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A Case of Necrotizing Epiglottitis Due to

Nontoxigenic Corynebacterium
diphtheriae
Jessica A. Lake, MD, MPHa, Matthew J. Ehrhardt, MD, MSb, Mariko Suchi, MD, PhDc, Robert H. Chun, MDd,
Rodney E. Willoughby, MDe

Diphtheria is a rare cause of infection in highly vaccinated populations and abstract


may not be recognized by modern clinicians. Infections by nontoxigenic
Corynebacterium diphtheriae are emerging. We report the first case of
necrotizing epiglottitis secondary to nontoxigenic C diphtheriae. A fully
vaccinated child developed fever, poor oral intake, and sore throat and was
found to have necrotizing epiglottitis. Necrotizing epiglottitis predominantly
occurs in the immunocompromised host. Laboratory evaluation revealed
pancytopenia, and bone marrow biopsy was diagnostic for acute
lymphoblastic leukemia. Clinicians should be aware of aggressive infections
that identify immunocompromised patients. This case highlights the features
of a reemerging pathogen, C diphtheriae.

Departments of aPediatrics, cPathology, dOtolaryngology,


Diphtheria was once a major cause of conditions, such as intravenous drug and eInfectious Disease, Medical College of Wisconsin,
Milwaukee, Wisconsin; and bDepartment of Oncology,
death and disability in children. In the users and homeless people. St Jude Children’s Research Hospital, Memphis, Tennessee
1920s, the United States saw up to Ten cases of necrotizing epiglottitis Dr Lake conceptualized this report, interpreted data,
200 000 cases and nearly 15 000 have been reported in the literature, 3 reviewed the references, and drafted the initial
deaths per year due to diphtheria.1 of them occurring in children.4–13 We report; Dr Ehrhardt conceptualized this report,
After the development and routine use describe the first reported case of interpreted data, and critically reviewed the
of diphtheria toxoid in vaccines in the manuscript; Drs Suchi and Willoughby interpreted
necrotizing epiglottitis in a child
data and reviewed and revised the manuscript; Dr
1940s, toxigenic diphtheria became infected by nontoxigenic Chun interpreted data, reviewed and revised the
a rare infection in the United States, Corynebacterium diphtheriae. manuscript, and provided the images; and all
with only 5 cases reported between authors approved the final manuscript as
2000 and 2012.1 Worldwide, toxigenic submitted.
diphtheria remains endemic in CLINICAL RECORD www.pediatrics.org/cgi/doi/10.1542/peds.2014-3157
countries with low vaccination A 3-year-old, previously healthy girl DOI: 10.1542/peds.2014-3157
coverage, including 7088 cases presented with fever, poor oral intake, Accepted for publication Apr 14, 2015
reported in 2008.1,2 In the early 1990s, fatigue, and sore throat. Examination Address correspondence to Jessica Lake, MD, MPH,
157 000 cases and .5000 reported was notable for cervical adenopathy. Department of Pediatrics, 8701 W Watertown Plank
deaths occurred in the Soviet Union.1,2 Streptococcal antigen and Monospot Road, Milwaukee, WI 53226. E-mail: jelake@mcw.edu
As recent as 2013, an outbreak tested negative. The next day the child PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
occurred in a resettlement camp in developed tender submandibular 1098-4275).
Kandahar, Afghanistan, resulting in 50 swelling, drooling, halitosis, and a high- Copyright © 2015 by the American Academy of
cases and 3 deaths1–3 Seventy-four pitched voice. Laboratory evaluation Pediatrics
percent of the cases in Afghanistan revealed a white blood cell count of FINANCIAL DISCLOSURE: The authors have indicated
were in children ages 5 to 14.3 Severe 300 cells/mL (reference range they have no financial relationships relevant to this
disease is most often seen with 4000–12 000 cells/mL), absolute article to disclose.
toxigenic diphtheria but can be seen neutrophil count of 0 (reference range FUNDING: No external funding.
with the non–toxin-producing form, 3000–8000 cells/mL), hemoglobin 8.0 POTENTIAL CONFLICT OF INTEREST: The authors have
especially in immunocompromised g/dL (reference range 11.5–14.5 g/dL), indicated they have no potential conflicts of interest
patients or those with predisposing and platelets 125 000 cells/mL to disclose.

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PEDIATRICS Volume 136, number 1, July 2015 CASE REPORT
(reference range 150 000–450 000
cells/mL). Cervical radiographs
identified prevertebral soft tissue
prominence. The patient was
transferred to our pediatric center for
additional evaluation and
management.
Growth parameters were appropriate
for age. Her vaccinations were
current with the recommended
guidelines, including diphtheria,
tetanus, and acellular pertussis
vaccinations at 2, 4, 6, and
18 months.14 Vital signs revealed
tachycardia and tachypnea.
Examination was significant for an FIGURE 1
afebrile, ill-appearing child with A, Postcontrast sagittal CT scan of the neck revealing retropharyngeal edema (thin arrow) and
prominent neck swelling and left a normal-appearing epiglottis (thick arrow). B, Postcontrast axial CT scan of the neck with retro-
pharyngeal edema (thin arrow) and enlarged bilateral lymph nodes (thick arrows).
neck redness. She had conjunctival
erythema, cracked, red lips, and
bilateral tonsillar exudates. Cervical without evidence of within the established protective
nodes were tender and not fluctuant. a pseudomembrane. Culture of the levels after vaccination. Polymerase
Plantar desquamation was present. excised left tonsil grew Prevotella chain reaction analysis of the isolate
She did not have stridor, respiratory bivia and few Haemophilus influenzae. and an Elek test, an in vitro assay for
distress, cardiac murmur, or A bone marrow biopsy revealed toxigenicity, were performed at the
organomegaly. The remainder of the atypical lymphoid aggregates Centers for Disease Control and
examination was normal. Additional consistent with B-cell lymphoblastic Prevention and confirmed
laboratory evaluation revealed leukemia (B-ALL). The patient began nontoxigenic C diphtheriae, biotype
fibrinogen of 1116 mg/dL (reference induction chemotherapy with belfanti. The patient was extubated
range 200–400 mg/dL) and ferritin of dexamethasone, PEG-asparaginase, after 2 weeks and discharged from
223 ng/mL (reference range 10–60 and vincristine for National Cancer the hospital after a 1-month
ng/mL) with normal lactate Institute standard risk B-ALL.15 hospitalization.
dehydrogenase, uric acid, and C diphtheriae was identified via
triglycerides. She was empirically phenotypic testing in combination
with 16s ribosomal DNA sequencing DISCUSSION
started on vancomycin and
cefotaxime. Computed tomography from a nasopharyngeal culture. She Case series from Russia and the
(CT) scans of the neck demonstrated needed persistent cardiopulmonary United Kingdom document outbreaks
a retropharyngeal collection support, and an echocardiogram was of severe disease and deaths
measuring 7.8 mm in thickness performed, demonstrating reduced associated with nontoxigenic
extending down behind the larynx, cardiac function. She was treated with C diphtheriae, suggesting that this is
with prominent bilateral posterior penicillin and diphtheria antitoxin. an emerging disease.2,16,17 Although
triangle lymphadenopathy indicating Before treatment, titers for diphtheria our case involved infection of the
retropharyngeal abscess (Fig 1). and tetanus were measured and respiratory tract, severe respiratory

On hospital day 2, the patient


developed progressive hypoxemia,
drooling, and stertor. She was
electively intubated in the operating
room. White membranes on the
laryngeal surface of the epiglottis and
left tonsil, compatible with necrosis,
were debrided (Fig 2). Pathology of
the left tonsil revealed extensive
coagulative necrosis and invading FIGURE 2
cocci and filamentous bacteria A, White membranes on laryngeal surface of the epiglottis. B, White membranes on the left tonsil.

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2 LAKE et al
infections due to nontoxigenic the epiglottis may lead to of leukemia. It also underscores
C diphtheriae are rare. A case of postoperative dysphagia, the goals of C diphtheriae as a potential cause of
afebrile pneumonia was described in surgery are eradication and diagnosis life-threatening infection in an
Japan in 2009 in a 60-year-old, of disease. All 3 children survived immunocompromised patient.
ventilator-dependent woman with their infections, although the first Prompt recognition of impaired
amyotrophic lateral sclerosis.18 case resulted in a spontaneous immunity in the presence of an
Additional, severe clinical abortion and loss of the epiglottis. In aggressive infection and tissue
manifestations, such as endocarditis our case and the 5-year-old reported culture and diagnosis are critical to
and arthritis, have been reported. In in the literature, both children good outcomes, as exemplified by this
the 1990s, Western Europe saw postoperatively had no aspiration and report.
multiple cases of endocarditis, arthritis, had mild dysphagia that improved in
and osteomyelitis from nontoxigenic both cases. Our patient had occult ACKNOWLEDGMENTS
C diphtheriae, mostly in injection drug B-ALL with absolute neutropenia and
therefore was also We acknowledge Drs Albert
users and homeless people.19
immunocompromised. She was fully Pomeranz and Kevin Boyd at the
C diphtheriae is an aerobic gram- Medical College of Wisconsin for their
immunized. Diphtheria vaccines
positive bacillus that becomes contributions to this report, including
protect against the toxin responsible
toxigenic when the bacillus is critical review of the submission and
for pseudomembranes,
lysogenized by a bacteriophage virus provision of images, respectively.
myocardiopathy, and peripheral
containing the tox gene.1 There are 4
neuropathy and are 97%
biotypes of C diphtheriae: gravis,
efficacious.1,16 Vaccines do not
intermedius, mitis, and a more protect against colonization by ABBREVIATIONS
recently discovered belfanti.1,20 Three nontoxigenic C diphtheriae.22 B-ALL: B-cell lymphoblastic
biotypes have toxin-forming
Although the toxin is the main leukemia
potential, but only nontoxigenic
virulence factor, the increase in CT: computed tomography
isolates of belfanti have been
described.21 Commonly reported invasive infections due to
subtypes of nontoxigenic disease nontoxigenic C diphtheriae suggests
include gravis and belfanti, the latter that other factors, such as those REFERENCES
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PEDIATRICS Volume 136, number 1, July 2015 3
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4 LAKE et al
A Case of Necrotizing Epiglottitis Due to Nontoxigenic Corynebacterium
diphtheriae
Jessica A. Lake, Matthew J. Ehrhardt, Mariko Suchi, Robert H. Chun and Rodney E.
Willoughby
Pediatrics; originally published online June 8, 2015;
DOI: 10.1542/peds.2014-3157
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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, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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A Case of Necrotizing Epiglottitis Due to Nontoxigenic Corynebacterium
diphtheriae
Jessica A. Lake, Matthew J. Ehrhardt, Mariko Suchi, Robert H. Chun and Rodney E.
Willoughby
Pediatrics; originally published online June 8, 2015;
DOI: 10.1542/peds.2014-3157

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/early/2015/06/03/peds.2014-3157

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, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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