Dermatology MCQ - Inflammatory Dermatoses - Morphoea pathophysiology

A skin biopsy from an active, inflammatory plaque of morphoea is examined. Which of the following immunohistochemical stains would be most likely to reveal the predominant inflammatory cell type driving the initial fibrotic process in the dermis?

A. CD20
B. CD3
C. CD68
D. CD1a
E. CD56

Correct Answer: B. CD3

Explanation

Morphoea (localized scleroderma) is characterized by excessive collagen deposition in the dermis and sometimes subcutaneous tissue. The pathophysiology is believed to involve an initial inflammatory phase, followed by fibrosis.

• Role of T-Lymphocytes: The early inflammatory infiltrate in morphoea is predominantly composed of T-lymphocytes. CD3 is a pan-T-cell marker that would highlight these cells. These activated T-cells are thought to release profibrotic cytokines, such as Transforming Growth Factor-beta (TGF-β) and Interleukin-4 (IL-4), which in turn activate fibroblasts to produce excessive collagen. This T-cell driven process is central to the initiation of the disease.

Why other options are incorrect

• A. CD20: This is a marker for B-lymphocytes. While B-cells and autoantibodies may play a role in some cases, the primary inflammatory infiltrate in morphoea is T-cell dominant, not B-cell dominant.

• C. CD68: This is a marker for macrophages and cells of the monocyte lineage. Macrophages are present in the inflammatory infiltrate and are a significant source of profibrotic cytokines like TGF-β, but they are not the most numerous cell type. The initial immune dysregulation is primarily T-cell mediated.

• D. CD1a: This is a marker for Langerhans cells and other dendritic cells. It is not characteristic of the inflammatory infiltrate in morphoea.

• E. CD56: This is a marker for Natural Killer (NK) cells and some neural tissues. NK cells are not a major component of the inflammatory infiltrate in morphoea.

Key Associations for Morphoea Pathophysiology

• Pathogenic Sequence: The sequence is thought to be: Unknown Trigger → Endothelial Cell Activation/Damage → Perivascular T-cell Infiltrate → Release of Profibrotic Cytokines (TGF-β, IL-4, IL-6, PDGF) → Fibroblast Activation and Myofibroblast Differentiation → Excessive Collagen and Extracellular Matrix Deposition.

• Key Cytokine - TGF-β: As in systemic sclerosis, Transforming Growth Factor-beta (TGF-β) is considered the master regulator of fibrosis in morphoea. It stimulates fibroblast proliferation and collagen synthesis.

• Histopathology: The histologic findings evolve with the stage of the disease:

  • Early/Inflammatory Stage: A perivascular and interstitial inflammatory infiltrate of CD4+ T-lymphocytes, along with plasma cells and macrophages, in the dermis and subcutis.

  • Established/Fibrotic Stage: Thick, homogenized collagen bundles in the reticular dermis, replacement of adipose tissue with collagen, and loss of adnexal structures. The inflammatory infiltrate becomes less prominent.

• Autoimmunity: There is a strong autoimmune association, with frequent personal or family history of other autoimmune diseases. Autoantibodies (particularly ANA and anti-single-stranded DNA) are common, but there are no specific pathogenic autoantibodies like those seen in systemic sclerosis.

• Distinction from Systemic Sclerosis: The key difference is the lack of systemic vascular involvement (e.g., no Raynaud's phenomenon, no digital vasculopathy, no scleroderma renal crisis) and the absence of SSc-specific autoantibodies (anti-centromere, anti-Scl-70). The fibrosis in morphoea is confined to the skin and underlying tissues.

• Clinical Implications: Understanding the T-cell driven, inflammatory early phase explains why treatments like phototherapy (UVA1) and methotrexate are effective—they target the inflammatory and immune cells that drive the fibrotic cascade.