DYSPNEIC AFTER EVERY COVID-19 SHOT: SUSPECTED BNT162B2 MRNA VACCINE-RELATED, DRUG-INDUCED PULMONARY EOSINOPHILIA

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Eosinophilia is the most commonly reported adverse event following administration of the Pfizer/BioNTech vaccine, accounting for 237 of 372 events (63.7%). Eosinophilic pneumonia has been described noted in 3 of all reported cases. CASE PRESENTATION: We present the case of a 73 year-old male presented to his PCP with a 3 week history of nonproductive cough and wheezing. He completed a 2-shot series of BNT162b2 mRNA (Pfizer/BioNTech) COVID vaccine 1 week prior to symptom onset. He had no history of respiratory symptoms, smoking, sick contacts, recent travel, chemical or biological exposures. On presentation, he was afebrile, tachycardic and required 3LPM supplemental oxygen to maintain peripheral oxygen saturation (SpO2) above 94%. Laboratory findings noted leukocytosis (13,200/mL) and eosinophilia at 5% (Absolute Eosinophil Count (AEC): 580 cells/L). Respiratory viral panel, procalcitonin, ESR and D-dimer were negative. Chest CT scan was unremarkable. He was treated with azithromycin, prednisone and inhaled bronchodilators with improvement in hypoxia. 2 weeks later, he reported intermittent dyspnea during a pulmonary clinic visit. Pulmonary function testing was normal (FEV1/FVC: 76%;FVC: 3.67L (90% predicted);FEV1: 2.80L (88% predicted). IgE level was normal and eosinophilia had resolved. 6 months after initial symptom onset, the patient received his third BNT162b2 mRNA vaccine dose. 2 weeks after vaccination, he presented to the ED with severe dyspnea, wheezing and cough with yellow sputum. He also noted a new itchy, erythematous bilateral forearm rash and painless oral ulcers. On exam, he was afebrile, tachypneic with SpO2 of 93% on 4LPM supplemental oxygen and audibly wheezing with a prolonged expiratory phase. Laboratory studies noted elevated creatinine and leukocytosis (23,100/mL) with marked eosinophilia (29.5 %, AEC: 6814 cells/L). Chest CT scan revealed a 2 cm rounded ground-glass opacity in the right upper lobe. (Figure 1.) Further workup revealed a weakly positive antihistone antibody (1:4 titer). IgE, ANA, ANCA, SS-A/B, anti-CCP, and complement levels were normal. Intravenous methylprednisolone treatment was initiated with rapid improvement in dyspnea, eosinophilia and renal function. A transbronchial biopsy (Figure 2.) of the RUL lung lesion revealed organizing pneumonia with mixed inflammatory infiltrate. Bronchoalveolar lavage analysis revealed elevated WBC (432 cells/L) with neutrophilic predominance (85%). Patient was discharged home on a prednisone taper with resolution of symptoms. DISCUSSION: Subsequent allergy work up did not indicate any apparent etiology of hypereosinophilia. Testing for strongyloides, coccidiosis and aspergillosis were also negative. A final diagnosis of BNT162b2 mRNA vaccine related pulmonary eosinophilia was made. CONCLUSIONS: Additional study is warranted into eosinophilic disease associated with the BNT162b2 mRNA vaccine. Reference #1: 1. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 03/11/2022, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Mar 11, 2022 1:18:37 PM DISCLOSURES: No relevant relationships by Matthew Haltom No relevant relationships by Nikky Keer No relevant relationships by Thekrayat Khader No relevant relationships by Muthiah Muthiah

TUBERCULOUS PLEURAL EFFUSION MASQUERADING AS DRUG-INDUCED LUPUS

SESSION TITLE: Critical Care Presentations of TB SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: TNFα plays a pivotal role in inflammation and maintenance of immune response against tuberculosis. The use of TNF inhibitors (TNFi) is associated with a significant increase in the incidence of tuberculosis (TB). TNFi may cause drug-induced lupus (ATIL) presenting as constitutional symptoms, rashes, pericardial and pleural effusions with positive autoantibodies. We present a case of pleural TB masquerading as drug-induced lupus. CASE PRESENTATION: A 68y/o woman with a history of ulcerative colitis (on infliximab, mesalamine), hypertension, T2DM, CAD, complained of low-grade fever, rashes, left-sided chest pain, dyspnea, and arthralgias for two weeks. Chest pain- worse with inspiration and cough. She emigrated from India to the USA 40 years ago. Six months before infliximab therapy, Quantiferon gold was negative. Exam: faint hyperpigmentation over shins, minimal swelling of MCPs and ankles, dullness to percussion over the left chest with decreased breath sounds. Labs: CRP 101 mg/dL, Hb 10.8 iron deficient, rheumatoid factor and anti-CCP negative, ANA 1:40, dsDNA 1:640, a reminder of ENA negative, anti-histone negative, C3/C4 normal, UA bland, protein/Cr 0.4 mg/gm, negative blood cultures, SPEP and LDH normal. CXR: opacification of the left lung up to midfield. CT chest: moderate left and small right pleural effusions, enlarged mediastinal lymph nodes. COVID and Quantiferon: negative. Thoracentesis: 850 ml of exudative fluid (2 out of 3 Light's criteria), lymphocytic predominance (76% of 4148 nucleated cells), adenosine deaminase (ADA) 42 U/L, gram stain, culture, acid-fast and MTB PCR negative, cytology negative. Thoracoscopy with biopsy of the parietal pleura: necrotizing granulomatous pleuritis with acid-fast bacilli. Sensitivity: pan-sensitive M. tuberculosis. Sputum: negative for TB. She was discharged on RIPE treatment for reactivation of TB. DISCUSSION: The incidence of infliximab-induced lupus is approximately 0.19% and confirming the diagnosis is challenging. The immunogenicity of infliximab is high, 66% of patients develop positive ANA. Anti-histone antibodies are less commonly associated with ATIL as opposed to classic drug-induced lupus and dsDNA is positive in up to 90% of cases of ATIL. Renal involvement is rare. The diagnostic usefulness of ADA (over 40 U/L) in lymphocytic pleural effusions for the diagnosis of tuberculosis in an immunosuppressed individual is demonstrated here. In countries with low TB burden, such as the USA, the positive predictive value of ADA in pleural fluid declines but the negative predictive value remains high. CONCLUSIONS: Tuberculous pleuritis is not always easily diagnosed since AFB smears and sputum may remain negative. When ADA level in lymphocytic pleural fluid is not low thorough search for TB with thoracoscopy and biopsy is justified. Reference #1: Shovman O, Tamar S, Amital H, Watad A, Shoenfeld Y. Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature. Clin Rheumatol. 2018 Feb;37(2):563-568. Reference #2: Benucci, M., Gobbi, F. L., Fossi, F., Manfredi, M. & Del Rosso, A. (2005). Drug-Induced Lupus After Treatment With Infliximab in Rheumatoid Arthritis. JCR: Journal of Clinical Rheumatology, 11 (1), 47-49. Reference #3: Valdés L, San José ME, Pose A, Gude F, González-Barcala FJ, Alvarez-Dobaño JM, Sahn SA. Diagnosing tuberculous pleural effusion using clinical data and pleural fluid analysis A study of patients less than 40 years-old in an area with a high incidence of tuberculosis. Respir Med. 2010 Aug;104(8):1211-7. DISCLOSURES: No relevant relationships by Adam Adam No relevant relationships by Moses Bachan No relevant relationships by Chen Chao No relevant relationships by Zinobia Khan No relevant relationships by Milena Vukelic

SLE After SARS-COV-2 Infection

SARS-COV-2 infection is often associated with exaggerated immune response, also referred to as a ‘cytokine storm’. There is growing concern that it may be linked to autoimmunity, with many cases of autoimmune diseases either triggered by or related to SARS-COV-2 having been reported, ranging from Guillain-Barre syndrome, Graves’ disease, multiple sclerosis, Kawasaki-like disease. Our patient was a 20-year-old female with a history of hidradenitis who presented with malaise, feet and ankle swelling, asthenia, anorexia, weight loss of 50 Ibs of 4 months. She had COVID pneumonia 7 months prior and was also seen in the ER thrice afterwards for ankle pain and fatigue managed with antibiotics and analgesics. Exam findings included tender bilateral lower extremity edema, diffuse hyperkeratotic and hyperpigmented purpuric rashes and bilateral suppurative axillary swellings. She was admitted for protein-energy malnutrition. Blood work showed WBC 13.5, low Hb 9.3, AST 509, ALT 104, BUN 29, Creatinine 0.9, Protein 7.5, albumin 1.5 (globulin gap of 6). Urine assay showed 3+ proteinuria Hb 3+ with RBC 3-10/hpf, absent nitrite, LE 1+, protein/creatinine ratio was 2949 mg/g. Blood cultures returned negative. US showed trace pericardial effusion and normal kidneys. Infectious workup returned negative for anti-streptolysin O, HIV, hepatitis B and C. Two days after, she developed AMS, fever, tachycardia and neck stiffness concerning for possible meningoencephalitis. CT head was normal. Lumbar puncture was performed. IV vancomycin and piperacillin-tazobactam was started. CSF fluid analysis revealed total protein of 125mg/dl, elevated IgG 79.8, concerning for an underlying inflammatory pathology. EEG was unremarkable. She became oliguric with creatinine and BUN both peaking at 2.6 and 58 respectively. Renal ultrasound revealed medical renal disease. Urine microscopy showed granular cast and no dysmorphic RBCs. ANA, anti-smith SSA, SSB, DS-DNA, RF, smooth muscle, anti-histone, anti-centromere, JO-1 and RNP antibodies were markedly elevated. She was unstable for CT trocar biopsy of the kidney. She subsequently went into cardiac arrest multiple times about a week into admission, before eventually expiring. Though causation was not established in our patient, SARS-COV-2 infection causing exaggerated immune response may unmask SLE or be associated with SLE.

CULTURAL BARRIERS AND PANDEMIC RESTRICTIONS RESULT IN A DELAYED DIAGNOSIS OF DRUG INDUCED LUPUS (DIL) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

CASE: A 58-year-old female with a history of hypertension, type 2 diabetes and hyperlipidemia presented with a two- week history of abdominal pain and fevers. Per the patient, family history was unremarkable, and she denied alcohol, tobacco, or recreational drug use. She denied recent travel or sexual activity and had moved to the U.S. in the 1970s from Cambodia. Medications included amlodipine, atorvastatin, dapagliflozin, lisinopril, metformin and sitagliptin. Physical exam was notable for bilateral axillary lymphadenopathy, hepatomegaly, and right sided abdominal tenderness. Laboratory data was notable for microcytic anemia, thrombocytopenia, and elevated transaminases, D-dimer, and C- reactive protein. Urinalysis demonstrated microscopic hematuria and proteinuria. Imaging showed diffuse lymphadenopathy and hepatomegaly. Autoimmune work-up was strongly positive for ANA, anti-histone, and anti DS DNA. Kidney biopsy was suggestive of glomerulonephritis. Liver biopsy was suggestive of drug induced liver injury or autoimmune hepatitis. A diagnosis of DIL and SLE was not reached until additional historical data from the patient's son was provided on hospital day 4;namely that the patient had a 30-lb unintentional weight loss, took unknown herbal supplements and had a daughter who passed away from complications of lupus. IMPACT/DISCUSSION: DIL is a rare adverse reaction to many drugs that generally manifests with mild systemic symptoms such as low-grade fevers, anorexia, and fatigue and rarely involves classic symptoms of SLE such as skin findings and major organ involvement. Notably, DIL can unmask clinically silent SLE and thereby lead to lupus like syndromes. This patient presented with mild symptoms and underwent an extensive workup due to missing key historical data which led to a delayed diagnosis. Due to COVID-19 restrictions on visitation, it was not until hospital day 4 when the patient's son visited that the team became aware of an unintentional 30-lb weight loss, unknown herbal supplement use, and a family history of SLE. The lack of such critical information stemmed from the fact that we did not ask about the use of supplements properly and never revisited it in a different manner. The patient did not share the cause of her daughter's passing as she was unaware of it, which may speak to cultural limitations in sharing health information among family members. It is imperative that as clinicians we constantly revisit the history and diversify our questions. A more complete history would optimize our workup and limit unnecessary testing, including blood draws and painful biopsies, which unfortunately occurred in this patient. CONCLUSION: A thorough history is important to achieving a timely diagnosis and to avoid excessive testing and procedures. Revisiting the history is necessary to finding key information and clinicians should consider incorporating available family members early in the diagnostic work up, especially if the diagnosis is unclear.

A Rare Case of Concurrent New-Onset Microscopic Polyangiitis and Thrombotic Thrombocytopenic Purpura in a 77-Year-Old Woman

Introduction: Microscopic polyangiits (MPA) is a rare ANCA-associated necrotizing vasculitis that affects the small vessels, often involving the lung or kidney. When presenting with diffuse alveolar hemorrhage, this disease warrants emergent treatment, often with plasma exchange. Here, we present a rare case of a patient presenting with alveolar hemorrhage in the setting of MPA and concurrent thrombotic thrombocytopenic purpura (TTP) with an extremely reduced ADAMTS13 activity. Case Report: A 77 y/o woman with HTN and PUD presented to outside facility with new onset anemia (Hb 6.3 g/dL). Positive Coombs test gave her a tentative diagnosis of hemolytic anemia, and she was transfused 2 U RBCs. Ten days later, she presented to our hospital with respiratory distress. Hb remained stable at 10.7 but had leukocytosis with WBC 22,000 with left shift, platelets 439. Vitals not consistent with sepsis though saturating 70-80% on room air. In the ED, she developed frank hemoptysis and was emergently intubated. CTA chest was negative for pulmonary embolus but demonstrated diffuse ground-glass opacities. COVID test negative. Bronchoscopy was consistent with diffuse alveolar hemorrhage (DAH), and she received tranexamic acid, crystalloids, 1 U RBCs. Suspicious for underlying vasculitic process, she was given pulse dose IV steroids (1 g methylprednisolone daily) and started plasma exchange. Creatinine on presentation was elevated at 1.77 but she continued to have adequate urine output and appropriate volume status. Her hospital course was marked by progressive thrombocytopenia with schistocytes appreciated on peripheral smear. ADAMTS13 activity <5% with inhibitor detected, consistent with TTP. Vasculitic workup revealed positive myeloperoxidase antibodies and p-ANCA consistent with MPA. Other rheumatologic workup ANA positive 1:640 and positive IgM cardiolipin antibodies;she had no personal autoimmune history but some family autoimmune disease including one daughter with systemic lupus erythematosus and another relative with Guillian-Barre. She remained intubated for 4 days and post-extubation experienced some short-lived ICU delirium but after made a remarkable recovery. She completed 12 total sessions of of plasma exchange and 3 of 4 planned doses of rituximab, to continue on oral steroids outpatient and prophylactic TMP-SMX. She was discharged to rehab facility on hospital day 20. Discussion: With diffuse alveolar hemorrhage on presentation, initial differential remained broad including delayed presentation of transfusion-related lung injury (TRALI) given recent history of transfusion. She had recently started hydralazine outpatient. Along with positive ANA, this could suggest drug-induced lupus. However, histone antibodies were negative, but results may have been compromised by steroids and plasma exchange. Both MPA and TTP can be deadly but are managed with similar treatment. Luckily, our patient was rapidly initiated on plasma exchange following hospitalization. Although further workup including ADAMTS13 and vasculitis labs were pending at the time, it is important to not delay treatment while awaiting results. Cased of concurrent TTP and ANCA-associated vasculitis have been described in the literature, but the full relationship between these two entities remains unclear. TTP may develop after starting glucocorticoids in the setting of ANCA vasculitis, so close monitoring is recommended. Disclosures: No relevant conflicts of interest to declare.