A 35-year-old man develops severe serum sickness-like reaction 10 days after receiving intravenous cephalosporin for meningitis. He presents with fever, arthralgia, lymphadenopathy, and urticarial rash. What is the drug of choice for managing this Type III hypersensitivity reaction?

Explanation

## Management of Serum Sickness (Type III Hypersensitivity) ### Pathophysiology of Type III Hypersensitivity Type III reactions involve **immune complex deposition** (antigen–IgG–IgM complexes) in blood vessel walls and tissues: 1. Antigen (drug metabolite) binds to IgG/IgM antibodies 2. Circulating immune complexes deposit in vessel walls, joints, kidneys 3. Complement activation (C3a, C5a) → inflammation 4. Neutrophil infiltration and tissue damage **Onset:** 7–21 days after drug exposure (time for antibody production) ### Clinical Features of Serum Sickness | Feature | Mechanism | |---------|----------| | Fever | Systemic inflammation | | Arthralgia/arthritis | Immune complex deposition in synovium | | Urticarial rash | Vasculitis of skin vessels | | Lymphadenopathy | Lymph node activation | | Glomerulonephritis | IC deposition in glomeruli | | Vasculitis | Complement-mediated vessel inflammation | ### Drug of Choice: Corticosteroids (Prednisolone) **Key Point:** Systemic corticosteroids are first-line for serum sickness. They suppress T-cell and B-cell responses, inhibit complement activation, and reduce inflammatory cytokine production. **High-Yield:** Typical dosing: prednisolone 0.5–1 mg/kg/day for 5–7 days, then taper. Most cases resolve within 2–3 weeks after drug withdrawal and steroid initiation. ### Mechanism of Corticosteroid Action in Type III Reactions 1. **↓ Antibody production** — suppresses B-cell differentiation 2. **↓ Complement activation** — inhibits C3 convertase 3. **↓ Neutrophil migration** — reduces adhesion molecules 4. **↓ Cytokine production** — IL-1, TNF-α, IL-6 suppression 5. **Stabilizes mast cells** — reduces mediator release (secondary benefit) **Clinical Pearl:** Mild serum sickness (urticaria, mild fever) may resolve with NSAIDs and antihistamines alone; **severe cases with systemic symptoms, renal involvement, or vasculitis require corticosteroids**. ### Comparison of Treatment Options | Agent | Role in Serum Sickness | Onset | Efficacy | |-------|------------------------|-------|----------| | **Corticosteroids** | **First-line** | 6–12 hours | Excellent; resolves symptoms in days | | NSAIDs | Adjunctive (fever, arthralgia) | 1–2 hours | Partial; insufficient alone for severe cases | | Antihistamines | Adjunctive (pruritus) | 15–30 min | Minimal; does not address immune complexes | | Immunosuppressants (azathioprine) | Chronic/recurrent cases only | Weeks | Not indicated for acute serum sickness | **Warning:** Do NOT confuse serum sickness (Type III, delayed, immune complex) with anaphylaxis (Type I, immediate, IgE-mediated). Anaphylaxis requires epinephrine; serum sickness requires corticosteroids. ### Management Algorithm ```mermaid flowchart TD A[Serum sickness suspected]:::outcome --> B{Severity?}:::decision B -->|Mild: urticaria, fever only| C[Discontinue drug + NSAIDs + antihistamines]:::action B -->|Moderate-severe: systemic symptoms| D[Discontinue drug + Corticosteroids]:::action D --> E[Prednisolone 0.5-1 mg/kg/day]:::action E --> F[Taper over 5-7 days]:::action F --> G[Resolution in 2-3 weeks]:::outcome C --> H{Improvement?}:::decision H -->|No| D H -->|Yes| I[Continue supportive care]:::action ``` **Mnemonic for Type III Hypersensitivity: "IMMUNE COMPLEX"** - **I**mmune complexes (antigen–antibody) - **M**edium-sized (circulating) - **M**ediators: complement, cytokines - **U**rtication, vasculitis - **N**eutrophil infiltration - **E**ndothelial damage [cite:Robbins 10e Ch 6]