Capillaritis

Rheumatologic Disease-Associated Capillaritis

• Dermatopolymyositis (see Dermatopolymyositis)
• Goodpasture Syndrome (see Goodpasture Syndrome)
  • Physiology
    • Capillaritis is Variably Present
• Isolated Pulmonary Capillaritis (ANCA-Positive or Negative) (see Isolated Pulmonary Capillaritis)
• Mixed Connective Tissue Disease (MCTD) (see Mixed Connective Tissue Disease)
• Primary Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
• Scleroderma (see Scleroderma)
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)

Systemic Vasculitis-Associated Capillaritis

• Behcet’s Disease (see Behcet’s Disease)
• Eosinophilic Granulomatosis with Polyangiitis (EGPA) (Churg-Strauss Syndrome) (see Eosinophilic Granulomatosis with Polyangiitis)
  • Epidemiology
    • DAH Occurs in 0-20% of Cases
• Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) (see Granulomatosis with Polyangiitis
• Henoch-Schonlein Purpura (HSP) (see Henoch-Schonlein Purpura)
• Immune Complex-Associated Glomerulonephritis (see Immune Complex-Associated Glomerulonephritis)
• IgA Nephropathy (see IgA Nephropathy)
• Microscopic Polyangiitis (see Microscopic Polyangiitis)
• Mixed Cryoglobulinemia (see Cryoglobulinemia)
• Pauci-Immune Glomerulonephritis (see xxxx)
• Polyarteritis Nodosa (PAN) (see Polyarteritis Nodosa)
  • Epidemiology
    • Rare Case Reports of DAH

Drug-Associated Capillaritis

• Carbimazole (Neo-Mercazole) (see Carbimazole)
  • Hydralazine (Apresoline) (see Hydralazine) (Proc-Bayl Univ Med Cent, 2019) [MEDLINE]
  • Physiology
    • Vasculitis
• Mycophenolate Mofetil (Cellcept) (see Mycophenolate Mofetil)
  • Epidemiology
    • Case Report
  • Physiology
    • Capillaritis
• Phenytoin (Dilantin) (see Phenytoin)
• Propylthiouracil (PTU) (see Propylthiouracil)
• Tumor Necrosis Factor (TNF)-α Antagonists (see xxxx)
  • Agents
    • XXXX
• Retinoic Acid Syndrome (see All-Trans-Retinoic Acid)

Other Capillaritis

• Acute Lung Transplant Rejection (see Acute Lung Transplant Rejection)
• Acute Antibody-Mediated Lung Transplant Rejection (see Acute Antibody-Mediated Lung Transplant Rejection)
  • Physiology
    • Capillaritis is Often Present
• Hematopoietic Stem Cell Transplant (HSCT) (see Hematopoietic Stem Cell Transplant)
  • Epidemiology
    • Rare
  • Mechanisms
    • Hemoptysis May Be Due to Diffuse Alveolar Hemorrhage (as an Early Complication of HSCT)
    • Hemoptysis May Be Due to Idiopathic Pneumonia Syndrome (as a Late Complication of HSCT): idiopathic pneumonia syndrome is due to diffuse lung injury (from a combination of drugs, radiation, and/or thrombocytopenia) (Am J Respir Crit Care Med, 2011) [MEDLINE]
    • Underlying Viral/Fungal Infection Can Also Contribute to Diffuse Alveolar Hemorrhage or Idiopathic Pneumonia Syndrome
  • Prognosis
    • May Be Fatal
• Infective Endocarditis (see Endocarditis)
• Leptospirosis (see Leptospirosis)
  • Physiology
    • Reported Cases Demonstrate Leptospiral Antigen within Macrophages in the Septa and Alveoli (Rev Soc Bras Med Trop, 2002) [MEDLINE]
    • Clinical
      • Life-Threatening Hemoptysis May Occur
• Ulcerative Colitis (UC) (see Ulcerative Colitis)

Bland Alveolar Hemorrhage

• Goodpasture Syndrome (see Goodpasture Syndrome)
  • Physiology
    • Capillaritis is Variably Present
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
• Coagulopathy (see Coagulopathy)
  • General Comments
    • Usually Results in Diffuse Alveolar Hemorrhage in Association with an Underlying Pulmonary Disease, Such as Lung Cancer/Bronchiectasis/Infection, or with Combination of Anticoagulants
  • Acquired Vitamin K Deficiency (see Vitamin K) (Respiration, 2000) [MEDLINE]
  • Anticoagulation
    • Coumadin (see Coumadin)
    • Factor IIa (Thrombin) Inhibitors (see Factor IIa Inhibitors)
      • Argatroban (Acova) (see Argatroban)
      • Bivalirudin (Angiomax, Angiox) (see Bivalirudin)
      • Dabigatran (Pradaxa) (see Dabigatran) (Am J Kidney Dis, 2013) [MEDLINE]
      • Desirudin (Iprivask, Revasc) (see Desirudin)
      • Lepirudin (Refludan (see Lepirudin)
    • Factor Xa Inhibitors (see Factor Xa Inhibitors)
      • Apixaban (Eliquis) (see Apixaban)
      • Betrixaban (Bevyxxa) (see Betrixaban)
      • Danaparoid (Orgaran) (see Danaparoid)
      • Edoxaban (Lixiana) (see Edoxaban)
      • Fondaparinux (Arixtra (see Fondaparinux)
      • Rivaroxaban (Xarelto) (see Rivaroxaban)
    • Heparins
      • Dalteparin (Fragmin) (see Dalteparin)
      • Enoxaparin (Lovenox) (see Enoxaparin)
      • Heparin (Unfractionated) (see Heparin)
  • Antiplatelet Agents (Cardiovasc Revasc Med, 2011) [MEDLINE]
    • Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid)
    • Clopidogrel (Plavix) (see Clopidogrel)
    • Prasugrel (Effient) (see Prasugrel)
    • Ticagrelor (Brilinta) (see Ticagrelor)
  • Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
  • Platelet Dysfunction (Uremic, etc)
  • Platelet Glycoprotein IIb/IIIa Inhibitors (see IIb IIIa Inhibitors)
    • Abciximab (ReoPro) (see Abciximab)
    • Eptifibatide (Integrilin) (see Eptifibatide)
    • Tirofiban (Aggrastat) (see Tirofiban)
  • Thrombocytopenia (see Thrombocytopenia)
  • Thrombolytics (see Thrombolytics)
  • Von Willebrand Disease (see Von Willebrand Disease)
• Idiopathic Pulmonary Hemosiderosis (IPH) (see Idiopathic Pulmonary Hemosiderosis)
• Leptospirosis (see Leptospirosis)
  • Physiology
    • Reported Cases Demonstrate Leptospiral Antigen within Macrophages in the Septa and Alveoli (Rev Soc Bras Med Trop, 2002) [MEDLINE]
  • Clinical
    • Life-Threatening Hemoptysis May Occur
  • Mitral Stenosis (see Mitral Stenosis)
• Promyelocytic Leukemia (see xxxx)
• Radiographic Contrast (see Radiographic Contrast)
  • Epidemiology
    • Case Reports of DAH Associated with Iodinated Contrast Use (Eur J Case Rep Intern Med, 2020) [MEDLINE]
• Valproic Acid (XXXX) (see Valproic Acid)
  • Epidemiology
    • Case Reports of DAH (Eur J Neurol, 2011) [MEDLINE]

Diffuse Alveolar Damage (DAD)

• Acute Interstitial Pneumonia (AIP) (see Acute Interstitial Pneumonia)
  • Epidemiology
    • XXXX
• Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)
  • General Comments
    • Diffuse Alveolar Damage is the Most Common Pathologic Finding in Acute Respiratory Distress Syndrome (ARDS)
  • Infection
    • Aspiration Pneumonia (see Aspiration Pneumonia)
    • Bacterial Pneumonia
    • Fungal Pneumonia (Pneumocystis Jirovecii, etc)
    • Viral Pneumonia (Influenza Virus, SARS-CoV2, etc)
  • Massive Transfusion
  • Sepsis (see Sepsis)
  • Trauma
  • Drug/Toxin
    • Amiodarone (Cordarone) (see Amiodarone)
    • Amphetamine (see Amphetamine)
    • Azathioprine (Imuran) (see Azathioprine): diffuse alveolar damage may occur (Am J Clin Pathol, 1984) [MEDLINE]
    • Crack Cocaine (see Cocaine)
      • Epidemiology
      • Hemoptysis (and Diffuse Alveolar Hemorrhage) Has Been Described in 6% of Habitual Free-Base (Crack) Cocaine Smokers
      • Levamisole-Contaminated Cocaine Has Been Associated with Pulmonary Hemorrhage in Several Case Reports
    • Electronic Cigarrettes/Vaping (see xxxx) (NEJM, 2020) [MEDLINE]
      • Clinical
      • E-Cigarette Use/Vaping Has Been Associated with ARDS/Diffuse Alveolar Damage, with Hemoptysis Present in 11% of Cases at Time of Presentation (NEJM, 2020) [MEDLINE
      • Vaping Has Also Been Associated with Acute Eosinophilic Pneumonia, Organizing Pneumonia, Lipoid Pneumonia, Hypersensitivity Pneumonitis, and Giant Cell Interstitial Pneumonitis
    • Fludarabine (Fludara) (see Fludarabine): DAH may occur (Haematologica, 2000) [MEDLINE], as well as diffuse alveolar damage (Chest, 2002) [MEDLINE]
    • Isocyanates (see xxxx)
    • Mitomycin (see Mitomycin): diffuse alveolar damage may occur (Cancer, 1980) [MEDLINE]
    • Nitrofurantoin (Macrodantin) (see Nitrofurantoin)
    • NItrogen Dioxide (see NItrogen Dioxide): diffuse alveolar damage may occur (J Intern Med, 1996) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2012) [MEDLINE] (Lung, 2007) [MEDLINE]
      • Exposures
      • Indoor Ice Arenas (Due to Propane-Powered Ice Surfacing Equipment with Inadequate Ventilation)
      • Silo Fillers
    • Penicillamine (see Penicillamine)
    • Propylthiouracil (PTU) (see Propylthiouracil)
    • Sirolimus (XXXXXXX) (see Sirolimus)
    • Trimellitic Anhydride (see Trimellitic Anhydride)
• Connective Tissue Disease
  • Dermatopolymyositis (see Dermatopolymyositis)
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
• Cryptogenic Organizing Pneumonia (COP) (see Cryptogenic Organizing Pneumonia)
• High-Altitude Pulmonary Edema (HAPE) (see High-Altitude Pulmonary Edema)
• Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis)
• Radiation Therapy/Radiation Pneumonitis (see Radiation Therapy and Radiation Pneumonitis and Fibrosis)
• Toxic Inhalation
  • Heavy Metal Fumes
    • Cadmium (see Cadmium)
    • Mercury (see Mercury)
    • Nickel Carbonyl (see Nickel Carbonyl)
  • Ozone (see Ozone)
  • Smoke Inhalation (see Smoke Inhalation)

Other

• Pulmonary Angiosarcoma (see Pulmonary Angiosarcoma)
• Choriocarcinoma (see XXXXXXXX)
• Epithelioid Hemangioepithelioma (see xxxx)
• Lymphangioleiomyomatosis (LAM)* (see Lymphangioleiomyomatosis)
• Metastatic Renal Cell Carcinoma (see xxxx)
• Pulmonary Capillary Hemangiomatosis (PCH) (see Pulmonary Capillary Hemangiomatosis)
• Pulmonary Vein Stenosis (see xxxx)
• Pulmonary Veno-Occlusive Disease (VOD) (see Pulmonary Veno-Occlusive Disease)
• Tuberous Sclerosis (TS) (see Tuberous Sclerosis)

Complete Blood Count (CBC) (see Complete Blood Count)

• Anemia (see Anemia)
• Leukocytosis (see Leukocytosis)

Serum Chemistry

• Elevated Creatinine: may be seen in cases with renal involvement

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

• Hypoxemia (see Hypoxemia)

Chest X-Ray (see Chest X-Ray)

• xxx

Chest CT (see Chest Computed Tomography)

• Findings
  • Alveolar Filling/Consolidation
  • Ground Glass Infiltrates
  • Interstitial Fibrosis: seen in chronic/Recurrent cases
• Example: diffuse alveolar hemorrhage in a patient with Wegener’s granulomatosis -> note the ground glass infiltrates in the right lung and extensive alveolar filling in the left lung (alveolar hemorrhage was confirmed in the left lower lobe by bronchoscopy)

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

• Restriction
• DLCO
  • Increased During Acute Diffuse Alveolar Hemorrhage: resolves within 48-72 hrs (as hemoglobin is degraded to hemosiderin)

Anti-Neutrophil Cytoplasmic Antibody (ANCA) (see Anti-Neutrophil Cytoplasmic Antibody)

• p-ANCA: much less specific than c-ANCA titers
  • p-ANCA: can be positive in microscopic polyangiitis, Churg-Strauss, pauci-immune glomerulonephritis, some cases of isolated pulm capillaritis, polyarteritis nodosa, and ulcerative colitis

Bronchoscopy (see Bronchoscopy)

• Bronchoalveolar Lavage (BAL): necessary to rule out infection and other etiologies of alveolar infiltrates
  • Increasingly Serial Bloody BAL Fluid is Diagnostic
  • Cell Count and Differential:: presence of hemosiderin-laden macrophages suggests chronic hemorrhage (rather than biopsy-related bleeding)
    • Quantitative Scoring of Alveolar Macrophage Hemosiderin Concentration: sensitive for diagnosis of DAH

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery and Open Lung Biopsy)

• May Be Used in Cases with Equivocal Serology: but is usually not necessary

Renal Biopsy (see Renal Biopsy)

• May Be Positive: even in the absence of overt renal involvement

Duration of Symptoms

• Symptoms are Usually Present for Period of Days-Weeks

Pulmonary Manifestations

Acute Respiratory Failure (see Respiratory Failure)

• Epidemiology
  • May Occur in Severe Cases

Alveoar Infiltrates/Pneumonia-Like Presentation

• Clinical
  • Cough (see Cough)
  • Chest Pain (see Chest Pain)
  • Dyspnea (see Dyspnea)
  • Fever (see Fever)

Diffuse Pulmonary Ossification (DPO) (see Diffuse Pulmonary Ossification)

• Epidemiology
  • Diffuse Alveolar Hemorrhage Has Been Reported to Precede Diffuse Pulmonary Ossification in Some Cases

Hemoptysis (see Hemoptysis)

• Epidemiology
  • Common

Interstitial Pulmonary Fibrosis (see Interstitial Lung Disease)

• Epidemiology
  • Occurs with Recurrent Diffuse Alveolar Hemorrhage

Management of Post-Stem Cell Transplant Diffuse Alveolar Hemorrhage

• Corticosteroids (see Corticosteroids)
  • Methylprednisolone (Solumedrol) (see Methylprednisolone): 125-250 mg q6 hrs x 4-6 days, then taper over 2 wks) improve resp status and survival