Table 1.
Case Descriptions
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | |
|---|---|---|---|---|---|
| Presentation | |||||
| Sex | Male | Female | Female | Female | Female |
| Age at 1st known DAH (years) | 7 | 3 | 9 | 8 | 3 |
| Presenting Symptoms | Fever, rash, joint pain, respiratory failure | Persistent oxygen requirement | Recurrent pneumonia and aspiration | Respiratory Distress, hypoxia | Hemoptysis |
| Hemoptysis | No | No | No | No | Yes |
| Laboratory Resulta | |||||
| White Blood Cell Count | H | N | N | U | N |
| Hemoglobin | L | L | H | L | N |
| Platelets | L | N | N | U | N |
| Inflammatory Markers | |||||
| Erythrocyte Sedimentation Rate | H | H | N | U | N |
| C-reactive Protein | H | H | N | U | U |
| Ferritin | H | H | U | U | U |
| Antibodiesb | |||||
| Positive | – | – | C-ANCA, MPO | MPO | ANA, SSA, RNP, Smith, Histone, CCP, RF |
| Negative | ANCA, ANA | – | ANA, Anti-GBM | ANCA, PR3, ANA | – |
| Creatinine | H | U | U | U | |
| Investigationsb | |||||
| Echocardiogram | ND | Mild PAH | Mild PAH, AV regurgitation | Mild PAH, AV regurgitation and stenosis | ND |
| Bronchoscopy with BAL | ND | Bloody fluid return | Hemosiderin-Laden Macrophages | Bloody fluid return | Hemosiderin-Laden Macrophages |
| Chest CT | ND | Y | Y | Y | Y |
| Ground Glass Opacities | – | Y | Y | Y | Y |
| Cystic Lucencies | – | Y | Y | Y | Y |
| Other Findings | – | Atelectasis, small pleural effusions | Atelectasis, septal thickening | Diffuse centrilobular nodules, septal thickening | – |
| Lung Biopsyc | d | ||||
| Alveolar Hemorrhage | Mild | Mild | Marked | Mild | Moderate |
| Hemosiderin | Mild | Moderate | Marked | Marked | Minimal |
| Abnormal Alveolar Growth | Y | Y | Y | Y | Y |
| Pulmonary Artery Thickening | Moderate | Moderate | Moderate | Moderate | Moderate |
| Other Findings | Double capillary layer, focal interstitial fibrosis | Focal pneumonia, cholesterol clefts, subpleural type 2 cell proliferation | Airway Damage (repeat biopsy with plasma cell/CD3+ lymphocytes) | Double capillary layer, rare interstitial and pleural perivascular neutrophils | – |
| Treatment | |||||
| Glucocorticoids | Y | Y | Y | Y | Y |
| Other Medications | Antibiotics | Continued anakinra for SJIA | IVIG | IVIG, Rituximab | – |
| Outcome | |||||
| Deceased | Remained on 0.5 L/min of oxygen via nasal cannula 3 months later, then lost to follow up | Repeat BAL with red blood cells 1 year later. Therapy stopped after 20 months. No recurrences since (6 years). | 2 recurrences, both requiring ICU admission (one with Influenza B, one with Human Metapneumovirus). No recurrences since (1 year). | Recurrences through age 14. Glucocorticoids stopped with no known recurrences since (3 years). | |
Abbreviations: DAH Diffuse Alveolar Hemorrhage, PAH Pulmonary Arterial Hypertension, AV Atrioventricular Valve, ANCA Anti-neutrophil cytoplasmic antibody, MPO Anti-myeloperoxidase antibody, PR3 Anti-serine protease 3 antibody, BAL Bronchoalveolar lavage, SJIA Systemic Juvenile Idiopathic Arthritis, IVIG Intravenous Immunoglobulin, SSA Anti-Sjogrens-Syndrome-related antigen A, RNP Anti-Ribonucleoprotein, CCP Anti-Cyclic-Citrullinated Peptide, RF Rheumatoid Factor, ICU Intensive Care Unit
aH = High, L = Low, N = Normal, U = Unknown
bNot listed or (−) = unknown
bY = Yes, N = No, ND = Not Done
cAll performed after exposure to glucocorticoids,
dHistopathology from autopsy