Diphtheria
Summary
Diphtheria is a serious, toxin-mediated bacterial infection caused by Corynebacterium diphtheriae (Gram-positive bacillus). It is now rare in vaccinated populations but remains endemic in parts of the world with low vaccination coverage. The hallmark is a grey, adherent pseudomembrane on the tonsils/pharynx that bleeds when scraped and can cause life-threatening airway obstruction. Cervical lymphadenopathy with surrounding oedema produces the characteristic "Bull Neck". The diphtheria toxin is absorbed systemically and causes serious complications including myocarditis (Heart failure, Arrhythmias) and neuropathy (Cranial nerve and peripheral nerve paralysis). Management requires Diphtheria Antitoxin (DAT) to neutralise circulating toxin, antibiotics (Erythromycin/Penicillin), and airway support. Diphtheria is a notifiable disease.
Key Facts
- Causative Organism: Corynebacterium diphtheriae (Gram-positive bacillus, "Chinese letter" arrangement).
- Transmission: Respiratory droplets. Close contact.
- Hallmark: Grey, Adherent Pseudomembrane on pharynx/tonsils. Bleeds if removed.
- Bull Neck: Cervical lymphadenopathy + Oedema.
- Toxin Complications: Myocarditis (ECG changes, Heart Failure), Neuropathy.
- Treatment: Diphtheria Antitoxin (DAT) + Antibiotics (Erythromycin).
- Prevention: DTaP Vaccine (Part of 6-in-1).
- Notifiable: Report to public health authorities.
Clinical Pearls
"The Membrane Bleeds": Attempting to remove the pseudomembrane causes bleeding – This is characteristic.
"Bull Neck = Neck Oedema + Adenopathy": Extensive cervical swelling indicates severe disease.
"Myocarditis Kills": Toxin-induced myocarditis is the main cause of death. Monitor ECG.
"Give DAT Early": Antitoxin only neutralises UNBOUND toxin. Give as soon as diagnosis suspected.
Why This Matters Clinically
Diphtheria is rare but potentially fatal. Clinicians must recognise it in unvaccinated travellers or in areas with outbreaks. Early DAT prevents mortality.
Incidence
- Rare in Developed Countries: Due to vaccination (DTaP/Td).
- Endemic in: South Asia, Africa, Some Eastern European countries.
- Outbreaks: Can occur when vaccination coverage falls.
- UK: ~0-5 cases/year (Imported or cutaneous).
Risk Factors
| Factor | Notes |
|---|---|
| Unvaccinated / Incompletely Vaccinated | |
| Travel to Endemic Areas | |
| Overcrowding / Poor Hygiene | |
| Close Contact with a Case |
Organism
| Feature | Detail |
|---|---|
| Corynebacterium diphtheriae | Gram-positive bacillus. |
| Morphology | Club-shaped. "Chinese letter" or "V/L" arrangement. |
| Culture | Tellurite agar (Black colonies). Loeffler's serum slope (Metachromatic granules). |
| Toxin | Produced by strains with tox gene (Phage-mediated). |
| Biotypes | Mitis, Intermedius, Gravis. ("Gravis" = NOT more severe.) |
Toxin Mechanism
| Step | Detail |
|---|---|
| Uptake | Toxin enters cells via Heparin-Binding EGF-Like Growth Factor receptor. |
| ADP-Ribosylation | Inactivates Elongation Factor 2 (EF-2). |
| Result | Protein synthesis inhibited. Cell death. |
| Target Tissues | Heart (Myocarditis), Nervous System (Demyelination). |
Incubation
Pharyngeal/Tonsillar Diphtheria (Most Common)
| Feature | Notes |
|---|---|
| Sore Throat | Moderate. |
| Low-Grade Fever | |
| Malaise | |
| Pseudomembrane | Grey-green/Grey-white. Adherent. Covers tonsils, Pharynx, Can extend to larynx/trachea. Bleeds when scraped. |
| Cervical Lymphadenopathy | Tender, Swollen. |
| "Bull Neck" | Extensive cervical node swelling + Oedema. Indicates severe disease. |
| Foul Odour | Sweet, "Mousy" smell from breath. |
Laryngeal Diphtheria
| Feature | Notes |
|---|---|
| Stridor | Airway obstruction. |
| Hoarseness | |
| Barking Cough | Croupy. |
| Respiratory Distress | Emergency. May require intubation/tracheostomy. |
Cutaneous Diphtheria
| Feature | Notes |
|---|---|
| Skin Ulcer | Chronic, Non-healing. Often with pseudomembrane. |
| Location | Tropics. Legs. Pre-existing wounds. |
| Toxicity | Less systemic toxicity than respiratory. |
Nasal Diphtheria
| Feature | Notes |
|---|---|
| Bloodstained Nasal Discharge | |
| Membrane in Nares |
Myocarditis
| Timing | Weeks 1-2 (Or later). | | Features | Arrhythmias (Heart Block, Ventricular arrhythmias), Heart Failure, Cardiomegaly. | | ECG | ST/T changes, Prolonged PR, Bundle Branch Block, Heart Block. | | Outcome | Major cause of death (~50% mortality with severe myocarditis). |
Neuropathy
| Timing | Weeks 2-6 (Or later). | | Features | Cranial Neuropathies (Palatal paralysis – Nasal regurgitation, Diplopia). Peripheral Neuropathy (Limb weakness – Ascending, GBS-like). | | Outcome | Usually recovers over weeks-months if patient survives. |
Other
| Complication | Notes |
|---|---|
| Airway Obstruction | Pseudomembrane extension. Emergency. |
| Nephritis | Acute tubular necrosis. |
| Thrombocytopenia |
Diagnosis
| Test | Notes |
|---|---|
| Throat Swab (Under Pseudomembrane) | Culture on Tellurite agar / Loeffler's. Notify lab of suspected diphtheria. |
| Toxin Testing (Elek Test / PCR) | Confirms toxigenic strain. |
Do NOT wait for lab confirmation before starting treatment.
Supportive
| Test | Purpose |
|---|---|
| ECG | Daily monitoring for myocarditis. |
| Cardiac Enzymes (Troponin) | Myocarditis. |
| FBC, U&E |
Principles (EMERGENCY)
- Secure Airway (Tracheostomy/Intubation if needed).
- Diphtheria Antitoxin (DAT) Early.
- Antibiotics.
- Isolation (Droplet Precautions).
- Monitor for Myocarditis/Neuropathy.
- Notify Public Health.
- Contact Tracing / Prophylaxis.
Diphtheria Antitoxin (DAT)
| Feature | Detail |
|---|---|
| Mechanism | Equine-derived antibodies. Neutralises CIRCULATING (Unbound) toxin. |
| Indication | Give as soon as diphtheria is suspected clinically. Do NOT wait for lab confirmation. |
| Source | WHO stockpile. Not routinely available – Liaise with Public Health / UKHSA. |
| Dose | Variable (20,000-120,000 units IV/IM depending on severity). |
| Precautions | Risk of Anaphylaxis (Equine serum). Test dose. Have Adrenaline ready. |
Antibiotics
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Erythromycin | 40-50mg/kg/day in divided doses (Max 2g/day). | 14 days. | Preferred. |
| Penicillin G | IM/IV. | 14 days. | Alternative. |
Antibiotics eradicate carriage but do NOT neutralise toxin.
Isolation
- Droplet precautions until 2 negative cultures (24 hours apart) after completing antibiotics.
Monitoring
- ECG Daily (Myocarditis).
- Cardiac Enzymes.
- Neurology (Watch for palatal weakness, limb weakness).
- Bed Rest (Reduces cardiac workload).
Contact Management
| Contact | Action |
|---|---|
| Close Contacts | Throat swab. Prophylactic antibiotics (Erythromycin 7-10 days). Booster vaccine if > years since last dose. |
Vaccination
| Vaccine | Schedule (UK) |
|---|---|
| DTaP/IPV/Hib/HepB (6-in-1) | 8, 12, 16 weeks (Primary course). |
| DTaP/IPV (Pre-school booster) | 3 years 4 months. |
| Td/IPV (Teenage booster) | 14 years. |
| Td/IPV (Adult booster) | If required for travel / outbreak. |
5 doses provide lifelong protection.
| Scenario | Mortality |
|---|---|
| Untreated Respiratory Diphtheria | ~50%. |
| With DAT + Antibiotics | ~5-10%. |
| Myocarditis | ~50% mortality if severe. |
| Cutaneous Diphtheria | Low mortality. |
Sequelae
- Neuropathy usually recovers.
- Cardiac damage may be permanent.
Key Guidelines
| Guideline | Organisation | Notes |
|---|---|---|
| WHO | World Health Organization | Global guidance. DAT access. |
| UKHSA (PHE) Green Book | UK Health Security Agency | UK Immunisation schedule. Outbreak management. |
| CDC Pink Book | Centers for Disease Control | US guidance. |
Scenario 1:
- Stem: A 6-year-old unvaccinated child returns from South Asia with sore throat, fever, and a grey membrane on the tonsils that bleeds when touched. What is the diagnosis and immediate management?
- Answer: Diphtheria. Secure airway. Give Diphtheria Antitoxin (DAT) immediately. Start Erythromycin. Isolate. Notify Public Health.
Scenario 2:
- Stem: What is the mechanism of diphtheria toxin?
- Answer: Diphtheria toxin ADP-ribosylates Elongation Factor 2 (EF-2), inhibiting protein synthesis and causing cell death.
Scenario 3:
- Stem: A patient with diphtheria develops heart block on day 10. What is the complication?
- Answer: Myocarditis (Toxin-mediated). Major cause of mortality.
| Scenario | Urgency | Action |
|---|---|---|
| Suspected Diphtheria | Emergency | A&E. Isolation. DAT. Antibiotics. Public Health notification. |
| Respiratory Distress / Stridor | Emergency | Airway management (Anaesthetics/ENT). ICU. |
| Contact of Confirmed Case | Urgent | Swab. Prophylaxis. Vaccination. |
What is Diphtheria?
Diphtheria is a serious bacterial throat infection. It causes a thick grey coating in the throat that can block breathing. The bacteria also produce a toxin that can damage the heart and nerves.
Why is it rare now?
Vaccination has almost eliminated diphtheria. It is still seen in parts of the world with low vaccination rates.
How is it treated?
- Antitoxin: Medicine to stop the toxin from causing more damage.
- Antibiotics: To kill the bacteria.
- Airway support: If breathing is blocked.
Key Counselling Points
- Vaccination Saves Lives: "Make sure your children are fully vaccinated."
- Travel Precautions: "Check your vaccinations before travel to endemic areas."
| Standard | Target |
|---|---|
| DAT given within hours of clinical suspicion | 100% |
| Public Health notification | 100% |
| ECG monitoring for myocarditis | 100% |
| Contact tracing initiated | 100% |
- "The Strangling Angel of Children": Historical name due to airway obstruction.
- Antitoxin (1890s): Emil von Behring developed serum therapy. Nobel Prize 1901.
- Toxoid Vaccine (1920s): Led to dramatic decline in cases.
- Outbreaks (1990s): Former Soviet Union saw large outbreaks post-USSR due to vaccination decline.