Polydermatomyositis

Epidemiology

  • Incidence: 2-10 per 100k persons
  • Age
    • Bimodal age peaks: in childhood and in 30-40’s
  • Sex: F:M ratio is 2.5:1
  • Genetics: familial cases have been reported
    • Dermatomyositis is associated with HLA-B8/DR3, HLA-B14, HLA-B40
    • Polymyositis is associated with HLA-B8/DR3 and in African-Americans, HLA-B7 and HLA-DRw6
    • Lung manifestations are associated with HLA-DRB11302-DQA10102-DQB10604 and HLA-DRB10405-DQA103-DQB10401
  • Malignancy: controversial risk factor
    • 5-8% of of polydermatomyositis cases have associated lung, ovarian, breast, or GI neoplasm
    • Onset of symptoms may occur up to 1-2 years prior to diagnosis of malignancy: however, 33% of cases have diagnosis of polydermatomyositis and malignancy at the same time

Physiology

  • Cell-mediated immunologic mechanism
    • T-cells from patients are myotoxic to cultured myoblasts and fibroblasts (unclear is degree of toxicity is correlated with disease activity or response to therapy)

Pathology

  • Lung Pathologic patterns (most common):
    • Diffuse Alveolar Damage (DAD):
    • UIP-Like Pattern: interstitial fibrosis and infiltration with lymphocytes and plasma cells is usually also seen
    • BOOP:
    • Medial Intimal Thickening of Small Arteries and Arterioles: commonly seen associated with above patterns
      • May lead to pulmonary HTN
    • Interstitial Ossification (rare)

Diagnosis

  • CK/Aldolase: elevated
  • EMG/NCV: myopathic pattern
  • Serology
    • Jo-1: targets histidyl tNRA synthetase
      • Positive in 20-30% of cases with inflammatory myopathy
      • Positive in 50-100% of cases with inflammatory myopathy and interstitial lung disease
    • PL-7: targets threonyl tNRA synthetase
      • Positive in <3% of cases with antisynthetase syndrome
    • PL-12: targets alanyl tNRA synthetase
      • Positive in <3% of cases with antisynthetase syndrome
    • EJ: targets glycyl tNRA synthetase
      • Positive in <2% of cases with antisynthetase syndrome
    • OJ: targets isoleucyl tNRA synthetase
      • Positive in <2% of cases with antisynthetase syndrome
    • Mi-2: targets nuclear proteins
      • Positive in <8% of dermatomyositis cases
      • Associated with acute onset of classic dermatomyositis
    • Ku: targets nuclear proteins
      • Associated with myositis-connective tissue disease overlap syndromes
    • Anti-Cytoplasmic Ribonucleoprotein (positive in 30% of cases of inflammatory myositis): considered a myositis-specific Ab
    • ANCA: negative
  • Muscle Biopsy: myositis -> diagnostic
    • Select a muscle site that is weak but not wasted

Clinical

Pulmonary Manifestations (45-64% of cases)

ILD (see [[ILD-Etiology]])

  • Epidemiology
    • Present in 32% of cases
    • Less common in patients with amyotropic disease
    • 3-5x more common in females than males
    • Most commonly presents in 40’s
    • May precede systemic manifestations by months-years or may occur with established disease (no correlation between systemic and lung involvement)
    • There is no correlation between pulmonary involvement and musculoskeletal involvement
  • Diagnosis
    • ABG: hypoxemia (exercise desaturations)
    • PFT’s: restriction
      • DLCO: decreased (although may be increased during alveolar hemorrhage)
      • MIP/MEP/MVV: decreased in cases with muscular involvement
    • FOB-BAL: neutrophilia or lymphocytosis
      • Neutrophilia: likely is associated with clinical deterioration
    • CXR/Chest CT Patterns
      • Reticular or Reticulonodular Infiltrates (lower-lobe predominance): pleural effusions are usually absent
        • Low lung volumes (with atelectasis) may occur as well
        • Mimics that of idiopathic pulmonary fibrosis
      • Mixed Alveolar-Interstitial Infiltrates: may occur early in course
        • Combination of consolidation + peripheral reticular infiltrates is characteristic
      • Honeycombing: small cysts (seen best in lower fields) seen late in course
    • OLB: usual interstitial pneumonitis or non-specific interstitial pneumonia patterns
    • CK: low CK levels are correlated with more rapidly progressive interstitial lung disease
  • Clinical
    • Presents with dyspnea, non-productive cough, basilar rales, absence of clubbing: mimics presentation of idiopathic pulmonary fibrosis
    • Some cases are rapidly progressive (these cases may have Raynaud’s, arthralgias, arthritis)

Acute Lung Injury-ARDS (see [[Acute Lung Injury-ARDS]])

  • Epidemiology: may occur as the initial presentation of the disease (without pre-existing lung manifestations)
  • Diagnosis
    • HRCT -> diffuse ground-glass infiltrates and/or consolidation, reticular infiltrates, honeycombing (mimics accelerated idiopathic pulmonary fibrosis)
    • OLB: diffuse alveolar damage
  • Clinical: acute respiratory deterioration
  • Treatment and Prognosis: most cases die within months, despite steroid therapy
    • Case reports describe the use of cyclosporine A + either prednisolone or cyclophosphamide
      [Diffuse Alveolar Damage: Uncommon Manifestation of Pulmonary Involvement in Patients With Connective Tissue Diseases. Chest 2006; 130:553–558]

Cryptogenic Organizing Pneumonia (see [[Cryptogenic Organizing Pneumonia]])

  • Epidemiology: may occur in some cases

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology: uncommon

Aspiration Pneumonia (see [[Aspiration Pneumonia]])

  • Epidemiology: occurs in 20% of cases
  • Physiology
    • Pharyngeal and esophageal dysfunction and impaired cough reflex: important cause of mortality
    • Cricopharyngeal achalasia: has been reported

Respiratory Muscle Weakness with Acute/Chronic Hypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])

  • Epidemiology: respiratory muscle weakness and hypercapnic respiratory failure occurs in 25% of cases
  • Physiology: inspiratory and expiratory muscle dysfunction
  • Clinical: atelectasis with small lung volumes may occur

Bilateral Diaphragmatic Paralysis

  • Epidemiology: has been reported

Pulmonary Infection

  • Physiology
    • Aspiration
    • Steroid administration

Spontaneous Pneumothorax (see [[Pneumothorax]])

  • Epidemiology: has been reported

Pleural Involvement (see [[Pleural Effusion-Exudate]])

  • Epidemiology: pleural effusions are rare

Pulmonary Alveolar Proteinosis (see [[Pulmonary Alveolar Proteinosis]])

  • Epidemiology: rare reports

Diffuse Alveolar Hemorrhage (see [[Diffuse Alveolar Hemorrhage]])

  • Epidemiology: only 2 reported cases of DAH in association with polydermatomyositis (both cases exhibited alveolar hemorrhage as the initial manifestation of disease, in association with myositis)
  • Clinical
    • Absence of glomerulonephritis

Soft Tissue Calcification

  • Diagnosis
    • CXR/Chest CT: extraosseous dystrophic calcification (in areas of muscle damage) is seen in soft tissues
    • PFT’s: extensive soft tissue calcification may result in chest wall restriction

Neuro Involvement

  • Symmetric Proximal Muscle Weakness with Myopathy: typically insidious -> may progress to involve respiratory and upper airway muscles
  • Myalgia: variably present

Derm Involvement

  • Heliotrope Rash: violaceous or purplish rash surrounding the eyelids
  • Gottron’s Tubercles: scaly eruptions on extensor surfaces of finger joints

Treatment

  • Parameters: may follow MIP/MEP/MVV to monitor therapy
  • Corticosteroids: improve interstitial lung disease symptoms, CXR, and PFT’s in up to 40% of cases (however, natural history of interstitial lung disease is unknown)
    • Active Inflammation (Especially COP) on Biopsy: predicts good steroid response
    • Diffuse Alveolar Damage on Biopsy: predicts poor response to steroids
    • Coexistent Malignancy: poorer steroid response
  • Cyclophosphamide:
  • Azathioprine:
  • Cyclosporine A:
  • Methotrexate: used for refractory cases
  • IVIG: used for refractory cases
  • Cellcept: used for systemic disease, but no trials in interstitial lung disease
  • Treatment of Diffuse Alveolar Hemorrhage: usually requires corticosteroids + cytotoxics

Prognosis

  • Prognosis is related to pulmonary and cardiac complications
    • Pulmonary complications are the most frequent cause of death
  • Patients have a higher rate of mortality from cancer than normals (middle-aged men are most affected)

References

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