A 5-year-old girl is brought to the emergency department with acute onset of stridor, respiratory distress, and drooling. She has a 4-day history of low-grade fever and sore throat. Her parents report she has never received vaccination. Laryngoscopy reveals a thick, adherent pseudomembrane covering the larynx and trachea. A rapid antigen test and PCR for *Corynebacterium diphtheriae* tox gene are positive. Which complication is the patient at highest risk for in the next 2–3 weeks if antitoxin is not administered immediately?

Explanation

## Laryngeal Diphtheria: Systemic Complications **Key Point:** Laryngeal (croup-like) diphtheria is a severe form that carries high risk of **myocarditis**, the leading cause of death in diphtheria. Myocarditis typically develops 1–3 weeks after symptom onset, even if the local infection resolves. ### Pathophysiology of Diphtheria Myocarditis **High-Yield:** Diphtheria toxin circulates systemically and targets the **myocardium** preferentially: 1. **Toxin-mediated myocyte necrosis:** ADP-ribosylation of EF-2 → protein synthesis inhibition → myocyte apoptosis 2. **Inflammatory response:** Toxin triggers release of cytokines (TNF-α, IL-6) → myocardial inflammation 3. **Conduction system involvement:** Toxin damages the conduction pathways → various degrees of heart block (1st, 2nd, 3rd degree) 4. **Myocardial dysfunction:** Leads to: - Arrhythmias (ventricular tachycardia, atrial fibrillation) - Cardiogenic shock - Sudden cardiac death ### Timeline of Diphtheria Complications ```mermaid flowchart TD A["Symptom Onset<br/>Days 1-3: Pharyngitis/Laryngitis"]:::outcome A --> B["Pseudomembrane formation<br/>Respiratory obstruction risk"]:::outcome B --> C["Days 7-14: Systemic toxin effects"]:::action C --> D{"Organ involvement"}:::decision D -->|"Myocardium (most common)"| E["Myocarditis with conduction defects"]:::urgent D -->|"Peripheral nerves"| F["Cranial nerve palsies, respiratory paralysis"]:::urgent D -->|"Kidney"| G["Acute tubular necrosis"]:::outcome E --> H["Days 14-21: Peak risk of arrhythmias, shock"]:::urgent F --> I["Respiratory failure if phrenic nerve involved"]:::urgent ``` ### Clinical Features of Diphtheria Myocarditis | Feature | Mechanism | Timing | | --- | --- | --- | | Tachycardia out of proportion to fever | Direct myocardial damage + inflammatory response | Days 7–14 | | Muffled heart sounds, new murmur | Myocardial edema, ventricular dysfunction | Days 7–14 | | ECG changes: prolonged PR, widened QRS, ST changes | Conduction system and myocardial necrosis | Days 7–21 | | Heart block (1°, 2°, 3°) | Toxin damage to conduction pathways | Days 10–21 | | Arrhythmias (VT, AF) | Myocardial irritability from necrosis | Days 14–28 | | Cardiogenic shock, sudden death | Severe myocardial dysfunction | Days 14–28 | **Clinical Pearl:** Myocarditis in diphtheria is **not always accompanied by severe local respiratory disease**—a patient with mild pharyngitis can develop fatal myocarditis. This is why **systemic monitoring and early antitoxin administration are critical**. ### Why Antitoxin Must Be Given Immediately **Warning:** Antitoxin is effective **only if given early** (ideally within 48 hours of symptom onset, but up to 7 days may still help). Once toxin binds to EF-2 and enters the cell, antitoxin cannot reverse the damage. In this case, the patient is already at day 4—antitoxin is still indicated but myocarditis risk is already elevated. ### Management of Laryngeal Diphtheria 1. **Immediate airway management:** Prepare for intubation/tracheostomy (stridor indicates laryngeal involvement) 2. **Antitoxin (horse serum):** 20,000–100,000 units IV/IM depending on severity and duration 3. **Antibiotics:** Penicillin G 2–4 million units IV q4h or ceftriaxone 4. **Supportive care:** Oxygen, cardiac monitoring (continuous ECG), ICU admission 5. **Cardiac monitoring:** Serial ECGs, troponin, echocardiography to assess ventricular function **High-Yield:** The mortality in diphtheria is primarily from **myocarditis and its complications** (arrhythmias, shock), not from respiratory obstruction or sepsis. [cite:Park 26e Ch 28; Harrison 21e Ch 139]