A 7-year-old unvaccinated boy from rural Maharashtra presents with a 3-day history of sore throat, low-grade fever (38.2°C), and progressive dysphagia. On examination, he has a thick, adherent, greyish-white pseudomembrane covering the pharynx and tonsils that bleeds on attempted removal. Cervical lymph nodes are enlarged and tender. A throat swab is sent for culture. Which of the following is the most likely causative organism and the toxin-mediated pathophysiology?

Explanation

## Diagnosis: Diphtheria **Key Point:** The clinical presentation of a thick, adherent pseudomembrane in the pharynx with systemic toxicity in an unvaccinated child is pathognomonic for diphtheria caused by *Corynebacterium diphtheriae*. ### Pseudomembrane Characteristics - Greyish-white, leathery appearance - Firmly adherent to underlying tissue (bleeds on removal) - Extends beyond tonsils to pharynx, larynx, or nasopharynx - Composed of fibrin, necrotic epithelium, and bacterial colonies ### Diphtheria Toxin Mechanism 1. Lysogenic bacteriophage carries *tox* gene (only in lysogenized strains) 2. Toxin is an A-B toxin: catalytic domain inactivates elongation factor 2 (EF-2) 3. Inhibition of EF-2 prevents translocation during protein synthesis 4. Results in cell death and tissue necrosis → pseudomembrane formation 5. Systemic effects: myocarditis, neuritis (cranial and peripheral nerves) **High-Yield:** Only *lysogenized* strains of *C. diphtheriae* produce toxin. Non-lysogenized strains cause mild pharyngitis without systemic toxicity. ### Clinical Pearls - **Bull neck appearance**: Severe cervical edema and lymphadenopathy - **Complications**: Myocarditis (arrhythmias, heart block), cranial nerve palsies (CN IX, X, XII), respiratory obstruction - **Diagnosis**: Culture on Loeffler's medium or tellurite agar; toxin production confirmed by Elek test or PCR for *tox* gene - **Treatment**: Antitoxin (neutralizes circulating toxin, does NOT reverse already-bound toxin) + antibiotics (penicillin or erythromycin) **Mnemonic: DIPHTHERIA toxin = Diphtheria toxin Inactivates Protein synthesis via EF-2 (Elongation Factor 2)** ### Why Other Organisms Don't Fit - *S. pyogenes*: Causes exudative pharyngitis, NOT a pseudomembrane; toxins are superantigens - *S. aureus*: Causes localized skin/soft tissue infection; alpha-toxin is cytolytic, not neurotoxic - *C. albicans*: Causes oral thrush (white patches, not adherent membrane); seen in immunocompromised patients