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Pediatric Diphtheria Clinical Presentation

  • Author: Cem S Demirci, MD; Chief Editor: Russell W Steele, MD  more...
Updated: Mar 10, 2016


Severity of disease due to C diphtheriae depends on the site of infection, the immunization status of the patient, and the dissemination of toxin (which is influenced by administration of antitoxin). Initial infection usually is localized and is categorized by the site of involvement.

  • Tonsils and pharynx: Tonsillar and pharyngeal diphtheria are most common; symptoms begin with a sore throat, usually in the absence of systemic complaints. Fever, if it occurs, is usually lower than 102°F, and malaise, dysphagia, and headache are not prominent features.
    • In individuals with diphtheria infection who are not immune, membrane formation begins after the 2-day to 5-day incubation period and grows to involve the pharyngeal walls, tonsils, uvula, and soft palate. The membrane may extend to the larynx and trachea, causing airway obstruction and eventual suffocation.
    • Underlying tissue of the throat and neck becomes edematous, and lymphadenopathy develops. Marked edema of the neck may lead to a bull-neck appearance with a distinct collar of swelling; the patient throws the head back to relieve pressure on the throat and larynx. Erasure edema associated with pharyngeal diphtheria obliterates the angle of the jaw, the borders of the sternocleidomastoid muscle, and the medial border of the clavicles. Swallowing may be made difficult by unilateral or bilateral paralysis of the muscles of the palate.
    • If toxin production is unopposed by antitoxin and severe disease occurs, early localized signs and symptoms give way to circulatory collapse, respiratory failure, stupor, coma, and death.
  • Larynx: In a minority of patients, the larynx is the initial site of infection, with initial presenting symptoms similar to laryngotracheobronchitis from other causes. Initial hoarseness may progress to loss of voice and severe respiratory tract obstruction. Initially, nasal diphtheria may present as a common viral upper respiratory tract infection. A foul odor may develop. This form of diphtheria is most common in infants.
  • Skin: Cutaneous diphtheria may occur at one or more sites, usually localized to areas of previous mild trauma or bruising. It is more common in tropical climates, but outbreaks have occurred in the United States. Pain, tenderness, and erythema at the site of infection progress to ulceration with sharply defined borders and formation of a brownish gray membrane. Local disease may persist for weeks to months.
  • Other sites: Additional sites of infection have included the external ear, the eye (usually the palpebral conjunctivae), and the genital mucosa. Rare sporadic cases of endocarditis have been reported, usually due to nontoxigenic strains. Septicemia caused by C diphtheriae is rare but universally fatal.


Infection of the anterior nares (more common in infants) causes serosanguineous, purulent, erosive rhinitis with membrane formation. Shallow ulceration of the external nares and upper lip is characteristic. Mild pharyngeal infection is followed by unilateral or bilateral tonsillar membrane formation, which extends variably to affect the uvula, soft palate, posterior oropharynx, hypopharynx, and glottic areas. Underlying soft tissue edema and enlarged lymph nodes can cause a bull-neck appearance. The degree of local extension directly correlates with profound prostration, bull-neck appearance, and fatality from airway compromise or toxin-mediated complications. The leatherlike adherent membrane, extension beyond the faucial area, relative lack of fever, and dysphagia help differentiate diphtheria from exudative pharyngitis due to Streptococcus pyogenes and Epstein-Barr virus.

  • Classic cutaneous diphtheria is an indolent nonprogressive infection characterized by a superficial, ecphymic, nonhealing ulcer with a gray-brown membrane. Diphtheritic skin infections cannot always be differentiated from streptococcal or staphylococcal impetigo, and they frequently occur together. In most patients, underlying dermatoses, lacerations, burns, bites, or impetigo have become contaminated secondarily. Extremities are affected more often than the trunk or head. Pain, tenderness, erythema, and exudate are typical. Local hyperesthesia or hypesthesia is unusual. Respiratory tract colonization or symptomatic infection and toxic complications occur in a minority of patients with cutaneous diphtheria.
  • C diphtheriae occasionally causes mucocutaneous infections at other sites, such as the ear (otitis externa), eye (purulent and ulcerative conjunctivitis), and genital tract (purulent and ulcerative vulvovaginitis). Skin is the probable portal of entry, and almost all strains are nontoxigenic. Sporadic cases of pyogenic arthritis, mainly due to nontoxigenic strains, are reported in adults and children. Do not dismiss diphtheroids isolated from sterile body sites as contaminants without careful consideration of the clinical setting.
  • Toxic cardiopathy occurs in approximately 10-25% of patients with diphtheria and is responsible for 50-60% of deaths.
  • Neurologic complications parallel the extent of primary infection and are multiphasic in onset.


Among nonimmunized populations, diphtheria most often occurs during fall and winter, although summer outbreaks have occurred. Disease spreads more quickly and is more prevalent in poor socioeconomic conditions, where crowding occurs and immunization rates are low.

International travel could pose a risk to persons who are unvaccinated or inadequately vaccinated. The last case of fatal respiratory diphtheria in United States was reported in an unvaccinated Pennsylvania resident who had visited Haiti in October 2003.[6]

Contributor Information and Disclosures

Cem S Demirci, MD Consulting Staff, Division of Endocrinology/Diabetes, Connecticut Children's Medical Center

Disclosure: Nothing to disclose.


Walid Abuhammour, MD, MBA, FAAP Professor of Pediatrics, Michigan State University College of Medicine; Director of Pediatric Infectious Disease, Department of Pediatrics, Al Jalila Children's Hospital

Walid Abuhammour, MD, MBA, FAAP is a member of the following medical societies: American Medical Association, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

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, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Ashir Kumar, MD, MBBS FAAP, Professor Emeritus, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine

Ashir Kumar, MD, MBBS is a member of the following medical societies: Infectious Diseases Society of America, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

  1. Lai J, Fay KE, Bocchini JA. Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2. Curr Opin Pediatr. 2011 Aug. 23(4):470-81. [Medline].

  2. Dittmann S, Wharton M, Vitek C, et al. Successful control of epidemic diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned. J Infect Dis. 2000 Feb. 181 Suppl 1:S10-22. [Medline].

  3. 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. 2000 Feb. 181 Suppl 1:S237-43. [Medline].

  4. Oyo-Ita A, Nwachukwu CE, Oringanje C, Meremikwu MM. Interventions for improving coverage of child immunization in low- and middle-income countries. Cochrane Database Syst Rev. 2011 Jul 6. CD008145. [Medline].

  5. Swart EM, van Gageldonk PG, de Melker HE, van der Klis FR, Berbers GA, Mollema L. Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study. PLoS One. 2016. 11 (2):e0148605. [Medline].

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

  7. Januszkiewicz-Lewandowska D, Gowin E, Bocian J, Zając-Spychała O, Małecka I, Stryczyńska-Kazubska J, et al. Vaccine-Derived Immunity in Children With Cancer-Analysis of Anti-Tetanus and Anti-Diphtheria Antibodies Changes after Completion of Antineoplastic Therapy. Pediatr Blood Cancer. 2015 Dec. 62 (12):2108-13. [Medline].

  8. 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. 2006 Dec 15. 55:1-37. [Medline]. [Full Text].

  9. Murphy TV, Slade BA, Broder KR, et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 May 30. 57:1-51. [Medline]. [Full Text].

  10. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap) in Pregnant Women and Persons Who Have or Anticipate Having Close Contact with an Infant Aged 1111111111MMWR Morb Mortal Wkly Rep</i>. 2011 Oct 21. 60:1424-6. [Medline].

  11. Additional recommendations for use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap). Pediatrics. 2011 Oct. 128(4):809-12. [Medline].

  12. 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. 2006 Mar 24. 55(RR-3):1-34. [Medline]. [Full Text].

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

  14. Boughton B. Diphtheria Vaccine Administered in the Thigh Appears Safer. Medscape Medical News. Jan 14 2013. Available at Accessed: March 18, 2013.

  15. Chen RT, Broome CV, Weinstein RA, et al. Diphtheria in the United States, 1971-81. Am J Public Health. 1985 Dec. 75(12):1393-7. [Medline].

  16. Farizo KM, Strebel PM, Chen RT, et al. Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. Clin Infect Dis. 1993 Jan. 16(1):59-68. [Medline].

  17. Galazka A. The changing epidemiology of diphtheria in the vaccine era. J Infect Dis. 2000 Feb. 181 Suppl 1:S2-9. [Medline].

  18. Hodes HL. Diphtheria. Pediatr Clin North Am. 1979 May. 26(2):445-59. [Medline].

  19. Jackson LA, Peterson D, Nelson JC, Marcy SM, Naleway AL, Nordin JD, et al. Vaccination site and risk of local reactions in children 1 through 6 years of age. Pediatrics. 2013 Feb. 131(2):283-9. [Medline].

  20. Kulkarni PS, Sapru A, Bavdekar A, Naik S, Patwardhan M, Barde P, et al. Immunogenicity of two diphtheria-tetanus-whole cell pertussis-hepatitis B vaccines in infants: A comparative trial. Hum Vaccin. 2011 Sep 1. 7(9):941-4. [Medline].

  21. Lewis LS, Hardy I, Strebel P, et al. Assessment of vaccination coverage among adults 30-49 years of age following a mass diphtheria vaccination campaign: Ukraine, April 1995. J Infect Dis. 2000 Feb. 181 Suppl 1:S232-6. [Medline].

  22. Long SS. Diphtheria. Behrman RE, Kliegman R, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. WB Saunders Co; 2000. 817-20.

  23. Long SS, Pickering LK, Prober CG. Corynebacterium diphtheriae. Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone; 1997. 861.

  24. Lubran MM. Bacterial toxins. Ann Clin Lab Sci. 1988 Jan-Feb. 18(1):58-71. [Medline].

  25. Mattos-Guaraldi AL, Moreira LO, Damasco PV. Diphtheria Remains a Threat to Health in the Developing World- An Overview. Mem Inst Oswaldo Cruz, Rio de Janeiro. 2003. 98(8):987-93.

  26. McMillan JA, Feigin RD. Diphtheria. McMillan JA, Warshaw JB, DeAngelis CD, eds. Oski's Pediatrics: Principles and Practice. 3rd ed. Wolters Kluwer Co; 1999. 961-4.

  27. Prospero E, Raffo M, Bagnoli M, et al. Diphtheria: epidemiological update and review of prevention and control strategies. Eur J Epidemiol. 1997 Jul. 13(5):527-34. [Medline].

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