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, greyish-white pseudomembrane covering the posterior pharynx and soft palate that does not bleed when gently scraped. His neck shows "bull neck" appearance with marked cervical lymphadenopathy and soft tissue edema. A throat swab is sent for culture. Which organism is most likely responsible, and what is the primary mechanism of tissue damage in this patient?

Explanation

## Clinical Diagnosis: Diphtheria **Key Point:** The classic triad of diphtheria—pseudomembrane (thick, greyish-white, adherent), bull neck appearance (cervical edema and lymphadenopathy), and systemic toxicity—is pathognomonic for *Corynebacterium diphtheriae* infection. ### Pathophysiology of Diphtheria Toxin **High-Yield:** *C. diphtheriae* produces diphtheria toxin (a lysogenic bacteriophage-encoded exotoxin) via the tox gene. The toxin has two subunits: 1. **Fragment A (catalytic):** Catalyzes ADP-ribosylation of elongation factor-2 (EF-2) 2. **Fragment B (binding):** Facilitates cellular entry via receptor-mediated endocytosis **Mechanism of Damage:** - ADP-ribosylation of EF-2 → inhibition of peptide translocation → cessation of protein synthesis - Results in cell death, especially in myocardium, peripheral nerves, and kidney - Leads to myocarditis (arrhythmias, heart block), neuropathy (cranial nerve palsies, respiratory paralysis), and acute tubular necrosis ### Clinical Features Explained | Feature | Cause | | --- | --- | | Pseudomembrane | Fibrin, RBCs, WBCs, necrotic epithelium; non-bleeding (unlike strep) | | Bull neck | Cervical lymphadenopathy + soft tissue edema from toxin-mediated inflammation | | Systemic toxicity | Circulating toxin causes myocarditis, neuropathy, renal damage | **Clinical Pearl:** The pseudomembrane in diphtheria is **non-hemorrhagic and does not bleed when scraped**—this distinguishes it from streptococcal pharyngitis, where the membrane is friable and bleeds easily. ### Diagnosis & Culture - **Culture media:** Löffler's serum medium or Tinsdale medium (selective for *C. diphtheriae*) - **Gram stain:** Gram-positive bacilli with metachromatic granules ("beads on a string") - **Toxin confirmation:** Elek immunodiffusion test or PCR for tox gene **Warning:** Culture may be negative if antibiotics have been started; toxin detection is more reliable in acute phase. ### Management 1. **Antitoxin (horse serum):** Must be given early (within 48 hrs of symptom onset) before toxin binds to tissues 2. **Antibiotics:** Penicillin G or erythromycin to eradicate organism 3. **Supportive care:** Airway management, cardiac monitoring for myocarditis 4. **Prevention:** Vaccination (DPT/Td) in unvaccinated contacts [cite:Park 26e Ch 28]