Autoimmune Screen Research Articles

ACUTE SUB FULMINANT HEPATITISINDUCED BY ANTI-TUBERCULOSIS DRUGS

Introduction :Hepatotoxicity is a prominent adverse effect of anti-tuberculosis drugs, with a frequency of up to 20%, but it is often reversible on cessation of treatment, and fatal outcome is exceptional. We report an observation of acute subfulminant hepatitis induced by antituberculosis treatment. Observation : A 60-year-old patient with a three-year history of insulin-dependent diabetes was started on anti-tuberculosis treatment for smear-positive pulmonary tuberculosis. After two months of treatment, the patient complained of asthenia, epigastric pain, and conjunctival jaundice. Physical examination revealed only jaundice, with no signs of chronic liver disease. Laboratory tests showed hepatic cytolysis (transaminases 10 times the upper limit of normal), associated with cholestasis (alkaline phosphatase 2 times the upper limit of normal, total bilirubin 98 μmol/L), and hepatic insufficiency (prothrombin time = 53%). Despite adjustment of anti-tuberculous drug doses based on serum concentrations, the decision was made to discontinue anti-tuberculosis treatment and admit the patient to the hospital. During the etiological work-up, viral serologies (hepatitis B, C, and HIV) were all negative, as was the autoimmune screening. There was no inflammatory syndrome or hyper eosinophilia. The patient denied alcohol consumption, and no potentially hepatotoxic medications were identified on medication review. Abdominal ultrasound and CT showed normal hepatic and biliary structures with the presence of ascites. Paracentesis revealed transudative fluid, attributed to hypoalbuminemia of 12 mg/L. Liver biopsy was deferred due to clinical and biochemical deterioration (total bilirubin elevated to 288 μmol/L) and worsening hepatic failure (prothrombin time at 7%, unresponsive to vitamin K supplementation). The patient died from grade III hepatic encephalopathy 35 days after discontinuation of treatment. Discussion et Conclusion: In the light of this observation, we emphasise the role of screening and early diagnosis of toxic hepatitis, and we reiterate the importance of monitoring patients on anti-tuberculosis drugs to avoid a severe and fatal course due to adverse liver reactions.

P34 A case of haemophagocytic lymphohistiocytosis triggered by primary Epstein–Barr virus infection

Abstract Introduction Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic hyperinflammatory state characterised by uncontrolled activation of the immune system. HLH may occur in a primary (familial) form, but more commonly occurs secondary to another disease process. Such triggers include infections, autoimmune disease and malignancy. We present the case of a 24-year-old female who was previously fit and well, who was diagnosed with HLH secondary to primary Epstein-Barr virus (EBV) infection. Case description The patient was admitted with a 10-day history of fever, sore throat and abdominal pain. On examination she had bibasal crackles and epigastric and right upper quadrant tenderness. There was pharyngeal erythema but no exudate. No rash or joint inflammation. Admission blood tests showed WBC 11.7 x109/L, neutrophils 6.5 x109/L, lymphocytes 4.3 x109/L, platelets 142 x109/L, CRP 179 mg/L, ALT 330 U/L, ALP 1022 U/L, bilirubin 37 mmol/L and lactate 1.81 mmol/L. A CT chest/abdomen/pelvis showed bibasal consolidation with small bilateral pleural effusions and mild splenomegaly. The patient was hypotensive and tachycardic, and was spiking temperatures greater than 39 °C. She subsequently developed type 1 respiratory failure and was transferred to the intensive care unit. She was treated with broad-spectrum antibiotics for suspected sepsis secondary to pneumonia. She remained unwell with high spiking fevers. HLH was suspected and ferritin was >100,000 mg/L with triglycerides 6.19 mmol/L, fibrinogen 1.1 g/L and LDH >1800 U/L. Her HScore was 200, indicating a high probability of HLH. Autoimmune screen including rheumatoid factor, ANCA and ANA were negative. A comprehensive infection screen identified a strongly positive EBV viral capsid antigen (VCA) IgM, positive EBV VCA IgG and negative EBV nuclear antigen (EBNA) with a viral load of 49,600 copies/ml. These results were consistent with acute primary EBV infection. Bone marrow biopsy confirmed haemophagocytosis. A diagnosis of HLH triggered by primary EBV infection was made. The patient was discussed with the specialist HLH service at University College Hospital and was commenced on intravenous methylprednisolone and anakinra 200 mg twice daily. She was additionally given antivirals, antibiotics and antifungals as prophylaxis against secondary infection. The patient improved clinically and biochemically. The dose of anakinra was reduced and eventually discontinued, and the patient was discharged on a tapering course of prednisolone. Discussion HLH carries a high mortality rate and early recognition and treatment is vital. However, diagnosis is often delayed as HLH may resemble other conditions such as sepsis. Signs and symptoms of HLH include fever, hepatosplenomegaly, cytopenias, hyperferritinaemia, hypertriglyceridaemia, liver dysfunction and coagulopathy. There may be multi-organ dysfunction. The characteristic histopathological finding is haemophagocytosis on biopsy of bone marrow, lymph node, liver or spleen, however this may initially be absent. EBV is the most common infective trigger for HLH, but it may occur with other viral and bacterial infections including tuberculosis. The most common autoimmune conditions associated with HLH include adult-onset Still’s disease (AOSD), systemic juvenile idiopathic arthritis and lupus. Haematological malignancy, in particular lymphoma, is another important cause and can sometimes be challenging to identify. The initial presentation of AOSD can share many of the same clinical features as EBV infection, including fever, rash, sore throat, hepatosplenomegaly, lymphadenopathy and liver dysfunction. The rash of AOSD is classically salmon-pink coloured and comes and goes with the fever, and the fever typically occurs at the same time each day. In our patient, the absence of arthralgia, rash and leucocytosis meant AOSD was felt to be unlikely, but this was kept under review. Key learning points • Early recognition and treatment of HLH is crucial to reducing mortality • The HScore tool can be used to assess the probability of HLH • Management of HLH involves supportive care, immunosuppression and treatment of the underlying cause • Agents that may be used include steroids, cyclosporine, etoposide, anakinra and intravenous immunoglobulin

MCM9 compound heterozygosity in an adolescent with premature ovarian insufficiency.

Delayed puberty in girls is often related to late maturation but is occasionally the first sign of premature ovarian insufficiency (POI). POI is a condition that affects ovarian function and fertility, and its etiology is unknown in most cases. Genetic factors have recently been identified in 20-25% of women with POI, involving genes that regulate various aspects of ovarian development and maintenance. We report a case of delayed puberty due to POI in an adolescent from a non-consanguineous family who carried two variants in the MCM9 gene. MCM9 is essential for DNA replication and repair, and its dysfunction can lead to chromosomal instability and ovarian failure. Our case highlights the importance of targeted gene panel analysis, particularly in POI patients with negative autoimmunity screening, and evidence of ovarian or uterine dysgenesis on pelvic imaging. Delayed puberty in girls is often self-limiting, but it can also indicate underlying conditions with lifelong implications, such as premature ovarian insufficiency (POI). Patients with POI, negative autoimmune screening, a normal karyotype, and no FMR premutation should undergo further genetic testing, preferably through targeted gene panels. Compound heterozygous variants in MCM9 can cause POI, presenting with delayed puberty and primary amenorrhea in girls without a consanguineous family.

HLA Genotyping in Children With Celiac Disease Allows to Establish the Risk of Developing Type 1 Diabetes.

Celiac disease (CD) and type 1 diabetes (T1D) often co-occur and share genetic components in the human leukocyte antigen (HLA) class II region. We aimed to study the usefulness of HLA genotyping in predicting the risk of developing T1D in patients with CD and the temporal relationship between these diseases. A cohort of 1,886 Sardinian patients, including 822 with CD, 1,064 with T1D, and 627 controls, underwent HLA class II typing. Seventy-six of 822 patients with CD were also affected by T1D (CD-T1D), and their HLA genotypes were analyzed for specific HLA associations with CD, T1D, and controls. High-risk HLA-DQ genotypes, including HLA-DQ2.5/DQ8, -DQ2.5/DQ2.5, and -DQ2.5/DQ2.3, were strongly associated with CD-T1D with frequencies of 34.5%, 15.9%, and 18.8%, respectively. Conversely, certain HLA genotypes associated with CD seemed to confer protection against T1D development. Therefore, HLA genotyping allows for the identification of those patients with CD who might develop T1D. The frequency of patients with CD preceding T1D is higher in younger children than older ones, with implications for the early childhood approach to diabetes prevention. CD is a condition for future T1D development, and specific HLA genotypes can predict this risk. Early screening for celiac autoimmunity and subsequent HLA typing in CD children could help identify those at high risk of T1D, allowing for proactive interventions and immunotherapies to preserve β-cell function. These findings may support the re-evaluation of HLA typing in children with CD.

CLINICAL CHALLENGE: AORTITIS IN THE EMERGENCY DEPARTMENT

Abstract A 67 yo woman presented to the ED for a sustained episode of palpitations and acute chest pain. Past medical history: suspected psoriatic arthritis previously treated with steroids and hydroxychloroquine; previous suspicion of rheumatic polymyalgia and Horton arteritis, regressed with steroids; gastroesophageal reflux disease; mild hypercholesterolemia and a family history of premature coronary artery disease. In the ED the patient was hemodynamically stable. On physical examination: tachyarrhythmic heart sounds with no murmurs. The peripheral arterial pulses were preserved and symmetrical. The remaining physical examination was unremarkable. ECG: atrial fibrillation at 150 bpm. The D–dimer was increased, normal hs–troponin and normal haemoglobin. On echocardiography: normal biventricular structure and function; normal aortic root with dilatation of proximal ascending aorta (47 mm), without visible intimal flaps. The anterior wall of the proximal ascending aorta was thickened. A moderate circumferential pericardial effusion was present, without signs of hemodynamic impact. On suspicion of an acute aortic syndrome with possible intramural haematoma of an ascending aortic aneurism, an urgent CT scan was ordered. It showed a severe dilatation of ascending aorta (52 mm) involving of the proximal aortic arch. The anterior aortic wall was thickened (5 mm), without clear images of IMH, aortic dissection or penetrating ulcer. The pericardial effusion had a supra–fluid density without blood density. A repeated CT at 6 hours showed no changes. The case was suggestive of an inflammatory aetiology. The patient was admitted to the cardiac intensive care unit. A PET–CT scan showed signs of an inflammatory disease of the great vessels. A serological autoimmunity screening was negative. The patient was diagnosed with inflammatory aortitis (giant cell vs Takayasu arteritis) and started on high dose iv glucocorticoid therapy. Given the high risk of severe aortic complications, adjunctive therapy with tocilizumab was prescribed. The therapy was gradually tapered, with subsequent switch to oral steroids plus tocilizumab. At one and a half month of follow–up, a CT scan was repeated, documenting stable aortic diameters and the disappearance of the abnormal thickness and of the enhancement of the aortic wall. A follow–up PET–CT scan has been scheduled at 6 months time. An elective aortic intervention has been indicated after remission of the inflammatory phase.

Spontaneous Hypoglycaemia due to Insulin Autoimmune Syndrome in Six Cases, Response to Steroid Therapy and Rituximab.

Dr. Hirata of Japan first described insulin autoimmune syndrome (IAS) in 1970. Seven hundred ninety-five cases of this rare syndrome have been reported from Japan and China and 29 from India. IAS has the following characteristic features 1) severe spontaneous attacks of hyperinsulinemic hypoglycaemia, 2) high total immunoreactive insulin levels, 3) elevated insulin autoantibody (IAA) titres, 4) no prior exposure to exogenous insulin, and 5) no pathological abnormalities of the pancreatic islet cells. We treated six cases of IAS with high doses of prednisolone for 4-6 weeks and then gradually reduced the doses. Diagnosis of IAS was established by documenting Whipple's triad of symptoms and signs of hypoglycaemia, blood sugar <55 mg/dl, improvement of symptoms with dextrose infusion, inappropriately increased insulin levels >3 uU/ml, C-peptide levels >0.6 ng/ml, and increased titres of anti-insulin autoantibodies. Insulinoma and non-pancreatic tumours were ruled out by CECT (contrast-enhanced computerised tomography) or MRI (magnetic resonance imaging) of the abdomen and if necessary endoscopic ultrasonography and gallium 68 Dotanoc PET (positron enhanced tomography). Autoimmune screening and serum electrophoresis were done to rule out multiple myeloma. Monitoring of the patient's blood sugars was done by the laboratory, glucometer readings, and a freestyle libre glucose monitoring system. Remission of hypoglycaemic episodes, hyperglycaemic episodes, and marked reduction of serum insulin and insulin autoantibodies in four out of six patients with diet therapy and steroids. Two patients resistant to steroids were treated with rituximab successfully. Patient 6 developed serious complications of cytomegalovirus and Pneumocystis carnii after rituximab, which were treated successfully. A careful history including recent infections, medications, and vaccinations provides vital clues in the evaluation. An increased awareness of IAS will prevent unnecessary and costly investigations and surgery. Although it is often self-remitting, steroids are contributory in severe cases. Immunosuppressives are used successfully in cases refractory to steroids. Continuous glucose monitoring system (CGMS), by freestyle libre glucose monitoring system, provided real-time blood sugar values, total time in hypoglycaemia, and total time in the range (TIR), which proved very valuable in managing IAS patients. Low CGMS values should be corroborated clinically and with laboratory or glucometer values.

One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program

Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon sign rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P= .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

AbstractBackgroundUnderstanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is essential to reduce its consequences. This study was aimed at determining the activities of new‐onset primary Sjögren syndrome (pSS) since the emergence of SARS‐CoV‐2.MethodsThis retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group (n = 24) or vaccinated and infected group based on exposure (n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS‐CoV‐2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS‐CoV‐2 were assigned to a vaccinated and infected group. The controls comprised age‐ and sex‐matched patients who had not been exposed to SARS‐CoV‐2 before December 2019 (n = 21). We then compared data among the three groups.ResultsThe vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti‐nuclear antibody (ANA) titers &gt; 1:320 (n = 12; 50%) and anti‐phospholipid antibodies (aPL) (n = 7; 29%) than the controls. The frequency of anti‐Ro/SSA antibodies (13, 65%), ANA titers &gt; 1:320 (n = 16; 80%), and aPLs (n = 7; 29%) (n = 5; 25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups (p &lt; 0.05, for all).ConclusionsPatients with new‐onset pSS and a history of vaccination and SARS‐CoV‐2 infection might have more active disease. Further strengthening the assessment of people with a clear history of SARS‐CoV infection and the monitoring of potential populations for autoimmune screening should not be overlooked.

Searching The New Culprit of Optic Neuritis: The Role of Vitamin D

Abstract&#x0D; Introduction : Low vitamin D status has long been associated in multiple sclerosis patient with higher risk of disease progression and frequent relapses. Vitamin D plays an important role in modulating the immune process responsible for demyelination. To this date, the study on vitamin D deficiency in optic neuritis case is still rare.&#x0D; Case Illustration : Female, 20 years old, presenting with bilateral sudden visual loss since 1 week prior. The patient looked relatively pale and complained of accompanying headache and myalgia. Visual acuity in both eyes were light perception with dilated pupils and posterior segment showing optic disc swelling. CBC, infection and autoimmune screening came within normal limit and brain MRI further confirmed the presence of optic neuritis. The patient was given high dose intravenous steroid but showed no improvement. Later, she was screened for nutrient deficiency and found sign of low serum 25-hydroxyvitamin D. After one week of oral supplementation and neuroprotective agents, her vision drastically improved to 6/6 in both eyes.&#x0D; Discussion : Vitamin D deficiency nowadays is getting more prevalent in high risk individuals with low dietary intake and sunlight exposure. Recent study found that mean serum vitamin D level were significantly lower in autoimmune optic neuritis (ON) and were associated with ON attack severity. Vitamin D sufficiency is associated with better inflammatory outcome and long term neurodegenerative measures in demyelinating diseases, as shown by improvement in RNFL thickness after attack.&#x0D; Conclusion : Screening for vitamin D deficiency is essential to consider in managing patient with atypical optic neuritis.

Systemic Sclerosis Sine Scleroderma Presenting as Pulmonary Arterial Hypertension - A Case Report

A 60-year-old married male farmer with a significant medical history, including STElevation Myocardial Infarction (STEMI), coronary artery bypass grafting (CABG), and Raynaud’s disease, presented to the emergency department with sudden-onset syncope and progressive shortness of breath on exertion. The syncope episode involved an abrupt loss of consciousness, with spontaneous recovery and no associated symptoms like jerky movements or tongue biting. The shortness of breath had been gradually worsening over several weeks, becoming noticeable even during minimal exertion. On examination, the patient appeared chronically ill but had stable vital signs cardiovascular examination revealed bilateral pedal edema, while respiratory assessment and Neurological evaluation were normal. Blood tests indicated normal full blood count (FBC) and urea and electrolytes (U+E), but slight elevations in CRP 29 mg/L and ESR 20 mm/hr. Troponin levels remained stable, but brain natriuretic peptide (BNP) was markedly elevated at 2061 pg/mL. The electrocardiogram (ECG) showed right axis deviation and incomplete right bundle branch block (RBBB). A CT scan of the brain ruled out any acute pathology, such as stroke or hemorrhage. A previous echocardiogram (ECHO) had shown a left ventricular ejection fraction (LVEF) of 50-55%, indicating good left ventricular function. Given the findings, the patient was started on Furosemide 40 mg daily and advised to follow a fluid restriction regimen to prevent worsening of overload symptoms. A repeat echocardiogram revealed deterioration in right ventricular (RV) function with a significantly (RVSP) of 80 mmHg, suggesting severe pulmonary hypertension (PHTN). A D-dimer test was negative for pulmonary embolism (PE). Cardiology consultation raised concerns about possible chronic thromboembolic disease, leading to further testing, including a computed tomography pulmonary angiogram (CTPA) and an autoimmune screen, along with potential right heart catheterization (RHC). The CTPA was negative for PE, but the autoimmune screen returned positive results for antinuclear antibodies (ANA &gt;1200) and anticentromere antibodies. Right heart catheterization confirmed pre-capillary pulmonary hypertension (PAH) with pulmonary artery pressure exceeding 44 mmHg and no nitrate response. A rheumatology review, in light of the patient’s history of Raynaud’s disease, positive ANA, and confirmed PAH, led to the diagnosis of Systemic Sclerosis Sine Scleroderma–a form of systemic sclerosis without skin involvement. The patient was initiated on Tadalafil, (PDE-5) for PAH management and prescribed home oxygen therapy, particularly during exertion. He was discharged with a plan for multidisciplinary followup involving rheumatology, cardiology, and pulmonology to manage his complex condition. Conclusion: Multidisciplinary is essential for optimizing outcomes in SSc and PAH.

Post-malaria neurological syndrome (PMNS): a rare case report with brain biopsy findings

Post-malaria neurological syndrome (PMNS) is a rare, self-limiting condition that presents with a wide range of neurological manifestations after clearance of malarial infection, especially \U0001d617\U0001d62d\U0001d622\U0001d634\U0001d62e\U0001d630\U0001d625\U0001d62a\U0001d636\U0001d62e f\U0001d622\U0001d62d\U0001d624\U0001d62a\U0001d631\U0001d622\U0001d633\U0001d636\U0001d62e, most patients recover without residual deficits. Here we present a case of a 29-year-old, male with a recent history of malaria treated successfully, who presented due to a generalized tonic-clonic seizure, without any other neurological symptoms, the examination and labs were unremarkable, he underwent a computer tomography (CT) scan and Magnetic resonant imaging (MRI) which both showed two areas of vasogenic edema involving the subcortical white matter of left frontal and right posterior parasagittal regions, all autoimmune screens, infection workup from blood and CSF were negative, he underwent a brain biopsy that showed intense perivascular inflammation with neuronal loss and gliosis, findings are nonspecific and can be seen in a variety of condition. The patient’s condition improved, and he was discharged without any complications.

Factor V Inhibitor in COVID-19 an Unusual Presentation

Introduction : A huge variety of haematological manifestations and derangements have been frequently published with COVID-19 infections, however Factor V deficiency and COVID-19 infection has not been documented. We are reporting a case of acquired Factor V deficiency due to inhibitor caused by COVID 19 infection . Factor V deficiency is a rare bleeding disorder having either inherited or acquired forms. Acquired factor V deficiency (AFVD) can present at any age, with the manifestations ranging from abnormal deranged PT/PTT to serious bleeding and quite often challenging to diagnose. The risk factors for development of inhibitors include surgical procedures, Hepatitis, antibiotic, Urinary tract infections, blood transfusions, haemodialysis, malignancies like multiple myeloma, amyloidosis and autoimmune disorders. Around 30% of cases of AFVI are found to be idiopathic. Studies suggest that there is a temporal Connection between SARS-CoV-2 infection and the development of coagulopathy. This could be possible since COVID -19 infection is well associated with autoimmune coagulation abnormalities such as lupus anticoagulant, antiphospholipid antibodies, and venous thromboembolism. The precise mechanisms behind the relationship between Covid19 infection and development of Factor V deficiency is not fully understood. SARS-CoV-2 infection induces a proinflammatory state causing endothelial damage, platelet activation and hyperviscosity. We suggest that the factor V inhibitor was formed in the setting of immune dysregulation from the underlying COVID-19 as coagulation profile was normal before admission to hospital. Result and method: A 62 year old gentleman with background of dyslipidemia and IBS was admitted to the hospital with asymptomatic COVID pneumonia. The patient was started on Lopinavir-Ritonivir 500mg BID and enoxaparin 40mg OD. Upon routine testing patient was found to have a deranged coagulation profile (PT: 41.9sec/APTT: 104.7sec/INR: 3.5/Fibrinogen: 3.04gm/L/ D-dimer: &amp;lt;0.30mg/L FEU). Daily results kept showing a steady rise of coagulation parameters (PT: 46.5sec/APTT: 122.0sec/INR: 3.9) however the patient was asymptomatic. Results demonstrated severe factor V deficiency (&amp;lt;5.7%) with mildly reduced Factor VII (53.8%) and a mildly elevated factor VIII (195.4%). PT and APTT mixing studies showed no correction of the prolonged clotting times before and after 2 hours incubation, hence the failure of correction suggested the presence of an inhibitor for which Bethesda test for Inhibitor's titer and autoimmune screening were sent. Considering the Factor V inhibitor deficiency with background of active COVID-19 infection and to prevent bleeding complications, the patient was started on Inhibitor eradication therapy with Dexamethasone 20 mg, and Immune globulin intravenous 45 gm. Inhibitor titers came back positive for an inhibitor level of 9 BU/ml. Autoimmune screen for ANA and anti-B2 glycoprotein came back negative. Malignancy was ruled out. Throughout the hospital stay , we did not encounter any bleeding manisfestions or drop in haemoglobin. Since the patient had a previous record of normal coagulation profile in 2019, a diagnosis of COVID-19 infection-related Factor V deficiency with inhibitor was made. After a four-days course of inhibitors eradication, PT INR and aPTT started coming down with no significant complications, the patient was discharged on oral prednisolone and vitamin K. Follow up in the clinic after 3 weeks showed complete normalization of coagulation profile. Conclusion: A wide range of haematological manifestation have been reported with COVID-19 infection, but the association of Factor V deficiency due to inhibitors and COVID-19 infection have not been reported in the literature earlier. Treatment will be focusing on treating the primary cause and eradication of the inhibitors.

A rare presentation of acute myocarditis as a manifestation of adult-onset Still’s disease: a case report

Abstract Background Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory condition characterized by a classical triad of symptoms that include prolonged fever, polyarthritis, and a characteristic salmon-pink skin rash. It can affect a variety of organ systems resulting in many different clinical presentations and is usually a diagnosis of exclusion. Myocarditis complicated by cardiogenic shock is a rare and life-threatening manifestation of AOSD, typically affecting younger patients. There is a limited experience and evidence in how best to manage this challenging patient cohort. Case summary A previously fit and well 22-year-old male presented with fever, arthralgia, and general malaise. On clinical examination, he was pyrexial and hypotensive, requiring vasopressor support for presumed septic shock. Subsequent transthoracic echocardiography and cardiac MRI findings were in keeping with fulminant myocarditis. Further septic and auto-immune screens were negative although he responded well to high-dose intravenous corticosteroids. Attempts to wean immunosuppression were unsuccessful, and his ferritin was markedly elevated (20 233 μg/L). A diagnosis of AOSD was suspected after exclusion of other possible causes. The successful addition of tocilizumab (an interleukin-6 receptor antagonist) therapy allowed for gradual de-escalation of steroid therapy and disease remission, with on-going remission at 18 months on maintenance therapy. Discussion This case highlights the importance of considering AOSD as a rare cause for myocarditis, especially when fever is present, or disease is severe. Failure to improve with first-line therapy involving high-dose corticosteroids, or inability to wean that therapy, should prompt consideration for escalation of therapy, with tocilizumab seemingly an effective treatment option.

Current modalities for the diagnostic and management approach of buerger’s disease: a case report and comprehensive review

Background: Thromboangiitis obliterans (TAO or Buerger’s disease) is a non-atherosclerotic inflammatory vascular disease usually related to smoking. Until now, there is no consensus establishing the diagnosis and standard treatment. Case Illustration: A 74-year-old smoker woman complained of blackening and painful fingertips in both upper limbs. On upper-extremities examination, we found necrotic gangrene at the 3rd fingertips of the right hand, and the 2nd and 4th fingertips of the left hand, with limitation of the movement at the affected finger due to the pain. On laboratory findings, there was a leukocytosis, mild Anemia, no coagulopathy, and normal autoimmune screening. Doppler Ultrasonography showed vascular incompetence of the left palmar arch artery, with no deep or superficial vein thrombosis. Arteriography revealed multiple stenosis of the Left Radial artery and Right Ulnar artery with collateral corkscrew-shaped. The patient was diagnosed with peripheral Critical Limb Threatening Ischemia caused by TAO, which underwent conservative management for 10 days and Percutaneous Trans Angioplasty (PTA) ballooning. Discussion: Buerger disease commonly affects smoker men between 40-45 years old. Several clinical criteria were used to establish TAO, including Shinoya and Olin's criteria. There are still no specific management guidelines for TAO, and smoking cessation is the only accepted effective treatment to prevent the progression of the disease and avoid amputation, followed by conservative and interventional management for patients with Critical Limb Ischemia. Conclusions: Awareness of the entity and familiarity with the clinical, angiographic, and pathologic features are the keys to a prompt and correct diagnosis of TAO. Although still controversial, endovascular intervention is regarded as a potentially efficacious approach in TAO with critical limb ischemia management.

P08 Appearance matters: a case of adult-onset Parry-Romberg syndrome with linear scleroderma en coup de sabre and neurological involvement

Abstract Introduction We describe the case of an adult patient who initially presented with neurological symptoms. Investigations were suggestive of a neuroinflammatory disorder but the diagnosis was unclear. It was only as time passed that the cutaneous signs and symptoms of Parry-Romberg syndrome (PRS) and linear scleroderma en coup de sabre (LSCS) became apparent to clinicians as the underlying cause for her presentation. Case description This female patient, with no past medical history, presented in 2015 when she was 43 years old. She reported a one-day history of malaise and lethargy, left-sided headache, numbness affecting the right face and right arm and dysphasia. Her symptoms gradually improved over the following few days. An MRI brain showed extensive T2 hyperintensity in the right frontal and frontoparietal regions. Cerebrospinal fluid (CSF) showed a lymphocytosis and oligoclonal bands, which were present in the CSF only. A repeat MRI brain a few weeks later showed slightly less extensive changes. This was treated by neurologists as a neuroinflammatory disorder with intravenous methylprednisolone pulses. At follow-up, she mentioned that she had noticed a change in her appearance, with the right side of her face becoming increasingly asymmetrical over the last few years. Neurologists were puzzled regarding the diagnosis, but given that she was almost asymptomatic at review, they decided to monitor her with serial MRI scans. There were no further neurological episodes and no interval changes on repeat scans. In 2020, she was referred to ophthalmology, as she had noticed that her right eye had become increasingly sunken. MRI of the orbits and sinuses was reported to show enophthalmos of no obvious cause. Around the same time, she was also referred to dermatology for an enlarging patch of alopecia over the right frontoparietal scalp. Autoimmune screening blood tests including ANA, ENA, dsDNA and centromere were negative. Scalp biopsy was inconclusive but was most in keeping with old alopecia areata. She was treated with intralesional steroids and had a partial response. It was only by 2021 that PRS with LSCS was recognised as the cause of her symptoms. We can be confident that her neuroinflammation is an extracutaneous manifestation, which occurred early on when cutaneous signs were subtle. Discussion PRS is a rare, acquired disorder characterised by progressive unilateral atrophy of facial skin, soft tissue, muscles, and underlying bony structures. LSCS is a subtype of linear scleroderma that occurs on the forehead or frontoparietal scalp. PRS and LSCS commonly coexist, and it is debated whether they are on a spectrum of the same disease. Both usually occur in childhood or adolescence, and adult-onset disease is very rare. The diagnoses are clinical and there are no specific diagnostic tests. Both are associated with neurological involvement, including seizures, headaches, focal neurological deficits and neuropsychiatric changes. Usually, the cutaneous lesion develops months to years before the onset of neurological symptoms. Our patient had noticed subtle changes in her appearance at least five years before her presentation in 2015. Neuroimaging abnormalities are predominately ipsilateral to the cutaneous lesions but may rarely be contralateral. Key learning points Given that adult-onset PRS and LSCS are very rare, there may be a lack of awareness of the conditions amongst adult physicians. This can lead to diagnostic delay. This case highlights that PRS and LSCS are not just conditions of the skin and connective tissues and that neurological involvement is a frequent extracutaneous manifestation. This case is also a reminder of the importance of a thorough examination of the skin, especially when the diagnosis is unclear.

Anxiety and Risk Perception in Parents of Children Identified by Population Screening as High Risk for Type 1 Diabetes.

To assess anxiety and risk perception among parents whose children screened positive for islet autoantibodies, indicating elevated risk for type 1 diabetes (T1D). The Autoimmunity Screening for Kids (ASK) study identified 319 children age 1 to 17 years at risk for T1D via screening for islet autoantibodies; 280 children with confirmed islet autoantibodies and their caregivers enrolled in a follow-up education and monitoring program to prevent diabetic ketoacidosis at diagnosis. Parents completed questionnaires at each monitoring visit, including a 6-item version of the State Anxiety Inventory (SAI), to assess anxiety about their child developing T1D, and a single question to assess risk perception. At the first ASK follow-up monitoring visit, mean parental anxiety was elevated above the clinical cutoff of 40 (SAI 46.1 ± 11.2). At the second follow-up monitoring visit (i.e., visit 2), mean anxiety remained elevated but started to trend down. Approximately half (48.9%) of parents reported their child was at increased risk for T1D at the initial follow-up monitoring visit (visit 1). Parents of children with more than one islet autoantibody and a first-degree relative with T1D were more likely to report their child was at increased risk. Most parents of autoantibody-positive children have high anxiety about their child developing T1D. Information about the risk of developing T1D is difficult to convey, as evidenced by the wide range of risk perception reported in this sample.

P17 Photosensitive rashes in the context of alcoholism: a diagnosis to remember

Abstract Pellagra is a disease defined by a deficiency in niacin and its precursor tryptophan. It is a clinical diagnosis characterized by the ‘four Ds’: dermatitis, dementia, diarrhoea and death (Badawy AA. Pellagra and alcoholism: a biochemical perspective. Alcohol 2014; 49:238–50; Pipili C. The diagnostic importance of photosensitivity dermatoses in chronic alcoholism. Dermatol Online J 2008; 14:15). It is predominantly a disease of non-Western countries with low niacin-containing diets, based on maize, with little meat or vegetables. In Western populations, the commonest causes of pellagra include alcoholism, gut malabsorption, some drugs and, rarely, carcinoid, which causes increased conversion of tryptophan to serotonin, depleting niacin precursor stores. The histopathological features of pellagra are nonspecific; however, pallor and keratinocyte ballooning in the upper third of the epidermis can be suggestive. We present two cases of pellagra in the context of alcoholism. Patient 1 was a 58-year-old woman who presented with a 6-week history of a rash on the dorsal hands which spread to the forearms and dorsum of both feet. Examination revealed a photodistributed erythematous rash with a prominent leading edge, wrinkling and hyperkeratosis. She described loss of appetite, diarrhoea and increasing confusion. A punch biopsy from the right forearm showed focal parakeratosis, perivascular inflammation and mild spongiosis with increased mucin in the superficial dermis. A clinical diagnosis of pellagra was suspected, and empirical niacin was prescribed. Patient 2 was a 60-year-old woman who presented with a 1-month history of a progressive itchy rash affecting her arms and legs. Examination revealed a striking photosensitive erythematous rash of her arms and legs, with complete sparing of the inner aspect of the arms. Skin biopsy showed mild keratosis, with subtle thickening of capillary walls. A diagnosis of pellagra was suspected and treatment with oral niacin commenced. Both patients drank alcohol to excess. Both had negative plasma porphyrins and had not started any new drugs and autoimmune screens were normal. The clinical appearance was identical in both cases. Patient 1 continued to drink excess alcohol, but the rash resolved with niacin supplementation. Patient 2 only took a short course of niacin due to significant flushing, but she managed to reduce her alcohol intake significantly and her rash fully resolved. Pellagra is a rare diagnosis in a Western population, but it is an important diagnosis to remember in patients presenting with a photosensitive rash, particularly in the context of alcohol abuse.

Sun, alcohol, and skin lesions

A 65-year-old man presented to the emergency room with blistered not itching skin lesions on the dorsal surface of both hands, which developed recurrently after exposure to sun and solved spontaneously with scarring. The patient had a history of hypertension, diabetes mellitus type 2 and hypercholesterolemia. His medications included ramipril, metformin, simvastatin, and acetylsalicylic acid. He denied smoke, but he used to consume a large amount of alcohol (1 Lt of red wine daily). His body mass index was 29 (overweight). Blood exams revealed: altered glucose metabolism (fasting and post-prandial blood glucose, respectively 172 mg/dL and 267 mg/dL), macrocytosis (mean cell volume 100.6 fL), increased transaminases (AST 62 U/L and ALT 79 U/L, normal value 10-37) and gamma-glutamyl transferase (GGT 255 U/L, normal value 7-40), and an iron assessment as follows: serum ferritin 2234 ng/mL, transferrin saturation 40%, serum iron 138 mcg/dL. Hepatitis C, hepatitis B, and HIV were excluded. Autoimmune screening was negative. Point of care ultrasound documented a grade 3 liver steatosis.

1294-P: Prevalence of Islet Autoantibodies in Adults from the General Population

Objective: Over half of cases of type 1 diabetes are diagnosed in adults, yet the prevalence of islet autoantibodies (IA) in general population adults is unknown. Methods: The Autoimmunity Screening for Kids (ASK) Study screened 1,087 adults (age 41±7 years, 78% female, 63% non-Hispanic white, 10% first-degree relatives) and 29,441 youth (age 1-17 years, 52%, 36%, and 5%, respectively) for IA to GAD, IA-2, insulin, and ZnT8 using electrochemiluminescence (ECL) or radiobinding assays (RBA). Results: In adults, 3.9% screened positive; 0.6% were positive for multiple IA, 1.7% were positive for a single high-affinity IA, and 1.6% were positive for a single low-affinity IA. GADA was most prevalent, found in 2.7%. Unexpectedly, the prevalence of IA in adults and youth screened by ASK was not statistically different (Figure). Conclusion: IA positivity is similar in youth and adults in the general population. Expanded access to type 1 diabetes screening and monitoring will aid in determining if early detection is similarly beneficial in adults as seen in youth, such as reducing rates of diabetic ketoacidosis at diagnosis of clinical type 1 diabetes. Disclosure M.Pauley: None. C.Geno rasmussen: None. F.Dong: None. K.M.Simmons: Advisory Panel; Provention Bio, Inc., Consultant; Dexcom, Inc., Provention Bio, Inc., Research Support; Novartis. M.Rewers: Research Support; Provention Bio, Juvenile Diabetes Research Foundation (JDRF), Hemsley Charitable Trust, Dexcom, Inc., Janssen Research &amp; Development, LLC. Funding National Institute of Diabetes and Digestive and Kidney Diseases (T325T32DK063687); JDRF (2-SRA-2022-1270-S-B)

#5430 ANTI-PLA2R ASSOCIATED MEMBRANOUS NEPHROPATHY AND CHRONIC LYMPHOCYTIC LEUKAEMIA, IS THERE A LINK?

Abstract Background and Aims The spectrum of glomerular lesion that occurs in the context of plasma cell dyscrasias (PCD) is wide, including type I and type II membranoproliferative glomerulonephritis (MPGN), focal proliferative GN, membranous nephropathy (MN), minimal change disease and amyloidosis. A clear-cut link between hematological dyscrasias and glomerulopathy is often offered by the finding of paraproteins in the kidney or by kidney leucocytic infiltration and, in these scenarios, malignancy treatment is often found to be also effective towards the glomerulopathy. In the context of PCD in which proliferation of the B-cell clone does not lead to plasma-cell terminal differentiation such as chronic lymphocytic leukemia (LLC) the physiopathological link with glomerulonephritis is not well established and it's hard to determine whether the combination of these two disorders is fortuitous. With regarding to MN, it's now well established that this histopathological pattern must be related to the presence of circulating autoantibodies, where anti-PLA2R auto-antibodies usually been associated with primary MN. To our knowledge association between LLC and anti-PLA2R associated MN has not been described. Case report We report the case of a 76-year-old man who was admitted in February 2022 with anasarca and acute kidney injury. He had recently been evaluated by a hematologist in the context of suspected chronic lymphocytic leukemia (CLL). Laboratory findings, along with typical CLL white blood cell count, showed decreased kidney function from baseline and were compatible with nephrotic syndrome, with proteinuria progressively increasing up to 27 gr/24 h in the following weeks. CLL was confirmed by lymphocyte typing. A total body CT scan showed mediastinal, abdominal and inguinal lymphadenopathies, but no suspected neoplastic lesions. Screening for autoimmunity tested completely negative, as well as infectious screening for common hepatic viruses (HBV, HAV, HCV), EBV, CMV, HIV, Parvovirus B19. Lymph node biopsy showed no aspects of aggressive lymphoproliferative disease and hematological consultation only indicated clinical and laboratory follow-up of LLC, with no further indication to specific therapies. A kidney biopsy was performed showing diffuse thickening of the basement membrane (Fig. 1) with granular deposition of IgG (+++) and C3 (++) along the glomerular capillary walls at immunofluorescence. Electron microscopy revealed subepithelial immune deposits (Fig. 2) with initial incorporation from the glomerular basement membrane (GBM). Anti PLA2R antibodies, found negative at first determination, subsequently tested positive at high titre (ELISA 1356.4 U/ml). A diagnosis of stage two membranous nephropathy was made, and the patient was treated with Rituximab 375 mg/m2 every week for four weeks. Clinical stability was obtained with repeated intravenous administration of diuretics (furosemide 60 mg + canrenone 200 mg) along with albumin. Nevertheless, nephrotic syndrome persisted, and kidney function progressively decreased with serum creatinine up to 2.8 mg/dL. Immunophenotype, which showed reduction but no suppression of CD19+ lymphocytes, was again repeated on November 2022 and showed typical LLC findings (CD 19+, CD 20+, CD 23+, CD 5+) with repopulation of CD19+ lymphocytes. Anti PLA2R antibodies gradually decreased instead, reaching a value of ELISA 1.8 U/ml in November 2022 and persisted negative until present. The patient recovered from nephrotic syndrome in Autumn 2022 and is currently on stage G3B chronic kidney disease with persistent sub-nephrotic proteinuria in supportive treatment. Conclusion Simultaneous diagnosis of primary MN and LLC led us to ask ourselves whether this patient could benefit from LLC-specific chemotherapy, even though there were no signs of aggressive hematological disease and no clear link with the nephropathy. We think that further investigations are required to deeply understand the connection between hematological and renal disorders, in order to identify whether there are two diseases to treat separately or two sides of the same disease to treat as one.