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Eosinophilic and Lymphadenopathy Associated With Vaping and Tetrahydrocannabinol Use Eric S. Mull, DO,a Guliz Erdem, MD,b Kathleen Nicol, MD,c Brent Adler, MD,d Richard Shell, MDa

Idiopathic acute eosinophilic pneumonia is a rare and potentially life- abstract threatening condition that is defined by bilateral pulmonary infiltrates and in the presence of pulmonary . It often presents acutely in fi Divisions of aPulmonary Medicine, bInfectious , previously healthy individuals and can be dif cult to distinguish from cRadiology, and dPathology, Nationwide Children’s Hospital, infectious pneumonia. Although the exact etiology of idiopathic acute Columbus, Ohio eosinophilic pneumonia remains unknown, an acute hypersensitivity reaction Dr Mull was the consulting pulmonary fellow who to an inhaled antigen is suggested, which is further supported by recent evaluated the patient and performed public health risks of vaping (electronic ) use and the development of a , and he was the primary author of this case report; Dr Erdem was the infectious disease. In this case, a patient with a year-long history of vaping in disease attending who managed the patient through conjunction with tetrahydrocannabinol cartridge use who was diagnosed with her primary service, and she contributed references idiopathic acute eosinophilic pneumonia with associated bilateral hilar and revisions to the manuscript; Dr Adler provided fi lymphadenopathy is described. radiologic gures and corresponding interpretations for the manuscript; Dr Nicol performed a cytologic review of the bronchioalveolar lavage sample, provided corresponding figures with descriptions for this manuscript, and contributed revisions to the CASE REPORT and and a one-week manuscript; Dr Shell, section chief of pulmonary history of abdominal discomfort, medicine, was the precepting physician for Dr Mull, A 16-year-old white girl who resides on and he contributed revisions to the manuscript; and a farm in Ohio where corn is grown and diarrhea, fever, and chest pain. Four all authors approved the final manuscript as animals are raised, including pigs, days before her ED encounter, she was submitted. horses, and dairy cattle, took 5-mg seen at a local urgent care facility, DOI: https://doi.org/10.1542/peds.2019-3007 where a was obtained. levocetirizine daily because of Accepted for publication Dec 9, 2019 a medical history of seasonal . She was diagnosed with left lower lobe pneumonia and was started on a 5-day Address correspondence to Eric S. Mull, DO, Division Her farmhand work was limited to of Pulmonary Medicine, Department of Pediatrics, moving hay and feeding the animals in course of azithromycin from the urgent Nationwide Children’s Hospital, 700 Children’sDr, the mornings. She had a one-year care facility. She reported compliance Columbus, OH 43205. E-mail: erics.mull@ history of vaping from a Juul device with administering her prescription of nationwidechildrens.org with nonbranded mint-flavored inhaled mometasone while using PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, cartridges that she had purchased from albuterol 4 to 5 times a day, with no 1098-4275). friends at school. The patient reported reported improvement since beginning Copyright © 2020 by the American Academy of recent cessation immediately after her the treatment. Pediatrics brief admission for pneumonia FINANCIAL DISCLOSURE: The authors have indicated 3 months before this reported In the ED, the patient was afebrile, with they have no financial relationships relevant to this admission, but she continued to have a peripheral saturation of 92% article to disclose. secondhand exposure to vaping and a respiratory rate of 32 breaths per FUNDING: No external funding. through her boyfriend. She was minute. The POTENTIAL CONFLICT OF INTEREST: The authors have prescribed albuterol and inhaled revealed a distressed girl with indicated they have no potential conflicts of interest mometasone by her pediatrician after tachypnea, labored breathing, to disclose. her initial discharge from the hospital. wheezing, and rales in both lower lung fields. Because of her distressed To cite: MullES,ErdemG,NicolK,etal. She presented to the emergency appearance and complaints of Eosinophilic Pneumonia and Lymphadenopathy department (ED) with complaints that shortness of breath with chest pain, Associated With Vaping and Tetrahydrocannabinol Use. Pediatrics. 2020;145(4):e20193007 included a 3-month history of a urine toxicology test,

Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 145, number 4, April 2020:e20193007 CASE REPORT electrocardiogram, and computed tomography (CT) chest angiogram were obtained. The results of the urine toxicology test were positive for tetrahydrocannabinol, which she admitted to using in conjunction with vaping one month before. Her acknowledgment was questionable given the time line of tetrahydrocannabinol in the urine FIGURE 1 test and her reports of vaping A, CT image at presentation revealing subsegmental ground-glass nodules without centrilobular cessation 3 months before. Although thickening or cavitation. The image is slightly asymmetric but diffuse and both peripheral and her CT chest angiogram proved central. B, Enlarged lymph nodes in the right hilum (arrows); similar lymph nodes were found on unremarkable for a pulmonary the left. embolism, it revealed multifocal airspace ground-glass opacities in all histoplasmosis serology results were for respiratory support. It was lobes and hilar lymphadenopathy negative. The results of the sputum determined that a bronchoscopy with (Fig 1). These pulmonary findings acid-fast bacillus smear, fungal bronchioalveolar lavage (BAL) was were observed on her chest polymerase chain reaction, blood warranted as a result of persistent radiograph obtained during this cultures, purified protein derivative radiologic findings and no clear hospital course. On her past for , and QuantiFERON etiology. The procedure was admission, similar findings were assay were also negative. Her uncomplicated, and no significant observed on her chest radiograph was within clinical fi ndings were observed. A (Fig 2A). Because of her history of normal limits, although her complete BAL sample was obtained and then previous pneumonia and the blood count 3 months before sent for a cytology review, where the completion of the ED workup, the indicated considerable peripheral sample was noted to have patient was admitted to the infectious eosinophilia (33.3% [reference range: considerable pulmonary eosinophilia disease service for hypoxia secondary 1%–4%]), which was not evaluated of 62% (normal .10%), and Charcot- to suspected recurrent bacterial and resolved by this reported Leyden crystals were present (Fig 3) pneumonia. admission to 1.5%. with no signs of parasitic larvae or fi Further laboratory evaluation during eggs. These ndings were consistent Because of the negative infectious fi the initial 24 hours of her with the ndings of hypersensitivity workup and persistent radiologic hospitalization included or acute eosinophilic findings, paired with a history of a comprehensive infectious and pneumonia. vaping that was similar to cases immunologic workup. The obtained reported in a recent public health With these cytologic findings and the test results included the following announcement from the Centers for comprehensive evaluation that ruled inflammatory markers: an Disease Control and Prevention, the out infectious etiologies, the patient erythrocyte sedimentation rate of pulmonary service was consulted. was started on systemic 34 mm/hour, a C-reactive protein The patient required 2 L of low-flow . Within 24 hours of level of 1.6 mg/L, a quantitative nasal cannula supplemental oxygen treatment, the patient was immunoglobulin G level of 584 mg/ dL (reference range for age 16–19 years: 549–1584 mg/dL), an immunoglobulin M level of 257 mg/ dL (reference range for age 16–19 years: 23–259 mg/dL), an immunoglobulin A level of 69 mg/dL (reference range for age 16–19 years: 61–348 mg/dL), an immunoglobulin E level of 413 mg/dL (reference range for age 16–19 years: 150–1000 UI/ FIGURE 2 mL), and a CD4/CD8 ratio of 1.5 A, Initial image 3 months before presentation revealing upper lobe patchy alveolar disease and hilar lymph node enlargement. B, More right-upper lobe disease with similar hilar lymph node en- (reference range: 1–2). The largement at the time of admission. C, Resolution of alveolar opacities and lymph node enlargement Legionella, Strongyloides, and 1 week into therapy.

Downloaded from www.aappublications.org/news by guest on September 29, 2021 2 MULL et al diagnosis, and for the cytologic examination, an eosinophilic percentage must be .25%.

Because eosinophilic pneumonia frequently mimics infectious pneumonia at presentation, it often leads to an inappropriate use of antibiotics in a disease process during which the mainstay of therapy consists of systemic corticosteroids. FIGURE 3 After appropriate therapy is initiated, A, Cytospin preparation (Wright-Giemsa stain, original magnification 3100) revealing eosinophilia. B, Image of a cell block section (hematoxylin and eosin, original magnification 3100) revealing eo- there is often rapid resolution of sinophilia with the Charcot-Leyden crystals. symptoms, as observed in the patient presented in this case.3

Through the example in this case, we successfully weaned off supplemental parasitic , such as intend to convey the potential risk of oxygen. She was discharged from the Strongyloides. Despite potential the unstudied and unregulated vaping hospital and prescribed a 2-week environmental exposure from and illicit tetrahydrocannabinol use course of corticosteroids, followed by residing on a farm, the workup that is currently popular among a prolonged steroid taper of an results for these infections were teenagers and young adults. For the additional 4 weeks. Although there negative in our patient. Other first time after several decades of was no concern for an infectious potential causes, including steady decline of cigarette smoking disease, the patient was seen in the eosinophilic granulomatosis with among 15- to 19-year-old infectious disease clinic one week polyangiitis, were ruled out during adolescents, the statistics have not after discharge to follow-up on the this workup. Through the diagnosis of changed significantly between 2015 serologies from her hospitalization. exclusion, a potential pulmonary and 2017. The proportion of Radiologic findings revealed the irritant via drug or inhaled toxins was adolescents who vaped at least 2 resolution of opacities and the determined. It is worth noting that in 20 days within a month increased lymphadenopathy while on a previous case series, 32 of 33 from 20% in 2017 to 28% in 2018.4 corticosteroid therapy (Fig 2). Long- patients were active smokers of As of October 1, 2019, the Centers for term follow-up with her pediatrician tobacco at disease onset, with 21 Disease Control and Prevention and pulmonary clinic was established. patients having started 1 month released a statement on nearly 1100 She reported the complete resolution before disease onset, suggesting cases reported from 48 different of symptoms within 2 weeks of a strong association between states and 18 confirmed death from 3 initiating therapy. Her physical the two. 15 states that suggested a potential examination findings were connection with the use of vaping unremarkable, with no adventitious This disease process that is generally (electronic ) in conjunction fi lung sounds. characterized by in ltration of with tetrahydrocannabinol use. Each into the and case exhibited the associated associated with acute onset of DISCUSSION symptoms and radiologic findings dyspnea, and fever can progress to consistent with this presented fi Idiopathic acute eosinophilic signi cant that patient.5,6 pneumonia is a relatively rare requires the use of invasive condition with an unclear etiology, mechanical ventilation or even After the negative result of the and it is even rarer with the presence extracorporeal membrane workup with the patient’s symptoms of associated bilateral hilar oxygenation. Radiologic imaging may of chest pain, dyspnea, and diarrhea, lymphadenopathy.1 Although the be useful for diagnostic purposes, coupled with the pertinent history of etiology is not always with chest radiographs typically vaping and tetrahydrocannabinol use, straightforward, the differential revealing reticular opacities the necessity of a bronchoscopy with diagnosis for this condition should be bilaterally and CT scans revealing BAL was indicated. A delay in an inclusive of fungal infections, such as ground-glass opacification in accurate diagnosis, compounded by Coccidioides immitis and less association with septal thickening. ineffective therapy of antibiotics, can commonly Histoplasma capsulatum, Ultimately, bronchoscopy with BAL is pose the serious risk of a potential while encompassing potential necessary for confirming the progression of a life-threatening

Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 145, number 4, April 2020 3 hypoxic respiratory failure, which 2. Kovalszki A, Weller PF. Eosinophilia. associated severe lung disease. Lancet was avoided in this patient.7 Prim Care. 2016;43(4):607–617 Respir Med. 2019;7(11):934–935 3. Akuthota P, Weller PF. Eosinophilic 6. Centers for Disease Control and . Clin Microbiol Rev. 2012; Prevention. Outbreak of lung injury ABBREVIATIONS 25(4):649–660 associated with the use of e-cigarette, or vaping, products. 2019. Available at: BAL: bronchioalveolar lavage 4. Hammond D, Reid JL, Rynard VL, et al. https://www.cdc.gov/tobacco/basic_ CT: computed tomography Prevalence of vaping and smoking information/e-cigarettes/severe-lung- ED: emergency department among adolescents in Canada, England, disease.html. Accessed October 5, 2019 and the United States: repeat national cross sectional surveys. BMJ. 2019;365: 7. Giovannini-Chami L, Blanc S, Hadchouel A, et al. Eosinophilic pneumonias in REFERENCES l2219 children: a review of the epidemiology, 1. Cottin V. Eosinophilic lung disease. Clin 5. Furlow B. US state governments diagnosis, and treatment. Pediatr Chest Med. 2016;37(3):535–556 investigate suspected vaping- Pulmonol. 2016;51(2):203–216

Downloaded from www.aappublications.org/news by guest on September 29, 2021 4 MULL et al Eosinophilic Pneumonia and Lymphadenopathy Associated With Vaping and Tetrahydrocannabinol Use Eric S. Mull, Guliz Erdem, Kathleen Nicol, Brent Adler and Richard Shell Pediatrics originally published online March 26, 2020;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2020/03/25/peds.2 019-3007 References This article cites 6 articles, 2 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2020/03/25/peds.2 019-3007#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): http://www.aappublications.org/cgi/collection/pulmonology_sub /Immunology http://www.aappublications.org/cgi/collection/allergy:immunology_s ub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 29, 2021 Eosinophilic Pneumonia and Lymphadenopathy Associated With Vaping and Tetrahydrocannabinol Use Eric S. Mull, Guliz Erdem, Kathleen Nicol, Brent Adler and Richard Shell Pediatrics originally published online March 26, 2020;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2020/03/25/peds.2019-3007

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2020 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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