Random Dermatology MCQ - HLA-B27 in Psoriasis

A 40-year-old man with a long history of plaque psoriasis presents with insidious onset of lower back pain and stiffness that is worse in the morning and improves with activity. He also reports pain and swelling in his right knee. Radiographs of his sacroiliac joints show bilateral sacroiliitis. Which of the following HLA associations is most strongly linked to this specific musculoskeletal manifestation of his disease?

A) HLA-B27
B) HLA-Cw6
C) HLA-DR7
D) HLA-B51
E) HLA-DR4

Correct Answer: A) HLA-B27

Explanation

This patient has psoriasis and is now presenting with symptoms and radiological findings indicative of psoriatic arthritis (PsA), specifically the spondyloarthritis subtype. The HLA-B27 allele is critically important in this context.

Key Clinical Features of Psoriatic Spondyloarthritis:

• Axial Involvement: Inflammatory back pain (worse with rest, improves with activity), morning stiffness, and sacroiliitis.

• Peripheral Arthritis: Often asymmetric oligoarthritis.

• Skin Findings: Pre-existing or concurrent psoriasis.

HLA-B27 Association:

• Strongest Link: HLA-B27 is the major genetic susceptibility allele for the spondyloarthritis subset of psoriatic arthritis. It is present in 30-50% of patients with psoriatic spondylitis, compared to its prevalence of about 8% in the general population.

• Pathogenesis: The exact mechanism is not fully understood but is thought to involve molecular mimicry (where the HLA-B27 molecule presents a self or bacterial peptide that triggers an autoimmune response) and endoplasmic reticulum stress in cells expressing HLA-B27.

• Contrast with HLA-Cw6: While HLA-Cw6 is the primary association for cutaneous psoriasis vulgaris, HLA-B27 is the key marker for the axial arthritis phenotype.

Why Not the Other Options?

• (B) HLA-Cw6: This is the primary association for cutaneous psoriasis vulgaris, especially early-onset type I disease. It is not strongly associated with the spondyloarthritis phenotype.

• (C) HLA-DR7: Associated with psoriasis in some populations, but it is a weaker link and not specific for arthritis.

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

• (E) HLA-DR4: Associated with rheumatoid arthritis, pemphigus vulgaris, and type 1 diabetes, not psoriatic spondylitis.

Management:

• NSAIDs: First-line for pain and inflammation in spondyloarthritis.

• DMARDs: Methotrexate or sulfasalazine for peripheral arthritis.

• Biologics: TNF-alpha inhibitors (e.g., adalimumab, infliximab) and IL-17 inhibitors (e.g., secukinumab) are highly effective for both skin and axial disease.

Prognosis:
The spondyloarthritis subtype can lead to progressive spinal fusion and significant functional impairment if not treated aggressively.

Note: It is crucial to distinguish the HLA associations in psoriasis. HLA-Cw6 drives the skin disease, while HLA-B27 is a key player in the axial arthritis component. A patient can be positive for one, both, or neither. This association helps explain why some patients with psoriasis develop severe spinal involvement while others do not.