Open Forum Infectious Diseases

REVIEWARTICLE

Acute Epiglottitis in the Immunocompromised Host:

Case Report and Review of the Literature
Cheng Chen,1 Mukil Natarajan,2 David Bianchi,3 Georg Aue,4 and John H. Powers5
1University of Cambridge, Cambridge, United Kingdom; 2Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute

of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3National Institute on Deafness and Communication Disorders, National
Institutes of Health, Bethesda, Maryland; 4Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland;
5Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland

We present a case of acute epiglottitis in a 16-year-old with severe aplastic anemia. He was admitted with a history suggestive of a severe
upper airway infection and an absolute neutrophil count of 0 per cubic millimeter. Despite his immunocompromised state, he presented
with the classical signs and symptoms of epiglottitis. We review here the presentation and comorbidities of immuno-compromised
patients with epiglottitis. In addition, the appropriate choice of empirical antibiotic therapy is important for the man-agement of
epiglottitis in immunocompromised patients, especially in the post–Haemophilus influenza type B vaccination era. In our patient,
Enterobacter cloacae was isolated from endoscopically directed throat cultures, and treatment was successful without the need for
intubation. The current literature suggests that in immunocompromised patients, particularly those who are neutropenic, there is a
potentially wide range of organisms, both bacterial and fungal, that may play a role in the pathology of acute epiglottitis.
Keywords. aplastic anemia; Enterobacter cloacae; epiglottitis; immunocompromise; malignancy; neutropenia.

Epiglottitis is a life-threatening condition, characterized by acute here a case of acute epiglottitis with Enterobacter cloacae in a
inflammation of the supraglottic region of the orophar-ynx, with 16-year-old male with severe aplastic anemia with a review of
the potential risk of fatal airway obstruction. Effective the literature, exploring the clinical presentation, outcomes,
management requires rapid diagnosis, airway management, and and microbial etiologies in immunocompromised patients.
treatment of the causative agent. Epiglottitis is an inflamma-tory
disease, yet it still occurs in patients whose inflammatory CASE REPORT
responses are blunted by neutropenia and immunocompro-mised A 16-year-old Jamaican male presented to his local hospital with
patients. Although these patients are known to be more fatigue, epistaxis, and dyspnea. He had no significant past
susceptible to infections, it has yet to be demonstrated whether medical history or family history of serious medical illness. Initial
epiglottitis in immunocompromised patients presents differently blood tests showed a white cell count of 1900 per cubic
or follows a different clinical course. Previously, 75%–90% of millimeter (absolute neutrophil count 90 per cubic millimeter),
cases of epiglottitis were caused by Haemophilus influenza type B hemoglobin 5.3 g per deciliter, and platelets 36 000 per cubic
(Hib). Vaccination, introduced in 1985, significantly reduced the millimeter. He was hospitalized 3 months later, and bone mar-row
incidence of epiglottitis [1]. Cases presenting today show a mixed biopsy performed 1 month into the admission was con-sistent
microbial etiology, with a relative increased incidence in older with aplastic anemia. He was discharged after receiving packed
children [2]. Epiglottitis in immunocompromised patients may be red blood cells, pooled platelet transfusions, and intra-venous
caused by a wider variety of organisms than epiglotti-tis in antibiotics of unknown type, dose, and duration.
immunocompetent children and adolescents. We present Five months after initial presentation, he was admitted to the
US National Institute of Health Clinical Center with a 1-week
history of fever, dysphagia, odynophagia, cough, and scant
Received 4 December 2017; editorial decision 9 February 2018; accepted 14 February 2018. hemoptysis. He was enrolled in an institutional review board–
Correspondence: J. H. Powers III, MD, Clinical Research Directorate/Clinical Monitoring Research
approved clinical research protocol, and informed con-sent was
Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, 5601 Fishers
Lane, Room 4D50, Bethesda, MD 20892 (john.powers@nih.gov). obtained and documented. On examination, his body temperature
o
Open Forum Infectious Diseases® was 38.2 C, blood pressure 126/91 mm Hg, heart rate 88 beats
© The Author(s) 2018. Published by Oxford University Press on behalf of Infectious
Diseases Society of America. This is an Open Access article distributed under the terms per minute, respiratory rate 18 breaths per min-ute, and oxygen
of the Creative Commons Attribution-NonCommercial-NoDerivs licence saturation 98% breathing ambient room air. He appeared thin and
(http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial
lethargic, but was not in acute distress, and was spitting blood-
reproduction and distribution of the work, in any medium, provided the original work is not
altered or transformed in any way, and that the work is properly cited. For commercial re- tinged saliva into a cup. He denied dyspnea and was phonating
use, please contact journals.permissions@oup.com DOI: 10.1093/ofid/ofy038 normally. He was tender diffusely around

Epiglottitis in the Immunocompromised • OFID • 1

Figure 1. Topogram and sagittal view of the neck on computerized tomography scan performed on the day of presentation showing
classic “thumbprint” sign due to swelling of epiglottis.

the neck. There were no other abnormal examination findings. right tonsillar area isolated Enterobacter cloacae resistant to
His laboratory findings showed a white cell count of 1430 per cefa-zolin, cefoxitin, ceftazidime, ceftriaxone, co-amoxiclav,
cubic millimeter (absolute neutrophil count 0 per cubic mil- ampi-cillin, aztreonam, and piperacillin/tazobactam;
limeter), hemoglobin 10.7 g per deciliter, and platelets 33 000 per subsequently, he was prescribed meropenem (750 mg, every 8
cubic millimeter. Radiographic imaging showed a classic hours). He clinically improved with this antibiotic regimen,
“thumbprint” sign at the site of the epiglottis (Figure 1). Direct and follow-up laryngoscopy 17 days later showed significant
laryngoscopy showed an erythematous, enlarged, and pos-teriorly improvement in the appearance of the epiglottis (Figure 3).
ptotic epiglottis that was not necrotic (Figure 2). The patient
immediately received intravenous piperacillin/tazo-bactam (3.375 DISCUSSION
g, every 6 hours), vancomycin (400 mg, every 6 hours), and
Epiglottitis is a medical emergency, with the potential serious
micafungin (100 mg, once daily), as well as intrave-nous
complication of airway compromise secondary to the inflam-
dexamethasone (4 mg, every 6 hours) and nebulized race-mic
matory response to infection in the upper airway. It is a clinical
epinephrine (0.5 mL of 2.25%, every 6 hours). He clinically
diagnosis characterized by odynophagia, stridor, drooling, and a
improved while being closely monitored in the intensive care
“hot potato” voice. The patient may also show signs of sep-sis in
unit; there was no need for definitive airway management by
cases of severe infection. Direct fibreoptic laryngoscopy shows an
intubation. Blood cultures showed no growth, but endoscop-ically
inflamed and swollen epiglottis; however, examination should be
directed cultures from directly observed exudate on the
done with caution as it can lead to rapid airway com-promise.
Radiology, including lateral x-ray of the cervical spine or
computerized tomography, may aid in diagnosis by showing a
classic “thumbprint sign,” evidence of soft tissue swelling of the
epiglottis. While antimicrobials are part of treatment, additional
support, including steroids [3], is used to reduce the inflamma-
tion, and intubation/tracheostomy under carefully monitored
conditions maintains the collapsing airway. In cases where there
is abscess formation, surgical debridement may also be neces-
sary. Isolated necrosis of the epiglottis also can occur [29].
Demographics of Epiglottitis in the Immunocompromised
We performed a literature search evaluating epiglottitis in the
immunocompromised host, which yielded 48 published cases
from 34 published reports (Table 1) [4–37 ]. Patient ages ranged
from 4 months to 70 years, with a mean age of 35.5 years, with 23
male and 25 female patients. Twenty-four had immuno-
compromise secondary to cancer and/or chemotherapy, and 12
patients were positive for HIV. The remainder had a variety of
Figure 2. Laryngoscopy image of epiglottis showing causes of immunocompromise, including Epstein-Barr virus
erythematous and enlarged epiglottis. (EBV) mononucleosis, renal transplantation, and drug-induced

2 • OFID • Chen et al
 In our patient, there was no stridor or pus on laryngoscopy.
Neutrophils are the key effector cells of the innate immune
system, so when patients become neutropenic (<500 per cubic
millimeter), they become susceptible to infections. Sore throat
due to mucositis may be common in patients receiving chemo-
therapy for malignancy, but there should be a high index of
suspicion if symptoms worsen or progress to include difficulty
swallowing, clearing secretions, or breathing. We postulate that
there are 3 reasons why, despite the ongoing inflammation and
medical intervention, this patient’s airway remained competent
without any need for airway support. First is that, anatomic-ally,
this 16-year-old’s head and neck anatomy may be different
compared with younger children with Hib epiglottitis. There is
more space for the swelling to expand before impinging on the
airway. Second, there is an inverse correlation between patient
age and risk of laryngospasm [38]. Third, the severity of his
Figure 3. Follow-up laryngoscopy image showing significant immunocompromise from aplastic anemia may have limited the
improvement in ery-thema and swelling. extent of host response, thereby presenting a lower-than-ex-
pected degree of inflammation and swelling.
neutropenia (see the footnote to Table 1). Of these 48 patients, 18 Clinical Course, Treatment, and Outcomes of
were neutropenic, defined by an absolute neutrophil count and/or Epiglottitis in the Immunocompromised
The majority of cases were empirically treated initially with
total white cell count of less than 1000 per cubic millim-eter. The
broad-spectrum antibiotics. Of the 21 patients in whom fun-gal
range of underlying causes of immunocompromise in neutropenic
organisms were isolated, 7 empirically received antifungal agents,
patients was similar to that in non-neutropenics.
including 2 patients with concomitant neutropenia. As many of
Clinical Presentation of Epiglottitis in the Immunocompromised
the organisms isolated are part of the normal oro-pharyngeal
Epiglottitis has previously been reported in 1 other patient
flora, especially Candida sp, their role in infection vs colonization
with aplastic anemia [12]. Our patient presented with typical
often is unclear. The benefits or harms of adminis-tering
signs and symptoms of epiglottitis similar to those observed in
antifungals empirically are unclear from this case series.
immunocompetent patients. Specifically, in the reviewed case
Prognosis of Epiglottitis in the Immunocompromised
reports of immunocompromised patients, patients presented
Of the 48 case reports, 13 people died and 35 survived (27%
with symptoms of respiratory distress, stridor, fever, drooling,
overall mortality), highlighting the life-threatening nature of
sore throat, odynophagia, and dysphagia [4–37].
epiglottitis. Of the neutropenic patients, 6 died and 12
survived, giving a slightly higher mortality of 33% (Table 1).
Table 1. Demographics of Epiglottitis in the Immunocompromised
Two of 3 patients with tongue involvement were neutropenic.
According to 48 Cases from Published Studies [4–37] Table 2 shows the interventions used in addition to anti-
microbial agents and their associated mortalities in the
Demographic Data for Cases patients who received them.
Mean age (SD, range), y 35.5 (20.1, 4 mo–70 y) It is not possible to determine the effects of various interven-
Sex Male 23 48% tions on mortality from this case series. Intubation and trache-
Female 25 52%
ostomy may be used in more severe cases, so higher mortality
Underlying condition Malignancy 24 50%
HIV 12 25%
with these interventions may reflect higher baseline risk of death
Othera 12 25%
independent of the interventions administered.
Neutropenia ANC or WBC <1000 18 38%
Organisms Isolated in Immunocompromised Patients
Mortality Neutropenic 33%
In 29 patients, a single organism was isolated from cultures of the
Not neutropenic 23%
throat, sputum, blood, or tissue biopsy (either from an isolated
Abbreviations: ANC, absolute neutrophil count; WBC, total white blood cell count.
aOther causes of immunocompromise included Epstein-Barr virus (EBV) mononucleosis site or from multiple sites), while 3 patients had either no growth
in pregnancy, bone marrow aplasia of unknown origin, hypocellular bone marrow of on cultures or they were not done. The remaining 16 patients
unknown origin, aplastic anemia, virus-associated hemophagocytic syndrome secondary
to EBV infection, renal transplantation, procainamide-induced neutropenia, infection-re- grew multiple organisms. A summary of organisms is shown in
lated hemophagocytic lymphohistiocytosis, Cytomegalovirus-related pancytopenia, sys-
temic lupus erythematosus, and drug-induced agranulocytosis. In 1 patient, the cause of
Table 3. The most frequent organism isolated from either cul-
immunocompromise was not documented. tures or biopsy was Candida spp, followed by Streptococcus spp.

Epiglottitis in the Immunocompromised • OFID • 3

Table 2. Supportive Treatments Used in Addition to Antimicrobial Therapy rod-shaped organism often found in the normal flora of the
in the 48 Published Cases of Epiglottitis in the Immunocompromised [4–37]
gastrointestinal tract [39]. It is also a nosocomial pathogen,
with previous documentations of E. cloacae outbreaks [40].
Supportive Treatment No. Mortality, %
Flynn et al. suggested that Enterobacter from patients’
Intubation 30 37
endogen-ous flora can be the source of “nosocomial”
Tracheostomy 10 40
Steroids 9 33
Enterobacter infec-tion [41]. Our patient did recently have a
Granulocyte stimulating factor 5 20 hospital admission in Jamaica and receipt of prior antibiotics,
Surgical debridement 2 0 so it is unclear whether the source of his infection was
Racemic epinephrine 2 0 nosocomial or com-munity acquired. Nonetheless, this finding
has implications for the choice of empirical antimicrobial
therapy for the initial management of epiglottitis in
Eight of the neutropenic patients grew Candida spp and were
immunocompromised patients. Gram-negative and fungal
subsequently treated with antifungal agents (11 of 31 non-neu-
infections should be considered in this setting.
tropenic patients grew Candida spp). The organisms grown from
neutropenic patients showed more variety and were less predict- CONCLUSIONS
able, such as Prevotella spp and Serratia marcescens, compared
In the immunocompromised patient, there should be a low
with primarily Streptococcus pneumoniae and Candida albicans
threshold of suspicion for diagnosing acute epiglottitis, particu-
in non-neutropenic patients. In 2 patients, cultures were not done,
larly in those who are neutropenic. The immunocompromised
diagnosis was made on a clinical basis, and the infection resolved
state and neutropenia do not rule out diseases caused by neutro-
without intervention. There was 1 case where there was no
philic infiltration as tissue-based inflammation still may result in
growth from blood cultures, throat swabs, or tracheal aspir-ate,
disease. Epiglottitis in reported cases presents similarly in immu-
but the patient survived and the disease resolved after receipt of
nocompromised and immunocompetent patients. Early recog-
cefotaxime, erythromycin, and metronidazole.
nition can allow prompt treatment, including administration of
Here we report the first documented case of acute epiglot-
broad-spectrum antimicrobials and perhaps antifungals, given the
titis associated with Enterobacter cloacae, a gram-negative
wide range of organisms isolated. The impact of broad-spec-trum
antimicrobials with additional antifungals on outcome is unknown
Table 3. Organisms Grown From 48 Cases of Epiglottitis in
given that the organisms isolated also are part of the normal
Immunocompromised Patients From Published Cases [4–37] oropharyngeal flora, and whether they are colonizing or causing
infection often is unclear. Airway management is para-mount, but
Organism Isolated Neutropenic Total % of All Cases endotracheal intubation is not always necessary and was not
Candida spp 8 19 40 necessary in our patient. Sedation, inhalers, and racemic
Streptococcus spp 2 12 25 epinephrine should be avoided [3]. Rapid treatment with steroids
Staphylococcus spp 2 5 10 to reduce the immediate inflammation, along with antimicrobials
Cytomegalovirus 2 5 10
to treat the underlying infection, has been associated with shorter
Aspergillus spp 2 4 8
intensive care unit and overall length of hospital stay; close mon-
Serratia spp 3 3 6
Enterococcus spp 2 2 4 itoring and good nursing care are essential for the appropriate
Corynebacterium diphtheriae 1 2 4 management of epiglottitis in the immunocompromised patient.
Escherichia coli 1 2 4
Neisseria spp 1 2 4 Acknowledgments
Prevotella spp 2 2 4 Financial support. This project has been funded in whole or in part with
Pseudomonas spp 1 2 4 federal funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E. The content of this pub-lication
Klebsiella pneumoniae 0 1 2
does not necessarily reflect the views or policies of the Department of Health
Actinomyces israelii 0 1 2
and Human Services, nor does mention of trade names, commer-cial products,
Bacteroides spp 0 1 2
or organizations imply endorsement by the US Government.
Diplococcus 0 1 2 Potential conflicts of interest. None of the authors have any conflict of
Eikenella corrodens 1 1 2 interest related to this work. All authors have submitted the ICMJE Form
Haemophilus influenzae 1 1 2 for Disclosure of Potential Conflicts of Interest. Conflicts that the editors
Kingella kingae 1 1 2 consider relevant to the content of the manuscript have been disclosed.
Mucormycosis 0 1 2
Stenotrophomonas maltophilia 1 1 2 References
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