Random Dermatology MCQ - Type III Hypersensitivity

A 45-year-old woman presents with palpable purpura on her lower extremities, arthralgias, and abdominal pain. A skin biopsy of a lesion reveals leukocytoclastic vasculitis with perivascular deposition of IgG and C3. Which of the following is the most likely underlying immunologic mechanism?

A) Type III hypersensitivity reaction
B) Type I hypersensitivity reaction
C) Type II hypersensitivity reaction
D) Type IV hypersensitivity reaction
E) Direct cellular toxicity

Correct Answer: A) Type III hypersensitivity reaction

Explanation

This presentation is classic for leukocytoclastic vasculitis (LCV), a hallmark of a Type III hypersensitivity reaction.

Key Features of Type III Hypersensitivity:

• Mechanism: Also known as immune complex-mediated hypersensitivity.

  1. Formation: Antigen-antibody (Ag-Ab) complexes form in circulation.

  2. Deposition: These soluble immune complexes deposit in small blood vessels, particularly in the skin (lower extremities due to hydrostatic pressure), joints, and kidneys.

  3. Inflammation: The deposited complexes activate the complement system (especially C5a), generating chemotactic factors that attract neutrophils.

  4. Tissue Damage: Neutrophils release lysosomal enzymes and reactive oxygen species, causing fibrinoid necrosis of the vessel wall and the clinical signs of vasculitis.

Clinical and Histologic Correlation:

• Palpable Purpura: Caused by inflammation and RBC extravasation from damaged vessels.

• Arthralgias: From immune complex deposition in joints.

• Abdominal Pain: Can indicate visceral vasculitis.

• Biopsy Findings:

  • Leukocytoclastic vasculitis: Neutrophilic infiltration and nuclear debris (leukocytoclasis) in and around vessel walls.

  • Deposition of IgG and C3: Demonstrated by direct immunofluorescence, confirming the presence of immune complexes.

Why Not the Other Options?

• (B) Type I hypersensitivity: An IgE-mediated reaction (e.g., urticaria, anaphylaxis). It causes wheals (superficial, transient edema), not palpable purpura or vasculitis.

• (C) Type II hypersensitivity: An antibody-mediated cytotoxic reaction (e.g., pemphigus vulgaris, bullous pemphigoid). Antibodies bind directly to tissue antigens, leading to cell destruction, not immune complex deposition.

• (D) Type IV hypersensitivity: A T-cell-mediated delayed reaction (e.g., allergic contact dermatitis, tuberculin reaction). It presents with eczema and a lymphocytic infiltrate, not acute neutrophilic vasculitis.

• (E) Direct cellular toxicity: Refers to non-immune injury from toxins, drugs, or chemicals, which would not involve immune complex deposition.

Common Triggers of Type III Reactions:

• Infections (e.g., Hepatitis B or C, Streptococcus)

• Autoimmune diseases (e.g., SLE, rheumatoid arthritis)

• Drugs (e.g., penicillin, thiazides)

• Idiopathic

Management:

• Identify and treat the underlying cause.

• Corticosteroids are first-line for severe or systemic disease.

Prognosis:
Often self-limiting if the trigger is removed. Chronic or systemic disease requires immunosuppression.

Note: The combination of palpable purpura + systemic symptoms (arthralgia, abdominal pain) + biopsy showing LCV with Ig/C3 deposition is diagnostic of an immune complex-mediated (Type III) vasculitis. This is a classic presentation of Henoch-Schönlein Purpura (IgA deposition) or hypersensitivity vasculitis.