Autoimmune Panel Research Articles

Evaluation of autoimmune neurology testing clinical utility and stewardship initiatives

Abstract Testing for neural autoantibodies associated with autoimmune neurological diseases has an important role in clinical care. However, as they are niche tests for relatively rare diseases, they often have longer turn-around-times and more expensive costs than many other laboratory tests. In addition, due to the low yield of positive results, they often appear as attractive stewardship targets. Our objective was to review current utilization and ordering patterns and evaluate the impact of ongoing stewardship efforts to inform next steps regarding stewardship of these tests. Methods: Data on utilization and ordering patterns of autoimmune and paraneoplastic neural autoantibody panels from January 1 to December 31, 2023, was obtained from reference laboratory and electronic medical record (EMR) data. Additional data on best practice advisories from the most recent six months was obtained from the EMR. Results: Overall, we observed that providers tested 2270 patients both from our defined test menu (five total tests, ~89% of total orders) and through the miscellaneous route (12 total tests, ~11% of total orders), which allows providers to place orders for tests not currently on our menu. Just under one third of the orders were in cerebrospinal fluid (CSF) (n=725), while the remaining were for serum (n=1545). The percent positivity was generally higher in serum specimens, ranging from 0 to 50% per test (n=227 total positive specimens). The percent positivity in CSF specimens ranged from 0 to 40% per test (n=29 total positive specimens), which is generally consistent with previously published literature. Most of the orders were placed by neurology providers (56%). The best practice advisories (BPAs) currently in use are soft stops that target repeat tests in the same specimen type within thirty days of a previous order. Of note, these BPAs can only catch orders placed through the defined process. In six months, the BPA for repeat serum orders fired 104 times for 42 unique patients; the BPA for repeat CSF orders fired 96 times for 38 unique patients. The serum BPA resulted in elimination of the repeat order for 43% of patients (n=18), while the CSF BPA resulted in elimination of the repeat order for 24% of patients (n=9). We observed some situations in which the BPA appeared to be firing when previous orders were incorrectly collected and so not able to be sent out. Conclusion: Based on these data, we plan three main steps to continue to refine autoimmune neurology testing: 1) update our test menu to offer the most clinically useful orders through the defined route, 2) pilot review of tests ordered through the miscellaneous route, and 3) optimize BPAs to target situations with inappropriate utilization rather than technical issues.

12511 Rhabdomyolysis Related Acute Kidney Injury Presenting as First Manifestation of Autoimmune Hypothyroidism: A Case Report

Abstract Disclosure: A. Tiwari: None. S. Mantravadi: None. N. Doshi: None. A. Dabaja: None. C. Saad: None. Introduction: Autoimmune thyroiditis is the predominant cause of primary hypothyroidism, with an incidence of estimated 0.3-1.5 cases per 1000 people, with female to male predominance of 7-10[1]. Hypothyroid myopathy affects 79 % of the affected population. Its common presentation is fatigue and cramp but in rare instances rhabdomyolysis can occur with trivial triggers like alcohol, exercise2, Case Presentation: A 32-year-old male with no significant medical history, presented with generalized weakness, myalgia, and facial puffiness for last three months. The patient engaged in regular-intensity workouts and reported consuming 12 beers several times a week for past 5 years. Physical examination revealed facial puffiness and proximal muscle weakness. Initial Laboratory findings showed elevated creatinine (1.68 mg/dL, baseline 1.0 mg/dL in April 2020), CK (8113 U/L), AST (260 U/L), ALT (129 U/L). Urinalysis revealed hematuria and mild proteinuria. Serum electrolytes were unremarkable. Abdominal ultrasound showed diffuse hepatic steatosis with normal kidney appearance. This could not explain the reason for the Acute Kidney Injury and further workup showed TSH (>150 mIU/L) and TPO antibodies (197.9 U/mL). Autoimmune panel was unremarkable. Thyroid ultrasound done subsequently revealed a markedly heterogeneous gland. Treatment included parenteral crystalloids, low-dose prednisone which was empirically added for suspected autoimmune myositis and was later discontinued once the autoimmune panel was negative, and Levothyroxine at the recommended dose. At the time of discharge, his creatinine was reduced to 1.33 mg/dL and CK to 2,298 U/L. Discussion: Severe rhabdomyolysis is a rare but significant complication of autoimmune thyroiditis, potentially leading to acute kidney injury (AKI) if not promptly diagnosed and treated. Resident physicians often attribute symptoms like myalgia and generalized weakness in males to clear evident rhabdomyolysis if they find a cause like alcohol consumption and exercise, potentially overlooking the actual etiology. We recommend thyroid workup in such patients to promptly detect and manage underlying etiology predisposing to muscle damage and subsequent kidney injury. Our patient never had any Physician encounter as his prior medical history was unremarkable, however we suggest thorough family history and thyroid profile should be a part of outpatient workup as well for patients who show other risk factors for rhabdomyolysis like daily alcohol consumption, vigorous workout, consume medications like HMG CoA inhibitors, antipsychotics etc. Presentation: 6/3/2024

An uncommon diagnosis of a young female with fever of unknown origin (FUO): Idiopathic Hemophagocytic Lymphohistiocytosis (HLH)

Background. Hemophagocytic Lymphohistiocytosis (HLH), characterized by the uncontrolled activation of immune cells leading to a hyperinflammatory state, is seldom considered in the initial differential diagnosis of FUO. The rarity of idiopathic HLH, especially in young individuals without an identifiable trigger, emerges as an uncommon and particularly challenging diagnosis. This case report presents a compelling narrative of a young female grappling with the complexities of FUO, ultimately revealing the rare and life-threatening entity of idiopathic HLH. Case report. A 25 year old female was referred to our hospital in view of persistent high grade fever since 3 months. Patient has no other complaints. Vitals stable. General and systemic examination normal. Lab investigations showed a total leukocyte count 18000 cell/μL, hemoglobin 9.2 g/dL, and platelets 68000 cells/μL. Other blood investigations showed erythrocyte sedimentation rate (ESR) 88 mm/h, C-reactive protein 21 mg/L, ferritin 670 ng/mL, triglyceride 281 mg/dL, and fibrinogen 1.2g/L. She also had transaminitis with AST 80, ALT 92 and ALP 1442. The entire infectious diseases panel was done which came negative for all, including viral serologies and hepatitis markers. Procalcitonin level was normal and no other relevant investigations came positive. Autoimmune panel analysis also came negative. Blood cultures came negative in two different samples. Also, there is no evidence of vegetation in echocardiography. Coming to the invasive investigations, bone marrow biopsy and aspiration were done to arrive at a diagnosis and it showed hemophagocytosis. Endoscopy and colonoscopy were done, which came normal. CT thorax and abdomen also showed no significant abnormalities, ruling out the probability of missing any gross malignancies. After all this extensive work up and according to Hscore, which is used to estimate an individual’s risk of having reactive hemophagocytic syndrome, this patient was diagnosed with HLH. According to the current HLH guidelines, initial treatment for the disease consists of etoposide, corticosteroids (dexamethasone), or cyclosporine given for 8 weeks. The patient was started on the same above treatment regimen, but only with corticosteroids for a period of 8 weeks, after a consultation with the hematologist. No recurrence is seen in her 6-months of follow-up. The regimen was well tolerated by the patient. Studies also have shown that therapeutic plasma exchange also has a role in HLH treatment, which can be tried in familial and relapsing cases. Conclusion. In our case, this young female was diagnosed to have idiopathic HLH, after ruling out all the familial and secondary causes of HLH including infections, malignancy and autoimmune diseases. The patient was also started on treatment early after the bone marrow and other relevant investigations according to HScore suggested the diagnosis of HLH and the patient improved accordingly. Hence, apart from clearly knowing the etiology or clinical manifestations, HLH is associated with a high mortality rate if appropriate treatment not given. Generally, the underlying etiology determines the prognosis of the disease. But, it is not a good idea to delay the treatment in order to find the cause and type of HLH, because the exhaustive work up might lead to unacceptable delays in improvement and prognosis of the patient. The diagnostic work up and treatment should be done simultaneously in the patient, which has been done in our case and it lead to a good outcome. Though HLH is a fatal and dangerous disease and also highly challenging to make a diagnosis due its uncommon and largely variable clinical presentation, smart work up and early initiation of treatment will lead to better prognostic outcomes.

AUTOIMMUNE MYOCARDITIS IN MELANOMA IMMUNOTHERAPY–COMPLEX CLINICA PRESENTATION AND ADVERSE THERAPEUTIC RESPONSE

Abstract A 68–year–old Caucasian female presented to the ED with cardiac chest pain and dyspnea. The patient had a history of arterial hypertension and was equipped with a biventricular pacemaker due to atrial fibrillation with low ventricular response. She had recently been diagnosed with metastatic melanoma and initiated treatment with nivolumab and ipilimumab two weeks prior. Troponin levels were elevated (700 ng/ml), and no ST–segment elevation was observed on the electrocardiogram (ECG). In suspicion of NSTEMI–ACS, coronary angiography was performed, revealing an intact epicardial coronary circulation without stenotic lesions. The echocardiogram showed borderline left ventricular systolic function (EF 50%), and the right ventricle exhibited initial signs of reduced systolic function (TAPSE, 15 mm; S RV, 9.5 m/s). The following day, there was a deterioration in hemodynamics and respiratory exchange, with evidence of apical and mid–distal interventricular septum hypokinesia of the left ventricle (EF 40%) and dilated right ventricle (BD 4.8 cm; MD 4 cm) with severely reduced systolic function (TAPSE 10 mm, S RV 7 m/s, FAC, 20%), and severe tricuspid regurgitation. Urgent computed tomography pulmonary angiography (CTPA) excluded pulmonary embolism. Additionally, there was a new troponin increase (5000 ng/ml) and elevated hepatic biomarkers. The clinical picture raised suspicion of myocarditis related to immune checkpoint inhibitor therapy. Corticosteroid therapy was initiated with a daily administration of methylprednisolone 1000 mg. Diagnostic confirmation was sought through autoimmune panel and viral marker assessments, which yielded negative results. Endomyocardial biopsy (EMB) revealed CD4 and CD8–positive lymphocytic infiltration and myocardial necrosis. Despite initial clinical improvement, an arrhythmic storm developed. Despite treatment with a defibrillator, intravenous antiarrhythmic therapy (beta–blocker, amiodarone, and lidocaine), and sedation, the patient unfortunately succumbed. Immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of many solid tumors. However, the dysregulation of immune mechanisms can rarely (2%) lead to autoimmune events involving multiple organs. Myocarditis, despite optimal treatment, is characterized by a mortality rate exceeding 50%, representing a significant challenge in the Intensive Care Unit.

P013 A case report of posterior orbital inflammation associated with VEXAS(Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome

Abstract Background/Aims VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly recognised adult-onset acquired autoinflammatory disease caused by somatic mutations of the UBA1 gene in the blood precursor cells. It is characterised by systemic inflammation and haematologic abnormalities. Methods Here we report a case of a 66 year old male who presented with orbital inflammation as one of the striking features of his underlying VEXAS. Results Our patient has a history of type 1 insulin dependent diabetes, otitis externa and recurrent lower limb distal venous thrombosis. He presented to Eye Emergency in May 2023 with rapid onset painful diplopia, left retrobulbar pain and peri-orbital swelling. He had recently been referred to Haematology with new anaemia and constitutional symptoms. MRI demonstrated inflammatory changes of some left extraocular muscles and cranial nerves. He was pulsed with three days of intravenous methylprednisolone with significant clinical response. Bone marrow biopsy reported reactive morphology and no clear myelodysplasia. In August 2023, the patient re-attended eye clinic with right sided facial swelling. Rheumatology were consulted for further opinion. The patient had previously been known to the department over 10 years ago, after presenting with arthritis labelled as diabetic cherioarthropathy. Extensive autoimmune panel was requested, including normal IgG subclass, weakly positive c-ANCA with a negative PR3. The patient had a new macrocytic anaemia (Hb 103 g/L, MCV 103 fl) and previous thrombocytopenia. Inflammatory markers were raised, CRP between 8-180, ESR 60 to 110 and Ferritin 878. Ultrasound of neck showed normal parotid and small reactive lymph nodes. Urgent PET-CT reported bone marrow reactivation with no significant findings. Prednisolone 40mg was given with marked resolution of the facial swelling. Opinion was sought by Haematology about any features of VEXAS on previous myelodysplasia screening. A week later, we received the result of the genetic testing showing a mutation of the UBAE gene, consistent with the diagnosis of VEXAS. The patient had re-occurrence of his inflammatory symptoms on several occasions [including diplopia, headache, rash, ocular pain, or periocular swelling] which were all steroid responsive. After discussion with multiple specialities, including Haematology, Ophthalmology and Immunology colleagues with a specialist interest in VEXAS, Tocilizumab was felt to be the most appropriate initial treatment. The patient is due for their first infusion in October 2023. Conclusion We report a unique case of VEXAS who presented with orbital inflammation, a less well-characterised feature of VEXAS. VEXAS is perhaps not as exceptionally rare as we first thought, it is likely more similar cases will present and we need to have a high degree of clinical suspicion in patients with unexplained systemic inflammation, especially those presenting initially with ocular inflammation. These patients require a multi-disciplinary approach to ensure best management of a very challenging condition. Disclosure C.A. Zollinger-Read: None. A. Zewar: None. L. Dunkley: None. J. Jefferis: None.

A291 ANA-NEGATIVE AUTOIMMUNE HEPATITIS IN A 30-YEAR-OLD FEMALE: A DIAGNOSTIC CHALLENGE

Abstract Background Autoimmune Hepatitis (AIH) is a chronic liver condition arising from the immune system's attack on liver cells. Its diagnosis is typically supported by the presence of autoantibodies, notably ANA. However, cases have been identified where AIH occurs in the absence of these conventional serologic markers. Prior studies have reported that ANA-negative AIH patients showed more acute presentations and higher frequencies of histologic acute hepatitis compared to those with positive autoimmune serology. As such, ANA-negative subset of patients presents a diagnostic challenge but highlights the evolving understanding of autoimmune processes in liver diseases. Aims To detail the clinical presentation, investigative measures, and treatment approach in a an otherwise healthy 30-year-old female diagnosed with ANA-negative autoimmune hepatitis. Methods The diagnostic approach included clinical symptomatology, biochemical tests, imaging via abdominal ultrasound, and histopathological evidence from an ultrasound-guided liver biopsy Results The patient presented initially with epigastric pain, jaundice, and pruritus over two weeks. Blood tests revealed acute hepatitis: ALT at 2723 U/L[JA1] , AST at 1428 U/L, and hyperbilirubinemia at 503 μmol/L, with GGT and ALP remaining normal. An abdominal ultrasound presented a typical liver morphology and biliary system. Initial autoimmune liver disease panels, including ANA, and viral hepatitis screenings, returned negative results. Furthermore, the patient's medication and drug history provided no additional clues for drug-induced aetiologies. For more conclusive diagnostics, an US-guided liver biopsy was performed during the admission revealing moderate acute hepatitis characterized by both interface hepatitis and lobular inflammation, prompting the suspicion for ANA-negative AIH. Initiating prednisone treatment (40 mg daily) based on clinical and biopsy evidence led to a significant reduction in liver enzymes and bilirubin. By the time of her discharge, her primary residual symptoms were mildly controlled jaundice and pruritus. She was transitioned to a tapering dose of prednisone, and Azathioprine was later added to her regimen. Subsequent close follow up revealed complete resolution of her symptoms. Notably, a 7-month follow-up unveiled a previously undetected AIH marker: ASMA with a titre of 1:80. Conclusions ANA-negative AIH, as showcased in this case, emphasizes the importance of a thorough and iterative diagnostic approach. Traditional serological markers may not always be present, necessitating reliance on a combination of clinical presentations and histopathology. Regular follow-ups and periodic re-evaluations are essential. This approach is crucial for pinpointing the diagnosis, guiding effective therapeutic interventions, and ultimately ensuring positive outcomes for patients navigating complex autoimmune liver conditions. Funding Agencies None

A rare case of alpha-methyldopa-induced hepatitis in pregnancy

Introduction. There are three groups of disorders during pregnancy: disorders specific for pregnancy that resolve spontaneously or soon after delivery, acute hepatic disorders coinciding with pregnancy, and chronic disorders. Drug-induced liver disease prevails among women and it is estimated to be a leading cause of acute liver injury. Drug-induced hepatitis is rare in pregnancy with only a few cases reported in literature. Alpha-methyldopa is one of the commonly used drugs in pregnancy that could cause hepatotoxicity with different clinical presentations and possible adverse effects on normal course of pregnancy. Case outline. We reported a rare case of hepatotoxicity caused by alpha-methyldopa in 26 gestational weeks pregnancy in a 35-year-old patient admitted because of jaundice and elevated liver function tests. She had been using antihypertensive drug, alpha-methyldopa, from 12th gestational week, and no other medication or supplementation was recorded. Ultrasound of the abdomen excluded obstruction or any other abnormalities. Autoimmune panel was done. Biochemical analyses were indicative of toxic acute liver injury caused by alpha-methyldopa according to values of transaminase. After 13 days, patient was discharged recovered from the hospital. Conclusion. Diagnosis of alpha-methyldopa hepatotoxicity is challenging since the low incidence, unpredictability, diverse symptomatology and absence of specific biomarkers. That is why timely diagnosis is crucial for the well-being of both future mother and child.

Diagnosis and Treatment of Immune Heamolytic Aneamia

Immune hemolytic anemia (IHA) stands as a multifaceted hematologic disorder characterized by accelerated destruction of red blood cells due to immune system dysregulation. This paper aims to elucidate the nuanced landscape of IHA, focusing on its diverse diagnostic approaches and evolving treatment strategies. Diagnostic considerations encompass a range of laboratory tests, including direct and indirect Coombs tests, hemolysis markers, and autoimmune antibody panels, elucidating their roles in confirming IHA etiology and subtype classification. Additionally, advancements in imaging modalities aid in identifying underlying causative factors contributing to hemolysis. The paper further scrutinizes therapeutic interventions, spanning corticosteroids, immunosuppressive agents, and monoclonal antibodies, while also appraising emerging modalities like rituximab and splenectomy. Moreover, the role of supportive care and transfusion strategies in managing IHAassociated complications is delineated. Challenges in IHA management, including refractory cases and adverse effects of therapies, are deliberated alongside the potential of future advancements in precision medicine and targeted therapies. By assimilating the latest diagnostic methodologies and treatment paradigms, this review provides a comprehensive outlook on navigating the complexities of immune hemolytic anemia to optimize patient care and outcomes. Keywords: haemolytic anaemia, anaemia, immunity, diagnosis, treatment

NCMP-21. AQP4-MOG DOUBLE-POSITIVE PARANEOPLASTIC NEUROLOGICAL SYNDROME IN A PATIENT WITH TRIPLE NEGATIVE BREAST CANCER

Abstract We report a rare case of paraneoplastic neurological syndrome (PNS) with dual seropositivity of anti-aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) antibodies in a 40 year-old lady with metastatic triple negative breast cancer with involvement of mediastinal, right axillary, and supraclavicular lymph nodes. She received multiple lines of anti-neoplastic treatment including immunotherapy with pembrolizumab as well as chemotherapy with taxol, carboplatin, gemcitabine, capecitabine, cytoxan, sacituzumab and nevalbine. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis extending from T11-12 that symptomatically improved with high dose intravenous methylprednisolone. One month later she developed left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid (CSF) analysis during both episodes revealed normal glucose, protein, elevated white blood cell count. Cytology was negative for malignancy. CSF was positive for neuromyelitis optica (NMO) IgG antibody APQ-4 and autoimmune myelopathy panel was positive for MOG antibody. Patient had significant clinical and radiographic improvement after completion of plasmapheresis and intravenous immunoglobulin. There was resolution of pleocytosis on repeat CSF testing. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every six months and daily low dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case demonstrates that these antibodies can occur concurrently and cause clinical features like both neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or CSF profile negative for leptomeningeal carcinomatosis.

Abstract 14871: Mitral Valve Involvement in Systemic Sclerosis, Post COVID-19 Infection

Introduction: We report a case of mitral valve regurgitation as cardiac involvement of systemic sclerosis (SSc) in a 52-year-old woman post COVID-19 infection. Case Description: 52-year-old female presented with new-onset, progressive dyspnea, dryness and thickness of the skin, intermittent palpitations, and weight loss 3 months after recovered from COVID-19. Initial laboratory studies showed low hemoglobin levels and elevated pro-BNP, troponin-T, hs-CRP and ESR. An autoimmune panel was ordered and revealed positive antinuclear antibodies (ANA) and positive scleroderma related antibodies (anti-RNA polymerase III). Chest radiography and Chest CT without contrast both showed septal and bronchial wall thickening. A transthoracic echocardiogram was performed and showed a severely dilated left atrium and mildly thickened mitral valve leaflets with severe mitral regurgitation. A transesophageal echocardiogram revealed a thickened anterior mitral leaflet and restricted mobility of the posterior leaflet with mitral regurgitation being moderate in severity. These findings were consistent with the reported changes seen on echocardiogram and in autopsies in patients with SSc. The diagnosis of SSc in this patient was made and the patient was started on mycophenolate. Conclusions: This case highlights the possible mechanisms through which COVID-19 may trigger the development of autoimmune and inflammatory reactions which, in our case, lead to the development of mitral regurgitation as a sequela of SSc. Imagine 1. Imagine 2.

Abstract 087: Cocaine‐Induced Acute Spinal Cord Ischemia Syndrome

Introduction Acute spinal cord ischemia syndrome (ASCIS) is a rare disease that is thought to comprise roughly only 1.2% of all strokes [1, 2]. These strokes primarily occur in the anterior spinal cord artery (ASA) and/or the posterior spinal cord artery (PCA) territory and can have widely variable clinical presentation. The use of recreational cocaine in young adults is well known to be responsible for acute ischemic and hemorrhagic strokes in individuals who lack other vascular risk factors. What is significantly rarer with few reported cases, however, is cocaine‐related ASCIS as the etiology of non‐traumatic acute spinal cord myelopathy [3‐7]. Methods N/A Results A 40‐year‐old female with a history of type I Diabetes mellitus, bipolar disorder, and polysubstance abuse presented with acute‐onset bilateral lower limb weakness, sensory loss, neck pain, and bladder incontinence. On admission, she reported using intravenous crack cocaine in the evening before admission and experiencing a fall in the bathroom a few hours after. She was unable to move her lower limbs following this fall. On examination, there was flaccid weakness in both lower extremities with decreased pinprick sensation below the T4 level and absent sensation below the thighs on both sides. She had no trauma preceding her symptoms and denied any recent vaccinations or travel history. An urgent CT (computed tomography) scan of the cervical, thoracic, and lumbar spine ruled out any obvious traumatic injury. Her urine drug screen was positive for cocaine, opiate, cannabinoid, and benzodiazepine. MRI (Magnetic Resonance Imaging) of the brain without contrast was unremarkable. MRI of the spine with contrast demonstrated two areas of T2 hyperintensities from C5‐C6 and T4 to the conus with cord expansion. The lesion in the thoracic spinal cord showed contrast enhancement and spared the dorsal column. Lumbar puncture was traumatic and showed elevated protein (>300 mg/dl) as well as elevated glucose (186 mg/dl). CSF studies, including meningitis/encephalitis panel, gram stain and culture, flow cytometry, cytology, and oligoclonal bands were negative. Serum autoimmune myelopathy panel, serum Aquaporin‐4 antibodies and MOG (Myelin Oligodendrocyte Glycoprotein) antibodies were negative. The other etiologies of non‐traumatic myelopathy, including HIV, Treponema pallidum, and HTLV‐I/II antibodies, were negative. A diagnostic spinal angiogram was completed with no evidence of arteriovenous fistula or aortic dissection. She completed five days of plasma exchange without any improvement and was transferred to an acute rehabilitation facility. At four months follow‐up, she continues to be flaccid in her lower limbs and requires a urinary catheter leading to frequent urinary tract infections. Conclusion While cocaine‐related cerebrovascular events are well documented, very few cases of cocaine‐related ASCIS have been described. The mechanism is thought to be multifactorial due vasospasm, cerebral vasculitis, vascular thrombosis, cardioembolism from cocaine‐induced myocardial infarction or cardiomyopathy, and hypertensive surges [9]. Due to the scarcity of these events, the patient outcomes are unclear. Other studies on outcomes of spinal cord ischemia have shown that ASIA Impairment Scale (AIS) score, lesion level, and patient age were the strongest predictors of neurologic and functional outcomes, whereas etiology of the ischemia had no effect on outcomes [10].

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

BackgroundImmune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb).MethodsWe used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity.ResultsA total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).ConclusionsOverall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).

Subacute thyroiditis and rapidly developing goiter in a 16-year-old female: a case report

Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid gland with multiple etiologies and clinical features, often challenging to recognize. The classic presentation is the painful, granulomatous thyroiditis (DeQuervain’s) characterized by diffuse swelling of the gland, usually preceded by an upper respiratory tract infection. A painless variant, also referred to as autoimmune subacute thyroiditis, has been documented and is strongly linked to postpartum state, reported following ~10% of pregnancies. It can be differentiated from the former by the presence of anti-thyroid antibodies, which classifies it as an autoimmune thyroiditis. Any spontaneous development of painful swelling of the thyroid gland warrants a complete work up that includes thyroid hormones, thyroid autoimmune panel, acute phase reactant titers, and, if available, imaging that may lead to the diagnosis of an inflammatory or infectious cause of thyroiditis.

SAT325 Recurrent Pericardial Effusion As Initial Presentation Of Primary Adrenal Insufficiency

Abstract Disclosure: S. Ward: None. A.L. Champion: None. A. Mrkaic: None. Recurrent Pericardial Effusion as Initial Presentation of Primary Adrenal Insufficiency: Background: Primary adrenal insufficiency (PAI) is a rare but serious endocrinopathy. High clinical suspicion is important to avoid delay in diagnosis and treatment. We present a rare case of recurrent pericardial effusion as initial presentation. Clinical Case: 63 year old male with hypertension and diabetes presented to ED complaining of SOB and chest pain. Workup revealed pericardial effusion causing cardiac tamponade treated with emergent pericardiocentesis. He was admitted to ICU for hypotension. He was also diagnosed with COVID-19 and acute kidney injury. Labs showed hyperkalemia ranging from 5.3 to 7.2 mmol/l (n= 3.5-5.1 mmol/l) and hyponatremia 132 mmol/L (n= 136-145 mmol/L). He was started on dexamethasone for COVID-19 infection. Etiology of pericardial effusion was unclear; infectious disease workup was unremarkable, cytology showed no malignant cells, autoimmune panel was negative. Initial echo showed EF &amp;gt;55%. After initiation of steroids, symptoms improved with normalization of electrolytes and improvement of hypotension, however was discharged on midodrine 2.5 mg TID. Seven days after discharge patient called 911 complaining of worsening shortness of breath. He was found to be severely hypotensive with BP 67/40. Echo showed moderate to large pericardial effusion causing tamponade. Emergent pericardial window was performed. Labs showed hyponatremia 123 mmol/L and potassium ranging from 4.9-5.4 mmol/L. Patient remained hypotensive requiring pressors despite pericardial effusion drainage. With persistent hypotension, hyperkalemia, and hyponatremia there was strong suspicion for adrenal insufficiency and workup was consistent with PAI. Labs showed 8:00 am cortisol 2.7 ug/dl (n= 3.7-19.4 ug/dl), ACTH 256.0 pg/ml (n=7.2-63.3pg/ml), aldosterone &amp;lt;1.0 ng/dL, renin 4.216 ng/mL/hr (n= 0.167-5.380 ng/mL/hr). Due to his critical illness patient was started on stress dose hydrocortisone 50 mg Q6 hr. With initiation of steroids, hyponatremia, hypokalemia, and hypotension resolved. Patient was weaned to physiological doses of hydrocortisone and started on fludrocortisone at time of discharge. Conclusion: Timely diagnosis of PAI is essential and can be lifesaving, if untreated it can lead to adrenal crisis with high mortality. Having a high clinical suspicion is crucial to a prompt diagnosis. Pericardial effusion should prompt clinical suspicion for PAI as multiple cases have now been reported in the literature. Our patient has multiple potential causes of pericardial effusion including PAI, acute kidney injury, and COVID-19 infection. Although we cannot show definitive causation from PAI, it most certainly contributed and prompt diagnosis and treatment may have prevented recurrence. It is important to raise awareness of PAI as a differential in pericardial effusion. Presentation: Saturday, June 17, 2023

FRI438 A Unique Case Of Secondary Hypogonadism And The Covid Booster Vaccine

Abstract Disclosure: O.Z. Syed: None. M. Shakir: None. K. Sajid: None. A. Sood: None. N. Bansal: None. 38-year-old male with no past medical or surgical history presented for an evaluation of his low testosterone. The patient transports patients in the hospital, he denies any medication use, including steroids, opioids, and antibiotics. He has a biological 8-year-old son and denied any history of viral infection recently and denied any history of testicular trauma, mumps, or radiation therapy. He started having fatigue, chronic mild headache, and generalized weakness after receiving his third dose of covid vaccine in January, however, he denied any diplopia, galactorrhea, hirsutism, or sexual dysfunction. He did not report any side effects with the previous 2 covid vaccines. After a couple of months of persistent symptoms accompanied by 40 pounds of weight loss( half of which he regained in a few months without intervention), he went to his PCP for evaluation. On physical examination, there were no abnormalities seen and as per the patient, there was no change in testicular size either. The patient was found to have mildly elevated prolactin of 17.8 with low free and total testosterone of 134 accompanied by FSH of less than 1.0 and LH of 1.4. The remaining labs include but are not limited to CBC, CMP, TSH, Vitamin D, CK, Sex hormone-binding globulin, and cortisol. The autoimmune panel, Hepatitis, HIV, and tick panels were negative. While he was being worked up he tested himself multiple times for covid and was negative. The patient had an MRI done which did not show any mass or lesions. Furthermore, he also had a Chest x-ray and CT of his abdomen/pelvis along with an Ultrasound of the abdomen, which did not show any concerning findings. The patient was started on testosterone gel at the endocrinology clinic with regular follow-ups to assess for response and side effects.As per the currently available literature, there have been multiple associations made between Covid 19 infection and hypogonadism. There have been reports of low testosterone following covid 19 infections and conversely there have been worse outcomes of covid 19 related to men with lower levels of testosterone. This could possibly be due to ACE 2 expression on testicular cells or due to secondary inflammation and oxidative stress inhbitiing steroidogenesis. However no literature was found linking the covid 19 vaccine to secondary hypogonadim other than a case of pituitary apoplexy. These findings in light of our case warrant further research into possible association between the covid vaccine and hypogonadism. In patients presenting with generalized weakness and similar vague symptoms, we need to consider a history of covid vaccination as it could potentially be a cause of secondary hypogonadism. Furthermore, more detailed and larger-scale studies need to be done concerning the covid booster vaccines and hypogonadism. Presentation: Friday, June 16, 2023

FRI523 A Case Of Acute Liver Failure Within 48 Hours Of Initiation Of High Dose Thionamides For Thyroid Storm

Abstract Disclosure: L. Noor: None. J. Mullally: None. Thionamides, including methimazole and propylthiouracil, are medications used to treat hyperthyroidism and have rarely been associated with liver failure. Based on prior large retrospective studies, the onset of hepatotoxicity from thionamides occurs most commonly 4-12 weeks after ​​initiation, with the earliest cases occurring 7 days after initiation. We describe a case of very early onset acute liver failure within two days of initiation of high dose methimazole and PTU. A 43 year old female with past medical history of long-standing Graves’ disease and atrial fibrillation, presented to an outside hospital with upper respiratory symptoms and weight loss. On presentation, her vitals and physical examination were within normal limits. Initial labs showed normal LFTs, undetectable TSH, high FT3 6.75 pg/ml (n 2.0-4.4 pg/ml), high TT4 18 μg/dL (n 5.0-12.0 μg/dL) and PCR positive for COVID-19. She was started on methimazole 40 mg every 12 hours, beta-blocker, dexamethasone and remdesvir. The next day, she was found to be tachycardic, tachypneic with EKG showing atrial fibrillation with RVR and chest Xray showing flash pulmonary edema. She was intubated, methimazole was changed to PTU 200 mg every 4 hours and dexamethasone was changed to hydrocortisone 100 mg every 8 hours. An esmolol drip, potassium iodide and cholestyramine were started. She also received a single dose of intravenous amiodarone 300 mg for atrial fibrillation with RVR. The next day, labs showed new LFT abnormalities with AST 6647(n&amp;lt;35 U/L), ALT 1694 (n&amp;lt;55 U/L), ALP 132 (n&amp;lt;150 U/L), total bilirubin 8.4 (n&amp;lt;1.3 mg/dl). PTU was stopped and she was transferred to our hospital for liver transplant evaluation. On admission to our hospital, labs showed ALT 2728, AST 4930, ALP 180, T bilirubin 15.7, TSH 0.002, FT4 1.5 and TT3 29.6. She was started on hydrocortisone and propranolol. Viral and autoimmune hepatitis panel, acetaminophen and alcohol levels were negative. Abdominal ultrasound was unremarkable. Liver biopsy showed severe cholestatic hepatitis, perivenular necrosis and marked bile duct damage with neutrophilic inflammation, consistent with DILI. LFTs gradually improved over the following weeks. On hospital day 23, an uneventful total thyroidectomy was performed for definitive management of Graves’. We present a unique and rare case of acute liver failure within 48 hours of high dose methimazole and PTU administration for presumed thyroid storm. The patient recovered with gradual improvement in her LFTs and was successfully managed with total thyroidectomy. To our knowledge, this case represents the earliest onset of acute liver failure from thionamide use. Risk factors appear to include very high dose methimazole and PTU exposure as well as potentially the patient’s intermittent use of methimazole in the past. Further study is needed to clarify potential risk factors of thionamide-induced hepatotoxicity as data is limited. Presentation: Friday, June 16, 2023

FRI567 Insulin Autoimmune Syndrome And Grave’s Disease

Abstract Disclosure: A.M. Skariah: None. T. Porter: None. Background: Insulin autoimmune syndrome (IAS), also known as Hirata’s disease, is a rare condition characterized by immune mediated post prandial hypoglycemia, due to presence of high titers of insulin autoantibodies (IAA). Most cases reported in Asian population with strong association with HLA-DR4 and specifically with the DRB1*0406. Clinical case: Patient is 36-year-old Asian female with no significant past medical history got evaluated by primary care physician because of fatigue, weight loss and neck swelling. Her symptoms are consistent with hyperthyroidism, got evaluated and found to have elevated thyroid hormone levels and suppressed TSH. At the time of diagnosis, free T3 2922 pg/dl(230-420pg/dl), free T4 &amp;gt; 7.7 ng/dl (0.9-1.7 ng/dl), TSH &amp;lt; 0.01uIU/ml (3-4uIU/ml), total T3 599 ng/dl (80-195 ng/dl), total T4 19.6Ug/dl (5-11 Ug/dl). Patient was started on methimazole, and beta blocker. Other labs including autoimmune panel were positive for TSI (2.8 with normal &amp;lt;1.3) and thyroid receptor antibody &amp;gt;40 (&amp;lt;15.5 IU/l) confirming Graves' disease. 4 weeks after starting treatment with methimazole, patient was experiencing episodes of hypoglycemia, related to food intake. She checked her blood sugar and the lowest blood sugar she noticed was 53 mg/dl. She had no history of diabetes and never used insulin or any other oral diabetic medications. Insulin levels &amp;gt;1000 uIU/ml (2.6-24.9uIU/ml), insulin antibody levels &amp;gt;625 uU/ml (&amp;lt;5 uU/ml), C-peptide as high as 9.5ng/ml (1.1-4.4 ng/ml), Insulin/C-peptide ratio 105, proinsulin elevated 40.3pmol/l (0.0-10 pg/l), and oral hypoglycemic agent screening negative. With the lab results, diagnosis of Hirata’s syndrome was made, Management discussed with the patient. Since patient still having labs consistent with hyperthyroidism, continued methimazole and started on diet interventions including low-carb diet and including complex carbohydrates in the diet. Patient gradually responded to dietary interventions with decrease episodes of hypoglycemia. Never required acarbose or steroids. Follow-up labs shows that patient is responding decrease in the levels of insulin antibodies 116 uU/ml and insulin levels 19.5 uIU/ml. Patients’ hyperthyroidism responded to methimazole, and dose reduced eventually to 5 mg daily with latest labs of free T4 1.21 ng/dl, Free T3 2.7 pg/ml and TSH 2.010 uIU/ml. Conclusion: Association between methimazole and IAS has been already reported before. When a patient is presenting outside Asian countries with similar symptoms, differential of IAS can be missed due to its rarity. But because of globalization; people from all races are seen in every part of the world. It will be beneficial to screen patients for IAS which can decrease cost of work up and treatment, when considering imaging modalities which were included as the part of the work up. Presentation: Friday, June 16, 2023

Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Characterization of autoimmune eye disease in association with Down's syndrome.

Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Refractory Seizures with Encephalopathy May be Due to Hashimoto Encephalopathy

Background: Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, is a relatively uncommon neurological disorder, mostly in adults, with an extremely rare occurrence in children. Clinical Description: A 9-year-old girl presented with unprovoked seizures and encephalopathy. She had been diagnosed with hypothyroidism, at around 6 ½ years of age, though was noncompliant to therapy with levothyroxine. Management: The child was managed with intravenous (IV) antiepileptics and other supportive care. Seizures were refractory and with worsening sensorium, she required mechanical ventilation. The magnetic resonance imaging of the brain was unremarkable, as also the cerebrospinal analysis. Autoimmune encephalitis panel was negative. The electroencephalogram showed background activity of 10–11 Hz and few areas with generalized slow waves. As she was a known case of hypothyroidism without taking thyroid supplements for the past few months, thyroid profile was sent. Reports showed FT3-1.1 pg/dL, FT4-0.515 ng/dL, and thyroid-stimulating hormone (TSH) - 107.3 μIU/mL. Thyroid antibody profile revealed antithyroid peroxidase antibody &gt;500 IU/mL and antithyroglobulin antibody &gt;1000 IU/mL. Following this, an ultrasound of the neck was done which showed features of thyroiditis. Considering the possibility that the underlying thyroiditis could explain the obtunded state and refractory seizures, the patient was started on levothyroxine and IV methylprednisolone. The sensorium of the child improved dramatically, and she got extubated. There were no further seizures and her TSH level reduced gradually and eventually, she was discharged. Conclusions: In a child with altered sensorium and refractory seizures, Hashimoto encephalopathy is a diagnosis of exclusion and may be considered when most of the common causes of encephalopathy and seizures have been ruled out, especially in the setting of some clinical clues of hypothyroidism. The condition is often reversible with good response to steroid therapy.