Diphtheria in Children: Clinical Case Discussion
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 6 years, Gender: Male, Informant: Mother (Reliable)
Chief Complaints
- Sore throat and low-grade fever – 3 days
- Hoarse voice and noisy breathing – 2 days
- Neck swelling – 1 day
History Summary
The child developed low-grade fever and sore throat 3 days ago, followed by hoarseness and a barking, croupy cough. Breathing has become progressively noisy (stridor). Mother noticed a foul-smelling, blood-tinged nasal discharge and a grayish-white patch in the throat that bled when she tried to wipe it. The child is poorly immunized — received only one dose of DPT at 6 weeks, after which the family relocated and follow-up was missed. No prior episode of stridor. No rash, no seizures.
Born at term via NVD. Birth weight 2.9 kg. Lived in a semi-urban, overcrowded locality. No family member with similar illness. No known drug allergy.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Temperature | 38.2°C | Low-grade fever (characteristically not high) |
| RR | 38/min | Tachypnea (airway compromise) |
| HR | 120/min | Tachycardia |
| SpO2 | 93% (room air) | Hypoxemia — impending airway obstruction |
| Voice | Hoarse, "hot potato" voice | Laryngeal involvement |
| Neck | Bilateral cervical lymphadenopathy with periglandular edema | "Bull neck" appearance |
Throat examination: Grayish-white, tough, leathery pseudomembrane covering both tonsils and extending to the pharynx and soft palate. Membrane is firmly adherent — attempts to remove it cause bleeding. Foul fetor oris. Bilateral tonsillar enlargement.
Respiratory: Inspiratory stridor. Subcostal and intercostal retractions. No wheeze.
CVS: Normal S1 S2. No murmur at presentation.
Immunization status: Incomplete — only 1 dose of DPT received.
✅ Complete Diagnosis
Laryngopharyngeal Diphtheria (Faucial + Laryngeal) with Bull Neck Appearance and Impending Airway Obstruction in an Incompletely Immunized Child.
📝 History — Exam Q&A
Corynebacterium diphtheriae — a non-encapsulated, non-motile, aerobic gram-positive bacillus. On microscopy it shows a characteristic Chinese letter / cuneiform arrangement and metachromatic (Babes-Ernst) granules on Albert's stain. The toxin gene is encoded by a lysogenic bacteriophage (corynephage β). Only toxigenic strains cause the classical disease. C. ulcerans and C. pseudotuberculosis can also produce diphtheria toxin.
- Age: Predominantly children 1–10 years; adults in low-vaccination settings
- Transmission: Respiratory droplets (primary), direct contact with infected secretions or skin lesions
- Incubation period: 2–5 days (range 1–10 days)
- Season: More common in cooler months
- Risk factors: Incomplete/no immunization, overcrowding, poor socioeconomic status, travel to endemic areas
- Humans are the only reservoir
- Infectivity: Patient is contagious until 2 negative cultures are obtained (usually 2–4 weeks if untreated; becomes non-infectious 48 hours after starting antibiotics)
| Type | Site | Key Feature |
|---|---|---|
| Faucial (Tonsillopharyngeal) | Tonsils / pharynx | Most common (~75%); classic pseudomembrane |
| Laryngeal / Laryngotracheal | Larynx ± trachea | Stridor, croup, most dangerous for airway |
| Nasal | Anterior nares | Serosanguineous nasal discharge; milder toxemia |
| Cutaneous | Skin wounds | Chronic ulcer with membrane; more common in tropics |
| Other (rare) | Conjunctiva, ear, vulva | Very rare |
💡 Pearl
Nasal diphtheria has the least systemic toxicity because toxin absorption from nasal mucosa is minimal. Laryngeal diphtheria carries the highest risk of mechanical death due to airway obstruction.
Day 1–2: Low-grade fever, malaise, anorexia, mild sore throat. Small whitish spot on the tonsil.
Day 2–3: White patch enlarges and becomes a grayish-white, tough, adherent pseudomembrane covering the tonsils. Membrane extends to pharynx, uvula, and soft palate. Foul-smelling breath. Cervical lymphadenopathy develops.
Day 3–5: If larynx involved — hoarseness, barking cough, inspiratory stridor. Bull neck (periglandular edema). Systemic toxemia — pallor, tachycardia, weakness.
Week 2 onwards: Risk of myocarditis (toxin effect on heart) and neuropathy (palatal palsy earliest).
🚨 Key Characteristic
Fever in diphtheria is characteristically low-grade despite severe local disease. High fever suggests secondary bacterial infection.
Bull neck refers to the appearance of massive bilateral cervical lymphadenopathy combined with brawny, non-pitting periglandular edema of the neck, giving a "bull-like" appearance. It indicates:
- Severe, extensive pharyngeal/tonsillar disease with significant toxin absorption
- Higher risk of systemic complications (myocarditis, neuropathy)
- Toxic/severe diphtheria — poor prognosis without prompt treatment
- Immunization history — number of DPT doses, last dose, schedule completion (most important)
- Contact history — exposure to anyone with sore throat / similar illness
- Nasal discharge — blood-tinged discharge = nasal diphtheria
- Voice change / stridor — laryngeal involvement
- Swallowing difficulty — pharyngeal involvement / palatal palsy
- Palpitations / syncope — suggests myocarditis
- Residence / travel — endemic area, overcrowded locality
Local disease: C. diphtheriae colonizes the mucosal surface (iron-limiting conditions activate toxin production). The exotoxin causes local tissue necrosis → coagulation of fibrin, dead epithelial cells, neutrophils → forms the tough gray pseudomembrane. The membrane bleeds on removal because it is firmly adherent to the underlying inflamed mucosa.
Systemic disease (toxin mechanism):
- Toxin is a 58 kDa polypeptide with two fragments: Fragment B (binding) binds to HB-EGF receptor on cell surface → receptor-mediated endocytosis
- Fragment A (active/enzymatic) enters cytosol and performs ADP-ribosylation of Elongation Factor-2 (EF-2) using NAD⁺ → inactivates EF-2 → protein synthesis is irreversibly halted → cell death
- One molecule of Fragment A can kill a cell — extremely potent
- Tissues most vulnerable: myocardium and peripheral nerves (highest metabolic demand for protein synthesis)
💡 Mnemonic
"B Binds, A Acts" — Fragment B binds to receptor; Fragment A performs ADP-ribosylation of EF-2.
A carrier is a person who harbors C. diphtheriae in the upper respiratory tract without clinical symptoms. Carriers can be toxigenic or non-toxigenic. They are a significant source of transmission.
Management:
- Treat with antibiotics: Erythromycin 40–50 mg/kg/day orally for 14 days (or Penicillin)
- Confirm eradication with two consecutive negative cultures taken at least 24 hours apart and at least 24 hours after completing antibiotics
- Diphtheria antitoxin (DAT) is NOT required for carriers
- Ensure up-to-date vaccination
🩺 Examination — Exam Q&A
The pseudomembrane is the pathognomonic sign of diphtheria. Its key characteristics:
- Color: Initially white → becomes grayish-white or dirty gray as it matures
- Consistency: Tough, leathery, fibrinous
- Adherence: Firmly adherent to the underlying mucosa — bleeds when forcibly removed
- Extent: Starts on tonsils → may spread to pharynx, soft palate, uvula, larynx, trachea, and bronchi
- Odor: Foul, putrid fetor
- Composition: Fibrin, dead epithelial cells, neutrophils, and colonies of C. diphtheriae
🚨 Never forcibly remove the membrane
Forcible removal causes bleeding and may dislodge the membrane into the airway, precipitating sudden asphyxiation.
| Feature | Diphtheria | Infectious Mononucleosis | Streptococcal Tonsillitis | Vincent's Angina |
|---|---|---|---|---|
| Membrane color | Grayish-white, dirty gray | White/gray | White/yellow exudate (not membrane) | Grayish, necrotic ulcer |
| Adherence | Firmly adherent, bleeds on removal | Easily removed, no bleeding | Easily wiped off | Moderately adherent |
| Extent beyond tonsil | Yes — extends to pharynx, uvula | Confined to tonsils | Confined to tonsils | Unilateral, ulcerative |
| Fever | Low-grade | High-grade | High-grade | Low-grade |
| Cervical LN | Bilateral + brawny edema (bull neck) | Marked bilateral (including posterior) | Tender anterior cervical | Unilateral |
| Organism | C. diphtheriae | EBV | Group A Streptococcus | Fusobacterium + Spirochetes |
- Hoarseness of voice ("hot potato voice")
- Barking / croupy cough
- Inspiratory stridor (due to subglottic membrane)
- Intercostal, subcostal, and suprasternal retractions
- Respiratory distress progressing to cyanosis and asphyxia if untreated
- Aphonia (complete loss of voice) in severe cases
🚨 Airway Emergency
Laryngeal diphtheria is a medical emergency. The membrane can extend down the tracheobronchial tree or be dislodged, causing sudden complete airway obstruction and death from asphyxia.
Diphtheritic myocarditis — occurs in 10–25% of cases; most common cause of death from diphtheria.
- Timing: Typically 1–2 weeks after onset (can occur as late as 4–6 weeks)
- Signs: Tachycardia out of proportion to fever, muffled heart sounds, gallop rhythm, cardiac enlargement, hypotension, circulatory collapse
- ECG changes: ST-T wave changes, prolonged PR interval, complete heart block (3rd degree AV block — most dangerous), bundle branch blocks, dysrhythmias (VT, VF)
- Key observation: Paradoxical improvement in throat symptoms as cardiac symptoms worsen — "as the membrane improves, the heart deteriorates"
💡 Pearl
Complete (3rd degree) AV block in diphtheria is a grave prognostic sign. Temporary cardiac pacing may be required.
Diphtheritic neuropathy is a demyelinating polyneuropathy due to toxin-mediated inhibition of myelin protein synthesis. Complications occur in a characteristic sequence:
| Timing | Neurological Complication | Presentation |
|---|---|---|
| Week 1–3 (early, local) | Palatal palsy (most common early neuropathy) | Nasal regurgitation of fluids, nasal twang in voice, absent gag reflex |
| Week 3–5 | Oculomotor palsy | Accommodation palsy (blurred near vision), ptosis, diplopia, ophthalmoplegia |
| Week 5–8 | Peripheral motor neuropathy | Limb weakness, wrist drop, foot drop |
| Week 8–12 | Generalized polyneuropathy | Ascending paralysis similar to Guillain-Barré (rare, severe cases) |
| Late (rare) | Diaphragm palsy | Respiratory failure |
Good news: Diphtheritic neuropathy is fully reversible with recovery — unlike most other toxic neuropathies.
| Grade | Features |
|---|---|
| Mild (Nasal / localized tonsillar) | Membrane confined to tonsils, no toxemia, no systemic features |
| Moderate (Faucial/pharyngeal) | Membrane extends beyond tonsils to pharynx/palate, cervical lymphadenopathy, moderate toxemia |
| Severe (Laryngeal / Bull neck) | Membrane in larynx/trachea with stridor, bull neck appearance, severe toxemia, risk of airway obstruction |
| Very severe / Hypertoxic | Extensive membrane, profound toxemia, circulatory collapse, myocarditis early onset, hemorrhagic features |
The Schick test is an intradermal test to determine susceptibility to diphtheria.
- Method: 1/50 MLD of diphtheria toxin is injected intradermally in one forearm (test site); heat-inactivated toxin in the other arm (control site)
- Positive test (susceptible): Erythema and induration at test site within 24–36 hours, NOT at control site → person lacks protective antitoxin (< 0.03 IU/mL)
- Negative test (immune): No reaction at test site → person has adequate antitoxin levels → protected
- Pseudo-reaction: Reaction at both sites (due to non-specific hypersensitivity to proteins) — fades by day 4
- Combined reaction: Both sites positive — susceptible + hypersensitive individual
The Schick test is now largely replaced by serological antitoxin level measurement and is rarely performed clinically.
🔬 Investigations — Exam Q&A
Culture of C. diphtheriae from a throat/membrane swab — this is the gold standard for etiologic confirmation.
Important points about culture:
- Swab from the margin (edge) of the pseudomembrane or beneath it (not the surface) gives the best yield
- Transport in Loeffler's serum medium or tellurite transport medium — always inform the laboratory about clinical suspicion
- Culture on Loeffler's serum slope or Tellurite agar (Hoyle's/CTBA) — organisms appear as black colonies on tellurite agar
- Albert's stain (modified Neisser stain): Shows club-shaped bacilli with metachromatic (Babes-Ernst) granules — characteristic "Chinese letter / cuneiform arrangement"
- Culture results take 24–48 hours — DO NOT WAIT; start treatment empirically
Culture alone only identifies the organism; toxigenicity must be separately confirmed:
- Elek's gel precipitation test (Elek's test) — gold standard for in vitro toxigenicity testing. A strip of antitoxin-impregnated filter paper is placed on a culture plate; the bacteria are streaked perpendicular to it. If the strain is toxigenic, toxin diffuses out and forms a precipitation line with antitoxin (like an immunodiffusion/Ouchterlony plate) — a visible white "arrowhead" precipitation line forms.
- PCR for the diphtheria toxin gene (tox gene) — rapid, sensitive, and specific. Now the preferred method in reference laboratories.
- Guinea pig inoculation test (historical, rarely used now)
The Nagler reaction is NOT specific to diphtheria. It is used to identify Clostridium perfringens by its lecithinase activity on egg-yolk agar — colonies show opalescence inhibited by specific antitoxin on one side of the plate.
Do not confuse with Elek's test (which is specific for diphtheria toxigenicity).
🚨 Common Exam Trap
Nagler reaction → C. perfringens (alpha toxin / lecithinase). Elek's test → C. diphtheriae toxigenicity. Do not confuse them.
| Investigation | Finding / Significance |
|---|---|
| CBC | Moderate leukocytosis; thrombocytopenia in severe/toxic cases |
| ECG | Mandatory — ST-T changes, PR prolongation, heart block (AV blocks), dysrhythmias indicate myocarditis |
| Serum Troponin / CPK-MB | Elevated in myocarditis; useful for monitoring cardiac involvement |
| Echocardiogram | Assess ventricular function, wall motion abnormalities in myocarditis |
| Chest X-ray | Subglottic narrowing ("steeple sign") in laryngeal involvement; cardiomegaly if myocarditis |
| Neck X-ray (soft tissue lateral) | Subglottic and tracheal narrowing; pseudomembrane may be visible |
| Serum antitoxin levels | Protective level ≥ 0.1 IU/mL; levels < 0.01 IU/mL = fully susceptible |
| Medium | Feature |
|---|---|
| Loeffler's serum slope | Enrichment medium; enhances metachromatic granule formation; allows rapid growth |
| Tellurite blood agar (Hoyle's / CTBA) | Selective medium; C. diphtheriae reduces tellurite → black/grey colonies |
| Blood agar | Non-selective; no distinct appearance |
Gravis biotype: flat, grey, irregular colonies. Mitis biotype: black, shiny colonies. Intermedius biotype: small, flat colonies.
💊 Management — Exam Q&A
- Isolation — strict respiratory (droplet + contact) isolation immediately
- Airway assessment — assess for stridor, retractions, hypoxia; keep intubation/tracheostomy ready if laryngeal involvement
- Take cultures before antibiotics if possible — but do NOT delay treatment
- Diphtheria Antitoxin (DAT) — administer as soon as possible (primary treatment); perform horse serum hypersensitivity test first
- Antibiotics — start empirically
- ECG monitoring — for cardiac involvement
- Notify public health authorities — mandatory notifiable disease
- Contact tracing — identify and investigate close contacts
🚨 Critical Point
Diphtheria is a clinical diagnosis. DO NOT wait for culture confirmation before starting DAT and antibiotics. Delay in antitoxin administration is associated with significantly higher mortality.
DAT is an equine (horse serum) hyperimmune antitoxin — the cornerstone of treatment. It neutralizes free, unbound circulating toxin only. Once toxin has entered cells, it cannot be neutralized.
Before administration — hypersensitivity testing is MANDATORY:
- Intradermal test: 0.1 mL of 1:1000 diluted DAT in normal saline intradermally; read at 15–20 minutes. Wheal ≥ 3 mm with erythema = positive (hypersensitive)
- If positive: Desensitization protocol required (progressive dose escalation)
- Adrenaline 1:1000 must be kept ready at bedside before administration
| Severity / Type | DAT Dose (Units) | Route |
|---|---|---|
| Nasal diphtheria / mild pharyngeal | 20,000 – 40,000 IU | IM or IV |
| Moderate pharyngeal / laryngeal (≤48 hrs) | 40,000 – 60,000 IU | IV (preferred) |
| Severe / bull neck / late presentation (>48 hrs) | 80,000 – 1,20,000 IU | IV |
IV infusion: DAT diluted in 250–500 mL normal saline, infused over 1–2 hours (warm to 32–34°C before use). Given as a single dose only — repeated doses are NOT recommended.
Adverse effects: Anaphylaxis (< 1%), serum sickness (7–10 days later — fever, urticaria, arthralgia, lymphadenopathy)
Antibiotics eliminate the organism but do NOT neutralize toxin (that is the role of DAT).
| Antibiotic | Dose | Duration | Notes |
|---|---|---|---|
| Erythromycin (WHO preferred as per 2024 guidelines) | 40–50 mg/kg/day IV/oral in divided doses (max 2 g/day) | 14 days | Drug of choice per WHO 2024; macrolide |
| Azithromycin | 10–12 mg/kg/day orally once daily (max 500 mg/day) | 14 days | Alternative macrolide; WHO 2024 recommends macrolides over penicillin |
| Crystalline Penicillin G | 1,00,000–2,00,000 U/kg/day IV 4–6 hourly | 14 days | Alternative; switch to oral after improvement |
| Procaine Penicillin | 25,000–50,000 U/kg/day IM once daily | 14 days | Oral amoxicillin/penicillin V to complete 14 days |
💡 WHO 2024 Update
The new WHO 2024 guidelines recommend macrolides (erythromycin/azithromycin) over penicillin for treatment of diphtheria, based on better in vivo evidence for clearing the organism.
After completing antibiotics: confirm eradication with 2 consecutive negative throat cultures taken 24 hours apart.
- Supplemental oxygen immediately
- Humidified air — helps loosen secretions and reduce mucosal edema
- Upright positioning
- Administer DAT and antibiotics promptly — reduces membrane spread
- Intubation — for severe respiratory distress; have difficult airway equipment ready (membrane can make laryngoscopy and intubation challenging)
- Tracheostomy / cricothyrotomy — if intubation not possible or membrane extends below cords; may be life-saving in complete obstruction
- Mechanical aspiration of membrane — only by experienced personnel in controlled setting (risk of dislodging fragment)
- Strict bed rest — mandatory; physical activity increases cardiac risk
- ECG monitoring — continuous cardiac monitoring for dysrhythmias and heart blocks
- Treat heart failure: Diuretics, digoxin (use with extreme caution — increased sensitivity to digoxin toxicity in myocarditis); avoid if severe block
- Antiarrhythmic therapy as required
- Temporary cardiac pacing — for complete (3rd degree) AV block or symptomatic bradycardia
- Corticosteroids — NOT proven to be beneficial; not routinely recommended
- Carnitine supplementation — some evidence suggests benefit; under investigation
All close contacts (household members, caretakers, healthcare workers with direct exposure) should be managed as follows:
- Throat and nasal swab cultures taken regardless of symptoms or vaccination status
- Antibiotic prophylaxis: Erythromycin 40–50 mg/kg/day orally for 7–10 days OR single IM dose of Benzathine Penicillin G (6 lakh U for < 30 kg; 12 lakh U for ≥ 30 kg) — particularly when compliance with oral antibiotics is uncertain
- Vaccination: Check immunization status and give a booster dose of diphtheria toxoid-containing vaccine if last dose was > 5 years ago, or if not fully vaccinated
- DAT is NOT routinely given for prophylaxis to contacts (only in exceptional circumstances, e.g., unvaccinated high-risk contact who cannot take antibiotics)
- Surveillance for 7–10 days for development of symptoms
| Vaccine | Schedule | Route |
|---|---|---|
| DPT (Primary series) | 6 weeks, 10 weeks, 14 weeks | IM |
| DPT (Booster 1) | 16–24 months | IM |
| DPT (Booster 2 — DT or TT) | 5–6 years (school entry) | IM |
| Td (Tetanus-diphtheria) | 10 years and 16 years | IM |
- Full immunization (3 doses + boosters) confers ~95% protection
- Immunity wanes over time — boosters every 10 years with Td in adults
- Important: Natural diphtheria disease does NOT always confer lasting immunity — patients must be vaccinated during convalescence to ensure immunity
Overall case fatality rate: 5–10%; higher (up to 20–25%) in young children, elderly, and if treatment delayed. In untreated cases, mortality was historically 50%.
Poor prognostic factors:
- Young age (< 2 years)
- Bull neck appearance
- Laryngeal involvement with stridor
- Delay in DAT administration (> 3 days from onset)
- Early onset of myocarditis (within the first week)
- Complete (3rd degree) AV block
- Hypoxemia at presentation
- Elevated serum creatinine (renal involvement)
- Unvaccinated status
🔭 Recent Advances — Exam Q&A
WHO published its first-ever comprehensive clinical management guideline for diphtheria in February 2024, prompted by major outbreaks in Nigeria, Guinea, and surrounding countries in 2023. Key recommendations include:
- Antibiotics: Macrolides (erythromycin or azithromycin) are now preferred over penicillin antibiotics for all diphtheria cases based on better evidence for clearing the organism in vivo
- DAT: Strong recommendation to administer DAT as early as possible in suspected/confirmed respiratory diphtheria. DAT is NOT recommended for cutaneous diphtheria unless systemic features are present
- DAT availability: Guidelines highlight a global shortage of DAT and provide evidence-based dosing recommendations to enable use even when supply is limited
- Supportive care: Emphasized as critical — airway management, cardiac monitoring, nutritional support
- Vaccination remains the top priority for prevention
Diphtheria is considered a re-emerging disease in settings with declining vaccination coverage:
- 2023 Nigeria outbreak: One of the largest in decades, predominantly affecting unvaccinated children aged 5–10 years; mortality ~10–23% in hospitalized patients
- 2017–2018 Yemen and Rohingya refugee crisis (Bangladesh): Large outbreaks due to collapse of immunization programs during conflict
- Europe (2022–2024): Outbreaks of cutaneous diphtheria among refugees, especially along the Balkan migration route
- India: Diphtheria remains endemic, particularly in states with suboptimal DPT coverage (Bihar, UP, Rajasthan). Seasonal increase in winter months.
- Globally, WHO estimates ~16,000 cases annually with significant underreporting
PCR for the diphtheria tox gene (encoding the diphtheria toxin) is increasingly replacing the Elek's test as the preferred method for toxigenicity testing in reference laboratories.
- Advantages: Rapid (hours vs. 48 hours for Elek's), highly sensitive and specific, can be performed directly on clinical specimens (throat swabs) without culture
- Important caveat: A positive PCR for tox gene does NOT always mean the strain is toxin-producing (the gene may be present but not expressed); Elek's test or ELISA for the toxin confirms actual toxin production
- Real-time PCR and whole genome sequencing (WGS) are now used for outbreak investigation and strain typing
Non-toxigenic C. diphtheriae (NTCD) strains are increasingly recognized as pathogens. They lack the phage-encoded tox gene but can still cause:
- Pharyngitis and local throat disease (without pseudomembrane formation)
- Bacteremia and endocarditis (especially in patients with underlying cardiac disease or IV drug users)
- Septic arthritis, osteomyelitis
- Cutaneous infections
NTCD infections do NOT cause the systemic toxic complications (myocarditis, neuropathy) because they produce no diphtheria toxin. However, they are important as they can cause serious invasive disease and may acquire tox gene by transduction. Treatment is with antibiotics (no DAT needed).
Diphtheria toxin has been harnessed in immunotoxin therapy for cancer:
- Denileukin diftitox (Ontak): A fusion protein of IL-2 (targets IL-2 receptor on T-cells) linked to the active fragment of diphtheria toxin — used in cutaneous T-cell lymphoma (CTCL). It selectively kills IL-2 receptor-expressing tumor cells by inhibiting their protein synthesis.
- Moxetumomab pasudotox: Uses Pseudomonas exotoxin A (same EF-2 mechanism) — used in hairy cell leukemia
- The DT toxin mechanism (catalytic ADP-ribosylation of EF-2) is also used in research to selectively ablate specific cell populations in mice (Diphtheria Toxin Receptor / DTR mouse model)
⚡ Key Points — Quick Revision
One-Liners for Exam
- Organism: Corynebacterium diphtheriae — Gram-positive bacillus with Chinese letter arrangement; toxin gene on corynephage β
- Stain: Albert's stain → metachromatic (Babes-Ernst) granules
- Culture media: Loeffler's serum slope (enrichment) + Tellurite agar (selective — black colonies)
- Toxin mechanism: Fragment A → ADP-ribosylation of EF-2 → protein synthesis inhibited → cell death
- Pathognomonic sign: Grayish-white, firmly adherent pseudomembrane — BLEEDS on removal
- Pseudomembrane that does NOT bleed on removal: NOT diphtheria (think viral tonsillitis, EBV)
- Bull neck: Bilateral cervical lymphadenopathy + brawny periglandular edema = severe/toxic diphtheria
- Most dangerous complication: Myocarditis (most common cause of death) — appears 1–2 weeks after onset
- Earliest neurological complication: Palatal palsy → nasal regurgitation, nasal twang
- Diphtheritic neuropathy is FULLY REVERSIBLE
- Fever in diphtheria: Characteristically LOW-GRADE despite severe disease
- Gold standard Dx: Culture from margin of membrane + Elek's test for toxigenicity
- Toxigenicity test: Elek's gel precipitation test (in vitro) / PCR for tox gene
- Nagler reaction: C. perfringens (NOT diphtheria — common exam trap)
- Treatment 1 (MOST IMPORTANT): Diphtheria Antitoxin (DAT) — equine antitoxin; neutralizes FREE toxin only; single dose IV; test for horse serum hypersensitivity first
- Treatment 2: Erythromycin / Azithromycin × 14 days (WHO 2024 preferred over penicillin); eliminates organism
- Do NOT wait for culture results to start DAT and antibiotics
- Serum sickness: Adverse effect of DAT — appears 7–10 days after administration
- Contacts: Throat culture + erythromycin 7–10 days ± benzathine penicillin + booster vaccine
- Carrier culture clearance: 2 consecutive negative cultures ≥ 24 hours apart after completing antibiotics
- Natural infection does NOT guarantee immunity — vaccinate during convalescence
- WHO 2024: First formal clinical management guideline — recommends macrolides over penicillin
- DT in oncology: Denileukin diftitox (IL-2-DT fusion) → used in CTCL
- Schick test: Positive = susceptible; Negative = immune
🩺 Differential Diagnosis of Pseudomembrane (Quick Summary)
- Diphtheria: Grayish, adheres, bleeds, extends beyond tonsil, low-grade fever, bull neck
- EBV (IM): White, easily removed, confined to tonsil, high fever, generalized lymphadenopathy, hepatosplenomegaly
- Streptococcal: Yellow exudate, not a true membrane, easily removed, high fever, no bull neck
- Candida (Thrush): White patches on oral mucosa, easily scraped, underlying erythema; immunocompromised
- Vincent's angina: Unilateral, ulcerative, grayish necrotic, Fusobacterium + spirochetes