Random Dermatology MCQ - Neonatal Pemphigus Vulgaris

A newborn infant is born with a generalized, blistering skin disease. Investigation reveals high titers of circulating IgG autoantibodies against desmoglein 3. The mother has no history of skin disease. Which immunoglobulin class is primarily responsible for this neonatal condition, and what is its key unique property relevant to this case?

A) IgG; it is the only immunoglobulin that crosses the placenta
B) IgA; it is the primary immunoglobulin in mucosal secretions
C) IgM; it is the first antibody produced in a primary immune response
D) IgD; it functions primarily as a B-cell receptor
E) IgE; it mediates mast cell degranulation in type I hypersensitivity

Correct Answer: A) IgG; it is the only immunoglobulin that crosses the placenta

Explanation

This clinical scenario describes neonatal pemphigus vulgaris, a transient blistering disorder caused by the passive transfer of maternal IgG autoantibodies across the placenta.

Key Properties of Immunoglobulins in Relation to Skin:

1. IgG

   • Placental Transfer: IgG is the only immunoglobulin class that actively crosses the placenta via the neonatal Fc receptor (FcRn). This provides the newborn with passive humoral immunity for the first few months of life.

   • Role in Skin Disease: Pathogenic IgG autoantibodies are responsible for several autoimmune blistering diseases, including:

     • Pemphigus vulgaris (anti-desmoglein 3)

     • Bullous pemphigoid (anti-BP180, anti-BP230)

     • Pemphigus foliaceus (anti-desmoglein 1)

   • Mechanism: In pemphigus, IgG antibodies bind to desmogleins, disrupting desmosomal adhesion and causing acantholysis and blistering.

2. IgA

   • Location: Found abundantly in mucosal secretions (tears, saliva, breast milk) and to a lesser extent in the skin.

   • Role in Skin Disease: IgA autoantibodies are central to:

     • Dermatitis Herpetiformis (granular IgA in dermal papillae)

     • Linear IgA Disease (linear IgA at the basement membrane zone)

3. IgM

   • Function: The first antibody produced in a primary immune response. It is a pentamer, making it efficient at complement activation.

   • Role in Skin: Does not typically play a direct pathogenic role in primary blistering diseases.

4. IgE

   • Function: Binds to mast cells and basophils. Mediates Type I hypersensitivity (e.g., urticaria, atopic dermatitis, anaphylaxis).

   • Role in Skin: High levels are characteristic of atopic conditions.

5. IgD

   • Function: Primarily functions as a B-cell receptor. Its role in serum and skin disease is minimal and not well-defined.

Analysis of This Case:

The infant has blisters and circulating IgG autoantibodies, but the mother is asymptomatic. This is only possible because the mother's pathogenic IgG antibodies crossed the placenta and entered the fetal circulation, causing disease in the newborn. The condition is transient, resolving as the maternal IgG is catabolized over weeks.

Note: The passive transfer of IgG autoantibodies can also cause neonatal lupus erythematosus (from anti-Ro/SSA antibodies) and transient myasthenia gravis. Understanding which immunoglobulins cross the placenta is crucial for diagnosing neonatal autoimmune diseases.