Electronic cigarette or vaping product use–associated lung injury (EVALI) is a disease process that has become prevalent in the United States.1 The Centers for Disease Control and Prevention reported there have been almost 2700 cases of this condition in the United States as of January 14, 2020, with >50% of these patients aged ≤24.2 We present a 13-year-old boy with a history of functional abdominal pain who presented with recurrent episodes of nausea, emesis, periodic fevers, and severe episodic abdominal pain after a 12-month history of significant electronic cigarette use. On admission, he had severe abdominal pain and appeared anxious. A computed tomography scan of the abdomen was unremarkable, but a computed tomography scan of the chest demonstrated both multifocal ground-glass and crazy-paving pulmonary opacities bilaterally, with scattered septal thickening and dependent bibasilar opacities associated with volume loss. Inflammatory markers were significantly elevated, and cell counts were remarkable for leukocytosis and neutrophilia. The patient was ultimately diagnosed with EVALI and treated with intravenous methylprednisolone, resulting in improvement. This is an example of a case of EVALI in an adolescent, in which the presenting symptoms are largely gastrointestinal. It is important to keep EVALI in the differential diagnosis of patients who exhibit gastrointestinal symptoms, have markers of increased systemic inflammation, and endorse a history of vaping or are in the age range of electronic cigarette users. Although obtaining an accurate history of vaping can be challenging in the pediatric population, it is especially critical to do so.
Since their introduction to the US marketplace in 2007, electronic cigarettes (e-cigarettes) have become an increasingly popular method to use tobacco and marijuana.1,3,4 In 2014, it became the most popular method of tobacco use among American youth, and its popularity has only continued to soar.3 E-cigarette use increased among high school students from 1.5% (220 000 students) in 2011 to 20.8% (3.05 million students) in 2018.3 The general public has erroneously believed e-cigarettes to be a safe alternative to combustible cigarettes.4 As of January 14, 2020, there were close to 2700 cases of electronic cigarette or vaping product use–associated lung injury (EVALI) reported to the Centers for Disease Control and Prevention (CDC), the majority of which occurred in patients younger than the age of 25.2 In several case series and case reports, researchers have described concomitant gastrointestinal (GI) symptoms with EVALI, but there are a scarcity of reports in which researchers have described GI symptoms as the primary symptom of EVALI.
Case
A 13-year-old boy presented to the emergency department of hospital B with a 1-week history of worsening episodic abdominal pain and recurrent episodes of nausea; nonbloody, nonbilious emesis; nonbloody diarrhea; and periodic fevers. He lost 5 kg of weight in the month before presentation. Three months before presentation, he was admitted to hospital A for similar symptoms, including periodic, high-grade fevers and headache (Table 1). On presentation to hospital A, he had a respiratory rate of 24 breaths per minute and a pulse oximetry reading of 91% that was not treated with supplemental oxygen. Throughout admission at hospital A, he had significant elevation of inflammatory markers and an elevated white blood cell count (Table 1). Because of concern for inflammatory bowel disease, abdominal imaging was obtained. An abdominal ultrasound was unremarkable. An abdominal computed tomography (CT) scan was pertinent for mildly thickened loops of jejunum, dependent bibasilar atelectasis, and a left lower-lobe opacity. Chest radiography demonstrated mild vascular congestion. He was started on piperacillin and tazobactam before being switched to ciprofloxacin. He was also started on famotidine before being switched to pantoprazole. After an 8-day admission, he was discharged from hospital A on a course of ciprofloxacin to treat presumed enteritis and continued taking pantoprazole daily, as well as dicyclomine, as needed.
Laboratory Values Throughout Hospital Admissions
| Hospital A | Hospital B |
|---|---|
| Maximum temperature: 39.4°C | Erythrocyte sedimentation rate: 57 mm/h (reference range: 0–15 mm/h) |
| Erythrocyte sedimentation rate: 86 mm/h (reference range: 0–15 mm/h) | CRP: 225.3 mg/L (reference range: <10 mg/L) |
| CRP: 303 mg/L (reference range: <10 mg/L) | Aspartate aminotransferase: 189 U/L (reference range: 15–45 U/L) |
| Fecal calprotectin: 320 µg/g (reference range: <50 µg/g) | Alanine aminotransferase: 229 U/L (reference range: 15–55 U/L) |
| White blood cell count: 19.7 × 109/L (reference range: 4.5–13 × 109/L) | — |
| Hospital A | Hospital B |
|---|---|
| Maximum temperature: 39.4°C | Erythrocyte sedimentation rate: 57 mm/h (reference range: 0–15 mm/h) |
| Erythrocyte sedimentation rate: 86 mm/h (reference range: 0–15 mm/h) | CRP: 225.3 mg/L (reference range: <10 mg/L) |
| CRP: 303 mg/L (reference range: <10 mg/L) | Aspartate aminotransferase: 189 U/L (reference range: 15–45 U/L) |
| Fecal calprotectin: 320 µg/g (reference range: <50 µg/g) | Alanine aminotransferase: 229 U/L (reference range: 15–55 U/L) |
| White blood cell count: 19.7 × 109/L (reference range: 4.5–13 × 109/L) | — |
Laboratory values throughout the patient’s 2 hospitalizations. —, not applicable.
One month before presentation to hospital B, he underwent an upper GI series to evaluate his recurrent episodes of emesis and abdominal pain. The results were negative. He was scheduled to obtain an outpatient esophagogastroduodenoscopy and colonoscopy, but he presented to hospital B before the scheduled date of the procedure.
On presentation to hospital B, he was afebrile, hypertensive, and tachycardic, with an oxygen saturation of 97%. On examination, he was pale, irritable, delirious, and ill appearing but nontoxic. An abdominal examination was pertinent for diffuse tenderness with palpation, particularly in the left upper quadrant and epigastric regions. Complete blood cell count was notable for leukocytosis with neutrophilic predominance. Inflammatory markers were elevated (Table 1). A CT scan of the abdomen and pelvis revealed no evidence of fluid collections, abscesses, appendicitis, or inflammatory bowel disease. After obtaining blood and urine cultures, he was started on intravenous piperacillin and tazobactam and admitted. He became febrile to 39°C shortly after admission and defervesced with acetaminophen.
With symptom improvement on hospital day 2, he was to undergo bowel preparation for an esophagogastroduodenoscopy and colonoscopy. However, he developed abdominal pain, scaling 10 out of 10; pallor; tachypnea; and suprasternal retractions and had an episode of emesis. His oxygen saturation dropped to 75% on room air, and he was found to be hypertensive and tachycardic. A skin examination was pertinent for an evanescent, erythematous, nonpruritic, nonblanching macular rash distributed across his abdomen and chest (Fig 1). Supplemental oxygen was administered, and a rapid response was called. He received intravenous ketorolac, and a chest radiograph was notable for mild perihilar fullness and peribronchial thickening, with superimposed left lower-lobe pneumonia. The results of a respiratory pathogen panel were positive for rhinovirus and enterovirus. The esophagogastroduodenoscopy and colonoscopy were cancelled. A differential diagnosis was crafted, and neurology, pulmonology, infectious disease, and rheumatology subspecialists were consulted (Tables 2 and 3).
Photograph of the evanescent, erythematous, nonpruritic, nonblanching macular rash distributed across the patient’s abdomen and chest. This transient rash only appeared during episodes of abdominal pain and always resolved less than a minute after each appearance.
Photograph of the evanescent, erythematous, nonpruritic, nonblanching macular rash distributed across the patient’s abdomen and chest. This transient rash only appeared during episodes of abdominal pain and always resolved less than a minute after each appearance.
Differential Diagnosis
| Infection | Autoinflammatory Syndromes |
|---|---|
| Bacterial infection | Familial Mediterranean fever |
| Viral infection | Hyper-IgD syndrome |
| Parasitic infection | Tumor necrosis factor receptor-associated periodic syndrome |
| Fungal infection | Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome |
| Systemic lupus erythematosus | |
| Acute intermittent porphyria | |
| Vasculitis | |
| Juvenile idiopathic arthritis | |
| Hemophagocytic lymphohistiocytosis |
| Infection | Autoinflammatory Syndromes |
|---|---|
| Bacterial infection | Familial Mediterranean fever |
| Viral infection | Hyper-IgD syndrome |
| Parasitic infection | Tumor necrosis factor receptor-associated periodic syndrome |
| Fungal infection | Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome |
| Systemic lupus erythematosus | |
| Acute intermittent porphyria | |
| Vasculitis | |
| Juvenile idiopathic arthritis | |
| Hemophagocytic lymphohistiocytosis |
Differential diagnosis for this patient ultimately diagnosed with EVALI. IgD, immunoglobulin D.
Consultation Recommendations
| Service | Findings |
|---|---|
| Neurology | |
| EEG: unremarkable | |
| MRI: unremarkable | |
| Copper level to rule out Wilson disease: slightly elevated (1.48 μg/mL, reference range: 0.75–1.45 μg/mL) | |
| Pulmonology | |
| Differential diagnosis: systemic lupus erythematosus, granulomatosis with polyangiitis, antiglomerular basement membrane antibody disease, and pulmonary embolism | |
| D-dimer: 192 ng/mL (reference range: <230 ng/mL) | |
| Chest CT scan | |
| Multifocal ground-glass opacities and crazy-paving pulmonary opacities at the level of the secondary pulmonary lobule throughout both lungs | |
| Scattered septal thickening and dependent bibasilar opacities associated with volume loss | |
| Antinuclear antibody result: negative | |
| Antineutrophil cytoplasmic antibodies result: positive, perinuclear pattern | |
| Antiglomerular basement membrane antibody result: negative | |
| Antiphospholipid antibody panel | |
| Activated partial thromboplastin time lupus anticoagulant result: positive | |
| Anticardiolipin antibodies result: negative | |
| β-2 glycoprotein 1 antibodies result: negative | |
| Anti-DNA antibody result: negative | |
| Complement C3: 158 mg/dL (reference range: 88–171 mg/dL) | |
| Complement C4: 69.5 mg/dL (reference range: 15–48 mg/dL) | |
| Infectious disease | |
| Blood culture result: negative | |
| Urine culture result: negative | |
| Rheumatology | |
| Ferritin: 159 ng/mL (reference range: 10–300 ng/mL) | |
| Antinuclear antibody result: negative | |
| Extractable nuclear antigen result: negative | |
| Anti–double-stranded DNA antibody result: negative | |
| Complement C3: 158 mg/dL (reference range: 88–171 mg/dL) | |
| Complement C4: 69.5 mg/dL (reference range: 15–48 mg/dL) | |
| Urine protein and creatine ratio: 0.208 | |
| Angiotensin-converting enzyme: 16 U/L (reference range in adults: 16–85 U/L) |
| Service | Findings |
|---|---|
| Neurology | |
| EEG: unremarkable | |
| MRI: unremarkable | |
| Copper level to rule out Wilson disease: slightly elevated (1.48 μg/mL, reference range: 0.75–1.45 μg/mL) | |
| Pulmonology | |
| Differential diagnosis: systemic lupus erythematosus, granulomatosis with polyangiitis, antiglomerular basement membrane antibody disease, and pulmonary embolism | |
| D-dimer: 192 ng/mL (reference range: <230 ng/mL) | |
| Chest CT scan | |
| Multifocal ground-glass opacities and crazy-paving pulmonary opacities at the level of the secondary pulmonary lobule throughout both lungs | |
| Scattered septal thickening and dependent bibasilar opacities associated with volume loss | |
| Antinuclear antibody result: negative | |
| Antineutrophil cytoplasmic antibodies result: positive, perinuclear pattern | |
| Antiglomerular basement membrane antibody result: negative | |
| Antiphospholipid antibody panel | |
| Activated partial thromboplastin time lupus anticoagulant result: positive | |
| Anticardiolipin antibodies result: negative | |
| β-2 glycoprotein 1 antibodies result: negative | |
| Anti-DNA antibody result: negative | |
| Complement C3: 158 mg/dL (reference range: 88–171 mg/dL) | |
| Complement C4: 69.5 mg/dL (reference range: 15–48 mg/dL) | |
| Infectious disease | |
| Blood culture result: negative | |
| Urine culture result: negative | |
| Rheumatology | |
| Ferritin: 159 ng/mL (reference range: 10–300 ng/mL) | |
| Antinuclear antibody result: negative | |
| Extractable nuclear antigen result: negative | |
| Anti–double-stranded DNA antibody result: negative | |
| Complement C3: 158 mg/dL (reference range: 88–171 mg/dL) | |
| Complement C4: 69.5 mg/dL (reference range: 15–48 mg/dL) | |
| Urine protein and creatine ratio: 0.208 | |
| Angiotensin-converting enzyme: 16 U/L (reference range in adults: 16–85 U/L) |
Recommendations shared by the neurology, pulmonology, infectious disease, and rheumatology services.
C-reactive protein (CRP) throughout his admission reached a peak of 448.1 mg/L on hospital day 4 before trending downward. Liver function tests peaked on hospital day 5 (Table 1). A chest CT scan without contrast was notable for multifocal ground-glass and crazy-paving pulmonary opacities seen at the level of the secondary pulmonary lobule throughout both lungs, as well as scattered septal thickening and dependent bibasilar opacities (Fig 2). On further review of history by the pulmonology team, it was discovered that the patient had been vaping multiple times a day for the past 12 months before admission to hospital B. He used the JUUL brand of e-cigarettes, primarily the mint flavor pods, and was changing the pods every 2 days. Although the patient denied tetrahydrocannabinol usage, urine toxicology results were positive for cannabinoids. As a result of these findings, it was determined that he may have vaping-related lung disease.
Two views of a chest CT scan taken during admission. The scan revealed findings described as multifocal ground-glass and crazy-paving pulmonary opacities seen at the level of the secondary pulmonary lobule throughout both lungs. Scattered septal thickening and dependent bibasilar opacities were also appreciated on imaging.
Two views of a chest CT scan taken during admission. The scan revealed findings described as multifocal ground-glass and crazy-paving pulmonary opacities seen at the level of the secondary pulmonary lobule throughout both lungs. Scattered septal thickening and dependent bibasilar opacities were also appreciated on imaging.
He was started on 1 mg/kg per day of intravenous methylprednisolone and treated with a nicotine patch for potential nicotine withdrawal. He responded to corticosteroid administration in the setting of vaping cessation, with reduction of abdominal pain and resolution of nausea and emesis. He was transitioned to oral corticosteroids and discharged from hospital B on a 10-day course of prednisone after an 8-day hospital stay. At discharge, his respiratory rate was 18 breaths per minute and oxygen saturation was 99%. A repeat chest CT scan 1 month after discharge revealed minimal residual, scattered, subsegmental ground-glass opacities, with nearly complete resolution of previously seen pulmonary parenchymal and interstitial lung disease (Fig 3). The patient has abstained from vaping since hospital discharge and has subsequently regained weight.
Two views of a repeat chest CT scan taken 1 month after discharge posttreatment. The scan revealed minimal residual, scattered, subsegmental ground-glass opacities, with nearly complete resolution of previously seen pulmonary parenchymal and interstitial lung disease.
Two views of a repeat chest CT scan taken 1 month after discharge posttreatment. The scan revealed minimal residual, scattered, subsegmental ground-glass opacities, with nearly complete resolution of previously seen pulmonary parenchymal and interstitial lung disease.
Discussion
The number of EVALI cases requiring hospitalization has continued to decline since its peak in incidence in the fall of 2019.2 Much of the pathophysiology underlying EVALI remains unknown. Use of e-cigarettes containing tetrahydrocannabinol and vitamin E acetate have been linked to EVALI cases reported to the CDC and are thought to be playing a role in the outbreak.2 The main constituents of e-cigarette solutions are vegetable glycol, propylene glycol, flavorings, and nicotine.5 These substances are aerosolized at extremely high temperatures (vegetable glycol: 290°C, propylene glycol: 188°C, and nicotine: 247°C), the ingestion of which have been linked to chemical and/or lipoid pneumonitis in adults.6,7 Other types of lung injury associated with EVALI include acute eosinophilic pneumonia, hypersensitivity pneumonitis, organizing pneumonia, and diffuse alveolar hemorrhage.8–10 There have been concerns about the level of nicotine addiction in middle and high school students, given the high concentration of nicotine present in most e-cigarette solutions.3
Patients with a diagnosis of EVALI present with a wide range of symptoms, including cough, shortness of breath, fever, headache, dizziness, chest pain, nausea, vomiting, and abdominal pain.5,8,11–13 These symptoms may persist for days to weeks before care is sought.14 In a report on a series of patients in Wisconsin and Illinois who developed EVALI, GI symptoms were some of the most common symptoms noted.8
Although, researchers highlight respiratory symptoms in many of the case reports regarding EVALI in the literature, there are a scarcity of reports in which researchers focus specifically on the GI presentation. This patient met the probable case definition of EVALI, as defined by the CDC (Table 4).11,12,14–16 Common laboratory findings in EVALI include leukocytosis with associated neutrophilia, elevated levels of transaminases, and elevated inflammatory markers, all of which were found in this patient.8,11,13,14,17 It is important to note that although he was diagnosed with EVALI, he presented with mainly GI symptoms on 2 separate occasions. It was only after his desaturation episode that a chest CT scan was ordered and that his pulmonary findings were revealed.
EVALI Primary Case Definitions Established by the CDC
| Confirmed Case | Probable Case |
|---|---|
| Using an e-cigarette (vaping) or dabbinga 90 d before symptom onset AND | Using an e-cigarette (vaping) or dabbinga 90 d before symptom onset AND |
| Pulmonary infiltrate, such as opacities, on plain-film chest radiograph or ground-glass opacities on chest CT scan AND | Pulmonary infiltrate, such as opacities, on plain-film chest radiograph or ground-glass opacities on chest CT scan AND |
| Absence of pulmonary infection on initial workup. Minimum criteria are: | Infection identified via culture or polymerase chain reaction, but the clinical teamb believes this infection is not the sole cause of the underlying lung injury, OR minimum criteria to rule out pulmonary infection are not met (testing not performed), and the clinical teamb believes infection is not the sole cause of the underlying lung injury AND |
| 1. A negative respiratory viral panel result AND | No evidence in the medical record of alternative, plausible diagnoses (eg, cardiac, rheumatologic, or neoplastic process). |
| 2. A negative influenza polymerase chain reaction or rapid test result, if local epidemiology supports influenza testing AND | |
| 3. All other clinically indicated respiratory infectious disease testing (eg, urine antigen for Streptococcus pneumoniae and Legionella, sputum culture if productive cough, bronchoalveolar lavage culture if done, blood culture, HIV-related opportunistic respiratory infections if appropriate) is negative AND | |
| No evidence in the medical record of alternative, plausible diagnoses (eg, cardiac, rheumatologic, or neoplastic process). |
| Confirmed Case | Probable Case |
|---|---|
| Using an e-cigarette (vaping) or dabbinga 90 d before symptom onset AND | Using an e-cigarette (vaping) or dabbinga 90 d before symptom onset AND |
| Pulmonary infiltrate, such as opacities, on plain-film chest radiograph or ground-glass opacities on chest CT scan AND | Pulmonary infiltrate, such as opacities, on plain-film chest radiograph or ground-glass opacities on chest CT scan AND |
| Absence of pulmonary infection on initial workup. Minimum criteria are: | Infection identified via culture or polymerase chain reaction, but the clinical teamb believes this infection is not the sole cause of the underlying lung injury, OR minimum criteria to rule out pulmonary infection are not met (testing not performed), and the clinical teamb believes infection is not the sole cause of the underlying lung injury AND |
| 1. A negative respiratory viral panel result AND | No evidence in the medical record of alternative, plausible diagnoses (eg, cardiac, rheumatologic, or neoplastic process). |
| 2. A negative influenza polymerase chain reaction or rapid test result, if local epidemiology supports influenza testing AND | |
| 3. All other clinically indicated respiratory infectious disease testing (eg, urine antigen for Streptococcus pneumoniae and Legionella, sputum culture if productive cough, bronchoalveolar lavage culture if done, blood culture, HIV-related opportunistic respiratory infections if appropriate) is negative AND | |
| No evidence in the medical record of alternative, plausible diagnoses (eg, cardiac, rheumatologic, or neoplastic process). |
Official primary case definitions used to diagnose EVALI. Patients who meet the criteria described in the table in the setting of leukocytosis with associated neutrophilia, elevated levels of transaminases, and elevated inflammatory markers have an increased likelihood of being diagnosed with EVALI. —, not applicable.
Using an electronic device (eg, electronic nicotine delivery system [ENDS], electronic cigarette, e-cigarette, vaporizer, vape[s], vape pen, dab pen, or other device) or dabbing to inhale substances (eg, nicotine, marijuana, THC, THC concentrates, CBD, synthetic cannabinoids, flavorings, or other substances).
Clinical team caring for the patient.
The pathophysiology of EVALI on the GI system has not been clearly described. There could be a correlation between the amount of nicotine or tetrahydrocannabinol products found in vaping devices and the severity of the GI symptoms found in EVALI. One JUUL pod has been found to have as much nicotine as a pack of 20 cigarettes.1 Nicotine poisoning has been linked to symptoms, such as nausea, vomiting, and abdominal pain, whereas nicotine withdrawal has been linked to abdominal discomfort and nausea.6,18 Tetrahydrocannabinol has also been associated with GI symptoms.19 In addition, nausea and vomiting have been widely reported in recent reports regarding EVALI and in a past study comparing the number of adverse health effects reported to poison control centers due to either e-cigarette or conventional cigarette use.6,8,11,13,14,17,20,21 Various substances found in the aerosolized liquids of e-cigarettes may potentially cause inflammation and injury in the GI system.6 To truly determine the cause of the GI symptoms found in EVALI, further research is needed.
In several case reports, researchers have detailed success in treating EVALI with corticosteroids, supplemental oxygen, mechanical ventilation, and extracorporeal membrane oxygenation, but standard guidelines for treating EVALI have not been established.8,11,12,14,17 Antibiotics and antiviral therapy have not proven to be effective in treating EVALI.8,12,14 The CDC has stated that corticosteroids could be helpful in treating EVALI once other disease processes have been ruled out.11 Corticosteroid therapy may have contributed in reversing the inflammation in our patient’s GI tract and his lungs. It is unclear whether vaping cessation alone would have led to the same result.
Conclusions
In the case presented in this report, we highlight a presentation of EVALI that was primarily GI in nature. Although respiratory symptoms have commonly been reported, it is important to remember that patients with EVALI can initially present with only abdominal symptoms before developing respiratory symptoms later in the course of the illness. As we continue to better understand the effects of vaping on the human body, pediatric providers should have a low threshold for considering EVALI as a cause of their patient’s GI and pulmonary symptoms.
Acknowledgments
We thank Dr William Adam Gower for his review of the article and for forming relationships that were integral to the submission of this article. We also thank Dr Francisco Sylvester for his contribution to this article.
Dr Wekon-Kemeni drafted the initial manuscript and performed significant amounts of data acquisition and interpretation; Dr Santhanam assisted with data acquisition and organization; Drs Halani, Bradford, and Loughlin assisted with data analysis and interpretation; and all authors critically reviewed and revised of the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
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