Random Dermatology MCQ - Dermatomyositis

A 55-year-old woman presents with progressive muscle weakness in her proximal limbs, difficulty rising from a chair, and a violaceous rash on her eyelids. She also reports joint pain and shortness of breath. Serologic testing is positive for anti-Jo-1 antibodies. Which of the following is the most likely diagnosis and the significance of this autoantibody?

A) Dermatomyositis; associated with antisynthetase syndrome
B) Systemic lupus erythematosus; associated with renal disease
C) Systemic sclerosis; associated with pulmonary fibrosis
D) Polymyositis; associated with cardiac involvement
E) Mixed connective tissue disease; associated with high titers of anti-U1 RNP

Correct Answer: A) Dermatomyositis; associated with antisynthetase syndrome

Explanation

This presentation is classic for dermatomyositis (DM), specifically the antisynthetase syndrome subset, defined by the presence of anti-aminoacyl-tRNA synthetase antibodies, most commonly anti-Jo-1.

Key Clinical Features of Anti-Jo-1 Positive Dermatomyositis:

• Cutaneous Signs: Heliotrope rash (violaceous discoloration of eyelids), Gottron's papules (violaceous papules over knuckles).

• Myositis: Symmetrical proximal muscle weakness (difficulty climbing stairs, rising from a chair).

• Systemic Manifestations (Antisynthetase Syndrome):

  • Fever

  • Inflammatory arthritis

  • Mechanic's hands (fissured, hyperkeratotic fingers)

  • Interstitial lung disease (ILD) – a major cause of morbidity and mortality.

Significance of Anti-Jo-1 Antibody:

• Pathogenesis: Anti-Jo-1 is an antibody against histidyl-tRNA synthetase. Its presence defines a distinct clinical phenotype known as antisynthetase syndrome.

• Clinical Correlation: It is strongly associated with a high risk of rapidly progressive interstitial lung disease, which is often the most life-threatening manifestation.

• Diagnostic Utility: It is a myositis-specific autoantibody (MSA) and is a key serologic marker for this subtype of DM.

Why Not the Other Options?

• (B) Systemic lupus erythematosus (SLE): Associated with antibodies like anti-dsDNA and anti-Smith. The rash is typically a malar rash (sparing the nasolabial folds), not a heliotrope rash or Gottron's papules.

• (C) Systemic sclerosis (Scleroderma): Characterized by skin thickening (sclerodactyly) and is associated with anti-Scl-70 (for diffuse disease) and anti-centromere (for limited disease). Anti-Jo-1 is not typical.

• (D) Polymyositis: Presents with myositis but lacks the characteristic cutaneous findings of DM (e.g., heliotrope rash). Anti-Jo-1 can be present in some cases, but the rash points definitively to DM.

• (E) Mixed connective tissue disease (MCTD): Defined by high titers of anti-U1 RNP and features overlapping SLE, scleroderma, and myositis. Anti-Jo-1 is not a marker for MCTD.

Management:

• Systemic corticosteroids are first-line for myositis and ILD.

• Immunosuppressants like methotrexate, azathioprine, or mycophenolate mofetil are used for steroid-sparing effects and for refractory ILD.

• Regular screening for ILD with pulmonary function tests and high-resolution CT chest is mandatory.

Prognosis:
Guarded due to the association with ILD. Early and aggressive treatment is essential to preserve lung function.

Note: The presence of anti-Jo-1 antibody should prompt immediate evaluation for interstitial lung disease, as this often dictates the prognosis. The combination of myositis, characteristic rash, and ILD is highly suggestive of antisynthetase syndrome.