A 35-year-old man with a 10-year history of asthma presents with recurrent episodes of fever, eosinophilia (absolute count 4500/μL), and pulmonary infiltrates on chest X-ray that migrate from one lobe to another over weeks. He denies recent infections or drug use. Serum IgE level is markedly elevated at 2800 IU/mL. Sputum examination shows Aspergillus fumigatus. Which type of hypersensitivity reaction best explains the pathophysiology of his pulmonary disease?

Question

Accepted Answer

C. Type III hypersensitivity with immune complex deposition and complement-mediated inflammation. ## Allergic Bronchopulmonary Aspergillosis (ABPA)

This patient presents with **allergic bronchopulmonary aspergillosis (ABPA)**, a complex hypersensitivity disorder involving **both Type I and Type III hypersensitivity reactions**. The predominant pathophysiologic mechanism is **Type III hypersensitivity** (immune complex-mediated disease).

### Clinical Features of ABPA

| Feature | Finding in This Case |
|---------|----------------------|
| **Predisposition** | Pre-existing asthma (10 years) |
| **Fungal colonization** | *Aspergillus fumigatus* in sputum |
| **Pulmonary findings** | Migratory infiltrates (fleeting opacities) |
| **Systemic manifestations** | Fever, malaise |
| **Laboratory markers** | Elevated IgE (>1000 IU/mL), eosinophilia |
| **Immunologic basis** | IgE + IgG immune complexes |

### Pathophysiologic Mechanisms in ABPA

**Key Point:** ABPA involves a dual hypersensitivity response:

1. **Type I Hypersensitivity (IgE-mediated)**
   - IgE antibodies against *Aspergillus* antigens bind to mast cells
   - Causes acute bronchoconstriction and bronchial hyperresponsiveness
   - Contributes to elevated serum IgE

2. **Type III Hypersensitivity (Immune Complex-mediated)** — **PRIMARY MECHANISM**
   - IgG antibodies against *Aspergillus* antigens form immune complexes
   - Complexes deposit in pulmonary tissue (bronchial walls, alveoli)
   - Complement activation (C3, C5) → recruitment of neutrophils and eosinophils
   - Results in **eosinophilic inflammation**, bronchitis, and bronchiectasis
   - Causes the characteristic **migratory pulmonary infiltrates** (fleeting opacities)

### Why Type III Hypersensitivity Is Predominant

**High-Yield:** The key diagnostic clues pointing to Type III are:

- **Migratory infiltrates** — hallmark of immune complex deposition shifting as antigen-antibody ratios change
- **Eosinophilia** — complement-mediated recruitment of eosinophils (not typical of pure Type I)
- **Systemic symptoms** (fever) — characteristic of immune complex disease
- **Elevated IgG antibodies** against *Aspergillus* (Type III mechanism)
- **Chronic, progressive course** — Type III reactions are typically delayed and persistent

**Clinical Pearl:** ABPA is distinguished from simple allergic asthma (pure Type I) by the presence of:
- Pulmonary infiltrates (not just bronchospasm)
- Marked eosinophilia
- Elevated IgE *and* IgG anti-*Aspergillus* antibodies
- Migratory (not fixed) infiltrates

### Pathologic Changes

```mermaid
flowchart TD
  A[Aspergillus fumigatus colonization]:::outcome --> B[IgE + IgG antibody production]:::outcome
  B --> C{Type of Response}:::decision
  C -->|IgE-mediated| D[Mast cell degranulation]:::action
  D --> E[Acute bronchoconstriction]:::outcome
  C -->|IgG-mediated| F[Immune complex formation]:::action
  F --> G[Complement activation]:::action
  G --> H[Neutrophil + Eosinophil infiltration]:::action
  H --> I[Bronchitis, bronchiectasis, migratory infiltrates]:::outcome
  E --> J[ABPA phenotype]:::outcome
  I --> J
```

**Mnemonic:** **ABPA = Asthma + Bronchiectasis + Pulmonary infiltrates + Aspergillus** → Think immune complexes (Type III) + IgE (Type I)

Answer

A. Type II hypersensitivity with IgG-mediated cytotoxic damage to alveolar epithelium

Answer

B. Type IV hypersensitivity with Th1-cell-mediated granuloma formation

Answer

D. Type I hypersensitivity with IgE-mediated mast cell degranulation and acute bronchoconstriction

Explanation

Allergic Bronchopulmonary Aspergillosis (ABPA)

Clinical Features of ABPA

Pathophysiologic Mechanisms in ABPA

Why Type III Hypersensitivity Is Predominant

Pathologic Changes

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Feature	Finding in This Case
Predisposition	Pre-existing asthma (10 years)
Fungal colonization	Aspergillus fumigatus in sputum
Pulmonary findings	Migratory infiltrates (fleeting opacities)
Systemic manifestations	Fever, malaise
Laboratory markers	Elevated IgE (>1000 IU/mL), eosinophilia
Immunologic basis	IgE + IgG immune complexes