prior to this admission, she denied any fever, weight loss, rash or neuropathies. There was a history of spontaneous peri-renal haematoma and easy bruising. She had three successful pregnancies; two were Caesarean section deliveries, one of which was complicated by post-partum bleeding. There was no family history of connective tissue diseases, sudden deaths, aneurysms or visceral ruptures. There were no clinical features of connective tissue disease. She was noted to have acrogeria, small finger joint hypermobility, large eyes, a small nose, and absent earlobes. There were prominent veins on her lower back, chest, arms, and legs. She had a normal palate arch, normal appearances of previous surgical scars, and there was no skin hyperextensibility. Results Inflammatory markers prior to admission were normal, with no cytopenias or thrombocytosis. ANA, ENA, ANCA, HIV, Hepatitis B/C, treponemal antibody, and rheumatoid factor/anti-CCP were negative. CTA showed no thickening suggestive of vascular/perivascular inflammation. Histopathology of resected small bowel and mesentery showed no evidence of vasculitis. A diagnosis of probable vascular Ehlers-Danlos syndrome (EDS) was made. She was not treated with steroids. Genetic testing confirmed a heterozygous mutation for a pathogenic missense variant in the COL3A1 gene: c.574G&amp;gt;C,p.(Gly192Arg), not previously reported to be associated with disease. Her inflammatory markers improved over time. She was discharged on celiprolol for blood pressure control and close surveillance of aneurysms. An extended screen for the presence of aneurysms elsewhere showed a left vertebral artery aneurysm and dissection at the C4/5 intervertebral foramen on CTA head. Genetic testing was offered to her family members, especially her three sons. Conclusion Vascular EDS is under-recognised and should be in the differential diagnosis of non-inflammatory vasculitis mimics in patients presenting with arterial ruptures, dissections or aneurysms to avoid potentially harmful treatment with immunosuppressive therapy. Disclosure S. Yeoh: Grants/research support; Versus Arthritis (unrelated to this work). C. von Stempel: None. C. Thornton: None. S. Yalamanchili: None. J. Manson: None.

P221 Autoantibodies are common in patients with idiopathic interstitial lung disease, suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD related ILD (CTD-ILD) from idiopathic ILD, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD associated complications. Occasionally a lung biopsy may be necessary to ensure accurate diagnosis. Autoantibodies are a hallmark feature of CTD, are highly disease specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients with idiopathic ILD for the presence of autoantibodies that may suggest misdiagnosis. Methods The serum from three subgroups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 171 with a diagnosis of idiopathic ILD and non-specific organising pneumonia on HRCT and 27 with a diagnosis of idiopathic ILD and cryptogenic organising pneumonia on HRCT. Autoantibody status was determined by radio-immunoprecipitation. Results Results are summarised in Table 1. Overall CTD-autoantibodies were identified in 15.6% of patients with idiopathic ILD, and were more common in those with NSIP, see table. Autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF3. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert-CTD is likely to be common amongst patients diagnosed with idiopathic ILD, particularly idiopathic NSIP. More specific guidance on autoantibody testing could improve diagnosis and ensure patients receive appropriate immunosuppressive treatment. Disclosure S. Tansley: None. C. Cotton: None. F.K. McMorrow: None. H. Lu: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

OA12 Autoantibodies are common in patients labelled as “idiopathic” interstitial lung disease suggesting a high prevalence of undiagnosed autoimmune connective tissue disease

Abstract Background/Aims In some patients, interstitial lung disease (ILD) may be the dominant or even sole clinically overt manifestation of an otherwise unrecognised autoimmune connective tissue disease (CTD). Accurate diagnosis can be challenging given considerable overlap of the clinical, radiological and histological disease features. Distinguishing CTD-related ILD (CTD-ILD) from idiopathic ILD can avoid a lung biopsy, enables appropriate immunosuppressive treatment, informs prognosis and facilitates monitoring for other CTD-associated complications. Autoantibodies are a hallmark feature of CTD, are highly disease-specific and their presence is strongly suggestive of covert CTD-ILD. We investigated patients who had been labelled with “idiopathic” ILD by their local hospital teams for the presence of autoantibodies that may suggest misdiagnosis. Methods Serum from two groups of patients recruited to UK Biomarkers of Interstitial Lung Disease (BILD) were analysed: 183 with a local diagnosis of idiopathic non-specific interstitial pneumonia (iNSIP) and 34 with a local diagnosis of idiopathic or Cryptogenic Organising Pneumonia (COP). Autoantibody status was determined by radio-immunoprecipitation. Results Overall, CTD-autoantibodies were identified in 15% of patients with a prior label of “idiopathic” ILD. CTD autoantibodies were more common in those with a prior diagnosis of COP, where more than 1 in 5 patient samples contained a potentially relevant autoantibody, see table. The autoantibodies identified included those readily detectable e.g. anti-Jo1, in addition to rarer antibodies not included in standard assays e.g. anti-EIF2B. Nearly half of all autoantibodies detected were anti-synthetase autoantibodies. Conclusion Covert CTD-ILD is potentially being missed as a diagnosis in patients who have been labelled by local teams as having idiopathic forms of inflammatory ILD (COP or iNSIP). More specific guidance on autoantibody testing and the interpretation of these test results could improve diagnosis and ensure patients receive more appropriate management. Disclosure S.L. Tansley: None. C.V. Cotton: None. F.K. McMorrow: None. H. Lu: None. Z.E. Betteridge: None. R.P. New: None. L.G. Spencer: None. N.J. McHugh: None. R.G. Cooper: None.

A Closer Look at the Role of Anti-CCP Antibodies in the Pathogenesis of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Bronchiectasis.

Rheumatoid arthritis (RA) is an articular disease with extra-articular manifestations. Pulmonary manifestations are not uncommon and can involve all compartments of the lungs with airway disease in the form of bronchiectasis or bronchiolitis, interstitial lung disease (ILD), pleural effusions and parenchymal lung nodules. The pulmonary features may present synchronously or after the articular disease, but, importantly, it may be the first presentation in 10% of patients in the absence of articular symptoms. Here we discuss the pathogenesis of RA lung involvement, particularly interstitial lung disease and bronchiectasis, focusing on the role anti-CCP antibodies (ACPAs). We highlight the complex interplay among genetic, environmental and immune factors. Furthermore, we explore the relationship of citrullination and smoking as well as the concept of interstitial pneumonia with autoimmune features (IPAF), where patients do not have evidence of another known cause of interstitial pneumonia and have incomplete features of connective tissue disease (CTD). We surmise that the frequency and titers of rheumatoid factor (RF) and ACPAs are increased in bronchiectasis and RA-bronchiectasis compared to RA patients without lung disease. ACPA is associated with more severe disease in both RA-ILD and RA-bronchiectasis even in the absence of articular symptoms. There is no clear prediction of development of articular RA with high ACPA levels in the context of positive ACPA and ILD; however, in RA-bronchiectasis, patients with positive antibodies can develop RA within a year after diagnosis of bronchiectasis. Though the primary focus of this narrative is to highlight the role of ACPA in pathogenesis and clinical practice, we also discuss the current treatment options and trials in RA-ILD and RA-bronchiectasis. Currently, there are no clear treatment guidelines. The treatments are now focusing on using a combination of immunosuppression and antifibrotic agents. Combination treatment targets both the fibrotic and inflammatory components of the disease process. Further studies are needed to identify the use of ACPA as a biomarker to tailor the treatment in RA-ILD and RA-bronchiectasis.

Recognition of Connective Tissue Disease-Related Interstitial Pneumonia Based on Histological Score-A Validation Study of an Online Diagnostic Decision Support Tool.

Objectives: to evaluate the number of cases of idiopathic pulmonary fibrosis (IPF) that included histological features of connective tissue disease (CTD) and to check whether they demonstrated the clinical features of CTD, using a previously reported CTD-interstitial pneumonia (IP) index that histologically differentiates CTD-associated and idiopathic IP. Methods: patients diagnosed with IPF following video-assisted thoracoscopic biopsy through multidisciplinary team diagnosis between 2014 and 2017 were selected. Pathological observation was made by four pathologists who scored eight observational items needed for the CTD-IP index. Cases determined as CTD, by the CTD-IP index, were extracted, and their clinical features were compared. Results: a total of 94 cases of IPF were identified, of which 20 were classified into the CTD group using the CTD-IP index with reasonable interobserver agreement (k = 0.76). Cases pathologically classified into the CTD group were significantly associated with female sex, non-smoking history, autoantibody positivity, and CTD symptoms (p = 0.01, 0.03, 0.01, and 0.04, respectively). Conclusions: patients with IPF with pathological findings of CTD showed clinical characteristics similar to those of patients with CTD.

Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) mimicking idiopathic inflammatory myopathy: key points to prevent misdiagnosis.

Diagnosing the idiopathic inflammatory myopathies (IIMs) can be challenging as several conditions, including genetic myopathies such as limb girdle muscular dystrophy type R12 (LGMD 2 l, anoctaminopathy) mimic the presentation. Here we describe learning points identified from review of four patients with LGMD 2 l who were initially incorrectly diagnosed with IIM. Our aim is to provide clinicians working in adult rheumatology services with a toolkit to help identify non-inflammatory presentations of myopathy. We performed retrospective review of medical notes, laboratory results, muscle imaging and histological findings of four patients with LGMD 2 l who were previously misdiagnosed with IIM. We focussed on clinical presentation and progression, therapeutic agents used and events leading to revision of the diagnosis. Three male patients and one female patient with a mean age of 51 years at presentation were reviewed. In each case, treatment with immunosuppressants, in one case for >15 years, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and available myositis-associated/specific autoantibodies and associated connective tissue disease features were absent. Prominent fatty infiltration and selective muscle involvement on thigh MRI was found in common. Adult-onset genetic myopathies, particularly LGMD R12, can mimic IIM. Accurate diagnosis is crucial to avoid the use of potentially harmful immunosuppressive therapies, to allow appropriate genetic counselling and to facilitate involvement in research studies.

Interstitial pneumonia with autoimmune features: from research classification to diagnosis

The term interstitial pneumonia with autoimmune features (IPAF) was first proposed by an international task force in 2015 as a research classification to standardise nomenclature regarding patients with idiopathic interstitial pneumonia and features of connective tissue disease. However, how the use of this term and its proposed definition translates to clinical practice remains uncertain. This review will provide a comprehensive overview of studies of IPAF cohorts to date, discuss the consideration of IPAF as a distinct diagnostic entity and outline a suggested approach to patient management. Considerable heterogeneity exists between published IPAF cohorts, with some cohorts exhibiting similarities to those with connective tissue disease-associated interstitial lung disease (CTD-ILD), and others more similar to idiopathic interstitial pneumonias including idiopathic pulmonary fibrosis (IPF). Little data exist to inform the management of patients who fulfil the IPAF criteria. Preliminary data supports pragmatic management of these patients as having a working clinical diagnosis of either idiopathic interstitial pneumonia or CTD-ILD. Future research studies into this approach are required. The term IPAF, and its definition, have been of fundamental benefit to facilitating research in this diverse patient group. However, to date, there remain many unanswered questions regarding their natural histories and response to treatment.

Rheumatological evaluation of patients with interstitial lung disease

Objective: Interstitial lung disease (ILD) is a common feature of connective tissue disease (CTD). The diagnosis of CTD-ILD can be challenging and is important for therapeutic decisions. In this study, we aimed to determine whether a systematic rheumatological assessment could help pulmonologists in the diagnosis and care of ILD patients. Method: We conducted an observational single-centre study of patients with ILD. All patients underwent standardized pulmonary and rheumatological evaluations, including clinical evaluation (pulmonary symptoms and musculoskeletal signs), immunological screening, chest high-resolution computed tomography, pulmonary function tests, and ultrasonography (US) of joints and major salivary glands. Results: We included 100 consecutive ILD patients (47% women, mean ± sd age 67 ± 14 years); 15 patients already had CTD. The main extrapulmonary symptoms were joint pain (n = 52), joint swelling (n = 26), and sicca syndrome (n = 33). US of joints revealed synovitis, bone erosion, and tenosynovitis in 37, 17, and 13 patients, respectively. US of major salivary glands detected features associated with Sjögren’s syndrome in 13 patients. After rheumatological evaluation, CTD-ILD was confidently diagnosed in 39 patients; diseases were mainly rheumatoid arthritis (n = 20), primary Sjögren’s syndrome (n = 17), and inflammatory myopathies (n = 7). The diagnosis of CTD-ILD was associated with the presence of musculoskeletal symptoms and immunological and US abnormalities. The CTD diagnosis led to a therapeutic change in 21 patients. Conclusion: Our findings suggest that musculoskeletal symptoms are frequent in ILD patients, which supports multidisciplinary management, involving the rheumatologist, for evaluating patients with ILD.

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations.

Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.

P042 A rare case of constrictive pericarditis with co-existing positive COVID-19: probable autoimmune or immunoglobulin related disease

Background/Aims Constrictive pericarditis occurs most commonly after idiopathic pericarditis (in less than 1%) in the developed world. Other uncommon aetiologies include tuberculosis, rheumatological diseases and post-viral pericarditis. Methods We present a case of an 80-year-old Caucasian man admitted with shortness of breath (NYHA III), skin rash, loss of weight and peripheral oedema. He had no other features of connective tissue disease (CTD) or vasculitis. His past medical history included atrial fibrillation, gout, hiatus hernia and he was on rivaroxaban, ramipril, digoxin, allopurinol, bumetanide, ranitidine and finasteride. Investigations showed NT pro BNP at 6473 ng/L, CRP at 78 mg/ dL and lymphopenia (0.42 10*9/L). He has persistent hyponatraemia at 117 mmol/L with normal kidney function. His liver function test showed alkaline phosphatase of 239 U/L and globulin at 41 g/L. His COVID-19 swab test was positive whereas mycobacterial culture and hepatitis screen were both negative. He had weakly positive ANA at 0.7 but otherwise normal autoimmune profile. The level of immunoglobulin G was 25 g/L and paraprotein of 2 g/L. His electrophoresis showed a monoclonal IgG; Kappa/Lambda ratio was 2.03. CT chest and cardiac MRI: shows constrictive pericarditis, pericardial effusion and thickening, moderate pleural effusion and ground-glass changes scattered throughout the right lung which suggested probably inflammatory origin. Thoracoscopic surgery (RVATS) was done for drainage of pleural effusion, excision of fat pad and anterior partial pericardectomy. The pericardial biopsy concluded chronic fibrous pericarditis with focal submesothelial mononuclear cell infiltrate with numerous plasma cells and lymphocytes .There was no amyloid or immunoglobulin deposition or malignancy. After the operation, there was both clinical and biochemical improvement (CRP- 28 mg/ dL). He did not need any immunomodulatory therapy. Results Cardiac involvement is rapidly emerging in COVID -19 diseases with case reports of myopericarditis, atrial fibrillation, heart failure, Kawasaki disease, thromboembolism, cardiogenic shock and aortitis. The mechanism remains unexplained but it could be related to direct endothelial inflammation or the cytokine storm sequelae. In our case, pericardial biopsy concluded features suggestive of autoimmune or immunoglobulin associated disease, although there was no clinical evidence of autoimmune disease. There were no lytic lesions and MGUS was diagnosed and scheduled for six monthly monitoring. Conclusion We report a case of constrictive pericarditis with COVID-19, although this remained a differential among the co-existed immunoglobulin and autoimmune syndrome. Appropriate imaging, biomarkers and histology investigations need to be considered for rapid evaluation and escalation of treatment. Cardiac manifestations are an important feature of COVID- 19. Further research is required to guide the management plans for similar cases. Disclosure Z. Alkutobi: None. G. Ansari: None. A. Nandagudi: None.

Clinical characteristics of connective tissue disease associated interstitial lung disease in children

Objective: To elucidate the clinical features of connective tissue disease associated interstitial lung disease (CTD-ILD) in children. Methods: A total of 24 children diagnosed with CTD-ILD and treated in Department of Rheumatology and Immunology, Shanghai Children's Medical Center from January 2010 to December 2019 were included in the study. Their medical data including clinical features, lab test, imaging, pulmonary function test, treatment and outcome were analyzed statistically. Results: In these 24 patients, 4 were males and 20 females. Their main clinical presentations were cough (10/24, 42%), shortness of breath (10/24, 42%), tachycardia in quiet state (8/24, 33%), fatigue with activity (7/24, 29%), and fever (6/24, 25%). The main abnormal physical examination findings were moist rales (4/24, 17%) and acropachy (2/24, 8%). There were various abnormal findings in the patients' lab test. All the patients (100%) had pulmonary interstitial changes on chest CT. Eight patients had spirometry test, and all (100%) showed decreased diffusion capacity. After immunosuppressive treatment, 15 cases (63%) improved, 4 cases (17%) gave up or died, while 5 cases (21%) had no significant improvement on the imaging examination. Conclusions: The onset of pediatric CTD-ILD could be insidious. Early diagnosis and aggressive treatment may change the prognosis, but are both difficult and need further studies.