Random Dermatology MCQ - HLA-Cw6

A 25-year-old man presents with well-demarcated, erythematous plaques covered with silvery scale on his elbows, knees, and scalp. His nails show pitting and onycholysis. He reports that his father had a similar condition. Which of the following HLA associations is most strongly linked to this disease?

A) HLA-Cw6
B) HLA-B27
C) HLA-DR4
D) HLA-B51
E) HLA-A29

Correct Answer: A) HLA-Cw6

Explanation

This presentation is classic for psoriasis vulgaris, and the HLA-Cw6 allele is its strongest and most well-established genetic association.

Key Clinical Features of Psoriasis Vulgaris:

• Plaques: Well-demarcated, erythematous plaques with adherent silvery scale.

• Distribution: Extensor surfaces (elbows, knees), scalp, lumbosacral area.

• Nail Findings: Pitting, oil spots, onycholysis, subungual hyperkeratosis.

• Family History: Positive family history is common, indicating a strong genetic component.

HLA-Cw6 Association:

• Strongest Link: HLA-Cw6 is the major genetic susceptibility allele for psoriasis vulgaris, particularly for type I psoriasis (early onset, before age 40, positive family history).

• Pathogenesis: HLA-Cw6 is a Class I major histocompatibility complex (MHC) molecule. It is thought to present an unknown antigen to CD8+ T-cells, triggering the inflammatory cascade that leads to keratinocyte hyperproliferation.

• Clinical Correlation: Patients who are HLA-Cw6 positive often have a more severe disease course, a stronger family history, and are more likely to have the guttate subtype.

Why Not the Other Options?

• (B) HLA-B27: Associated with psoriatic arthritis (especially the spondylitis form), ankylosing spondylitis, and reactive arthritis. It is not the primary association for cutaneous psoriasis vulgaris.

• (C) HLA-DR4: Associated with pemphigus vulgaris, rheumatoid arthritis, and type I diabetes mellitus.

• (D) HLA-B51: Associated with Behçet's disease.

• (E) HLA-A29: Associated with birdshot chorioretinopathy.

Management:

• Topical therapy: Corticosteroids, vitamin D analogs.

• Phototherapy: NB-UVB.

• Systemic therapy: Methotrexate, cyclosporine, acitretin.

• Biologics: TNF-alpha inhibitors, IL-17/23 inhibitors (especially effective).

Prognosis:
Chronic, relapsing condition. HLA-Cw6 status does not currently guide treatment but is a key research and diagnostic clue.

Note: HLA-Cw6 is the cornerstone of psoriasis genetics. Its identification helped solidify the understanding of psoriasis as an immune-mediated disease. While not used routinely in clinical practice, it represents a critical piece of the pathophysiologic puzzle. The positive family history in this case further supports the strong genetic component.