eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Diphtheria: Differential Diagnoses & Workup

Author: Cem S Demirci, MD, Fellow in Endocrinology, Children's Hospital of Pittsburgh
Coauthor(s): Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center
Contributor Information and Disclosures

Updated: Jul 29, 2008

Differential Diagnoses

Epiglottitis
Herpes Simplex Virus Infection
Impetigo

Other Problems to Be Considered

Vincent angina
Exudative pharyngitis due to Streptococcus pyogenes and Epstein-Barr virus
Mucositis
Infective phlebitis

Workup

Laboratory Studies

Diagnostic tests used to confirm infection combine isolation of C diphtheriae on cultures with toxigenicity testing.

  • Bacteriologic culturing is essential to confirm the diagnosis of diphtheria.
    • In all patients in whom diphtheria is suspected and in their close contacts, obtain specimens from the nose and throat (ie, nasopharyngeal and pharyngeal swab) for culture.
    • Obtain a clinical specimen for culture as soon as possible when diphtheria (at any location) is suspected, even if treatment with antibiotics has been initiated.
    • Obtain specimens from the membrane as well as from the nose and throat. If possible, swabs also should be taken from beneath the membrane.
    • Alert the laboratory to the suspicion of diphtheria because isolation of C diphtheriae requires special culture media containing tellurite. C diphtheriae may be grown on various selective media, including tellurite agar or specially enriched Loeffler, Hoyle, Mueller, or Tinsdale medium.
    • Isolation of C diphtheriae from close contacts may confirm the diagnosis, even if results of cultures on specimens taken from the patient are negative.
    • After C diphtheriae has been isolated, determine the biotype: gravis, mitis, or intermedius (substrain).
  • Toxigenicity testing is also performed.
    • Perform toxigenicity testing using the Elek test to determine if the C diphtheriae isolate produces toxin.
    • Toxigenicity tests are not readily available in many clinical microbiology laboratories; send isolates to a reference laboratory with personnel proficient in performing the tests. The state health department or Centers for Disease Control and Prevention (CDC) can provide information on laboratories that offer this test (few laboratory staffs have the capability to test antibody levels).
    • Measurement of the patient's serum antibodies to diphtheria toxin before administration of antitoxin may help assess the probability of the diagnosis of diphtheria.
    • If antibody levels are low, diphtheria cannot be excluded, but if levels are high, C diphtheriae is less likely to produce serious illness.

Other Tests

Although no other tests for diagnosing diphtheria are commercially available, the CDC can perform a polymerase chain reaction (PCR) test on clinical specimens to confirm infection with a toxigenic strain.

  • The PCR test can detect nonviable C diphtheriae organisms from specimens taken after antibiotic therapy has been initiated.
  • Contact the state health department to report a suspected case and to arrange laboratory testing.
  • Although PCR results for the diphtheria toxin, as performed by the CDC diphtheria laboratory, provide supportive evidence for the diagnosis, data are not yet sufficient for PCR results to be accepted as a criterion for laboratory confirmation.
  • At present, a diagnosis of diphtheria should be classified as probable in a patient with positive results to PCR testing but in whom the organism was not isolated, histopathologic diagnosis has not been made, and no epidemiologic link can be made to a patient with laboratory-confirmed diphtheria.
  • When collecting specimens for culture, obtain additional clinical specimens for PCR testing at the CDC. Because isolation of C diphtheriae is not always possible (many patients have already received antibiotics for several days by the time a diphtheria diagnosis is considered), the PCR test can provide additional supportive evidence for the diagnosis of diphtheria.
  • The PCR assay allows detection of the diphtheria toxin gene (TOX).
  • Clinical samples (swabs, pieces of membrane, biopsy tissue) can be transported to the CDC with cold packs in a sterile empty container or in silica gel sachets. For detailed information on specimen collection and shipping and to arrange PCR testing, the state health department may contact the CDC diphtheria laboratory at (404) 639-1730 or (404) 639-4057.
  • Send all isolates of C diphtheriae, from any body site (respiratory or cutaneous), whether toxigenic or nontoxigenic, to the CDC diphtheria laboratory for reference testing. Clinical specimens should be sent to the CDC diphtheria laboratory for PCR testing. To arrange for specimen shipment, contact the state health department.

More on Diphtheria

Overview: Diphtheria
Differential Diagnoses & Workup: Diphtheria
Treatment & Medication: Diphtheria
Follow-up: Diphtheria
References
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References

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  2. Golaz A, Hardy IR, Strebel P, et al. Epidemic diphtheria in the Newly Independent States of the Former Soviet Union: implications for diphtheria control in the United States. J Infect Dis. Feb 2000;181 Suppl 1:S237-43. [Medline].

  3. Lurie P, Stafford H, Tran P. Fatal respiratory diphtheria in a U.S. traveler to Haiti--Pennsylvania, 2003. MMWR Morb Mortal Wkly Rep. Jan 9 2004;52(53):1285-6. [Medline].

  4. Kretsinger K, Broder KR, Cortese MM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep. Dec 15 2006;55:1-37. [Medline]. [Full Text].

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  6. Broder KR, Cortese MM, Iskander JK, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Mar 24 2006;55(RR-3):1-34. [Medline]. [Full Text].

  7. AAP. Diphtheria. Committee on Infectious Disease. In: The Red Book. 26th ed. American Academy of Pediatrics; 2003:263-6.

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Further Reading

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Keywords

diphtheria, Corynebacterium diphtheriae, strangling angel of children, toxin-mediated disease, mitis diphtheria, gravis diphtheria, intermedius diphtheria, diphtheroids, coryneform bacteria, respiratory tract infection, thrombocytopenia, cardiomyopathy, tonsillar diphtheria, pharyngeal diphtheria, respiratory failure, circulatory collapse, laryngotracheobronchitis, respiratory tract obstruction, septicemia, rhinitis, impetigo

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Contributor Information and Disclosures

Author

Cem S Demirci, MD, Fellow in Endocrinology, Children's Hospital of Pittsburgh
Disclosure: Nothing to disclose.

Coauthor(s)

Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center
Walid Abuhammour, MD, FAAP is a member of the following medical societies: American Medical Association and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Medical Editor

Ashir Kumar, MBBS, MD, FAAP, Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University; Consulting Staff, Department of Pediatrics, EW Sparrow Hospital
Ashir Kumar, MBBS, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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