Diffuse Ground-glass Opacities Research Articles

Diffuse Alveolar Hemorrhage as a Life-Threatening Feature of Juvenile Onset Systemic Lupus Erythematosus: A Case-Based Review

Diffuse alveolar hemorrhage is an uncommon but serious complication of systemic lupus erythematosus (SLE). We reported a 17-year-old boy with idiopathic thrombocytopenic purpura, who admitted with pallor and petechiae. He had Coombs positive hemolytic anemia and thrombocytopenia (hemoglobin 6.2g/dL, platelets 10,000/mm3 and lactate dehydrogenase 1024U/L), cough, tachypnea, and desaturation in the room air. Chest radiograph revealed bilateral diffuse alveolar opacities and computed tomography showed bilateral diffuse alveolar infiltrates and ground-glass opacity consistent with pulmonary hemorrhage. Anti-nuclear antibody (ANA) was 1:640 with positive Ro and anti-phospholipid antibodies, low C3 and C4, but negative anti-double-stranded DNA. He was treated with pulse methylprednisolone followed by tapering doses of steroids and with 6 doses of intravenous cyclophosphamide once every two weeks followed by mycophenolate mofetil. He had no relapse in the following 3 years. The case was reported to emphasise this life-threatening complication of juvenile-onset SLE and we reviewed the literature.

How well do you know COVID-19?

ACROSS1. Defined as thickened interlobular septa and intralobular lines superimposed on diffuse ground-glass opacities, a radiological feature of progressive COVID-19 disease but non-specific.5. A humanized monoclonal antibody used as a therapy in

Rapidly progressive respiratory failure after helminth larvae ingestion

BackgroundSelf-administration of helminths has gained attention among patients as a potential but unproven therapy for autoimmune disease. We present a case of rapidly progressive respiratory failure in a patient with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) as a result of self-administration of parasitic organisms.CaseA 45-year-old woman with a history of interstitial lung disease and PAH due to limited cutaneous SSc presented to pulmonary clinic with worsening dyspnea, cough, and new onset hypoxemia. Three months prior to presentation she started oral helminth therapy with Necator americanus as an alternative treatment for SSc. Laboratory evaluation revelaed eosinophilia and elevated IgE levels. IgG antibodies to Strongyloides were detected. High resolution computed tomography of the chest revealed progressive ILD and new diffuse ground glass opacities. Transthoracic echocardiogram and right heart catheterization illustrated worsening PAH and right heart failure. The patient was admitted to the hospital and emergently evaluated for lung transplantation but was not a candidate for transplantation due to comorbidities. Despite aggressive treatment for PAH and right heart failure, her respiratory status deteriorated, and the patient transitioned to comfort-focused care.ConclusionAlthough ingestion of helminths poses a risk of infection, helminth therapy has been investigated as a potential treatment for autoimmune diseases. In this case, self-prescribed helminth ingestion precipitated fatal acute worsening of lung inflammation, hypoxemia, and right heart dysfunction, highlighting the risk of experimental helminth therapy in patients, especially those with underlying respiratory disease.

Intestinal Beh\xe7et\u2019s disease complicated by myelodysplastic syndrome and secondary pulmonary alveolar proteinosis: a case report

BackgroundGastrointestinal lesions, which sometimes develop in Behçet’s disease (BD), are referred to as intestinal BD. Although rare, intestinal BD can be accompanied by myelodysplastic syndrome (MDS) with abnormal karyotype trisomy 8, which is refractory to immunosuppressive therapy. Pulmonary alveolar proteinosis is a rare lung complication of BD and MDS. Herein, we present an extremely rare case of intestinal BD presenting with MDS and several chromosomal abnormalities, followed by secondary pulmonary proteinosis.Case presentationA 58-year-old Japanese woman with a 3-year history of genital ulcers and oral aphthae was admitted to our hospital. The patient developed abdominal pain and persistent diarrhea. Colonoscopy revealed multiple, round, punched-out ulcers from the terminal ileum to the descending colon. Intestinal BD was diagnosed and the patient was treated with colchicine, prednisolone, and adalimumab. However, her symptoms were unstable. Bone marrow examination to investigate the persistent macrocytic anemia revealed the presence of trisomy 8, trisomy 9, and X chromosome abnormalities (48, + 8, + 9, X, i(X) (q10) in 12 out of the examined 20 cells). Based on her hypoplastic bone marrow, the patient was diagnosed with low-risk MDS (refractory anemia). At the age of 61, the patient developed pneumonia with fever and diffuse ground-glass opacities on the lung computed tomography (CT). Chest high-resolution CT and histopathology via transbronchial lung biopsy revealed the presence of pulmonary alveolar proteinosis (PAP). These findings combined with the underlying disease led to the diagnosis of secondary PAP.ConclusionsSecondary pulmonary proteinosis may accompany intestinal BD with MDS and several chromosomal abnormalities. Physicians should pay attention to lung complications, such as PAP, in patients with intestinal BD complicated by MDS. Genetic abnormalities may be associated with the development of such diseases.

Medication-induced Pulmonary Injury: A Scenario- and Pattern-based Approach to a Perplexing Problem.

Medication-induced pulmonary injury (MIPI) is a complex medical condition that has become increasingly common yet remains stubbornly difficult to diagnose. Diagnosis can be aided by combining knowledge of the most common imaging patterns caused by MIPI with awareness of which medications a patient may be exposed to in specific clinical settings. The authors describe six imaging patterns commonly associated with MIPI: sarcoidosis-like, diffuse ground-glass opacities, organizing pneumonia, centrilobular ground-glass nodules, linear-septal, and fibrotic. Subsequently, the occurrence of these patterns is discussed in the context of five different clinical scenarios and the medications and medication classes typically used in those scenarios. These scenarios and medication classes include the rheumatology or gastrointestinal clinic (disease-modifying antirheumatic agents), cardiology clinic (antiarrhythmics), hematology clinic (cytotoxic agents, tyrosine kinase inhibitors, retinoids), oncology clinic (immune modulators, tyrosine kinase inhibitors, monoclonal antibodies), and inpatient service (antibiotics, blood products). Additionally, the article draws comparisons between the appearance of MIPI and the alternative causes of lung disease typically seen in those clinical scenarios (eg, connective tissue disease-related interstitial lung disease in the rheumatology clinic and hydrostatic pulmonary edema in the cardiology clinic). Familiarity with the most common imaging patterns associated with frequently administered medications can help insert MIPI into the differential diagnosis of acquired lung disease in these scenarios. However, confident diagnosis is often thwarted by absence of specific diagnostic tests for MIPI. Instead, a working diagnosis typically relies on multidisciplinary consensus. ©RSNA, 2021.

Abstract 10367: An Unusual Vasodilator Response: Recognizing a Rare Subtype of Pulmonary Arterial Hypertension

Introduction: Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) caused by intimal fibrosis of the pulmonary venules and septal veins. While the hemodynamic profile is suggestive of pre-capillary pulmonary hypertension, vascular obstruction distal to the pulmonary capillary beds distinguishes PVOD from other forms of PAH. Case: A 29-year-old woman presented with progressive dyspnea and fatigue. She was tachycardic, hypotensive, and volume overloaded on exam. ECG was notable for right-axis deviation. TTE showed a dilated, hypokinetic RV and small LV with mild global hypokinesis and septal flattening throughout the cardiac cycle. A CTA chest excluded pulmonary embolism but showed diffuse centrilobular ground-glass opacities and lymphadenopathy which raised suspicion for PVOD. She underwent right heart catheterization with the following measurements (mmHg): RA 14, PA 99/56 (mean 71), PCWP 12, and CI 1.1 L/min/m 2 with PVR 28.1 WU. Following initiation of an epoprostenol infusion, she became increasingly hypoxemic with repeat CT chest demonstrating dramatic worsening of ground-glass opacities and vascular congestion. This response to a vasodilator challenge led to a clinical diagnosis of PVOD. She was urgently listed for and underwent bilateral lung transplantation. Explanted lung tissue subsequently confirmed the diagnosis. Conclusion: In most forms of PAH, vasodilators mitigate arteriolar narrowing and improve pulmonary blood flow, while in PVOD they exacerbate pulmonary capillary congestion due to increased arteriolar blood flow relative to the venous outflow due to fixed narrowing of the pulmonary venule network. Because lung biopsy is contraindicated in severe pulmonary hypertension, the clinician must recognize that worsening pulmonary edema in response to vasodilator challenge with normal PCWP is a critical clue pointing towards PVOD. Timely diagnosis is essential given the poor prognosis for this condition for which lung transplantation is the definitive treatment.

Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate

BackgroundDrug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings.Case presentationAn 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test.ConclusionsWe described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

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. DisclosuresNo relevant conflicts of interest to declare.

CT Appearance Pattern After Stereotactic Body Radiation Therapy Predicts Outcomes in Early-Stage Non-Small-Cell Lung Cancer.

BackgroundsComputed tomography (CT) appearance pattern after lung tumor stereotactic body radiation therapy(SBRT) might predicts survival. This study aimed to investigate the correlation between CT appearance pattern after SBRT and outcomes in patients with early-stage non-small-cell lung cancer (NSCLC).MethodsClinical data of inoperable patients with early-stage NSCLC undergoing SBRT were retrospectively analyzed from 2012 to 2015 at the Zhejiang Cancer Hospital. The relationship between CT appearance pattern after SBRT and patient’s survival was analyzed.ResultsThe data from 173 patients with early-stage lung cancer treated with SBRT were analyzed. One month after SBRT, diffuse consolidation was seen in 17 patients, patchy consolidation in 28 patients, diffuse ground-glass opacity (GGO) in 10 patients, and patchy GGO in 22 patients. The survival time was significantly longer in the “no evidence of increased density” group compared with the “consolidation or GGO” group [2-year overall survival (OS) rate, 96.1% vs 89.3%; hazard ratio (HR), 0.36; 95% confidence interval (CI), 0.16–0.85; P = 0.015]. A similar trend was found in the progression-free survival (PFS) analysis (2-year PFS rate, 91.3% vs 85.0%; HR, 0.35; 95% CI, 0.13–0.95; P = 0.015) and distant metastasis free survival(DMFS) (2-year DMFS rate, 93.3% vs 87.1%; HR, 0.41; 95% CI, 0.20–0.86; P = 0.031). However, no significant difference was found in recurrence-free survival between the two groups (P = 0.212).ConclusionsOne month after SBRT, the radiological change “no evidence of increased density” was prevalent. The OS, PFS, and DMFS were significantly longer in the “no evidence of increased density” group compared with the “consolidation or GGO” group. Further studies are needed to validate these findings.

GROUND GLASS OPACITIES: IT'S NOT ALL COVID

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: During the COVID-19 pandemic, superimposed infections with both bacterial and fungal organisms have been shown to complicate the viral process. Aspergillus and candida are the most common fungal organisms reported [2];but there have also been a few case reports with co-infection from Pneumocystis jirovecii pneumonia (PJP) [1,3]. We present a COVID patient with lymphopenia and diffuse ground glass opacities who was also diagnosed with PJP. CASE PRESENTATION: A 58-year-old male with past medical history of emphysema liver cirrhosis presented to the hospital with nausea, vomiting and abdominal distention. On examination he was afebrile, hypotensive with a blood pressure of 88/56, SpO2 was 96% on room air. His lungs were clear on auscultation and abdominal exam was notable for moderate ascites. There was 2+ pedal edema bilaterally. Laboratory work-up showed a WBC count of 12000/µL, only 7% of which were lymphocytes. Chest X-ray did not reveal any acute pathology and screening COVID-19 PCR was negative. He was admitted to the medical ward for management of alcohol withdrawal and decompensated liver cirrhosis. He developed hypoxic respiratory failure within 24 hours of presentation. CT chest (Figure 1) showed multifocal ground glass opacities along with bilateral pleural effusions and consolidative airspace disease at bases. A repeat COVID PCR resulted positive. His respiratory failure progressively worsened over the next two weeks despite being treated with remdesivir, dexamethasone and empiric broad spectrum antibiotics. He was intubated and placed on mechanical ventilation. Repeat imaging (Figure 2) showed worsening diffuse ground glass opacities now with more predominant cystic changes. Bronchoscopy with broncho-alveolar lavage (BAL) was performed, PCR testing of the BAL sample detected Pneumocystis jirovecii. He was then started on Bactrim in conjunction with steroids for the high A-a gradient. HIV antibody was negative, CD4 lymphocyte count was low at 304/µL and CD8 counts were normal at 311/µL. The patient slowly started to improve and was successfully extubated after three weeks. However, he later on developed septic shock from candidemia and was placed on hospice care by family due to his poor functional status. DISCUSSION: As with many viral infections, patient's with COVID-19 have demonstrated considerable risk for developing concomitant bacterial and fungal infections. We speculate that lymphopenia with low absolute CD4 count, combined with the use of corticosteroids may play a role in susceptibility to opportunistic infections in otherwise immunocompetent hosts. CONCLUSIONS: When critically ill COVID patient's fail to improve and have persistent lymphopenia, co-infections should be considered and appropriately worked up. REFERENCE #1: A case of COVID-19 and Pneumoncystis jirovecii Coinfection. A. Menon et al. Am J Respir Crit Care Med. 2020 Jul REFERENCE #2: Invasive Fungal Disease Complicating Coronavirus Disease 2019: When It Rains, It Spores. M.Hoenigl. Clinical infectious diseases. 2020 September REFERENCE #3: Pneumocystis and Severe Acute Respiratory Syndrome Coronavirus 2 Coinfection: A Case Report and Review of an Emerging Diagnostic Dilemma. C. Rubiano. Open Forum Infectious Diseases. January 2021. DISCLOSURES: No relevant relationships by Ahmed Mahgoub, source=Web Response No relevant relationships by Joseph Meharg, source=Web Response No relevant relationships by Leandro Ramirez, source=Web Response No relevant relationships by Ajit Thota, source=Web Response

A DUAL DIAGNOSIS: CYCLOPHOSPHAMIDE TOXICITY AND DIFFUSE ALVEOLAR-SEPTAL AMYLOIDOSIS CAUSING HYPOXEMIA

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Patients with cardiac amyloidosis have multiple possible causes of hypoxia including pulmonary edema, infection, drug toxicity, and pulmonary involvement of amyloidosis. Treatment varies significantly for these different etiologies. This broad differential can make diagnosis challenging and bronchoscopy is often needed to establish a definitive diagnosis. CASE PRESENTATION: A 72 yo male with cardiac AL amyloidosis presented with fever and hypoxic respiratory failure. He completed 4 cycles of cyclophosphamide, bortezomib, and dexamethasone 2 weeks prior to presentation. Right heart catheterization (RHC) demonstrated normal pressures. CT chest showed diffuse ground glass opacities (GGO) and basilar predominant interlobular septal thickening. He was diuresed but continued to require supplemental oxygen. Bronchoscopy with BAL and transbronchial biopsy was performed. BAL WBC was 121 with 48% lymphocytes and 48% macrophages. Infectious evaluation returned negative. Transbronchial biopsy returned with lambda-predominant plasma cell infiltrate and amyloid deposition. He was started on prednisone with improvement in symptoms and liberation from supplemental oxygen after 3 weeks of therapy. PFTs obtained at follow-up showed mild obstruction and moderately reduced DLCO. DISCUSSION: Pulmonary toxicity is a known complication of cyclophosphamide therapy that results in pneumonitis, typically occurring weeks after administration. CT imaging shows scattered or diffuse GGOs. Pathology demonstrates diffuse alveolar damage. Case series have shown improvement with drug cessation and steroids. Diffuse alveolar-septal amyloidosis (DASA) is 1 of several patterns of pulmonary amyloidosis. DASA is associated with AL amyloidosis. DASA is a common pathologic finding but is rarely symptomatic unless severe enough to impair gas exchange. CT imaging shows interlobular septal thickening, reticular opacities, and GGOs. Pathology reveals amyloid deposition within the alveolar septum and vessel walls and a plasma cell infiltrate. Treatment is systemic therapy for amyloidosis. This patient with cardiac amyloidosis and cyclophosphamide use was a diagnostic challenge. Given his fever, normal RHC, and failure to improve with diuresis, there was concern for infection vs cyclophosphamide toxicity. Infectious evaluation with BAL was negative and he was started on steroids with improvement in symptoms. However, pathology returned with findings consistent with DASA.His clinical presentation and rapid improvement with prednisone indicate a component of cyclophosphamide toxicity causing hypoxemia. His pathology findings and persistent reduction in DLCO suggest DASA also contributed to his hypoxemia. CONCLUSIONS: DASA and cyclophosphamide toxicity are uncommon causes of respiratory failure and have nonspecific findings on CT imaging. Distinguishing these etiologies can be challenging without bronchoscopy and histological samples. REFERENCE #1: Khoor A, Colby TV. Amyloidosis of the Lung. Arch Pathol Lab Med. 2017 Feb;141(2):247-254. doi: 10.5858/arpa.2016-0102-RA. PMID: 28134587. REFERENCE #2: Malik SW, Myers JL, DeRemee RA, Specks U. Lung toxicity associated with cyclophosphamide use. Two distinct patterns. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1851-6. doi: 10.1164/ajrccm.154.6.8970380. PMID: 8970380. REFERENCE #3: Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000 Sep-Oct;20(5):1245-59. doi: 10.1148/radiographics.20.5.g00se081245. PMID: 10992015. DISCLOSURES: No relevant relationships by David Dennis, source=Web Response No relevant relationships by David Zaas, source=Web Response

DIFFUSE ALVEOLAR HEMORRHAGE IN A PATIENT WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME: A RARE BUT SERIOUS ENTITY

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of a middle-aged female diagnosed with antiphospholipid syndrome (APS) with biopsy-proven pulmonary capillaritis coming with dyspnea and hemoptysis. CASE PRESENTATION: 66 years female with a history of APS with pulmonary vasculitis, multiple hospitalizations for recurrent pneumonia presented to Emergency Department (ED) with 2 weeks of worsening dyspnea, coughing out of blood clots, & nose bleeds for a day. She denied fever, chills, chest pain, and bleeding from elsewhere. ED vitals includes oxygen saturation of 70% on room air, otherwise afebrile with stable hemodynamics. Physical exam showed diffuse wheezing & crackles over bilateral lungs. Lab revealed pancytopenia requiring blood transfusion. Serology showed persistently positive antiphospholipid antibodies (ACL, Beta 2 Glycoprotein) but negative ANA, dsDNA, C-ANCA, P-ANCA, Anti-GBM antibody, hemolysis labs with normal complement 3 & 4, and ESR/CRP markers. Chest x-ray & CT chest showed diffuse ground-glass opacities. Echo revealed EF 71-75% with pulmonary hypertension. She was admitted to the ICU and started on pulse steroid & broad-spectrum antibiotics. She underwent 4 cycles of plasmapheresis followed by mycophenolate & rituximab for vasculitis flare. After a week, she improved without further need of supplemental oxygen and was discharged with mycophenolate, rituximab & oral steroid. DISCUSSION: Diffuse alveolar hemorrhage (DAH) can be a rare but fatal (21% mortality) manifestation of APS ( a hypercoagulable condition) where antiphospholipid antibodies (aPL) mediated pulmonary endothelial injury causes RBCs to leak into the alveoli [1,2]. The patient may recurrently present with dyspnea, fever, cough, hemoptysis with diffuse ground-glass opacity in chest film and dropping hematocrit [1,2,3]. A thorough history, examination, lab/imaging studies, or sometimes biopsy may be required to diagnose the underlying etiology so that specific treatment can be directed along with supportive care. Serological work-up should include ANCA Abs, ANA, dsDNA, Anti-GBM, complement 3 & 4 levels to identify underlying systemic vasculitis and cardiac echo should exclude heart failure [1]. Patient with this condition has persistently elevated & high titer of aPL antibodies [1,2]. Persistent bloody fluid in bronchoscopy with bronchoalveolar lavage supports DAH [1,3]. Though not recommended routinely, tissue biopsy shows pulmonary capillaritis more often than microvascular thrombosis in APS [1,2]. Respiratory support, maintenance of hemodynamics, temporary avoidance of anticoagulants, exclusion of infection, and initiation of high dose systemic steroid with immunosuppressive agents with or without plasma exchange are key to the management in patients with DAH secondary to capillaritis from underlying autoimmune condition [1,2,3]. CONCLUSIONS: Though rare, DAH should be suspected in patient with APS to direct the appropriate treatment timely. REFERENCE #1: Stoots SA, Lief L, Erkan D. Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome. Curr Rheumatol Rep. 2019;21(10):56. Published 2019 Sep 6. doi:10.1007/s11926-019-0852-7 REFERENCE #2: Deane KD, West SG. Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum. 2005 Dec;35(3):154-65. doi: 10.1016/j.semarthrit.2005.05.006. PMID: 16325656. REFERENCE #3: Gertner E. Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment. J Rheumatol. 1999 Apr;26(4):805-7. PMID: 10229400. DISCLOSURES: No relevant relationships by Varun tej Gonuguntla, source=Web Response No relevant relationships by Resha Khanal, source=Web Response No relevant relationships by Sharad Oli, source=Web Response No relevant relationships by Shital Oli, source=Web Response No relevant relationships by kiran para, source=Web Response No relevant relationships by Ankur Sinha, source=Web Response No relevant relationships by husnain waseem, source=Web Response

GADOLINIUM-INDUCED CARDIOPULMONARY ARREST IN A 57-YEAR-OLD FEMALE

TOPIC: Allergy and Airway TYPE: Medical Student/Resident Case Reports INTRODUCTION: Magnetic resonance contrast agents are used to better characterize disease processes during Magnetic Resonance Imaging (MRI). Gadolinium based contrast agents (GBCA) are widely used due to their safety profile. The incidence of adverse events after receiving GBCAs is less than 2%, most being mild and transient [1,2]. Here, we see a patient who developed cardiopulmonary arrest after GBCA administration. CASE PRESENTATION: A 57 year old female with a past medical history of asthma, hypertension, diabetes, hyperlipidemia and mild COVID19 infection, presented to outpatient brain MRI for evaluation of new hearing loss. After receiving Gadobutrol, she developed shortness of breath, abdominal pain, and emesis. In the emergency department, the patient was hypothermic, tachypneic, and hypoxic;no urticaria or rash noted. She was placed on non-invasive ventilation and treated for presumed anaphylaxis, but remained hypoxic and in respiratory distress. Subsequent intubation (without angioedema visualized) was complicated by cardiac arrest, requiring six minutes of cardiopulmonary resuscitation. Initial imaging was significant for CT chest showing diffuse ground glass and consolidative opacities and normal CT head. Despite standard care treatment, the patient's neurological exam worsened, one week into her admission she was observed to have minimal brainstem reflexes, with head CT showing findings of anoxic brain injury, cerebral edema and possible uncal herniation. She worsened clinically and expired thirteen days after admission. Autopsy performed showed clinicopathological correlation attributing anoxic brain injury secondary to anaphylaxis. DISCUSSION: Gadobutrol is approved for multiple indications in most ages. It was introduced in 1998, its safety profile has been studied in patients worldwide. The incidence of adverse events of GBCA has been reported to be 0.32-3.8%, commonly nausea, vomiting, urticaria and dizziness. Risk factors include patients' history of respiratory allergic disease, asthma, COPD, or prior history of reactions to iodinated contrast media [1,2]. The incidence of serious adverse drug reactions (ADR) involving the cardiopulmonary system is reported to be <0.1%;from 1998-2012 there were 614 cases of ADR of which 7.2% were fatal [3]. Our case presentation shows a severe ADR to gadolinium contrast for MRI. Though the patient's pre-existing history of asthma put her at slightly higher risk, proven safety of gadolinium contrast significantly weighs towards continued use of contrast enhanced MRI. Nevertheless, awareness and timely response to possible contrast-induced ADR is important for all clinicians. CONCLUSIONS: GBCA are widely used agents with good safety profiles. Although severe adverse events are rare, it's important for physicians to have a high index of suspicion and use caution in patients that are identified with risk factors for adverse reactions to these agents. REFERENCE #1: [1] Marie-France Bellin. MR contrast agents, the old and the new. European Journal of Radiology volume 60, Issue 3, 2006, 314-323. doi.org/10.1016/j.ejrad.2006.06.021. REFERENCE #2: [2] Endrikat, Jan MD, PhD*†;Vogtlaender, Kai PhD‡;Dohanish, Susan RA§;Balzer, Thomas MD, PhD∥;Breuer, Josy MD, PhD*Safety of Gadobutrol, Investigative Radiology: September 2016 - Volume 51 - Issue 9 - p 537-543 doi: 10.1097/RLI.0000000000000270 REFERENCE #3: [3] Raisch, D. W., Garg, V., Arabyat, R., Shen, X., Edwards, B. J., Miller, F. H.,… West, D. P. (2013). Anaphylaxis associated with GADOLINIUM-BASED contrast AGENTS: Data from the food and DRUG Administration's adverse event reporting system and review of case reports in the literature. Expert Opinion on Drug Safety, 13(1), 15-23. doi:10.1517/14740338.2013.832752 DISCLOSURES: No relevant relationships by Lauren Blackwell, source=Web Response No relevant relationships by Rostislav Gorbatov, source=Web Response No relevant relationships by Chinazor Iwuaba, source=Web Response

A RAPIDLY PROGRESSIVE AND RARE ILLNESS: AUTOANTIBODIES AGAINST MELANOMA DIFFERENTIATION-ASSOCIATED PROTEIN 5 (ANTI-MDA5): AMYOPATHIC DERMATOMYOSITIS WITH PROGRESSIVE INTERSTITIAL LUNG DISEASE THAT DEVELOPED AFTER COVID-19 VACCINE

TOPIC: Critical Care TYPE: Global Case Reports INTRODUCTION: Anti-MDA5 dermatomyositis is a subtype of dermatomyositis characterized by a high risk of rapidly progressive interstitial lung disease. It is characterized by fever, progressive shortness of breath, joint swelling and skin ulcerations. (1) There is invariable hyper-ferritinemia and radiographically there is a pattern of diffuse bilateral ground glass opacities. Complications with spontaneous pneumothorax and pneumomediastinum are not uncommon. Diagnosis is confirmed by biopsy as well as serum antibodies against MDA5. A known trigger is viral infection. (2) CASE PRESENTATION: We present the case of a 58-year-old man who was admitted to the Intensive Care Unit on account of respiratory failure and shock. He had a progressive Illness that started 4 days after receiving a novel mRNA COVID-19 Vaccine. He developed bilateral extremities edema, oral sores, worsening fatigue and dyspnea on exertion. He failed outpatient treatment for empiric pneumonia as well as prednisone for vaccine reaction. He presented to the hospital with fever, progressive dyspnea and fatigue. On physical exam he had oral blisters, digital tip ischemia and ulceration. His vital signs were pertinent for a SpO2 of 90% on ventilator support. A chest CT revealed diffuse and sub-pleural ground-glass opacities.There was an extensive negative infectious work up from serum, urine and BAL samples. These included negative SARS COV2 Antigen and SARS-Cov2 IgG. His inflammatory markers were pertinent for a positive ANA with titer of 1:320, Ferritin of 2,143 mcg/L, LDH of 1,105 U/L and CRP of 2.7mg/dL. Based on this information the differential for amyopathic dermatomyositis with progressive interstitial lung disease was considered. A skin biopsy of his index finger confirmed the diagnosis. His therapeutic interventions through his hospitalization included a trial of stress dose steroids, cyclophosphamide, IVIG, colchicine and tacrolimus. His ICU course was complicated by pneumomediastinum, pneumothorax and pericardial effusion. These were managed by placing a chest tube thoracotomy and pericardial drain respectively. His plan of care was changed to comfort measures after he had a drastic and prolonged desaturation episode without recovery. DISCUSSION: For conditions that lead to cytokine storm with subsequent development of ARDS or multi-organ dysfunction;there is a progressive clinical deterioration and high risk of death. We had insufficient evidence to definitively demonstrate a direct correlation between the vaccination and the patient's illness. CONCLUSIONS: In conditions that lead to Cytokine storm with multi-organ dysfunction targeting timely control of this inflammatory cascade via immunomodulation, cytokine antagonist and reduction of inflammatory cell infiltration in particular early in the process could lead to a reduction in mortality. REFERENCE #1: Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L. The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol. 2011;65(1):25-34. doi:10.1016/j.jaad.2010.09.016 REFERENCE #2: Sakamoto N., Ishimoto H., Nakashima S. Clinical features of anti-MDA5 antibody-positive rapidly progressive interstitial lung disease without signs of dermatomyositis. Intern Med. 2019;58(6):837–841. doi: 10.2169/internalmedicine. 1516-18. REFERENCE #3: Margherita Giannini,1 Mickael Ohana,2 Benoit Nespola,3 Giovanni Zanframundo,4,5 Bernard Geny,1,6 and Alain Meyer1,6,7 Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020 Sep;56(3): 2001618. Published online 2020 Sep DISCLOSURES: No relevant relationships by Ashlie Arthur, source=Web Response No relevant relationships by Leonel Carrasco, source=Web Response no disclosure on file for Chad Case;No relevant relationships by Juan Gaitan Rueda, source=Web Response

LEUKEMIC PULMONARY INFILTRATION: A RARE COMPLICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Fellow Case Reports INTRODUCTION: We report a rare case of pulmonary leukemic infiltration that posed a diagnostic dilemma. CASE PRESENTATION: A 61 year old female presented with weeks of weakness, nausea, vomiting, diarrhea. Initial laboratory evaluation revealed hyperleukocytosis of >100,000 cells/microliter with 86% blasts and thrombocytopenia. A bone marrow biopsy revealed B cell type ALL. Hydroxyurea was initiated for cytoreduction. On hospitalization day 3 she developed hypoxemia requiring 2-3 L supplemental oxygen. Chest radiograph revealed mild patchy airspace opacities. Extensive non-invasive infectious work up was negative. Over next week she developed worsening dyspnea and hypoxemia, with near tandem progression of radiographic airspace disease, despite antibiotics and stabilization of blood count. CT chest revealed diffuse patchy ground glass opacities, small pleural effusion and adjacent atelectasis. Bronchoscopy showed bloody secretions, with BAL differential showing abundant atypical cells with irregular nuclear contours, fine chromatin and prominent nucleoli, consistent with lymphoblastic leukemic blast cells. Concern was for pulmonary leukemic infiltration vs DAH with peripheral blood blast spillage. High dose corticosteroids were initiated. Her clinical condition deteriorated requiring endotracheal intubation and ICU admission. Due to her critically ill status, she was treated dose reduced, moderate intensity Cyclophosphamide and Vincristine chemotherapy. A repeat BAL revealed similar findings of ~30% blasts on differential. Subsequently her respiratory status improved, she was extubated and discharged on low supplemental oxygen. Bone marrow restaging 4 weeks after initial treatment showed persistent B acute lymphoblastic leukemia in the bone marrow. Her oncology team is planning for mini-HOP induction with Larson consolidation. DISCUSSION: Thoracic involvement of leukemia is varied, from leukemic pulmonary infiltration, hyperleukocytopathic reaction, leukostasis, DAH, lymphadenopathy, pleural effusion etc. CT findings of leukemic pulmonary infiltration are nonspecific, however leukemic cells have a tendency to involve the perilymphatic interstitium, producing smooth or nodular thickening of the bronchovascular bundles and interlobular septa. Nodules are also common and may be peribronchovascular, centrilobular, or random in distribution. Ground-glass and consolidative opacities are less common, predominately in peribronchial regions, by infiltration of the parenchyma adjacent to the perilymphatic interstitium. Accurate diagnosis usually requires bronchoalveolar lavage or lung biopsy to rule out other common etiologies. Response to primary chemotherapy usually depends on primary leukemia and patient's clinical status, but usually portends a poor prognosis. CONCLUSIONS: Clinicians need to thoroughly investigate pulmonary infiltrates in a leukemic patient in order to ensure appropriate therapy. REFERENCE #1: Shroff, G. S., et al (2019). Leukemic involvement in the thorax. Radiographics, 39(1), 44-61. DISCLOSURES: No relevant relationships by Jyotirmayee Lenka, source=Web Response No relevant relationships by Naman Sharma, source=Web Response

AN UNUSUAL CAUSE OF RECURRENT PNEUMONIAS

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a necrotizing small vessel vasculitis classically involving the upper and lower respiratory tract and kidneys. We present a patient with GPA which initially presented as "recurrent pneumonias" unresponsive to antibiotics ultimately culminating in a presentation with alveolar hemorrhage and respiratory failure. CASE PRESENTATION: A 70-year-old man presented to the Emergency Department with dyspnea and hemoptysis. He had been hospitalized several times over the preceding month for recurrent pneumonia, and recently had been started on systemic anticoagulation for a pulmonary embolism. On arrival he was afebrile, tachycardic, hypoxemic and tachypneic. Exam revealed coarse bilateral breath sounds. Laboratory studies were significant for anemia, leukocytosis, acutely elevated creatinine and microscopic hematuria. CT Chest showed diffuse consolidation and ground glass opacities markedly worse than 1 week prior. He was initiated on broad spectrum antibiotics and admitted to the ICU. The patient was intubated for progressive respiratory failure and hemoptysis; bronchoalveolar lavage demonstrated a progressively bloody return. C-ANCA and PR3 antibodies were positive; broad infectious evaluation and other autoimmune serologies were negative. A presumptive diagnosis of ANCA associated vasculitis was made and treatment with methylprednisolone 1,000 mg daily was initiated then transitioned to prednisone 1 mg/kg daily after 3 days. Renal biopsy confirmed GPA; rituximab was added with rapid improvement. DISCUSSION: GPA is a systemic vasculitis with variable pulmonary manifestations, ranging from asymptomatic disease to respiratory failure. Specific manifestations include tracheobronchial stenosis, inflammatory lesions, interstitial lung disease, and diffuse alveolar hemorrhage (DAH). Image findings include pulmonary nodules with or without cavitation, ground glass and consolidation. Delayed diagnosis is common, necessitating a high index of suspicion. Involvement and disruption of the alveolar capillaries leads to alveolar hemorrhage, and early bronchoscopy can facilitate identification of DAH, exclusion of other potential etiologies, and lead to early diagnosis and treatment. Induction therapy for severe GPA, defined as life or organ threatening disease, includes high dose intravenous corticosteroids in combination with cyclophosphamide or rituximab. While DAH may be a life-threatening complication of GPA, most patients achieve remission and survive to hospital discharge. CONCLUSIONS: Severe presentations of GPA include diffuse alveolar hemorrhage and respiratory failure. Image findings may be non-specific, and early bronchoscopy in the setting of persistent symptoms and pulmonary findings can accelerate identification and initiation of life saving treatment. REFERENCE #1: Chung MP, Yi CA, Lee HY, Han J, Lee KS. Imaging of Pulmonary Vasculitis. Radiology. 2010;255(2):322-341. doi:10.1148/radiol.10090105 REFERENCE #2: Polychronopoulos VS, Prakash UBS, Golbin JM, Edell ES, Specks U. Airway Involvement in Wegener's Granulomatosis. Rheumatic Disease Clinics of North America. 2007;33(4):755-775. doi:10.1016/j.rdc.2007.09.004 REFERENCE #3: Cartin-Ceba R, Diaz-Caballero L, Al-Qadi MO, et al. Diffuse Alveolar Hemorrhage Secondary to Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Predictors of Respiratory Failure and Clinical Outcomes. Arthritis & Rheumatology. 2016;68(6):1467-1476. doi:10.1002/art.39562 DISCLOSURES: No relevant relationships by Scott Canepa, source=Web Response No relevant relationships by Bryan Kelly, source=Web Response No relevant relationships by Alexander Niven, source=Web Response

MYCOPLASMA GORDONAE: A RARE CAUSE OF ARDS IN THE IMMUNOCOMPROMISED

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Mycobacterium gordonae, a commonly found species of mycobacteria. While frequently encountered in the environment and clinical laboratories it is almost always considered nonpathogenic. Despite being a non-virulent organism, there are many cases of clinically significant disease. Occasionally, it has been known to cause severe infections, especially in patients with an underlying predisposition or immunosuppression such as AIDS. CASE PRESENTATION: A 39-year-old male with no known PMH presents to the hospital with complaint of worsening dyspnea, fever, and nonproductive cough. He was in his usual state of health until 3 weeks prior when he began to experience body aches, sore throat, fever and shortness of breath. Continued symptoms prompted visit to the hospital at which time he discharged from the emergency department. The patient continued to have progressive worsening of dyspnea with fever prompting return to the hospital and subsequent admission for acute hypoxic respiratory failure. He lives at home with his wife and 4 children who do not have similar symptoms. He has lived in the US for 17 years and denies recent travel, sick contacts, history of autoimmune diseases, smoking history, vaping history, drug use, skin rash, joint pain. On admission vital signs and physical exam showed tachycardia and tachypnea with fever and inspiratory rales. Laboratory data including comprehensive metabolic panel and complete blood count with differential was unrevealing. Chest imaging showed diffuse bilateral dense ground glass opacities. Inflammatory markers including D-dimer, Ferritin, LDH, CRP were elevated. Influenza, COVID-19, mycoplasma, legionella antigen resulted negative. Testing for HIV returned positive with a CD4 count of 8. Given the clinical picture the patient was started on steroids, Bactrim, and Highly active antiretroviral therapy (HAART). Bronchoscopy with BAL was performed showing negative cytology, negative GMS-silver stain. However, AFB testing showed positive M. gordonae with fungal culture showing Candida albicans. Prednisone was discontinued and the patient was continued on HAART therapy along with Bactrim and sent for further treatment with Infectious Disease specialists. DISCUSSION: While there are reports of M. gordonae infections involving many organ systems, pulmonary infection is the most common site of symptomatic disease. Common symptoms include cough, weight loss, dyspnea, hemoptysis and fever. In addition to clinical symptoms and radiographic abnormalities, positive cultures from sputum, bronchial wash, transbronchial or lung biopsy are necessary for diagnosis. CONCLUSIONS: M.gordonae is capable of causing significant infections in both immunocompromised and immunocompetent hosts. Although the likelihood of this being a contamination is significant, its isolation should prompt further evaluation especially in those patients who are immunocompromised. REFERENCE #1: Weinberger M, Berg SL, Feurstein IM, Pizzo PA, Witebsky FG. Disseminated infection with Mycobacterium gordonae: Report of a case and critical review of the literature. Clin Infect Dis. 1992;14:1229–1239. REFERENCE #2: Asija A, Prasad A, Eskridge E. Disseminated Mycobacterium gordonae infection in an immunocompetent host. Am J Ther. 2011 May. REFERENCE #3: Brener ZZ, Zhuravenko I, Bergman M. Acute kidney injury in a patient with nontuberculous mycobacterial infections: a case report. Cases J. 2009 Jan 23. DISCLOSURES: No relevant relationships by mohammed halabiya, source=Web Response No relevant relationships by Richard Miller, source=Web Response No relevant relationships by Shawn Pate, source=Web Response

TOLUENE-INDUCED ACUTE LUNG INJURY: CASE REPORT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Toluene is an aromatic hydrocarbon widely used as a solvent in industrial and commercial products including paints, adhesives, ink, and rubber. It is occasionally used as an inhalant drug for its intoxicating properties. While mostly known for producing neurologic effects, here we report a case of toluene induced acute lung injury. CASE PRESENTATION: A 61-year-old female with a medical history of alcohol abuse, depression, congestive heart failure with preserved ejection fraction presented with one week of weakness and shortness of breath. She had been seen twice in the week prior having tested negative for SARS-COV2. In the emergency department, O2 saturation was 70% with respiratory distress on room air requiring high flow nasal cannula support. Labs were notable for a potassium of 2.7 mmol/L, acute kidney injury, elevated transaminases, lactate of 2.8 mmol/L and leukocyte count of 9800/nL. CT showed diffuse bilateral ground glass opacities involving the lung parenchyma concerning for atypical including viral pneumonia. Upon admission to the ICU she developed worsening hypoxia and respiratory failure requiring intubation.A discussion with the patient's husband revealed she had a history of glue sniffing. She had recently been decreasing her alcohol intake and substituting this with an increased frequency of sniffing both permanent markers and modeling glue. This raised suspicion for chemical pneumonitis secondary to toluene induced acute lung injury. DISCUSSION: Toluene is a highly lipophilic molecule readily inhaled via the lungs and distributed widely throughout the body producing side effects like ethanol intoxication via interfering mainly with GABA receptors. Neurologic manifestations range from euphoria and hallucinations to cognitive dysfunction and ataxia with chronic use. It specifically causes renal tubular acidosis typically manifesting as a normal anion gap hyperchloremic acidosis with hypokalemia. It can also cause hepatic injury and cardiac automaticity and conduction abnormalities.Acute lung injury secondary to toluene has been described but less frequently reported. Toxicity can result in Reactive Airway Dysfunction Syndrome (RADS) from acute or chronic exposure to various chemical irritants. All hydrocarbons, including toluene, can cause chemical pneumonitis by direct contact with the pulmonary parenchyma and destroying alveolar and capillary membranes resulting in vascular permeability and edema. Symptoms may include cough, wheezing, respiratory distress, and hypoxia. Bilateral interstitial infiltrates may be delayed for several hours after the development of pneumonitis. There is no specific antidote for toluene toxicity. CONCLUSIONS: Treatment for toluene and many chemical induced pneumonitides consists of supportive care, supplemental oxygen, bronchodilators, inhaled and systemic glucocorticoids and may require intubation and admission to an ICU in severe cases. REFERENCE #1: Camara-Lemarroy CR, Rodríguez-Gutiérrez R, Monreal-Robles R, González-González JG. Acute toluene intoxication--clinical presentation, management and prognosis: a prospective observational study. BMC Emerg Med. 2015;15:19. Published 2015 Aug 18. doi:10.1186/s12873-015-0039-0 REFERENCE #2: Alberts WM, do Pico GA. Reactive airways dysfunction syndrome. Chest. 1996;109(6):1618-1626. doi:10.1378/chest.109.6.1618 REFERENCE #3: Tormoehlen LM, Tekulve KJ, Nañagas KA. Hydrocarbon toxicity: A review. Clin Toxicol (Phila). 2014;52(5):479-489. doi:10.3109/15563650.2014.923904 DISCLOSURES: No relevant relationships by Ryan Lee, source=Web Response No relevant relationships by Dominic Valentino, source=Web Response

CRIZOTINIB-INDUCED INTERSTITIAL LUNG DISEASE

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: The versatility of emerging cancer therapies is due to the advancements in gene focused strategies whereby the identification of key driver mutations has led to the development of selectively targeted drugs. Crizotinib is one such drug used for non-small cell lung cancer (NSCLC). A rare but serious adverse effect (AE) of interstitial lung disease (ILD) has been reported in about 2% of patients on Crizotinib. CASE PRESENTATION: A 63 year-old man with metastatic squamous cell carcinoma of head and neck, history of Hodgkin's lymphoma post radiation, tobacco use presented with dyspnea, cough, and fever. Physical exam revealed respiratory distress, SpO2 89% on room air and diffuse rhonchi bilaterally. He was placed on 6 liters of nasal cannula with improvement in hypoxia. White blood cell was 11000/uL, c-reactive protein (CRP) 14.23 mg/d, procalcitonin 4.72ng/ml and brain natriuretic peptide 309 pg/ml. Sputum culture, COVID real time polymerase chain reaction (PCR), respiratory viral panel and a methicillin resistant Staphylococcus aureus nasal PCR swab were all negative. Chest radiograph showed bilateral consolidations, concerning for multifocal community acquired pneumonia for which he received broad spectrum antibiotics. However, the patient's respiratory status worsened on day 2. He was requiring 40L and FiO2 60% on high-flow nasal cannula (HFNC) to keep SpO2 > 92%. The patient then reported starting Crizotinib 250 mg oral twice/day 9 days ago and developed dyspnea and cough shortly thereafter. A computer tomography (CT) scan of the chest showed a right lower lobe segmental pulmonary embolism (PE) and severe bilateral airspace disease, with diffuse consolidation and ground glass opacities. He received anticoagulation for the PE and methylprednisolone 500mg IV twice/day due to concern for Crizotinib induced ILD. There was marked improvement in his respiratory status with decreasing oxygen requirements after steroid initiation. DISCUSSION: Crizotinib is a tyrosine kinase inhibitor (TKI) that suppresses anaplastic lymphoma kinase (ALK) gene activity. ILD due to Crizotinib is thought to be related to direct cytotoxicity to the pneumocytes. Risk factors include male sex, smoking, history of pulmonary fibrosis, history of radiation and combination therapy with immunotherapy. Our patient had several risk factors, except history of pulmonary fibrosis. There is no established therapy for TKI induced ILD, but some case reports recommend using systemic corticosteroids. Other case reports have demonstrated that continuing therapy with another ALK inhibitor, such as Alectinib, did not result in recurrence of ILD. CONCLUSIONS: TKIs are generally well tolerated but can rarely cause severe ILD. It is important to consider risk factors for TKI induced ILD prior to their administration. Prompt discontinuation of the drug and treatment with corticosteroids can cause symptomatic resolution of TKI induced ILD. REFERENCE #1: Fujiuchi S, Fujita Y, Sasaki T, Ohsaki Y. Successful alectinib treatment after crizotinib-induced interstitial lung disease. Respirol Case Rep. 2016 Apr 7;4(3):e00156. REFERENCE #2: Suh CH, Kim KW, Pyo J, Hatabu H, Nishino M. The incidence of ALK inhibitor-related pneumonitis in advanced non-small-cell lung cancer patients: A systematic review and meta-analysis. Lung Cancer. 2019;132:79-86. REFERENCE #3: He Y, Zhou C. Tyrosine kinase inhibitors interstitial pneumonitis: diagnosis and management. Transl Lung Cancer Res. 2019;8(Suppl 3):S318-S320. DISCLOSURES: No relevant relationships by Stephanie Ibrahim, source=Web Response No relevant relationships by Mahnoor Mir, source=Web Response No relevant relationships by Abhishek Pandya, source=Web Response No relevant relationships by Marcos Restrepo, source=Web Response

OCCUPATIONAL-HYPERSENSITIVITY PNEUMONITIS: A DIAGNOSIS NOT TO BE MISSED BY PROPER HISTORY TAKING

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypersensitivity Pneumonitis (HP) is an inflammatory and/or fibrotic disease affecting the lung parenchyma. Radiographic or histopathological findings help to categorize HP as either fibrotic (mixed inflammatory plus fibrotic or purely fibrotic) or non-fibrotic (purely inflammatory), being the primary determinant of prognosis. Rarely acute respiratory decline can be the first manifestation of chronic HP that may develop within a wide timeframe from weeks to years of exposure. CASE PRESENTATION: A 38-year-old male with no comorbidities or smoking history, presented with one week of progressive shortness of breath. Further questions revealed that since childhood he was working in a car painting shop without using protective equipment. Vital signs: Temperature 36.9, pulse 98 beats/min, respiratory rate 22 breaths/min, blood pressure 116/96 mmHg, and oxygen saturation 37% on room air, improved to 98% via a non-rebreather mask. He was not in respiratory distress. Findings included diffuse bilateral crackles over the lung fields. CXR showed diffuse patchy bilateral alveolar opacities. WBC count and serum procalcitonin were within normal limits. SARS-CoV-2 PCR performed was negative. Chest CT showed extensive diffuse bilateral lung consolidations, ground-glass opacities, honeycombing, and prominent mediastinal lymph nodes. Given the patient symptoms, high-risk exposure to isocyanate which exists in paints, radiologic findings, and by ruling out infectious etiologies, the suspected diagnosis of HP was made and treatment with IV Methylprednisone 60mg twice daily initiated. After 2 days, clinical status improved and oxygen requirements decreased to 8 LPM via Nasal Cannula. Bronchoscopy showed erythema throughout the tracheobronchial tree. Bronchoalveolar lavage (BAL) was performed and cytology showed: Reactive bronchial cells (24% Lymphocytes, 31% macrophages, 44% neutrophils). Consequently, a diagnosis of chronic, non-fibrotic HP was confirmed. Finally, after completing 7 days of IV steroid treatment, he was discharged home with 2 LPM supplemental oxygen. Instructions regarding oral corticosteroid tapering over a 3 week-period were provided. DISCUSSION: Diagnosis of chronic HP is predominantly based on exposure identification, CT scan pattern, and bronchoscopic/histopathological findings. BAL in the majority of the patients with non-fibrotic chronic HP shows elevated cell count with greater than 20% lymphocytes and this group responds to steroid therapy significantly. CONCLUSIONS: We would like to emphasize the high value of taking detailed patient history to detect causative agent exposure. Unprotected exposure to isocyanate was the key leading to further investigation including performing BAL in our patient. We also recommend health care providers educate their patients regarding proper safety equipment use, in case of occupational exposure to HP inducers. Prevention is always better than cure! REFERENCE #1: Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et. al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020; 202(3):e36–e69. REFERENCE #2: Koster MA, Thomson CC, Collins BF, Jenkins AR, Ruminjo JK and Raghu G. Diagnosis of hypersensitivity pneumonitis in adults, 2020 clinical practice guideline: summary for clinicians. Ann Am Thorac Soc 2020. DISCLOSURES: no disclosure on file for Manish Gugnani; No relevant relationships by Irina Gutierrez Puentes, source=Web Response No relevant relationships by Julio Piedra Butina, source=Web Response No relevant relationships by Asieh TakallooBakhtiari, source=Web Response