What are the clinical signs and symptoms of diphtheria, and is there a mnemonic to remember them?

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Diphtheria Signs and Symptoms

Diphtheria presents with the classic triad of sore throat, low-grade fever, and a gray adherent pseudomembrane on the tonsils, pharynx, or nose—remember "Gray Membrane, Sore Throat, Bull Neck" for the key features. 1

Primary Clinical Features

The hallmark presentation includes:

  • Sore throat is typically the first symptom and a cardinal feature of respiratory diphtheria 1
  • Low-grade fever accompanies the infection, distinguishing it from high-grade fevers seen in other pharyngeal infections 1
  • Gray pseudomembrane that is firmly adherent to the mucosa of the nasopharynx, tonsils, pharynx, larynx, or nose—this is the most distinctive diagnostic feature 1, 2
  • The membrane has a leathery appearance and bleeds when attempts are made to remove it 3, 4

Pathognomonic Signs

  • "Bull neck" appearance results from massive cervical lymphadenopathy and soft tissue edema caused by toxin-mediated vascular damage—this finding is virtually diagnostic 3
  • Neck swelling with cervical lymphadenopathy is prominent 5, 4
  • Bleeding with swabbing of the pharyngeal membrane distinguishes diphtheria from streptococcal pharyngitis 3

Progressive Respiratory Symptoms

  • Hoarseness of voice occurs as the membrane extends to involve the larynx 5
  • Inspiratory stridor indicates impending airway obstruction and represents a medical emergency 3
  • Extension of the pseudomembrane into the trachea-bronchial tree can cause life-threatening airway compromise 1
  • Odynophagia and dysphagia develop as the infection progresses 4

Systemic Complications from Toxin Dissemination

  • Myocarditis (toxin-mediated cardiac complications) can develop from systemic absorption of diphtheria toxin 1, 6
  • Neuropathy (toxin-mediated neurologic complications) results from toxin dissemination 1, 6
  • These systemic effects are associated with increased fatality risk and occur because diphtheria toxin inhibits protein synthesis and causes cell death 6

Easy-to-Remember Mnemonic: "DIPHTHERIA"

  • Diphtheric membrane (gray, adherent)
  • Inspiratory stridor (airway obstruction)
  • Pharyngitis (sore throat—first symptom)
  • Hoarseness
  • Temperature (low-grade fever)
  • Heart complications (myocarditis)
  • Edema of neck (bull neck)
  • Respiratory obstruction
  • Inadequate vaccination (key risk factor)
  • Antitoxin needed urgently

Clinical Variants

  • Cutaneous diphtheria presents as sharply demarcated skin lesions with a pseudomembranous base, though appearance may not be distinctive 7
  • Cutaneous forms are not reportable in the United States but can occur 1

Critical Risk Factor

  • Unvaccinated or inadequately vaccinated individuals are at highest risk for severe disease 1, 8
  • Most cases occur exclusively in those who are unimmunized or have incomplete immunization 7, 8

Common Pitfall

The key clinical error is failing to consider diphtheria in unimmunized patients with severe pharyngitis, even in industrialized countries where it is rare—the combination of bull neck, inspiratory stridor, and bleeding pseudomembrane should trigger immediate clinical suspicion and urgent antitoxin administration without waiting for laboratory confirmation 3, 9, 5.

References

Guideline

Diphtheria Clinical Manifestations and Complications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The pathology of diphtheria.

The Journal of infectious diseases, 2000

Guideline

Diphtheria Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Case Report: Pharyngeal Diphtheria in a Pregnant Woman from South India.

The American journal of tropical medicine and hygiene, 2022

Research

Diphtheria.

Nature reviews. Disease primers, 2019

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diphtheria: forgotten, but not gone.

Internal medicine journal, 2013

Guideline

Treatment of Corynebacterium Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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