Random Dermatology MCQ - Type II hypersensitivity

A 55-year-old man with a history of mantle cell lymphoma is admitted for fatigue and jaundice. Laboratory studies reveal a hemoglobin of 7.2 g/dL, elevated lactate dehydrogenase (LDH), low haptoglobin, and a positive direct antiglobulin (Coombs) test. The peripheral smear shows spherocytes. Which of the following best describes the underlying immunologic mechanism of this hematologic condition?

A) Type II hypersensitivity; IgG-mediated opsonization and phagocytosis
B) Type I hypersensitivity; IgE-mediated mast cell degranulation
C) Type III hypersensitivity; immune complex deposition
D) Type IV hypersensitivity; T-cell-mediated cytotoxicity
E) Type II hypersensitivity; complement-mediated lysis

Correct Answer: A) Type II hypersensitivity; IgG-mediated opsonization and phagocytosis

Explanation

This patient has autoimmune hemolytic anemia (AIHA), a classic example of a Type II hypersensitivity reaction. The warm antibody type (as suggested by the underlying lymphoma) is most common.

Key Diagnostic Features of Warm AIHA:

• Anemia: Low hemoglobin.

• Evidence of Hemolysis: Elevated LDH, low haptoglobin, jaundice (elevated indirect bilirubin).

• Direct Antiglobulin Test (Direct Coombs): Positive, confirming the presence of antibodies (and/or complement) bound to the surface of red blood cells (RBCs).

• Peripheral Smear: Spherocytes are seen due to partial phagocytosis of the antibody-coated RBC membrane by splenic macrophages.

Pathophysiology (Type II Hypersensitivity):

Type II reactions are antibody-mediated and directed against cell-surface or matrix antigens. In this case:

1. Autoantibody Production: The patient produces IgG autoantibodies directed against antigens on their own RBCs (often against the Rh system).

2. Opsonization: These IgG antibodies coat the RBCs.

3. Phagocytosis: The Fc portion of the IgG antibody is recognized by Fcγ receptors on macrophages in the spleen. This leads to extravascular hemolysis, where macrophages phagocytose the opsonized RBCs, leading to their destruction. The partial "nibbling" of the membrane by macrophages creates spherocytes.

4. Complement Activation (Secondary Role): The IgG antibodies can also activate the complement system via the classical pathway, leading to membrane attack complex (MAC) formation and intravascular hemolysis, but the primary mechanism in warm AIHA is Fc receptor-mediated phagocytosis.

Why Not the Other Options?

• (B) Type I hypersensitivity: Involves IgE, mast cells, and histamine release (e.g., anaphylaxis, urticaria). It does not cause hemolytic anemia.

• (C) Type III hypersensitivity: Involves soluble immune complexes depositing in tissues (e.g., serum sickness, lupus nephritis). It does not involve antibodies targeting cellular antigens.

• (D) Type IV hypersensitivity: A T-cell-mediated delayed reaction (e.g., contact dermatitis, tuberculin reaction). It is not antibody-mediated.

• (E) Type II hypersensitivity; complement-mediated lysis: While complement can be involved in some Type II reactions (e.g., transfusion reactions, cold agglutinin disease), the finding of spherocytes is highly specific for Fc receptor-mediated extravascular hemolysis in the spleen, which is the hallmark of warm AIHA. A purely complement-mediated lysis (as in paroxysmal nocturnal hemoglobinuria) would not typically show spherocytes as prominently.

Management:

• First-line: Corticosteroids to suppress antibody production.

• Second-line: Rituximab (anti-CD20), splenectomy, or other immunosuppressants.

Prognosis:
Depends on the underlying cause. In lymphoma-associated AIHA, treatment of the underlying malignancy is crucial.

Note: The Direct Coombs test is diagnostic for Type II hypersensitivity against RBCs. The presence of spherocytes points toward extravascular hemolysis via the Fc receptor pathway. This is a classic board exam scenario linking clinical findings, lab results, and fundamental immunopathology.