Random Dermatology MCQ - Paraneoplastic Pemphigus (PNP)

A 55-year-old man with a history of chronic lymphocytic leukemia (CLL) presents with severe, painful erosions on his lips and oral mucosa, along with polymorphic skin lesions including targetoid plaques, flaccid bullae, and lichenoid papules on his trunk. A direct immunofluorescence (DIF) of perilesional skin is likely to show a unique combination of which two patterns?

A) Granular IgA in the dermal papillae and linear IgG at the BMZ
B) Intercellular IgG and linear C3 at the BMZ
C) Linear IgG and shaggy fibrinogen at the BMZ
D) Intercellular IgG and granular C3 at the BMZ
E) Linear IgA and intercellular IgG

Correct Answer: B) Intercellular IgG and linear C3 at the BMZ

Explanation

This patient has paraneoplastic pemphigus (PNP), a severe autoimmune blistering disorder almost always associated with an underlying neoplasm, most commonly lymphoproliferative malignancies like CLL, lymphoma, or Castleman disease.

Key Diagnostic Features:

1. Clinical:

   • Intractable, painful stomatitis is a hallmark feature, often the most severe and presenting symptom.

   • Polymorphous skin eruption: Lesions can resemble pemphigus vulgaris (flaccid bullae), pemphigus foliaceus, erythema multiforme (targetoid lesions), lichen planus (lichenoid papules), or even bullous pemphigoid.

   • Lung involvement: Bronchiolitis obliterans is a feared and often fatal complication.

2. Immunopathology:

   • Direct immunofluorescence (DIF) is pathognomonic. It shows a combination of:

     • Intercellular deposition of IgG (like pemphigus)

     • Linear (or granular) deposition of IgG and/or C3 along the basement membrane zone (like bullous pemphigoid or epidermolysis bullosa acquisita).

   • This dual pattern is highly characteristic of PNP.

3. Serology:

   • Circulating antibodies react against a plakin family of proteins (e.g., desmoplakins I/II, BP230, envoplakin, periplakin) in addition to desmogleins.

Why Not Other Options?

• (A) Granular IgA + linear IgG: Seen in dermatitis herpetiformis (granular IgA) and bullous pemphigoid (linear IgG), not together.

• (C) Linear IgG + shaggy fibrinogen: Shaggy fibrinogen is typical for epidermolysis bullosa acquisita.

• (D) Intercellular IgG + granular C3: The BMZ finding in PNP is more typically linear, and granular C3 is not specific.

• (E) Linear IgA + intercellular IgG: This is the pattern for Linear IgA disease combined with pemphigus, which is not a feature of PNP.

Management:

• Treat the underlying malignancy (e.g., chemotherapy for CLL). This is the cornerstone of management.

• Immunosuppression: High-dose corticosteroids, rituximab, IVIG, or cyclosporine may be used, but the response is often poor.

• Prognosis is generally poor, especially with lung involvement, due to the aggressive nature of the disease and the underlying malignancy.