An adolescent female patient presenting with subacute onset of dysphagia and hoarseness underwent a direct laryngoscopy, which revealed epiglottitis. After 2 hospitalizations and multiple consultations and biopsies, all infectious testing results for viral, bacterial, fungal, and acid-fast bacilli etiologies were negative. The patient’s use of electronic cigarettes was the only exposure elicited with a likely role in her presentation. This case, combined with the growing body of evidence revealing the toxic effects of vaping and the increasing use of electronic cigarettes among adolescent patients, highlights the many unknowns and risks regarding the biological effects of this practice.
A previously healthy 15-year-old girl with no history of asthma, chronic respiratory illness, or inhaled medication use presented to an outside emergency department with complaints of acute respiratory distress and severe dysphagia. Her symptoms started subacutely 2 months before with mild hoarseness and increased throat clearing. Over the next 3 to 4 weeks, her symptoms evolved to include dysphagia (including a sensation that food was stuck in her throat), early-morning voice loss, episodes of regurgitation, and food avoidance. Her pediatrician attributed her symptoms to allergies and prescribed loratadine, which had no effect. Three weeks later, she presented to an urgent care center with similar symptoms and was prescribed a 3-day course of prednisone. Her symptoms temporarily improved, but 2 days after completing the steroid course, she worsened, feeling “as if she were breathing through a straw,” prompting the emergency department visit. She received intravenous dexamethasone, inhaled racemic epinephrine, and intravenous ampicillin and sulbactam. Results of both a rapid group A Streptococcus test and monospot test were both negative. Her respiratory complaints prompted a bedside laryngoscopy by Otolaryngology, revealing moderately severe edema of the epiglottis and arytenoids. She was transferred to our hospital, a pediatric quaternary care facility. The pediatric otolaryngology team repeated the laryngoscopy and again noted “moderate edema of the epiglottis extending along the aryepiglottic folds” and “mild/moderate edema of the hypopharyngeal mucosa with partial obstruction of the airway at the level of the epiglottis. Mucosa is pink with scattered area of thick chartreuse mucus draped over epiglottis.” Cultures were not obtained because of the concern for potentiating airway compromise. She was admitted to the PICU.
Infectious Diseases was consulted on the day of admission. A detailed history did not reveal any personal or family history suggestive of an autoimmune disorder or immunodeficiency. Physical examination features were not supportive of an abscess or viral infection. Fever was absent throughout her illness, although previous treatment with steroids may have masked a febrile response. She had received all immunizations for her age and had no history of travel or animal exposures. She denied sexual activity, illicit substance use, traditional cigarette use, or secondhand smoke exposure, but admitted to using a JUUL, an electronic cigarette (e-cigarette). She reported at least 3 to 5 uses with friends over 1 to 2 months with different fruit- or candy-flavored cartridges, none loaded with tetrahydrocannabinol, with the last use ∼2 weeks before symptom onset.
The result of a neck computed tomography scan was consistent with epiglottitis, without focal abscess. Otolaryngology aspirated a sample of fluid from her epiglottic region for bacterial and fungal cultures; final culture results yielded only normal respiratory flora. A nasopharyngeal swab specimen was tested for respiratory pathogens by using a multiplex polymerase chain reaction panel, including human rhinovirus and enterovirus, respiratory syncytial virus A and B, influenza A and B, parainfluenza 1 to 4, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia; all test results were negative. Results for serologies for cytomegalovirus, Epstein-Barr virus, HIV, and rapid plasma reagent were negative. Results of throat swabs for gonorrhea and Chlamydia were negative. The total peripheral white blood cell count was mildly elevated, but the C-reactive protein level, erythrocyte sedimentation rate, and complete metabolic panel were normal. She remained afebrile throughout her stay and slowly improved symptomatically. She transitioned to oral amoxicillin and clavulanate and was discharged from the hospital on hospital day 7 to complete a 10-day course of antibiotics.
One day after discharge, she developed odynophagia and noted white streaks on her pharyngeal mucosa. She returned for evaluation, and her examination suggested possible candidal infection. A mucosal swab was sent for herpes simplex virus polymerase chain reaction testing, and throat swabs were sent for repeat bacterial and fungal culture. Oral fluconazole and nystatin rinses were started, and she was readmitted to the hospitalist service. Within 24 hours of admission, she developed a diffuse body rash that was erythematous, blanching, papular, and nonpruritic. Infectious Diseases, Otolaryngology, Dermatology, and Rheumatology were consulted, and the differential diagnosis was broadened to include systemic inflammatory conditions, drug reaction, and unusual presentations of common disease processes. Dermatology suspected her rash to be a β-lactam antibiotic drug reaction, and amoxicillin and clavulanate was discontinued. With low suspicion for a bacterial process, no further antibiotics were administered, and her rash gradually resolved. Laboratory and clinical evaluation for rheumatologic disorders, including antinuclear antibody, antineutrophil cytoplasmic antibody screen, complement protein C3 and C4 levels, anti-proteinase-3, and myeloperoxidase antibodies, were not consistent with systemic vasculitis, sarcoidosis, or polychondritis. Repeat throat cultures yielded normal respiratory flora, and herpes simplex virus testing results were negative. Given the ongoing diagnostic uncertainty, biopsies of her oropharynx and epiglottis were obtained. With no yeast forms present on the initial review of the biopsy specimen or any cultures, nystatin and fluconazole were discontinued. After the biopsy, she slowly improved symptomatically and was discharged from the hospital on hospital day 6. In the year period since her presentation and full recovery, the patient has not returned to our institution for subsequent or recurrent episodes or other symptoms; it is not known if she continues to practice vaping.
Final cultures from biopsies yielded only normal flora. The final pathology of the samples from her arytenoid and soft palate revealed only ulcerated squamous mucosa with marked acute inflammation and reactive epithelial changes with abundant suppurative debris. The pathology from her tongue revealed similar reactive squamous mucosal changes with focal erosions. There was no evidence of fungal organisms, viral inclusion bodies, other infectious agents, or malignancy. Despite multiple detailed histories by several consulting services, the only plausible trigger for her presenting symptoms and findings was inhalation of chemical vapor via e-cigarette use. Her clinical course and biopsy findings were highly suspicious for direct chemical injury and/or subsequent inflammatory reaction. Without knowing the precise cartridges she used the exact exposure is unknown, although as we discuss in the following section, e-vapors can contain a myriad of potentially toxic substances.
Epiglottitis is an acute, life-threatening condition classically associated with infection. It is part of the differential diagnosis of any febrile child presenting with signs of respiratory distress involving the upper airway, along with tracheitis, croup, and peritonsillar or retropharyngeal abscess. Although Haemophilus influenzae type b is characteristically associated with epiglottitis, widespread routine childhood vaccination has led to a shift in epidemiology. The incidence of epiglottitis due to H influenzae type b has fallen, in some studies by 90%.1–4 Other organisms, such as streptococci, staphylococci, Moraxella, and other types of Haemophilus, are more common etiologies.1–5 Additionally, the age of affected patients has shifted from school age to adolescence and adulthood.1–3,5
Although age and etiology have shifted, initial management remains focused on rapid assessment, airway management, imaging or direct visualization of anatomy, and antibiotic therapy.4,5 Empirical therapy with ceftriaxone or a combination β-lactam and β-lactamase inhibitor is suggested.1,2,4
E-cigarettes, also known as vape pens, are devices designed to deliver nicotine (or other substances) for inhalation via aerosolization of an often flavored liquid.6–9 They are frequently marketed as a healthier alternative to smoking tobacco products.6,10,11 Use of these devices, JUUL in particular, has become increasingly prevalent in the adolescent population,9,11,12 and there is mounting evidence describing their toxicities and health risks,7–9,13,14 including potential microbial contamination.15
Data obtained from the 2011–2018 National Young Tobacco Survey revealed that e-cigarette use among US middle and high school students is on the rise. In 2018, 20.8% of all high school students and 4.9% of middle school students admitted to using the devices, making them the most commonly used tobacco product in those age groups.16 A longitudinal study of Connecticut high school students found that the use of e-cigarettes among teenagers was associated with an increased odds ratio of future traditional cigarette use.17
In adults, the use of e-cigarettes with nicotine-containing solutions may decrease the use of traditional cigarettes.10,18 Because the amount of nicotine delivered by each device can be adjusted, their use can decrease symptoms of nicotine withdrawal.10 Although some data suggest that overall, e-cigarettes may be less cytotoxic than traditional cigarettes, the full toxicological effects are not fully understood.8
In a review of studies analyzing the vapor produced, one group reported that nicotine levels fluctuated widely between “puffs” from the same cartridges and that vapor was found to contain substances similar to those found in traditional cigarette smoke, including heavy metals, tobacco alkaloids, volatile organic compounds, and aldehydes, many of which have potential or known detrimental health effects.6,13 Additionally, the nicotine levels in the vapor from some products were on par with those produced from traditional cigarettes.14
As work continues to understand the chemical exposures associated with e-cigarette use, researchers are also investigating its biological effects. Vaping liquid, with or without nicotine, can cause inflammatory changes in nasal cell mucosa19 and cytotoxic effects in other cell types20,21 through the oxidants and reactive oxygen species, which are produced in varying quantities from different flavors of fluid (higher levels detected in fruit- and candy-based flavors).22 These oxidative stresses may explain the increased secretion of pro-inflammatory cytokines,7,19,22,23 the observed increased rates of viral replication, and decreased antimicrobial activity of neutrophils and macrophages.7,24 Unsurprisingly, e-cigarette use causes immunosuppression in the nasal mucosa at a level consistent with traditional cigarettes.25 E-cigarette users also have an increased prevalence of mucosal lesions, including nicotine stomatitis, hairy tongue, and angular cheilitis, similar to former tobacco smokers.26 In adult smokers, after 5 minutes, e-cigarette use increased airway resistance and decreased fractional exhaled nitric oxide.27 An adolescent study found potentially carcinogenic compounds in the urine of e-cigarette users.28 It is reasonable to suspect that there is potential for allergenicity as well, although little direct research has been published on that topic.
In an adolescent with signs and symptoms of subacute epiglottis, the differential should expand beyond infectious etiologies. E-cigarettes are increasingly being used by our adolescent patients and should be a consideration in the evaluation of ororespiratory complaints.
Dr Bozzella performed the initial chart and literature reviews and wrote the initial draft of the case report; Dr Magyar contributed to the hospital summary and the discussion of the available literature; Drs DeBiasi and Ferrer provided supervision for the chart reviews and provided critical editing and revision to the final drafts of the report; and all authors approved the final manuscript as submitted.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.