Catastrophic antiphospholipid syndrome presented with coronary thrombosis, renal impairment, and suspected diffuse alveolar hemorrhage treated with rituximab biosimilar (CT-P10)

Catastrophic antiphospholipid syndrome (CAPS) is a lethal disease that occurs suddenly and progresses to multi-organ failure. We present a case of CAPS successfully treated with the rituximab biosimilar CT-P10. A 38-year-old man was referred with a sustained fever and unexplained elevated creatinine levels. Cardiac arrest by ventricular fibrillation occurred upon arrival at the hospital. We diagnosed probable CAPS because of coronary thrombus, renal impairment, suspected diffuse alveolar hemorrhage, and positive anticardiolipin antibody immunoglobulin G. We performed percutaneous coronary intervention for the cardiac arrest, and treated him with extracorporeal membrane oxygenation, mechanical ventilation, and continuous renal replacement therapy. When CAPS was diagnosed, we administered CT-P10 after administering high-dose glucocorticoid. Our case suggests that the use of a rituximab biosimilar is economically efficient in the treatment of CAPS, as in other rheumatic diseases. The patient was cured without recurrence at the 2-year follow-up.

Case Report: Pediatric Malignant Atrophic Papulosis With Small Bowel Perforation and Positivity of Anticardiolipin Antibody

Malignant atrophic papulosis (MAP) is a life-threatening vasculopathy affecting the skin, gastrointestinal tract, central nervous system, pleural membrane, and pericardium. MAP carries a poor prognosis primarily because of its systemic involvement. It is extremely rare in children. Herein, we report a pediatric case of MAP with small bowel perforation and anticardiolipin antibody positivity.

Acquired and Inherited Thrombophilia Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension: Value of Testing in an Academic Health Center

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country. Methods This is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki. Results and discussion The study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC). Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort. Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients. The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively. Conclusion This single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Coronavirus-disease-2019-induced antiphospholipid-like syndrome: a case report

Background This paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events. Case description The patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019. Conclusion According to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis.

Primary antiphospholipid antibody syndrome presenting as acute superior mesenteric vein thrombosis

Antiphospholipid antibody syndrome (APS) is an autoantibody mediated thrombophilia characterised by recurrent arterial or venous thrombosis and/or pregnancy morbidity. APS presenting as thrombosis in mesenteric venous system is relatively uncommon (10%). Here, we present a case of primary APS presenting as acute superior mesenteric vein (SMV) thrombosis in a 38-year-old female. She was admitted with the complaints of abdominal pain and constipation for five days. Her abdomen was distended with sluggish bowel sounds. Her abdominal contrast enhanced computed tomography revealed thrombosis of SMV, splenic vein and portal vein. She was initially kept on conservative management and started on anticoagulants. Her coagulation work-up revealed that she was positive for anticardiolipin antibody and therefore, the diagnosis of APS was made. She was continued on conservative management and anticoagulants. On the tenth day of admission, after starting oral diet, she developed severe abdominal pain and abdominal signs of peritonitis. She was then taken up for emergency laparotomy. Intraoperatively; there was 100 cm of gangrenous ileal segment, about 60 cm from ileocecal junction and 160 cm from duodenojejunal flexure. The gangrenous ileal segment was resected and a double barrel ileostomy was constructed. She had an uneventful postoperative recovery and was started on lifelong anticoagulants.

POS1404 ECHOCARDIOGRAPHIC FINDINGS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS AND ITS RELATION TO ANTIBODIES TITERS

Background:Systemic lupus erythematosus (SLE) is a chronic and autoimmune disease characterized by systemic involvement. Patients with SLE have accelerated atherosclerosis, resulting in an up to nine-fold increased risk of cardiovascular disease, compared to the general population (1), being the leading cause of death for these patients. Speckle tracking echocardiography (STE) is an accurate technique to estimate myocardial function and deformation.Objectives:This study aims to determine the association between echocardiographic findings and the presence of antibodies in SLE patients.Methods:This was a cross-sectional and observational study. A total of forty-three patients ≥18 years with a diagnosis of SLE according to EULAR/ACR 2019 criteria were included for this study. Those with a history of cardiovascular disease (myocardial infarction, cerebrovascular accident, or peripheral arterial disease) and pregnancy were excluded. Transthoracic echocardiogram was performed and reviewed by 2 board-certified cardiologists, in all study subjects. Blood samples obtained from all patients were analyzed for the following: anti-nuclear antibodies (ANA), anti, SSA/Ro, SSB/La antibodies, anti-cardiolipin antibodies (IgA, IgM, IgG), and complement levels. Distribution was evaluated with the Kolmogorov-Smirnov test. Correlations between numerical variables were done using Spearman’s rho, considering two-tailed p-values <0.05 as statistically significant.Results:The 39 female patients (90.7%) and 4 male patients (9.3%) had a mean age of 35.5 ± 12.0 years and a median disease duration of 72 months (14-132). At the time of inclusion, 90.7% of the patients were being treated with glucocorticoids and antimalarials. Concerning traditional cardiovascular risk factors; 20.9% of the patients had hypertension, 7.0% had dyslipidemia, 2.3% had diabetes mellitus and 18.6% were active smokers. Correlations between echocardiographic findings and antibodies are shown in Table 1. We found a moderate positive correlation between global circumferential strain and IgA anticardiolipin antibody (r=0.507, p=0.002), a low positive correlation in left ventricular ejection fraction with anti-Ro (r=0.397, p=0.012) and anti-La (r=0.397, p=0.012) and a low positive correlation between TAPSE and C3 levels (r=0.396, p=0.013).Conclusion:There is an association between anticardiolipin antibody titers, anti-Ro, and anti-La with echocardiographic alterations. All SLE patients especially those who had positive antibodies should be screened for the presence of structural cardiac abnormalities. STE can be helpful as a noninvasive diagnostic tool, that could result in earlier treatment and prognosis.References:[1]Hesselvig JH, Ahlehoff O, Dreyer L, et al. Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. Lupus 2017;26(1):48-53. doi: 10.1177/0961203316651739Table 1.Spearman rho correlations between antibody titers and echocardiographic findings.VariablesGLS,mean ± SD-19.11 ± 3.33LVEF,mean ± SD57.43 ± 7.17TAPSE,mean ± SD22.23 ± 3.24ANA, median (p25-p75)640 (160-2550)NSNSNSIgA Anti-Cardiolipin, median (p25-p75)2 (2-3)0.507**NSNSIgM Anti-Cardiolipin, median (p25-p75)2 (2-4)NSNSNSIgG Anti-Cardiolipin, median (p25-p75)4 (3-6)NSNSNSAnti-Ro, median (p25-p75)17 (2-80)NS0.326*NSAnti-La, median (p25-p75)3 (2-5.5)NS0.397*NSC3, mean ± SD91.41 ± 37.38NSNS0.396***Correlation is significant at the 0.01 level (2-tailed). *Correlation is significant at the 0.05 level. NS, not significant; GLS, global circumferential strain; LVEF, left ventricular ejection fraction; TAPSE, tricuspid annular plane systolic excursion.Disclosure of Interests:None declared

AB0313 THE CLINICAL CHARACTERISTICS OF PATIENTS WITH IMMUNE-ASSOCIATED ADVERSE PREGNANCY

Background:Immune-associated adverse pregnancy is the adverse pregnancy outcomes induced by autoimmune factors or autoimmune diseases, including infertility, recurrent spontaneous abortion, failed assisted reproduction, fetal growing restriction. It is helpful to explore the mechanism and improve the management by analyzing the clinical characteristics of patients with immune-associated adverse pregnancy.Objectives:To find the risk factors of Immune-associated adverse pregnancy by analyzing the clinical characteristics of patients with immune-associated adverse pregnancy.Methods:The patients involved in this study were from the multi-department clinic of immune-associated adverse pregnancy, during April 2019 and August 2020. They were diagnosed with autoimmune diseases according to relative classification standards or with autoimmune abnormality. Patients with adverse pregnancy due to anatomic, endocrine, infectious and chromosomal factors were excluded.Results:A total of 107 patients were included. The average age was 29.3 years old. The number of total adverse pregnancy was 115 and the average was 1.07. For the diagnosis, 22 (22.4%) were autoimmune abnormality (with autoantibody but cannot be classified to any autoimmune disease), 30 (28.0%) were antiphospholipid syndrome (APS), 17 (15.9%) were systemic lupus erythematosus (SLE), 13 (12.1%) were mixed connective tissue disease (MCTD), 8 (7.5%) were undifferentiated connective tissue disease, 5 (4.7%) were Sjogren syndrome (SS), other autoimmune disease account for 10 (9.4%). For the antibodies, the positive rate of ANA was 44.8% (48/107), anti-SSA 36.4% (39/107) anti-RNP 15.0% (16/107), anti-dsDNA8.4% (9/107), anti-Sm 9.3% (10/107), anticardiolipin antibody 17.8% (19/107), anti-B2GP1 24.3% (26/107), LA 8.4% (9/107), non-criteria antiphospholipid antibody 3.7% (4/107).Conclusion:Our data showed that autoimmune abnormality, SLE, APS, MTCD and SS impacted immune-associated adverse pregnancy the most. The most crucial antibodies were ANA, anti-SSA, anti-RNP, anti-dsDNA and antiphospholipid antibodies.Disclosure of Interests:None declared

P030 Antiphospholipid syndrome and giant cell arteritis: a coincidence or connection?

Background/Aims Antiphospholipid syndrome (APS) is a multisystem autoimmune disorder, which can be primary or associated with other conditions including systemic lupus erythematosus. Several studies have reported antiphospholipid antibodies, in patients with different vasculitides but little is known about the occurrence of APS and giant cell arteritis (GCA). We report a case of a patient diagnosed with concomitant extracranial GCA and APS. Methods A 74-year-old lady presented to the Emergency department following a fall at home. On further questioning, she reported a rapid history of weight loss (4kg in the previous 4 weeks) but no classical features of giant cell arteritis. Her temporal arteries were pulsatile bilaterally, not tender or thickened. Cranial nerve examination including fundoscopy was normal. Her gait was apraxic, with short stride length and veering to the right with a narrow base. The rest of the examination was unremarkable. Results Laboratory investigations showed an elevated CRP 98mg/L with a normal ESR 23mm/h, ferritin 380 ng/ml, negative ANCA and ANA, with an unremarkable myeloma screen. Microbiology investigations demonstrated negative serial blood cultures, hepatitis screen, and quantiferon. She subsequently underwent intracranial imaging [CT and MRI brain with Gadolinium] which did not demonstrate acute pathology. A PET CT confirmed features in keeping with a large vessel vasculitis without aneurysmal formation. She was treated with pulsed IV methylprednisolone 500mg for 3 consecutive days and started on 60mg oral prednisolone daily. Two days after starting this treatment she developed acute onset double vision: ophthalmologic examination revealed new onset right internuclear ophthalmolplegia (INO). A subsequent CT head angiogram showed non critical stenoses in aorta at origins of great vessels, left vertebral artery, and carotids. Interval MRI brain showed a new infarct in pons corresponding with her INO. Bloods revealed triple positive anti-phospholipid antibodies - [IgG anticardiolipin antibody 102 GPL (0-13), anti-β2 glycoprotein I antibodies 59.8 U/ml (0-18), Lupus anticoagulant detected]. She was commenced on warfarin [target INR 2.5] and aspirin. Due to mental health history and large vessel manifestations, she was started on IV Tocilizumab 8mg/kg and her prednisolone dose was reduced to 40mg when her CRP normalised. Following hospitalisation, she had persistent visual disturbance with ongoing poor spatial co-ordination. Although she remained ataxic, her functional mobility improved. She was transferred to a local stroke unit and was discharged home. Conclusion In summary, this is a case of GCA and APS, treated with prednisolone, aspirin, warfarin and tocilizumab. There is increasing evidence describing the presence of antiphospholipid antibodies in patients with vasculitis. However, the role of these antibodies in GCA and the clinical significance remains unclear. This case reports highlights the need for physicians to consider APS in patients who have a history of GCA and subsequently develop arterial or venous embolic events. Disclosure L. Sammut: None. E. Htut: None.

Autoantibodies among HIV-1 infected individuals and the effect of Anti-retroviral therapy (ART) on it.

Background:: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. Methods: A cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage positivity of antinuclear antibody was 5% among ART naïve and controls with a decrease to 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 was 4%, 1% and 3% among ART naïve, treated and controls respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre respectively (p<0.05). Conclusion: ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.