Table 1.
Children with DAH. Overview of diagnostic procedures.
| Diagnosis of pulmonary hemorrhage by: | |||||||
|---|---|---|---|---|---|---|---|
| Disease category/ subcategory | Number of patients in subcategory | Patients with DAH (n (percent of total) ) | Clinical diagnosis* | Bronchoscopic diagnosis** | Histopathologic diagnosis | BAL cytology additionally to other criteria (n (% hem.-laden macroph.)) | BAL cytology only*** (n (%hem.-laden macroph.)) |
| Systemic disease with DAH (n = 56; B1) | |||||||
| Sarcoidosis | 17 | 3 | 1 | 0 | 1 | 2 (99%, 25%) | 1 (11%) |
| Granulomatosis with polyangiitis (GPA) | 14 | 11 | 8 | 2 | 3 | 4 (39%, 60%, 19%, 81%) | 1 (40%) |
| Eosinophilic granulomatosis with polyangiitis (EGPA) | 6 | 3 | 1 | 0 | 2 | 0 | 0 |
| Langerhans cell histiocytosis | 11 | 2 | 0 | 0 | 2 | 0 | 0 |
| Hereditary hemorrhagic telangiectasia (HHT) | 9 | 3 | 3 | 1 | 1 | 0 | 0 |
| Ehlers Danlos syndrome | 2 | 2 | 1 | 1 | 0 | 1 (40%) | 0 |
| Filamin A deficiency | 9 | 3 | 1 | 0 | 1 | 1 (45%) | 1 (57%) |
| Aminoacyl-tRNA synthetase deficiency (-ARS) | 6 | 2 | 0 | 0 | 1 | 0 | 1 (12%) |
| Storage diseases | 8 | 1 | 0 | 0 | 0 | 0 | 1 (25%) |
| Cantu syndrome | 3 | 1 | 0 | 0 | 1 | 0 | 0 |
| Familial dysautonomia | 2 | 1 | 0 | 0 | 0 | 0 | 1 (% not given) |
| Systemic lymphatic disorder | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Immune-mediated/ collagen vascular disorders | 20 | 4 | 3 | 1 | 3 | 3 (58%, 2 not given) | 0 |
| Lane-Hamilton syndrome | 7 | 7 | 5 | 1 | 3 | 4 (100%, 99%, 90%, 1 not given) | 0 |
| Systemic lupus erythematosus (SLE) | 5 | 1 | 0 | 0 | 1 | 0 | 0 |
| Anti-glomerular basement membrane disease (Goodpasture’s syndrome) | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Diffuse alveolar hemorrhage due to vasculitis disorders | 2 | 2 | 1 | 1 | 0 | 1 (13%) | 0 |
| Microscopic polyangiitis | 1 | 1 | 1 | 1 | 0 | 1 (85%) | 0 |
| Pulmonary thrombotic microangiopathy due to atypical hemolytic uremic syndrome | 1 | 1 | 0 | 1 | 1 | 0 | 0 |
| Autoimmune interstitial lung, joint and kidney disease (COPA-syndrome) | 6 | 5 | 2 | 0 | 2 | 3 (53%, 25%, 31%) | 0 |
| Hyper-IgG4-syndrome | 1 | 1 | 0 | 0 | 0 | 0 | 1 (15%) |
| Cardiac disease with DAH (n = 4; B4) | |||||||
| Congestion due to congenital heart defect/cardiac dysfunction | 7 | 4 | 1 | 1 | 1 | 1 (70%) | 2 (20%, 60%) |
| Abnormalities of pulmonary vessels with DAH (blood, lymphatic; n = 33; B4, Ax, Ay) | |||||||
| Primary pulmonary hypertension (28 patients Ax/Ay, 2 of them with bleedings; 50 patients B4) | 78 | 15 | 1 | 1 | 9 | 2 (68%, 50%) | 3 (32%, 32%, 50%) |
| Pulmonary capillary hemangiomatosis/pulmonary veno-occlusive disease | 21 | 9 | 1 | 0 | 8 | 1 (% not given) | 0 |
| Pulmonary hemorrhage due to pulmonary vascular malformations | 3 | 3 | 2 | 1 | 2 | 2 (88%, 66%) | 0 |
| Pulmonary capillaritis | 3 | 3 | 3 | 0 | 2 | 2 (% not given) | 0 |
| Abnormalities of pulmonary lymphatic vessels | 9 | 3 | 0 | 1 | 2 | 0 | 1 (17%) |
| Exogenous trigger for DAH (n = 4; B4) | |||||||
| Pulmonary hemorrhage due to medication | 2 | 2 | 2 | 0 | 0 | 0 | 0 |
| Fictitious pulmonary hemorrhage | 2 | 2 | 2 | 0 | 0 | 0 | 0 |
| All patients from above categories (n = 97, plausible cause/ underlying condition for DAH identified) | 257 | 97 (38%) | 41 | 13 | 46 | 28 | 13 |
| No plausible cause/ underlying condition for DAH identified | 34 | 34 (100%) | 27 | 7 | 13 | 25 (37-99%; 13 not given) | 0 |
| All patients | 291 # | 131 (45%) | 68 | 20 | 59 | 53 | 13 |
Some patients fulfilled more than one criterion for diagnosis of DAH.
hemoptysis or combination of respiratory symptoms with strong hints for bleeding in chest CT and laboratory (anaemia),
macroscopic signs for bleeding in bronchoscopy and/or alveolar hemorrhage in procedure (bloody BAL),
hem-laden macroph. (hemosiderin-laden macrophages) > 10%.
B1: ILD related to systemic disease processes; B4: ILD related to lung vessels structural processes; Ax: ILD-unclear RDS in the mature neonate; Ay: ILD-unclear RDS in the almost mature neonate. Disease categories/ subcategories were adapted from Griese et al. (20, 21).
These subjects plus those in a category without cases with DAH (Supplemental Table 1) plus the 3 adult patients plus 14 patients lacking information add up to the 350 patients depicted in Figure 1.
Please note: In our databases, four more patients that were assigned to other disease categories as B1, B4, Ax/ pulmonary hypertension, Ay/ pulmonary hypertension showed pulmonary hemorrhage: a patient with an extralobar sequester (disease category C1: Locally, gross structural abnormalities of the lung), a patient with congenital alveolar dysplasia (disease category A1: Diffuse developmental disorders), a patient with an unclear diffuse ILD (disease category By: Unclear diffuse parenchymal lung disease in the non-neonate) and a patient with pulmonary graft-versus-host-disease after stem cell transplantation (disease category B3: Diffuse parenchymal lung diseases in the immunocompromised or transplanted host).