Dermatology MCQ - Inflammatory Dermatoses - Dermatomyositis pathophysiology

A 55-year-old woman presents with the classic heliotrope rash, Gottron's papules, and progressive proximal muscle weakness. A skin biopsy from a Gottron's papule is performed. The primary immunopathogenic process believed to underlie the vascular and cutaneous changes in dermatomyositis is best characterized by which of the following?

A. A neutrophilic urticarial vasculitis affecting medium-sized vessels.
B. A type I hypersensitivity reaction with deposition of IgE on mast cells in the dermis.
C. A cell-mediated cytotoxic attack on keratinocytes by CD8+ T-lymphocytes.
D. A complement-mediated microangiopathy targeting dermal capillaries.
E. An autoimmune response directed against hemidesmosomal proteins in the basement membrane.

Correct Answer: D. A complement-mediated microangiopathy targeting dermal capillaries.

Explanation

Dermatomyositis (DM) is distinct from other autoimmune connective tissue diseases in its primary pathophysiology. It is considered primarily a humoral-mediated process that targets the microvasculature.

• Key Pathogenic Mechanism: The initial event is believed to be the activation of the complement cascade, specifically the formation of the membrane attack complex (C5b-9), which deposits on and damages the endothelial cells of small capillaries and arterioles in the skin and muscle. This complement-mediated vascular injury leads to capillary loss, ischemia, and the characteristic clinical and histologic findings. The perifascicular atrophy seen in muscle biopsies is a direct result of this endofascicular hypoperfusion.

Why other options are incorrect

• A. A neutrophilic urticarial vasculitis affecting medium-sized vessels: This describes conditions like Polyarteritis Nodosa. DM involves a microangiopathy, not a true vasculitis of medium-sized vessels, and the infiltrate is not predominantly neutrophilic.

• B. A type I hypersensitivity reaction with deposition of IgE on mast cells in the dermis: This is the mechanism of classic urticaria. While pruritus can occur in DM, the fixed nature of the heliotrope rash and Gottron's papules, along with the histologic findings, rule this out.

• C. A cell-mediated cytotoxic attack on keratinocytes by CD8+ T-lymphocytes: This is the central pathogenic mechanism in polymyositis (affecting muscle) and is also seen in the interface dermatitis of lupus erythematosus. While a lymphocytic infiltrate is present in DM skin, it is secondary to the primary microvascular injury. The cytotoxic T-cell attack is not the primary driver of the dermal pathology in DM.

• E. An autoimmune response directed against hemidesmosomal proteins in the basement membrane: This describes the pathophysiology of bullous pemphigoid and other pemphigoid disorders, which are characterized by subepidermal blisters, not the inflammatory and vascular changes of DM.

Key Associations for Dermatomyositis Pathophysiology

• Histopathology (Skin): A skin biopsy from a DM lesion typically shows an interface dermatitis (vacuolar alteration of the basal layer), similar to lupus. However, a more specific feature is the presence of dermal mucin deposition and the critical finding of reduced capillary density and dilated, tortuous capillaries in the papillary dermis, reflecting the underlying microangiopathy.

• Histopathology (Muscle): The muscle biopsy shows perfascicular atrophy, inflammation (often perivascular B-cells and CD4+ T-cells, unlike the endomysial CD8+ T-cells of polymyositis), and evidence of microinfarction.

• Autoantibodies: DM is strongly associated with myositis-specific autoantibodies (MSAs), which define clinical subsets. Examples include:

  • Anti-Mi-2: Associated with classic cutaneous disease and good prognosis.

  • Anti-TIF1γ: Strongly associated with malignancy in adults.

  • Anti-NXP2: Also associated with malignancy and calcinosis.

  • Anti-MDA5: Associated with amyopathic DM and a high risk of rapidly progressive interstitial lung disease.

• Clinical Implications: Understanding the vascular pathogenesis explains several clinical features: the nailfold capillary changes (dilated and drop-out), the mechanic's hands (related to ischemia), and the calcinosis cutis (a consequence of chronic tissue damage and hypoxia).

• Differential Diagnosis: The cutaneous findings must be distinguished from systemic lupus erythematosus, psoriasis (for Gottron's papules), and allergic contact dermatitis. The pathophysiology is the key differentiator.