Antiphospholipid Syndrome Research Articles

How to treat patients with thrombotic antiphospholipid syndrome in 2024?

Antiphospholipid syndrome encompasses a range of clinical conditions, particularly thrombotic or obstetrical manifestations, associated with the presence of antiphospholipid antibodies. Managing thrombotic antiphospholipid syndrome in daily clinical practice can be challenging and requires thorough risk stratification and tailored treatment strategies. Primary prophylaxis focuses on improving traditional thrombosis risk factors and, in certain situations, may include low-dose aspirin and / or prophylactic anticoagulants (e.g., low-molecular-weight heparin). The treatment of thrombotic antiphospholipid syndrome primarily involves long-term anticoagulation with vitamin K antagonists. In some cases, a combination of vitamin K antagonists and low-dose aspirin, vitamin K antagonists with international normalized ratio target >3 or a switch to therapeutic doses of low-molecular-weight heparin might be employed. The use of hydroxychloroquine is essential for patients with secondary systemic lupus erythematosus and may be considered for patients with recurrent thrombosis. In other selected situations, the use of immunomodulatory agents can be considered.

Autoantibodies to protein S may explain rare cases of coagulopathy following COVID-19 vaccination.

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Peripheral Ischemia and Necrosis Revealing Buerger&amp;apos;s Disease in an Internal Medicine Department

Buerger&amp;apos;s disease is a systemic vasculitis strongly correlated with tobacco use. It entails a heavy socio-occupational impact. We report the case of a 26-year-old patient with ischemia of the lower limbs revealing Buerger’s disease. He is known smoker with passive exposure to Indian hemp. He was seen for ischemic foot pain that had been progressing for a year. Involvement began in the left big toe. Subsequently, hyperalgesic necrotic lesions were observed on the 3rd, 4th and 5th toes of the foot. Biological investigations revealed an inflammatory syndrome with normocytic anemia and increased C-reactive protein. Retroviral, syphilitic, Hepatitis B and C viruses and SARS-CoV-2 serologies were negative. Antinuclear antibodies were initially borderline at 100 IU with speckled fluorescence, then negative on control. Neutrophil cytoplasmic antibodies and antiphospholipid antibodies were negative. Investigation of thrombophilia was non-contributory, notably factor V mutation testing, antithrombin III assay, proteins C and S and fibrinogen. An arterial ultrasound revealed extensive arterial thrombosis with thickening of the femoral arterial vessel walls. Thromboangiitis obliterans was confirmed and the patient was put on corticosteroids and adjuvant therapy. Surgical treatment was performed 4 months later. Buerger&amp;apos;s disease is a serious vascular disorder which must be diagnosed very early in order to prevent complications. Early smoking cessation leads to remission in the early phase.

Rare connective tissue diseases in patients with C1-inhibitor deficiency hereditary angioedema: first evidence on prevalence and distribution from a large Italian cohort study.

In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity.

Utilizing Artificial Intelligence to Reconcile Indeterminate Lupus Anticoagulant Panel Results

Abstract Lupus anticoagulant (LA) is one laboratory criterion for diagnosing antiphospholipid antibody syndrome (APS), a condition associated with hypercoagulability, pregnancy complications, and death. LA diagnosis requires a complex panel, often performed at a specialized laboratory. Ruling out false positive or transient LAs requires ≥ two positive tests ≥ 12 weeks apart. Most LA tests are negative, with small subsets resulting positive or indeterminate. Indeterminates leave clinicians with limited understanding of appropriate clinical follow-up. Thus, the International Society on Thrombosis and Hemostasis discourages weak resulting nomenclature such as “indeterminate.” Our study used artificial intelligence to predict LA indeterminate results as positive or negative, identifying patients requiring further testing. This IRB approved study reviewed nearly 4000 LA tests performed from 2019-2023. Parameters included CBC, thromboelastography, renal/hepatic function assays, coagulation tests, antiphospholipid antibodies and LA tests. LA test components included screening tests (APTT, Dilute Russel Viper Venom Test (DRVVT) screen), mixing studies (1:1 APTT mix, DRVVT mix), phospholipid-dependent confirmation (DRVVT, hexagonal phase, platelet neutralization), and factor VIII. A positive LA test fulfilled 4 criteria: at least one positive screening test, mixing study and phospholipid-dependent assay and factor VIII inhibitor exclusion. An LA panel meeting 2-3 criteria resulted indeterminate. Studies meeting &amp;lt;2 criteria were negative. This analysis was performed using Machine Intelligence Learning Optimizer (MILO) platform which displays the performance of multiple models. MILO was trained with two classifications: positive and negative cases. Data was split into training (100 training positives; 100 negatives) and testing (primary and secondary validation) sets (100 positives; 1388 negatives). LA panels affected by drug interactions (9.4%) or containing incomplete datasets (21%) were excluded. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) determined model efficacy. 2903 negative (84%), 318 positive (9.1%), and 246 indeterminate (7.1%) LA results were included from 3467 patients. Only 84 of the 246 indeterminate patients (34%) were retested. Of these, 28 remained indeterminate, 43 became negative and 13 resulted positive. The best performing MILO models were the K-nearest neighbor (KNN) and logistic regression. The ability of these models to determine which indeterminate cases would become positive or negative was evaluated. KNN displayed the highest specificity (0.88) and PPV (0.57). All models had a high NPV and specificity due to substantive exposure to negative cases for the training and testing. Exclusion of some parameters did not improve the performance of the models. However, even the best model (various KNN models) had low sensitivity and PPV due to a small pool of positive training/testing cases and a much smaller group of indeterminate LA with subsequent positive results. Creating models accurately predicting indeterminate cases that may become positive enables appropriate clinical follow-up. Thus, improving model accuracy will require a larger sample size of positive indeterminates with follow-up.

A Tale of Two Cases: Acquired Hemophilia A and/or Lupus Anticoagulant?

Abstract Distinguishing between acquired hemophilia A (AHA) and lupus anticoagulant (LA) is essential for effective clinical management. This can be challenging due to similarities in laboratory tests and potential interference between their diagnostic tests. Here we present two complex cases. Case 1 is a 69-year-old female with PNH presenting with a subdural hematoma. Prolonged aPTT with no correction on mixing raised clinical suspicion of AHA. Factor VIII activity was low (2%) across three dilutions in the factor assay. A Bethesda assay revealed a low factor VIII inhibitor (1%). LA was negative by DRVVT. Antiphospholipid antibodies (Cardiolipin and Beta-2-Glycoprotein 1) were also negative. Treatment with prednisone and intravenous immunoglobulin was initiated with presumptive diagnosis of AHA. Subsequent samples to check other factor levels uncovered low Factor IX as well. Higher dilutions in factor assays exhibited non-parallelism in Factor IX and VIII, suggesting a non-specific inhibitor. Chromogenic Factor VIII was within the normal range. Another LA test, Staclot-LA was positive. Overall, this case was consistent with LA rather than AHA. The initial ‘positive’ Bethesda assay was attributed to interference by LA. Case 2 is a 20-year-old female with no significant medical history who was admitted elsewhere for a complicated C-section with intraabdominal hemorrhage. She had prolonged aPTT and positive LA by platelet neutralization test there. Upon transfer, the initial assessment confirmed prolonged aPTT and a time-dependent inhibitor pattern in mixing studies. Factor studies revealed significantly diminished factor VIII activity (&amp;lt;1%) using both one-stage clotting and chromogenic assays. A strong factor VIII inhibitor was identified through chromogenic Bethesda assay (126 BU). Non-parallelism was observed in other factors (Factor IX, XI, XII). LA was negative by DRVVT but positive by Staclot-LA. Cardiolipin and beta2-glycoprotein-1 antibodies were negative. The diagnosis of AHA was evident. But is there concurrent LA present? Both Staclot-LA and platelet neutralization tests are PTT-based and susceptible to interference from factor VIII inhibitor. The patient underwent treatment, and factor VIII inhibitor disappeared in 3 months. Staclot-LA also turned negative, suggesting that the initially ‘positive’ LA test was likely a result of interference. In both cases, adopting a holistic approach to differentiate between AHA and LA is beneficial. Relying solely on individual tests may lead to false interpretations, as LA can inhibit FVIII activity assays and produce false positives in the Bethesda assay. It is advisable to include higher dilutions in factor assays and/or chromogenic assays to mitigate interference. The presence of factor VIII inhibitor can also result in false-positive LA results such as Staclot-LA assay. For more reliable results, DRVVT and antibody tests are preferable. If the aPTT-based assay is the sole positive LA test, the presence of LA is suggested when it occurs before and/or after the presence of a factor inhibitor.

Antiphospholipid antibody positivity is associated with maturation failure and thrombosis of native arteriovenous fistula: a retrospective study in HD patients.

The prevalence of antiphospholipid antibody (aPL) is high among hemodialysis (HD) patients compared to the general population and is inconsistently associated with arteriovenous fistula (AVF) thrombosis or stenosis. The association with maturation failure has never been investigated. This study aims to evaluate native AVF complications (thrombosis, stenosis, and maturation failure) and primary patency in aPL positive HD patients. We retrospectively identified 116 HD patients with native AVF. We collected the aPL profiles, the clinical and biological data potentially involved in AVF maturation failure, thrombosis, and stenosis, and investigated the association of these complications and aPL positivity. Kaplan-Meier survival analysis was performed. In our cohort, the prevalence of aPL persistent positivity was 32.7% and this was strongly associated with AVF maturation failure defined by ultrasound. aPL persistent positivity was a strong predictor in multivariate analysis and this association was independent of AVF stenosis or thrombosis during maturation process. There was no association with primary and functional primary patency, and stenosis. However, aPL persistent positivity according to ACR/EULAR classification criteria was associated with thrombosis when compared to strictly negative aPL patients. In our cohort, aPL persistent positivity was significantly associated with AVF maturation failure and thrombosis but not with AVF stenosis. To our knowledge, we report for the first time, a statistically significant association between aPL positivity and delay or absence of native AVF maturation.

Clinical Presentation, Care Pathways, and Delays in Access to Specialized Care in Patients With Systemic Lupus Erythematosus: A Study From Lupus Midwest Network (LUMEN 💡).

To characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity (SLEDAI-2k), and SLICC/ACR damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 months (95% confidence interval [CI] 0.9-1.5); time to diagnosis 30.6 months (95% CI 18.9-48.1), and time to treatment initiation 4.7 months (95% CI 3.9-8.4). Approximately 25% (93/373) of patients experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (<2 SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, while hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with damage. Fewer manifestations, hematologic, or antiphospholipid antibodies were associated with delays.

Thrombotic complications in pregnancy: a case-based review of the evidence

Pregnancy is a prothrombotic state due to an estrogen-driven shift in the coagulation system, increased venous stasis, and external restriction of blood flow caused by the gravid uterus. Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in pregnancy. Preventing, recognizing, and treating thrombosis in pregnancy, as well as the postpartum period, often challenges decision making in the clinical setting. In early pregnancy, guidance with respects to thrombophilia testing and anticoagulation in increasing the likelihood of live birth among patients with recurrent miscarriages is evolving. This review explores emerging data that support clinical decision making in thrombosis care in women with common thrombotic complications in pregnancy. The first case outlines VTE diagnosis in pregnancy, initial anticoagulation management, management around delivery and postpartum, and subsequent long-term anticoagulation treatment. The second case examines testing for inherited and acquired thrombophilia in the setting of recurrent miscarriage and the management of obstetric antiphospholipid syndrome. Lastly, the third case reviews VTE risk assessment and prevention in pregnancy and the postpartum period, as well as duration and dose of postpartum thromboprophylaxis. Review of these common clinical scenarios surrounding thrombotic complications in pregnancy demonstrates recent advances in high-quality data, current gaps in knowledge, and variation in expert opinion. Ultimately, multidisciplinary discussion and teamwork remain key to optimal, safe care. Clinicians must prioritize collaborative, high-quality trials and prospective clinical management studies to better understand and define best practice in this population.

Complex Interaction between Gut Microbiome and Autoimmunity: Focus on Antiphospholipid Syndrome

Complex Interaction between Gut Microbiome and Autoimmunity: Focus on Antiphospholipid Syndrome

Challenges in Diagnosis and Management of SLE in Africa: An Online Survey.

We surveyed African physicians about challenges in diagnosis and management of systemic lupus erythematosus (SLE). We used a cross-sectional, online questionnaire-based survey of African specialist physicians on availability of laboratory tests, medications, and specialized services for the diagnosis of SLE. Our 226 respondents from 31 countries were dermatologists (38%), rheumatologists (28%), and nephrologists (23%), the majority practicing at university/state-funded hospitals (80.8%), but over half of patients (59.6%) were self-funded for laboratory tests and medications. Antinuclear antibody (ANA), antiphospholipid antibody, and complement tests were available to 79.4%, 67.6%, and 62.3% of respondents, respectively, but fewer in the East and West African regions. Median turnaround time for the ANA test was within two weeks but more than four weeks for 5.6% of respondents, and longer in West Africa compared with other regions (P = 0.0002). Availability of urine protein-to-creatinine test, skin and renal histopathology was 82%, 82.5%, and 76.2%, respectively. Median turnaround times were within one to two weeks, but more than four weeks for 13.8% of respondents for skin histology results and usually within four weeks but more than four weeks for 24.5% of respondents for renal histology. Glucocorticoids and antimalarials were readily available across all regions, with variable availability of immunosuppressants from 93.7% for methotrexate to 65% for calcineurin inhibitors and only 58.4% for the biologic rituximab. Intensive care units/high care facilities, hemodialysis, and renal transplantation were available to 69.8%, 91.9%, and 56.5% of respondents, respectively. Variable availability of laboratory tests, medications, and supportive services coupled with cost constraints are major impediments to early diagnosis and optimal management of SLE in most of Africa and are likely factors contributing to underreporting and poor prognosis of SLE in Africa.

5-oxoETE promote thrombosis in antiphospholipid syndrome by triggering NETs formation through PLC/PKC/ERK pathway.

One mechanism by which antiphospholipid syndrome (APS) IgG contribute to thrombotic events in patients with APS is through the potentiation of neutrophil extracellular traps (NETs) release. However, the exact mechanism by which APS IgG induces NETs formation and thrombosis has not been fully elucidated. We conducted untargeted metabolomics on serum samples from thrombotic APS patients to identify metabolic changes. The effect of 5-oxoETE on NETs formation and oxidative stress was evaluated in vitro by treating neutrophils with various concentrations of 5-oxoETE. The involvement of the PLC/PKC/ERK signaling pathway in 5-oxoETE-induced NETs formation was examined using pharmacological inhibitors. In vivo, we assessed the effects of inhibiting 5-oxoETE synthesis or blocking its receptor (OXE-R) on NETs formation and thrombosis in APS mouse models. Serum metabolomics revealed significantly elevated levels of 5-oxoETE in APS patients. In vitro experiments demonstrated that 5-oxoETE, via OXE-R activation of the PLC/PKC/ERK signaling pathway, increased NETs formation and oxidative stress in a dose-dependent manner. In vivo, inhibiting 5-oxoETE synthesis or OXE-R reduced NETs formation and attenuated venous thrombosis in APS mice models. This study identifies 5-oxoETE as a critical mediator of NET formation and thrombosis in APS. Targeting 5-oxoETE or OXE-R may offer a promising therapeutic approach for thrombotic APS and other NET-associated autoimmune diseases.

To Describe an Atypical Case of Neuroborreliosis with Catastrophic Antiphospholipid Syndrome

To Describe an Atypical Case of Neuroborreliosis with Catastrophic Antiphospholipid Syndrome

Thrombosis in Antiphospholipid Syndrome: Current Perspectives and Challenges in Laboratory Testing for Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) diagnosis hinges on identifying antiphospholipid antibodies (aPL). Currently, laboratory testing encompasses lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2-glycoprotein I antibodies (aβ2GPI) IgG or IgM, which are included in the APS classification criteria. All the assays needed to detect aPL antibodies have methodological concerns. LA testing remains challenging due to its complexity and susceptibility to interference from anticoagulant therapy. Solid phase assays for aCL and aβ2GPI exhibit discrepancies between different assays. Antibody profiles aid in identifying the patients at risk for thrombosis through integrated interpretation of all positive aPL tests. Antibodies targeting domain I of β2-glycoprotein and antiphosphatidylserine-prothrombin antibodies have been evaluated for their role in thrombotic APS but are not yet included in the APS criteria. Detecting these antibodies may help patients with incomplete antibody profiles and stratify the risk of APS patients. The added diagnostic value of other methodologies and measurements of other APS-associated antibodies are inconsistent. This manuscript describes laboratory parameters useful in the diagnosis of thrombotic APS and will concentrate on the laboratory aspects, clinical significance of assays, and interpretation of aPL results in the diagnosis of thrombotic APS.

6794 Primary Adrenal Insufficiency Following Bilateral Adrenal Hemorrhage Secondary To Antiphospholipid Syndrome

Abstract Disclosure: M. Alameri: None. A.M. Alnuaimi: None. Y. Alabrach: None. A. Abbas: None. S. Baroud: None. M. El Khazendar: None. Introduction: Adrenal insufficiency (AI) is a rare life-threatening complication of antiphospholipid antibody syndrome (APS) accounting for 0.4% to 0.5% of Al cases. Case report: A 26-year-old female with background history of primary antiphospholipid syndrome (PAPS) presented with 3 weeks history of dull abdominal pain and fatigue. Examination revealed dehydration, orthostatic hypotension and hyperpigmented skin. Biochemistry assessment was consistent with primary adrenal insufficiency (hyponatremia 125 mol/L, hyperkalaemia 6.8 mmol/L, low random cortisol 142 mol/L, high ATCH 440 pmol/L [N 1.6-13.9], low aldosterone &amp;lt;1.05 ng/dL and high renin 128 ng/L [N 4-23.7]). She received 100mg hydrocortisone followed by regular IV hydrocortisone q6hrs. CT abdomen revealed bilaterally enlarged hyperdense adrenal glands suggestive of haemorrhage. Adrenal MRI confirmed subacute bilateral adrenal haemorrhage (BAH) replacing whole adrenal glands with hemosiderin depositions and calcifications without evidence of underlying tumor. Anti-21-hydroxylase antibody came back negative. She was discharged on hydrocortisone, fludrocortisone and hydroxychloroquine. Education was given for sick days rule and hydrocortisone emergency kit was provided for adrenal crisis. Discussion and conclusion: We describe a patient with APS, who developed Al due to bilateral subacute adrenal haemorrhages. Adrenal haemorrhage is rare but life-threatening complication of APS. High clinical vigilance is important to consider adrenal haemorrhage in differential diagnosis of Al, specifically in patients with known antiphospholipid antibody syndrome (APS). Presentation: 6/3/2024

7112 A Case of Bilateral Adrenal Insufficiency Associated With Borderline Lupus and Antiphospholipid Syndrome

Abstract Disclosure: K.M. Hernandez Mendiola: None. Bilateral adrenal hemorrhage (BAH) is a rare condition leading to acute adrenal insufficiency with a mortality rate of 15%. Known etiologies include abdominal trauma, adrenal vein thrombosis, sepsis, shock, and anticoagulation. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are uncommon conditions associated with BAH. We describe here a 79-year-old woman with a history of hypertension and a 23-year history of borderline SLE treated with hydroxychloroquine (HCQ) who presented at the ED with epigastric pain, diarrhea, and nausea. Six months before, HCQ was discontinued. The exam showed no abnormal findings, and an abdominal CT showed inflammation of the ascending colon. Augmentin was instituted, and the patient was sent home. After a week, the patient returned to the ED due to the persistence of symptoms, complaining of fatigue and right lower quadrant abdominal pain. Upon examination, the abdomen was soft but tender, with the CT suggesting pancolitis, while an MRI showed BAH. Laboratory findings included anemia, thrombocytopenia, elevated PT, low fibrinogen, and 11 mcg/dl cortisol. The patient was then admitted to the hospital, and hydrocortisone (HCT) therapy was initiated. After 12 hours of glucocorticoid initiation, cortisol level was 37 mcg/dl. On day 1, the patient remained hemodynamically stable. On day 2, a positive lupus anticoagulant was detected, with cortisol level dropping to 2 mcg/dl, warranting the continuation of HCT. From day 3 to 6, the patient suffered worsening coagulation and kidney functions. By day 7, an abdominal CT showed an extension of BAH. On day 8, the patient experienced a cerebral intraparenchymal hemorrhage and was transferred to the ICU, where, after two days passed away. The report presented here describes a catastrophic case of BAH associated with borderline SLE and APS in a patient who previously discontinued long-term treatment with HCQ, thereby enhancing the likelihood of a lupus flare-up. The adrenal glands are susceptible to thrombosis and hemorrhage due to their rich vascularity. In stress, the adrenals receive a significant blood volume, causing vascular congestion, potentially exceeding their capacity for venous drainage, and increasing the risk of hemorrhage. Autoimmune conditions, particularly SLE and APS, have been implicated in the etiology of adrenal hemorrhage. Antiphospholipid antibodies may bind to phospholipid-binding plasma proteins, promoting thrombosis in the adrenal vein by disrupting the coagulation fibrinolysis balance and the adrenal blood outflow, ultimately causing bleeding into the adrenal gland parenchyma. Although in this case, no cardiovascular collapse was observed, when unrecognized or undertreated, adrenal insufficiency complicating BAH can evolve into an adrenal crisis. Infections and medications that increase cortisol metabolism can also contribute to this complication. Presentation: 6/3/2024

7917 Bilateral Adrenal Hemorrhages As The Initial Presentation Of Poorly Differentiated Bronchogenic Carcinoma

Abstract Disclosure: B. Malapur: None. M.G. Jakoby: None. V. Williams: None. Introduction: Bilateral adrenal hemorrhage is rare, and most cases occur in the setting of bacterial sepsis, coagulopathies such as antiphospholipid antibody syndrome, treatment with anticoagulants, surgery, or trauma. We present a patient with asynchronous bilateral adrenal hemorrhages that resulted in an eventual diagnosis of poorly differentiated bronchogenic carcinoma. Case: A 65-year-old female smoker was found to have a large right adrenal hematoma on computed tomography (CT) obtained for evaluation of acute onset right flank pain. No hemorrhage or anatomic abnormalities of the left adrenal gland were apparent, and the patient was discharged home after her pain was controlled. Approximately one month later, she returned to hospital with bilateral flank pain, and bilateral adrenal hemorrhages were diagnosed on repeat CT imaging. An 8 cm left upper lobe lung mass was revealed on a chest CT scan, and cytology from a bronchoscopic biopsy confirmed poorly differentiated bronchogenic carcinoma. The patient had no recent surgeries, abdominal trauma, or treatment with anticoagulants, serologic evaluation for coagulopathies and disseminated intravascular coagulation was unremarkable, blood cultures failed to grow bacterial pathogens, and acid-fast staining of lung tissue was negative. The patient was discharged from her second hospital admission on hydrocortisone and fludrocortisone. Discussion: Adrenal hemorrhage in the setting of malignancy is usually a complication of adrenal metastases. The prevalence of adrenal metastases in advanced stage cancer is approximately 3%, with lung and breast cancers and melanoma showing the highest predilection for adrenal metastases. This case is unusual because the patient had no focal masses or disruption of left adrenal contour on CT to indicate adrenal metastases at the time of right adrenal hemorrhage, and she did not have other established risk factors for pathologic bleeding in the setting of malignancy such as thrombocytopenia or treatment with chemotherapy agents, anticoagulants, or nonsteroidal anti-inflammatory drugs. Adrenal hemorrhage is also a rare inciting event resulting in the diagnosis of lung cancer; to date, there are only 29 published cases of spontaneous adrenal hemorrhage as the initial presentation of lung cancer. This case illustrates the importance of careful evaluation for malignancy in patients with spontaneous adrenal hemorrhage and no clear etiology for adrenal bleeding. Presentation: 6/1/2024

12386 Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy

Abstract Disclosure: A. Gondhi: None. M. Campana: None. M. Riofrio: None. J. Fazendin: None. D. Vodopivec: None. Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy Introduction: Spontaneous adrenal hemorrhage (SAH) in pregnancy is a rare and under recognized entity with an incidence of 0.14% - 1.1%, mostly unilateral. We present a case of unilateral SAH managed with adrenalectomy during pregnancy. Case presentation: A 24-year-old 14-weeks pregnant woman was referred for right flank pain and nausea due to right adrenal lesion. Medical history significant for 4 first trimester miscarriages and family history of Breast cancer and Uterine cancer in mother, Pancreatic cancer in multiple family members on paternal side. She was hemodynamically stable. Abdominal-US showed right adrenal lesion. Non-contrast MRI abdomen showed a large collection in the right adrenal gland measuring 9.6cm x 9cm. Ability to assess for underlying lesion challenging given the amount of blood products and lack of IV contrast. Laboratory analysis showed an appropriately suppressed cortisol with 1 mg overnight dexamethasone suppression test (cortisol 1.3 mcg/dl, N&amp;lt;1.8 mcg/d Dexamethasone level 332 ng/dl, N&amp;lt;180-550 ng/dl), normal DHEA-S (135 mcg/dl, N=18-391mcg/dl), non-suppressed ACTH (18 pg/ml, N 7.2-63 pg/ml), normal aldosterone (8.1 ng/dl, N=3-39.2 ng/dl) with a non-suppressed renin (17.8 pg/ml, N=4.2-52.2 pg/ml), normal fractionated plasma metanephrines (Free metanephrines &amp;lt;0.2 nMol/L, N&amp;lt;0.0.5nMol/L Free normetaphrines &amp;lt;0.2 nMol/L, N&amp;lt;0.9nMol/L), negative Antiphopholipid antibody testing (Beta 2 Glycoprotein I IgM &amp;lt;2 U/ml, N&amp;lt;20U/ml, Beta 2 Glycoprotein I IgG 2.2 U/ml, N&amp;lt;20U/ml). The patient underwent a laparoscopic converted to open right adrenalectomy. Pathology showed a 9.6cm adrenal gland with organizing hematoma, vascular congestion, and hemorrhage. It also showed periadrenal adipose tissue with atypia, MDM2 gene amplification by FISH negative – ruling out liposarcoma. Post-operatively, her symptoms resolved without complications to the pregnancy. Differentials for adrenal hemorrhage in this pregnant patient include: 1) underlying adrenal tumor (most commonly pheochromocytoma), 2) coagulopathy (e.g. antiphospholipid syndrome), and 3) pregnancy-related adrenal hemorrhage (rare, mostly unilateral due to increased vascular flow to the adrenal gland and the hypercoagulability). After evaluating the adrenal functionality, APLAS and assessing the malignant potential with imaging studies; conservative management is appropriate in stable patients. Our patient underwent surgery due to recurrent intractable pain, and uncertainty regarding malignant potential of the adrenal mass given history of multiple cancers in the family. Conclusion: Our case highlights that when indicated, adrenalectomy in the II trimester is a safe and effective option in pregnancy. Individualized treatment should be chosen for each patient following shared decision-making. Presentation: 6/1/2024

12238 A Case Of Drug-induced Vasculitis

Abstract Disclosure: C. Javier: None. M.H. Horani: None. Title: A Case of Drug-Induced VasculitisChristian Javier, DOMohamad Horani, MD Introduction: Graves’ disease is commonly managed with thionamides. These have rare but serious complications of drug-induced lupus-like syndrome and vasculitis. In patients who present with rheumatologic and inflammatory findings, it is important to consider the possibility of these complications . Case Presentation: We present a 30-year-old female with Graves disease, asthma, and hypertension with concerns for cough, body aches, fatigue, bilateral flank pain, erythema, itching and burning of the hands, in the setting of recent spontaneous miscarriage. She was diagnosed with Graves’ nearly 2 years ago and was started on methimazole, but discontinued due to adverse effects of the medication. She was then started on PTU. The patient had a seizure, and head CT revealed a left-sided 4 cm brain mass in the left frontal lobe. The patient was admitted to the ICU, intubated, and started on IV Decadron. Further imaging showed multiple enlarged lymph nodes in the axilla, mediastinum, and hilum. Her brain mass was biopsied showing acute inflammation with early acute necrosis and multifocal fibrinous vascular necrosis, which has been reported in ANCA vasculitis. She had undetectable TSH (0.35-5.0) and free T4 of 1.54 (4.87-11.72). She was also found to have proteinuria and AKI. At this point, PTU-induced vasculitis and drug-induced lupus were suspected and PTU was discontinued. She was found to have low complement levels (C3 40, C4 6.1), elevated p-ANCA (&amp;gt;1:1280), ANA (1:640), anti-histone IgG (2.3) dsDNA (1:160), SSB La antibodies (70), anti-Smith antibodies (319), anti-RNP antibodies (146). Renal biopsy is pending. After discontinuation of PTU and administration of IV steroids, her symptoms largely resolved and she was extubated and stable for discharge. Conclusion: In patients being treated for Graves’ disease with PTU, there are rare but life-threatening complications associated with this medication including lupus-like state or vasculitis with elevated ANCA antibodies. Common presenting symptoms of drug-induced vasculitis include fever, joint pains, myalgias, skin lesions, glomerulonephritis, cerebral angiitis, and pulmonary hemorrhage. The onset of vasculitis can occur at any time after starting medication, with one study showing an average onset of 36 months after initiation of therapy. Other case reports have demonstrated positive serologies for ANA and anti DS-DNA antibodies in those with PTU-induced lupus. Drug induced lupus can also occur in patients taking PTU, with kidney and CNS involvement being more uncommon. In those with p-ANCA associated vasculitis secondary to PTU, anti-GBM, antiphospholipid, and antinuclear antibodies can also be present. Presentation: 6/1/2024