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)
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: 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)
