2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T56bb,

Summary Table

Category	Details
Risk Factors	Unvaccinated or incompletely vaccinated children (typically 1-5 years), travelers to endemic regions (South/Southeast Asia, Africa, South America), crowded/poor hygiene settings, waning immunity in adults without boosters
Etiology	Corynebacterium diphtheriae, a gram-positive rod that produces diphtheria exotoxin (encoded by a beta-prophage); transmission via respiratory droplets or direct contact with skin lesions
Patient Presentation	Sore throat, low-grade fever, dysphagia, hoarseness, cervical lymphadenopathy progressing to respiratory distress; insidious onset over 2-5 days
Classic Physical Exam	Grayish-white pseudomembrane adherent to the pharynx/tonsils that bleeds when removed; "bull neck" appearance from cervical lymphadenopathy and soft tissue edema; stridor if laryngeal involvement
Key Diagnostic Results	Throat culture on Tellurite agar or Loeffler medium showing black/gray colonies; Elek test confirms toxin production; metachromatic granules on methylene blue stain
Management	Diphtheria antitoxin (DAT) immediately (do not wait for culture confirmation) + antibiotics (erythromycin or penicillin G for 14 days); supportive airway management; contact isolation
Keywords	Pseudomembrane, bull neck, Elek test, Tellurite agar, Loeffler medium, metachromatic granules, exotoxin, ADP-ribosylation of EF-2

1. Pathophysiology

Corynebacterium diphtheriae is a gram-positive, non-motile, non-spore-forming rod that colonizes the upper respiratory tract. The organism itself causes local tissue destruction, but the hallmark of disease severity comes from its exotoxin, which is only produced by strains lysogenized by a beta-prophage carrying the tox gene. This is a critical distinction: non-toxigenic strains can colonize but do not cause the systemic complications that define clinical diphtheria.

The exotoxin is an A-B toxin. The B subunit binds to heparin-binding epidermal growth factor (HB-EGF) receptors on host cells, facilitating entry. Once internalized, the A subunit catalyzes ADP-ribosylation of elongation factor 2 (EF-2), which irreversibly halts protein synthesis and leads to cell death. This mechanism explains why distant organs are damaged despite the infection remaining localized to the pharynx: the toxin is absorbed systemically through the bloodstream.

The pseudomembrane forms as a result of local tissue necrosis, fibrin deposition, inflammatory cells, and bacterial colonies accumulating on the mucosal surface. It is firmly adherent to the underlying tissue, and forceful removal causes bleeding, which is a classic exam finding. As the membrane extends from the tonsils into the larynx and trachea, it produces progressive airway obstruction with stridor and respiratory distress.

The "bull neck" appearance results from a combination of severe cervical lymphadenopathy and surrounding soft tissue edema caused by local inflammation and toxin-mediated tissue damage.

Systemic toxin effects target two organs preferentially. Myocarditis typically develops in the second week of illness because cardiac myocytes are rich in HB-EGF receptors, making them highly susceptible to toxin-mediated injury. This manifests as arrhythmias (especially heart block) and dilated cardiomyopathy. Peripheral neuropathy tends to appear later (weeks 3-6), beginning with palatal paralysis (bulbar symptoms like nasal voice, difficulty swallowing) followed by descending motor weakness. The neuropathy results from toxin-induced demyelination and is generally reversible over weeks to months.

2. Classification and Clinical Manifestation

Type	Site of Infection	Key Clinical Features	Severity
Pharyngeal/Tonsillar (most common)	Pharynx, tonsils	Sore throat, adherent grayish-white pseudomembrane, low-grade fever, dysphagia, cervical adenopathy	Moderate to severe; highest risk for systemic toxicity
Laryngeal	Larynx (extension from pharynx or primary)	Hoarseness, stridor, barking cough, progressive airway obstruction; pseudomembrane may not be directly visible	High; risk of acute airway compromise
Nasal	Anterior nares	Serosanguineous or purulent nasal discharge, often unilateral; mild systemic symptoms; membrane on nasal septum	Low; acts as a reservoir for transmission
Cutaneous	Skin (usually pre-existing wound)	Non-healing ulcer with grayish membrane, often co-infected with S. aureus or Streptococcus; common in tropical regions	Low; rarely causes systemic toxicity but can transmit to others

Complications

Complication	Timing	Mechanism	Clinical Features
Myocarditis	Week 1-2	Toxin-mediated cardiomyocyte death via EF-2 inhibition	Tachycardia out of proportion to fever, muffled heart sounds, arrhythmias (heart block, bundle branch block), elevated troponin, heart failure
Peripheral Neuropathy	Week 3-6 (can be later)	Toxin-induced demyelination	Begins with palatal paralysis (nasal speech, regurgitation), then cranial nerve palsies, followed by descending motor weakness; sensory involvement is less prominent
Renal Tubular Necrosis	Week 1-2	Direct toxin injury to renal tubular cells	Oliguria, proteinuria, hematuria

3. Diagnostic Workup

Test	Role	Key Finding
Clinical diagnosis	Best initial step	Pseudomembrane + bull neck + unvaccinated child = treat immediately
Throat swab culture on Tellurite agar	Confirmatory culture	Black/gray colonies (C. diphtheriae reduces tellurite); also grows on Loeffler coagulated serum medium (enhances metachromatic granule formation)
Methylene blue stain	Rapid microscopy	Metachromatic (volutin) granules within club-shaped rods arranged in V or L shapes ("Chinese letter" pattern)
Elek test	Confirms toxigenicity	Immunodiffusion assay detecting exotoxin production; distinguishes toxigenic from non-toxigenic strains
PCR for tox gene	Rapid molecular confirmation	Detects presence of the toxin gene; faster than Elek test
ECG	Screening for myocarditis	ST-T changes, prolonged PR interval, heart block, bundle branch block
Troponin, CK-MB	Cardiac biomarkers	Elevated in myocarditis

Diphtheria is fundamentally a clinical diagnosis. The moment you see a pseudomembrane in the pharynx of an unvaccinated patient with bull neck and low-grade fever, you must initiate treatment immediately. Waiting for culture results is a common trap because the antitoxin must be given before the toxin binds irreversibly to tissues.

The best initial test for laboratory confirmation is a throat culture on Tellurite agar, where C. diphtheriae produces characteristic dark colonies because the organism reduces potassium tellurite. Loeffler medium is the preferred medium for rapid initial growth (the organism grows faster on it than on Tellurite), and methylene blue staining from Loeffler medium reveals the classic metachromatic granules (polyphosphate storage bodies that stain reddish-purple against a blue background).

The Elek test is the gold standard for confirming toxin production. It is an in vitro immunodiffusion assay: a filter paper strip impregnated with diphtheria antitoxin is placed on an agar plate, the suspected organism is streaked perpendicular to the strip, and precipitation lines form where toxin and antitoxin meet if the strain is toxigenic. This distinction matters because only toxigenic strains cause the systemic complications.

All patients should receive an ECG on admission and serial monitoring, as myocarditis is the leading cause of death. Cardiac biomarkers help quantify myocardial injury.

4. Management and Treatment

Intervention	Details	Timing
Diphtheria Antitoxin (DAT)	20,000-100,000 units IV (dose based on disease severity and duration); perform skin test first for horse serum hypersensitivity	Immediately upon clinical suspicion; do NOT wait for culture
Erythromycin	40-50 mg/kg/day divided q6h (max 2 g/day) PO or IV for 14 days	Start concurrently with DAT
OR Penicillin G	100,000-150,000 units/kg/day IV divided q6h for 14 days	Alternative to erythromycin
Airway management	Intubation or tracheostomy if laryngeal obstruction	As needed for respiratory compromise
Droplet/contact isolation	Until two consecutive negative cultures taken 24 hours apart, obtained at least 24 hours after completing antibiotics	Throughout hospitalization
DPT/Td vaccination	Full vaccination series after recovery (infection does NOT confer reliable immunity)	During convalescence
Close contact prophylaxis	Erythromycin 7-10 days OR single dose benzathine penicillin G (1.2 million units IM for adults, 600,000 units for children <30 kg); throat culture; booster vaccine if >5 years since last dose	Immediately upon identifying contacts

Acute Management. The single most important intervention is diphtheria antitoxin (DAT), which neutralizes circulating unbound toxin. It does NOT reverse toxin already bound to tissues, which is why immediate administration is essential. DAT is derived from horse serum, so a skin test for hypersensitivity must be performed first. If the test is positive but DAT is still indicated (life-threatening disease), desensitization is performed before administration. The dose ranges from 20,000 units for localized nasal/tonsillar disease of less than 48 hours' duration to 100,000 units for extensive disease of 3 or more days' duration or with bull neck.

Antibiotics serve two purposes: eliminating the organism to halt toxin production and preventing transmission. Erythromycin is preferred because it achieves better tissue penetration and has slightly higher eradication rates, but penicillin G is an acceptable alternative. The duration is 14 days for both. After completing antibiotics, two negative throat cultures taken 24 hours apart confirm eradication.

Airway management is the primary concern in laryngeal diphtheria. The pseudomembrane can cause acute obstruction, and attempts to remove it mechanically risk hemorrhage and worsening edema. Tracheostomy may be required if intubation is not feasible.

Cardiac monitoring with telemetry is essential for at least 2 weeks given the risk of myocarditis. Bed rest is recommended during the acute phase and extended if myocarditis develops, as exertion can precipitate fatal arrhythmias.

Post-recovery vaccination is critical because natural infection does not guarantee protective immunity. Patients should receive a full primary series or booster as appropriate for their age.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Infectious mononucleosis (EBV)	Sore throat, tonsillar exudate, cervical lymphadenopathy, fever in a young patient	EBV exudate is whitish and easily removed without bleeding; associated with posterior cervical lymphadenopathy, hepatosplenomegaly, and atypical lymphocytes on smear; no pseudomembrane
Peritonsillar abscess	Severe sore throat, difficulty swallowing, "hot potato" voice, swollen neck	Unilateral tonsillar swelling with uvular deviation and trismus; no pseudomembrane; CT shows rim-enhancing abscess
Streptococcal pharyngitis (GAS)	Sore throat, tonsillar exudate, fever, cervical lymphadenopathy	Exudate is punctate or patchy, easily wiped away; high fever (>38.5C) with abrupt onset; rapid strep test/culture positive; no membrane formation
Epiglottitis	Stridor, drooling, respiratory distress, sore throat in a child	Acute onset with high fever, "tripod" positioning, cherry-red swollen epiglottis on lateral neck X-ray ("thumbprint sign"); no pseudomembrane
Vincent angina (trench mouth)	Pharyngeal ulceration with grayish membrane, foul breath	Caused by fusospirochetal organisms; membrane is on the gingiva primarily with necrotic ulceration; associated with poor dental hygiene; no systemic toxin effects
Retropharyngeal abscess	Neck swelling, stridor, dysphagia, drooling in a young child	Neck stiffness with refusal to extend the neck; lateral neck X-ray shows widened prevertebral space (>7mm at C2); no pharyngeal membrane
Croup (laryngotracheobronchitis)	Stridor, barking cough, hoarseness in a young child	Viral prodrome with runny nose; "steeple sign" on AP neck X-ray; no pseudomembrane; responds to racemic epinephrine and dexamethasone

6. Traps and High-Yield Pearls

The most common way students lose points on diphtheria questions is by delaying antitoxin while waiting for culture results. The vignette will present a classic pseudomembrane in an unvaccinated child and then ask for the "next best step." Students who select "throat culture" or "start antibiotics" before choosing antitoxin will get this wrong. Antitoxin must be given on clinical suspicion alone because it only neutralizes unbound toxin, and every hour of delay allows more toxin to bind irreversibly. Antibiotics and cultures are started simultaneously, but they are never the answer to "what do you do first."

A second frequent trap involves the timing of complications. Myocarditis in the second week and neuropathy in weeks 3-6 are heavily tested. A vignette may describe a patient who was treated for pharyngitis two weeks ago and now presents with new-onset heart block or heart failure. Recognizing this as a delayed complication of diphtheria (rather than attributing it to rheumatic heart disease or viral myocarditis) requires remembering the timeline.

Third, students often confuse the culture media. Loeffler medium is for rapid growth and granule visualization; Tellurite agar is for selective isolation (black colonies). The Elek test is for toxin confirmation, not organism identification. These three serve different roles and are commonly tested in isolation.

Finally, remember that infection does not confer immunity. A recovered patient still needs vaccination. This is occasionally tested as a follow-up management question.

The core competency being tested in diphtheria questions is the ability to recognize a classic clinical presentation (pseudomembrane + bull neck + unvaccinated), initiate the correct first-line intervention (antitoxin before anything else), and anticipate delayed systemic complications based on the toxin's mechanism of action.

1e:["$","$L2d",null,{"article":{"id":"66ca7ef9-bd06-4b33-b4dd-a5ea99ea2f3b","title":"Difteri","content":"$2e","category":"THT-KL","created_at":"2026-05-15T11:11:17.54649+00:00","status":"published","subcategory":null},"questionCount":6,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]