Pulmonary Hemosiderosis

Respiratory Disease MONDO:0008346 Pathograph 13 Respiratory disease Hemosiderosis

Pulmonary hemosiderosis is a rare respiratory disorder, usually represented clinically by idiopathic pulmonary hemosiderosis, in which recurrent diffuse alveolar hemorrhage causes blood to enter alveolar spaces. Alveolar macrophages ingest erythrocytes and accumulate hemosiderin, producing hemosiderin-laden macrophages in sputum, gastric aspirate, bronchoalveolar lavage, or lung tissue. Patients commonly present in childhood with iron deficiency anemia, cough, hemoptysis, pulmonary infiltrates or ground-glass opacities, dyspnea, and relapsing pulmonary hemorrhage. The initiating cause is idiopathic after exclusion of infections, cardiac disease, coagulation disorders, connective-tissue disease, vasculitis, celiac disease/Lane-Hamilton syndrome, and other secondary causes of diffuse alveolar hemorrhage.

Ask OpenScientist

Ask a research question about Pulmonary Hemosiderosis. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

1
Definitions
4
Pathophys.
1
Histopath.
30
Phenotypes
13
Pathograph
3
Treatments
7
References
1
Deep Research
📘

Definitions

1
Orphanet idiopathic pulmonary hemosiderosis definition
A respiratory disease, most often beginning in childhood, caused by repeated episodes of otherwise unexplained diffuse alveolar hemorrhage with anemia, cough, and chest-imaging infiltrates.
OTHER
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"Idiopathic pulmonary hemosiderosis is a respiratory disease due to repeated episodes of diffuse alveolar hemorrhage without any underlying apparent cause"
Orphanet defines IPH by unexplained repeated diffuse alveolar hemorrhage.
PMID:30278795 SUPPORT Human Clinical
"Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder that is responsible for recurrent episodes of diffuse alveolar hemorrhage"
The 107-patient pediatric cohort supports recurrent diffuse alveolar hemorrhage as the central clinical definition.
⚙

Pathophysiology

4
Recurrent idiopathic diffuse alveolar hemorrhage
The initiating lesion is recurrent bleeding into alveolar spaces without an identified secondary cause. Proposed environmental, allergic, autoimmune, and genetic contributors remain hypotheses rather than established causes.
alveolar capillary endothelial cell link
hemostasis link ↕ DYSREGULATED vascular permeability regulation link ↕ DYSREGULATED
alveolus of lung link
Downstream
Hemosiderin-laden alveolar macrophage accumulation
Recurrent hemorrhage-driven lung injury and remodeling
Diffuse alveolar hemorrhage
Hemoptysis
Pulmonary infiltrates
Show evidence (2 references)
PMID:15293620 SUPPORT Human Clinical
"Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology."
The clinical review supports unexplained diffuse alveolar hemorrhage as the initiating lesion.
PMID:30278795 SUPPORT Human Clinical
"There are four main etiological hypotheses of IPH described in the literature, including environmental, allergic, autoimmune, and genetic hypotheses."
The cohort review supports keeping the upstream cause as unresolved rather than assigning a single causal trigger.
Autoimmune serologic contribution to hemorrhage susceptibility
A subset of pediatric idiopathic pulmonary hemosiderosis cases show ANCA, ANA, or coeliac antibody positivity, supporting autoimmunity as a modifier or contributor rather than a universal primary cause.
immune response link ↕ DYSREGULATED
Downstream
Recurrent idiopathic diffuse alveolar hemorrhage
Show evidence (2 references)
PMID:24125570 SUPPORT Human Clinical
"In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%)."
The cohort documents autoimmune serology in screened children with IPH, supporting an immune contribution in a subset.
PMID:24125570 SUPPORT Human Clinical
"Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors."
The authors explicitly interpret potential contributors as supporting an autoimmune role in disease development.
Hemosiderin-laden alveolar macrophage accumulation
Alveolar macrophages phagocytose extravasated erythrocytes after repeated hemorrhage and accumulate hemosiderin iron. Detection of these siderophages in sputum, gastric lavage fluid, bronchoalveolar lavage fluid, or lung tissue is a diagnostic hallmark and links pulmonary blood loss to systemic iron deficiency.
alveolar macrophage link
phagocytosis link ↑ INCREASED heme catabolic process link ↑ INCREASED intracellular iron ion homeostasis link ↕ DYSREGULATED
alveolus of lung link
Downstream
Iron deficiency anemia
Pallor
Fatigue
Show evidence (2 references)
PMID:15293620 SUPPORT Human Clinical
"Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli."
The clinical review connects alveolar hemosiderin deposition with iron deficiency anemia.
PMID:30278795 SUPPORT Human Clinical
"Hemosiderin-laden macrophages were found in all of the patients."
The 107-patient cohort supports hemosiderin-laden macrophages as a consistent diagnostic finding.
Recurrent hemorrhage-driven lung injury and remodeling
Recurrent alveolar bleeding, iron/heme deposition, and inflammatory repair injure alveolar units and can progress to restrictive physiology, respiratory failure, and pulmonary fibrosis in severe or relapsing disease.
pulmonary alveolar type 2 cell link fibroblast link
wound healing link ↕ DYSREGULATED response to oxidative stress link ↑ INCREASED extracellular matrix organization link ↑ INCREASED
lung link
Downstream
Restrictive ventilatory defect
Pulmonary fibrosis
Respiratory failure
Show evidence (2 references)
PMID:30278795 SUPPORT Human Clinical
"Death may quickly occur with acute, massive, pulmonary hemorrhage or may occur over longer periods as the result of continued respiratory insufficiency and heart failure."
The cohort review supports chronic respiratory insufficiency as a consequence of persistent or recurrent pulmonary hemorrhage.
PMID:24125570 SUPPORT Human Clinical
"One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage."
The French cohort supports pulmonary fibrosis as a severe downstream complication.
✶

Histopathology

1
Hemosiderin-laden alveolar macrophages without vasculitis
Sputum, bronchoalveolar lavage fluid, gastric lavage fluid, or lung biopsy can show siderophages reflecting prior alveolar hemorrhage; classic IPH lacks pulmonary vasculitis or immune-complex deposition on biopsy.
Show evidence (2 references)
PMID:15293620 SUPPORT Human Clinical
"Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages)"
The review supports siderophages in respiratory samples as a characteristic finding.
PMID:15293620 SUPPORT Human Clinical
"the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis"
The review supports numerous alveolar siderophages without vasculitis as a histopathologic pattern.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Pulmonary Hemosiderosis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

30
Blood 2
Iron deficiency anemia VERY_FREQUENT Iron deficiency anemia (HP:0001891)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0001891 | Iron deficiency anemia | Very frequent (99-80%)"
Orphanet records iron deficiency anemia as very frequent.
PMID:30278795 SUPPORT Human Clinical
"anemia (n = 100, 93.45%)"
The pediatric cohort found anemia in 100 of 107 patients.
Diffuse alveolar hemorrhage OCCASIONAL Diffuse alveolar hemorrhage (HP:0025420)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0025420 | Diffuse alveolar hemorrhage | Occasional (29-5%)"
Orphanet records diffuse alveolar hemorrhage as occasional.
PMID:15293620 SUPPORT Human Clinical
"repetitive episodes of diffuse alveolar haemorrhage"
The clinical review supports recurrent diffuse alveolar hemorrhage as central to IPH.
Cardiovascular 2
Hepatosplenomegaly FREQUENT Hepatosplenomegaly (HP:0001433)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0001433 | Hepatosplenomegaly | Frequent (79-30%)"
Orphanet records hepatosplenomegaly as frequent.
Cardiomegaly OCCASIONAL Cardiomegaly (HP:0001640)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0001640 | Cardiomegaly | Occasional (29-5%)"
Orphanet records cardiomegaly as occasional.
Digestive 1
Hepatomegaly OCCASIONAL Hepatomegaly (HP:0002240)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0002240 | Hepatomegaly | Occasional (29-5%)"
Orphanet records hepatomegaly as occasional.
Integument 1
Pallor FREQUENT Pallor (HP:0000980)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0000980 | Pallor | Frequent (79-30%)"
Orphanet records pallor as frequent.
Metabolism 1
Fever OCCASIONAL Fever (HP:0001945)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0001945 | Fever | Occasional (29-5%)"
Orphanet records fever as occasional.
Respiratory 7
Hemoptysis FREQUENT Hemoptysis (HP:0002105)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0002105 | Hemoptysis | Frequent (79-30%)"
Orphanet records hemoptysis as frequent.
PMID:30278795 SUPPORT Human Clinical
"hemoptysis (n = 61, 57%)"
The pediatric cohort found hemoptysis in 61 of 107 patients at diagnosis.
Pulmonary infiltrates FREQUENT Pulmonary infiltrates (HP:0002113)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0002113 | Pulmonary infiltrates | Frequent (79-30%)"
Orphanet records pulmonary infiltrates as frequent.
Cough FREQUENT Cough (HP:0012735)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0012735 | Cough | Frequent (79-30%)"
Orphanet records cough as frequent.
PMID:30278795 SUPPORT Human Clinical
"cough (n = 68, 63.55%)"
The pediatric cohort found cough in 68 of 107 patients at diagnosis.
Restrictive ventilatory defect OCCASIONAL Restrictive ventilatory defect (HP:0002091)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0002091 | Restrictive ventilatory defect | Occasional (29-5%)"
Orphanet records restrictive ventilatory defect as occasional.
Dyspnea OCCASIONAL Dyspnea (HP:0002094)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0002094 | Dyspnea | Occasional (29-5%)"
Orphanet records dyspnea as occasional.
PMID:24125570 SUPPORT Human Clinical
"dyspnea (n = 17, 68%)"
The French cohort recorded dyspnea at diagnosis in 17 of 25 children.
Pulmonary fibrosis OCCASIONAL Pulmonary fibrosis (HP:0002206)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0002206 | Pulmonary fibrosis | Occasional (29-5%)"
Orphanet records pulmonary fibrosis as occasional.
PMID:24125570 SUPPORT Human Clinical
"One patient developed severe pulmonary fibrosis"
The French cohort documents pulmonary fibrosis as a severe complication.
Respiratory failure OCCASIONAL Respiratory failure (HP:0002878)
Show evidence (2 references)
ORPHA:99931 SUPPORT Other
"HP:0002878 | Respiratory failure | Occasional (29-5%)"
Orphanet records respiratory failure as occasional.
PMID:30278795 SUPPORT Human Clinical
"three died from massive pulmonary hemorrhage and respiratory failure"
The pediatric cohort documents respiratory failure in fatal severe presentations.
Constitutional 1
Fatigue FREQUENT Fatigue (HP:0012378)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0012378 | Fatigue | Frequent (79-30%)"
Orphanet records fatigue as frequent.
Growth 1
Failure to thrive OCCASIONAL Failure to thrive (HP:0001508)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0001508 | Failure to thrive | Occasional (29-5%)"
Orphanet records failure to thrive as occasional.
Other 14
Ground-glass opacification on pulmonary HRCT FREQUENT Ground-glass opacification (HP:0025179)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0025179 | Ground-glass opacification on pulmonary HRCT | Frequent (79-30%)"
Orphanet records ground-glass opacification on pulmonary HRCT as frequent.
Glomerulonephritis VERY_RARE Glomerulonephritis (HP:0000099)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0000099 | Glomerulonephritis | Very rare (<4-1%)"
Orphanet records glomerulonephritis as very rare.
Down syndrome OCCASIONAL Down syndrome (MONDO:0008608)
Show evidence (1 reference)
PMID:24125570 SUPPORT Human Clinical
"We identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome."
The French pediatric cohort documents Down syndrome in 5 of 25 IPH cases, supporting an occasional comorbidity association.
Rheumatoid factor positive OCCASIONAL Rheumatoid factor positive (HP:0002923)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0002923 | Rheumatoid factor positive | Occasional (29-5%)"
Orphanet records rheumatoid factor positivity as occasional.
Smooth muscle antibody positivity OCCASIONAL Anti-smooth muscle antibody positivity (HP:0003262)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0003262 | Smooth muscle antibody positivity | Occasional (29-5%)"
Orphanet records smooth muscle antibody positivity as occasional.
Antineutrophil antibody positivity OCCASIONAL Antineutrophil antibody positivity (HP:0003453)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0003453 | Antineutrophil antibody positivity | Occasional (29-5%)"
Orphanet records antineutrophil antibody positivity as occasional.
Antinuclear antibody positivity OCCASIONAL Antinuclear antibody positivity (HP:0003493)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0003493 | Antinuclear antibody positivity | Occasional (29-5%)"
Orphanet records antinuclear antibody positivity as occasional.
Allergy OCCASIONAL Allergy (HP:0012393)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0012393 | Allergy | Occasional (29-5%)"
Orphanet records allergy as occasional.
Reticular pattern on pulmonary HRCT OCCASIONAL Reticular pattern on pulmonary HRCT (HP:0025390)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0025390 | Reticular pattern on pulmonary HRCT | Occasional (29-5%)"
Orphanet records reticular pattern on pulmonary HRCT as occasional.
Nodular pattern on pulmonary HRCT OCCASIONAL Nodular pattern on pulmonary HRCT (HP:0025392)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0025392 | Nodular pattern on pulmonary HRCT | Occasional (29-5%)"
Orphanet records nodular pattern on pulmonary HRCT as occasional.
Autoimmune antibody positivity OCCASIONAL Autoimmune antibody positivity (HP:0030057)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0030057 | Autoimmune antibody positivity | Occasional (29-5%)"
Orphanet records autoimmune antibody positivity as occasional.
Heart murmur OCCASIONAL Heart murmur (HP:0030148)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0030148 | Heart murmur | Occasional (29-5%)"
Orphanet records heart murmur as occasional.
Crackles OCCASIONAL Crackles (HP:0030830)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0030830 | Crackles | Occasional (29-5%)"
Orphanet records crackles as occasional.
Cow milk allergy VERY_RARE Cow milk allergy (HP:0100327)
Show evidence (1 reference)
ORPHA:99931 SUPPORT Other
"HP:0100327 | Cow milk allergy | Very rare (<4-1%)"
Orphanet records cow milk allergy as very rare.
💊

Treatments

3
Systemic corticosteroid therapy
Action: corticosteroid agent therapy MAXO:0000640
Agent: corticosteroid ↗ prednisone ↗
Systemic corticosteroids are first-line therapy for acute episodes and are commonly used for initial control and maintenance, though recurrence during tapering is frequent.
Show evidence (3 references)
PMID:30278795 SUPPORT Human Clinical
"Glucocorticoids and immunosuppressive agents are the first choice for treating IPH."
The pediatric cohort review supports glucocorticoids as first-choice treatment.
PMID:26289251 SUPPORT Human Clinical
"Common medications respondents used for treatment at initial presentation and chronic maintenance therapy were corticosteroids (98.7 and 84.0 %, initial and chronic therapy respectively)"
The international physician survey supports common corticosteroid use for initial and chronic therapy.
PMID:33184706 SUPPORT Human Clinical
"Corticosteroid therapy represents the first line of treatment"
The treatment review supports corticosteroids as first-line therapy.
Steroid-sparing immunosuppressive therapy
Action: immune suppressant agent therapy MAXO:0000297
Agent: hydroxychloroquine ↗ azathioprine ↗ cyclophosphamide ↗ mycophenolate mofetil ↗
Hydroxychloroquine, azathioprine, cyclophosphamide, mycophenolate mofetil, and other immunomodulatory agents have been used when disease is severe, recurrent, steroid-refractory, or steroid-toxic.
Show evidence (4 references)
PMID:33184706 SUPPORT Human Clinical
"Additional immunomodulatory/immunosuppressive medications have been used with varying success, especially in the setting of steroid-refractory disease."
The treatment review supports steroid-sparing immunosuppression for steroid-refractory IPH.
PMID:30806370 SUPPORT Human Clinical
"We initiated hydroxy-chloroquine and azathioprine early in treatment along with steroids in seven children with idiopathic pulmonary hemosiderosis"
The pediatric series supports hydroxychloroquine and azathioprine as steroid-sparing options used with corticosteroids.
PMID:30806370 SUPPORT Human Clinical
"early introduction of second line immunosuppressants helped in reducing disease flare and steroid toxicity without serious adverse effects."
The series supports benefit of early steroid-sparing immunosuppression in seven children.
+ 1 more reference
Supportive care for acute anemia and respiratory compromise
Action: supportive care MAXO:0000950
Supportive management includes acute stabilization, oxygen or respiratory support when needed, and transfusion for severe anemia while disease-directed immunosuppression is initiated.
Show evidence (1 reference)
PMID:30278795 SUPPORT Human Clinical
"All of the 107 patients were provided symptomatic treatments before diagnosis, and 29 received blood transfusions."
The pediatric cohort documents symptomatic care and transfusion in a subset before definitive diagnosis.
{ }

Source YAML

click to show 
name: Pulmonary Hemosiderosis
category: Respiratory Disease
creation_date: "2026-05-09T18:28:00Z"
updated_date: "2026-05-09T20:47:29Z"
synonyms:
- Idiopathic pulmonary hemosiderosis
- IPH
- Idiopathic pulmonary haemosiderosis
- Pulmonary haemosiderosis
description: >
  Pulmonary hemosiderosis is a rare respiratory disorder, usually represented
  clinically by idiopathic pulmonary hemosiderosis, in which recurrent diffuse
  alveolar hemorrhage causes blood to enter alveolar spaces. Alveolar
  macrophages ingest erythrocytes and accumulate hemosiderin, producing
  hemosiderin-laden macrophages in sputum, gastric aspirate, bronchoalveolar
  lavage, or lung tissue. Patients commonly present in childhood with iron
  deficiency anemia, cough, hemoptysis, pulmonary infiltrates or ground-glass
  opacities, dyspnea, and relapsing pulmonary hemorrhage. The initiating cause is
  idiopathic after exclusion of infections, cardiac disease, coagulation
  disorders, connective-tissue disease, vasculitis, celiac disease/Lane-Hamilton
  syndrome, and other secondary causes of diffuse alveolar hemorrhage.
disease_term:
  preferred_term: pulmonary hemosiderosis
  term:
    id: MONDO:0008346
    label: pulmonary hemosiderosis
parents:
- Respiratory disease
- Hemosiderosis
external_assertions:
- name: Orphanet idiopathic pulmonary hemosiderosis record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:99931
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=99931
  description: >
    Orphanet's ORPHA:99931 structured record provides the disease definition,
    childhood age of onset, epidemiology, cross-references, and HPO phenotype
    rows used in this entry.
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "OMIM:178550 | Exact"
    explanation: Orphanet records an exact OMIM cross-reference for idiopathic pulmonary hemosiderosis.
definitions:
- name: Orphanet idiopathic pulmonary hemosiderosis definition
  definition_type: OTHER
  description: >
    A respiratory disease, most often beginning in childhood, caused by repeated
    episodes of otherwise unexplained diffuse alveolar hemorrhage with anemia,
    cough, and chest-imaging infiltrates.
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Idiopathic pulmonary hemosiderosis is a respiratory disease due to repeated episodes of diffuse alveolar hemorrhage without any underlying apparent cause"
    explanation: Orphanet defines IPH by unexplained repeated diffuse alveolar hemorrhage.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder that is responsible for recurrent episodes of diffuse alveolar hemorrhage"
    explanation: The 107-patient pediatric cohort supports recurrent diffuse alveolar hemorrhage as the central clinical definition.
prevalence:
- population: Europe
  percentage: "<1 / 1,000,000 annual incidence"
  notes: Orphanet records annual incidence below 1 per million in Europe.
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Europe | Annual incidence | EXPERT"
    explanation: Orphanet records the expert-estimated European annual incidence band.
- population: Europe
  percentage: Unknown point prevalence
  notes: Orphanet records European point prevalence as unknown.
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Unknown | Europe | Point prevalence | ORPHANET"
    explanation: Orphanet records unknown European point prevalence.
progression:
- phase: Childhood onset
  age_range: Childhood
  notes: Orphanet lists childhood as the age-of-onset category.
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Childhood"
    explanation: Orphanet records childhood onset.
- phase: Relapsing hemorrhage and diagnostic delay
  age_range: Childhood through adolescence
  notes: >
    Pediatric IPH often presents variably rather than with the complete classic
    triad, leading to high misdiagnosis rates and recurrence during treatment
    taper or withdrawal.
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The classic triad of pediatric IPH is not always present. The rates of misdiagnosis and recurrence of IPH are high."
    explanation: The cohort directly supports variable presentation, misdiagnosis, and recurrence.
- phase: Chronic pulmonary morbidity
  notes: >
    Repeated hemorrhage can cause recurrent respiratory insufficiency and, in a
    minority of patients, pulmonary fibrosis.
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Death may quickly occur with acute, massive, pulmonary hemorrhage or may occur over longer periods as the result of continued respiratory insufficiency and heart failure."
    explanation: The pediatric cohort review of prognosis links acute massive hemorrhage and chronic respiratory insufficiency to severe outcomes.
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage."
    explanation: The French pediatric cohort documents severe fibrosis and fatal hemorrhage as uncommon but important complications.
pathophysiology:
- name: Recurrent idiopathic diffuse alveolar hemorrhage
  description: >
    The initiating lesion is recurrent bleeding into alveolar spaces without an
    identified secondary cause. Proposed environmental, allergic, autoimmune,
    and genetic contributors remain hypotheses rather than established causes.
  role: trigger
  cell_types:
  - preferred_term: alveolar capillary endothelial cell
    term:
      id: CL:0002144
      label: capillary endothelial cell
  locations:
  - preferred_term: alveolus of lung
    term:
      id: UBERON:0002299
      label: alveolus of lung
  biological_processes:
  - preferred_term: hemostasis
    term:
      id: GO:0007599
      label: hemostasis
    modifier: DYSREGULATED
  - preferred_term: vascular permeability regulation
    term:
      id: GO:0043114
      label: regulation of vascular permeability
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:15293620
    reference_title: "Idiopathic pulmonary haemosiderosis revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology."
    explanation: The clinical review supports unexplained diffuse alveolar hemorrhage as the initiating lesion.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There are four main etiological hypotheses of IPH described in the literature, including environmental, allergic, autoimmune, and genetic hypotheses."
    explanation: The cohort review supports keeping the upstream cause as unresolved rather than assigning a single causal trigger.
  downstream:
  - target: Hemosiderin-laden alveolar macrophage accumulation
    causal_link_type: DIRECT
  - target: Recurrent hemorrhage-driven lung injury and remodeling
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Diffuse alveolar hemorrhage
    causal_link_type: DIRECT
  - target: Hemoptysis
    causal_link_type: DIRECT
  - target: Pulmonary infiltrates
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Autoimmune serologic contribution to hemorrhage susceptibility
  description: >
    A subset of pediatric idiopathic pulmonary hemosiderosis cases show ANCA,
    ANA, or coeliac antibody positivity, supporting autoimmunity as a modifier
    or contributor rather than a universal primary cause.
  role: modifier
  biological_processes:
  - preferred_term: immune response
    term:
      id: GO:0006955
      label: immune response
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%)."
    explanation: The cohort documents autoimmune serology in screened children with IPH, supporting an immune contribution in a subset.
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors."
    explanation: The authors explicitly interpret potential contributors as supporting an autoimmune role in disease development.
  downstream:
  - target: Recurrent idiopathic diffuse alveolar hemorrhage
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Hemosiderin-laden alveolar macrophage accumulation
  description: >
    Alveolar macrophages phagocytose extravasated erythrocytes after repeated
    hemorrhage and accumulate hemosiderin iron. Detection of these siderophages
    in sputum, gastric lavage fluid, bronchoalveolar lavage fluid, or lung
    tissue is a diagnostic hallmark and links pulmonary blood loss to systemic
    iron deficiency.
  role: effector
  cell_types:
  - preferred_term: alveolar macrophage
    term:
      id: CL:0000583
      label: alveolar macrophage
  locations:
  - preferred_term: alveolus of lung
    term:
      id: UBERON:0002299
      label: alveolus of lung
  biological_processes:
  - preferred_term: phagocytosis
    term:
      id: GO:0006909
      label: phagocytosis
    modifier: INCREASED
  - preferred_term: heme catabolic process
    term:
      id: GO:0042167
      label: heme catabolic process
    modifier: INCREASED
  - preferred_term: intracellular iron ion homeostasis
    term:
      id: GO:0006879
      label: intracellular iron ion homeostasis
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:15293620
    reference_title: "Idiopathic pulmonary haemosiderosis revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli."
    explanation: The clinical review connects alveolar hemosiderin deposition with iron deficiency anemia.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Hemosiderin-laden macrophages were found in all of the patients."
    explanation: The 107-patient cohort supports hemosiderin-laden macrophages as a consistent diagnostic finding.
  downstream:
  - target: Iron deficiency anemia
    causal_link_type: DIRECT
  - target: Pallor
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Fatigue
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Recurrent hemorrhage-driven lung injury and remodeling
  description: >
    Recurrent alveolar bleeding, iron/heme deposition, and inflammatory repair
    injure alveolar units and can progress to restrictive physiology, respiratory
    failure, and pulmonary fibrosis in severe or relapsing disease.
  role: downstream_pathology
  cell_types:
  - preferred_term: pulmonary alveolar type 2 cell
    term:
      id: CL:0002063
      label: pulmonary alveolar type 2 cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  biological_processes:
  - preferred_term: wound healing
    term:
      id: GO:0042060
      label: wound healing
    modifier: DYSREGULATED
  - preferred_term: response to oxidative stress
    term:
      id: GO:0006979
      label: response to oxidative stress
    modifier: INCREASED
  - preferred_term: extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: INCREASED
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Death may quickly occur with acute, massive, pulmonary hemorrhage or may occur over longer periods as the result of continued respiratory insufficiency and heart failure."
    explanation: The cohort review supports chronic respiratory insufficiency as a consequence of persistent or recurrent pulmonary hemorrhage.
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage."
    explanation: The French cohort supports pulmonary fibrosis as a severe downstream complication.
  downstream:
  - target: Restrictive ventilatory defect
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Pulmonary fibrosis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Respiratory failure
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
histopathology:
- name: Hemosiderin-laden alveolar macrophages without vasculitis
  description: >
    Sputum, bronchoalveolar lavage fluid, gastric lavage fluid, or lung biopsy
    can show siderophages reflecting prior alveolar hemorrhage; classic IPH
    lacks pulmonary vasculitis or immune-complex deposition on biopsy.
  diagnostic: true
  evidence:
  - reference: PMID:15293620
    reference_title: "Idiopathic pulmonary haemosiderosis revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages)"
    explanation: The review supports siderophages in respiratory samples as a characteristic finding.
  - reference: PMID:15293620
    reference_title: "Idiopathic pulmonary haemosiderosis revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis"
    explanation: The review supports numerous alveolar siderophages without vasculitis as a histopathologic pattern.
phenotypes:
- category: Hematologic
  name: Iron deficiency anemia
  frequency: VERY_FREQUENT
  description: Iron deficiency anemia is a cardinal manifestation of chronic pulmonary blood loss.
  phenotype_term:
    preferred_term: iron deficiency anemia
    term:
      id: HP:0001891
      label: Iron deficiency anemia
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001891 | Iron deficiency anemia | Very frequent (99-80%)"
    explanation: Orphanet records iron deficiency anemia as very frequent.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "anemia (n = 100, 93.45%)"
    explanation: The pediatric cohort found anemia in 100 of 107 patients.
- category: Constitutional
  name: Pallor
  frequency: FREQUENT
  description: Pallor accompanies anemia from recurrent pulmonary blood loss.
  phenotype_term:
    preferred_term: pallor
    term:
      id: HP:0000980
      label: Pallor
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000980 | Pallor | Frequent (79-30%)"
    explanation: Orphanet records pallor as frequent.
- category: Abdominal
  name: Hepatosplenomegaly
  frequency: FREQUENT
  description: Hepatosplenomegaly is a reported systemic finding.
  phenotype_term:
    preferred_term: hepatosplenomegaly
    term:
      id: HP:0001433
      label: Hepatosplenomegaly
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001433 | Hepatosplenomegaly | Frequent (79-30%)"
    explanation: Orphanet records hepatosplenomegaly as frequent.
- category: Pulmonary
  name: Hemoptysis
  frequency: FREQUENT
  description: Hemoptysis reflects alveolar hemorrhage but may be absent in children who cannot expectorate.
  phenotype_term:
    preferred_term: hemoptysis
    term:
      id: HP:0002105
      label: Hemoptysis
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002105 | Hemoptysis | Frequent (79-30%)"
    explanation: Orphanet records hemoptysis as frequent.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "hemoptysis (n = 61, 57%)"
    explanation: The pediatric cohort found hemoptysis in 61 of 107 patients at diagnosis.
- category: Pulmonary
  name: Pulmonary infiltrates
  frequency: FREQUENT
  description: Chest imaging commonly shows pulmonary infiltrates during hemorrhagic episodes.
  phenotype_term:
    preferred_term: pulmonary infiltrates
    term:
      id: HP:0002113
      label: Pulmonary infiltrates
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002113 | Pulmonary infiltrates | Frequent (79-30%)"
    explanation: Orphanet records pulmonary infiltrates as frequent.
- category: Constitutional
  name: Fatigue
  frequency: FREQUENT
  description: Fatigue is consistent with anemia and chronic respiratory disease.
  phenotype_term:
    preferred_term: fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
    explanation: Orphanet records fatigue as frequent.
- category: Pulmonary
  name: Cough
  frequency: FREQUENT
  description: Cough is one of the common respiratory manifestations.
  phenotype_term:
    preferred_term: cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012735 | Cough | Frequent (79-30%)"
    explanation: Orphanet records cough as frequent.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cough (n = 68, 63.55%)"
    explanation: The pediatric cohort found cough in 68 of 107 patients at diagnosis.
- category: Imaging
  name: Ground-glass opacification on pulmonary HRCT
  frequency: FREQUENT
  description: Ground-glass opacification on HRCT reflects alveolar filling during hemorrhage.
  phenotype_term:
    preferred_term: ground-glass opacification on pulmonary HRCT
    term:
      id: HP:0025179
      label: Ground-glass opacification
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025179 | Ground-glass opacification on pulmonary HRCT | Frequent (79-30%)"
    explanation: Orphanet records ground-glass opacification on pulmonary HRCT as frequent.
- category: Renal
  name: Glomerulonephritis
  frequency: VERY_RARE
  description: Glomerulonephritis suggests renal involvement or a pulmonary-renal differential diagnosis.
  phenotype_term:
    preferred_term: glomerulonephritis
    term:
      id: HP:0000099
      label: Glomerulonephritis
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000099 | Glomerulonephritis | Very rare (<4-1%)"
    explanation: Orphanet records glomerulonephritis as very rare.
- category: Growth
  name: Failure to thrive
  frequency: OCCASIONAL
  description: Chronic illness and recurrent anemia can impair growth.
  phenotype_term:
    preferred_term: failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001508 | Failure to thrive | Occasional (29-5%)"
    explanation: Orphanet records failure to thrive as occasional.
- category: Cardiac
  name: Cardiomegaly
  frequency: OCCASIONAL
  description: Cardiomegaly can accompany severe chronic cardiopulmonary burden.
  phenotype_term:
    preferred_term: cardiomegaly
    term:
      id: HP:0001640
      label: Cardiomegaly
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001640 | Cardiomegaly | Occasional (29-5%)"
    explanation: Orphanet records cardiomegaly as occasional.
- category: Constitutional
  name: Fever
  frequency: OCCASIONAL
  description: Fever can occur during acute presentations and may contribute to misdiagnosis as infection.
  phenotype_term:
    preferred_term: fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001945 | Fever | Occasional (29-5%)"
    explanation: Orphanet records fever as occasional.
- category: Pulmonary
  name: Restrictive ventilatory defect
  frequency: OCCASIONAL
  description: Restrictive physiology may emerge with chronic parenchymal injury or fibrosis.
  phenotype_term:
    preferred_term: restrictive ventilatory defect
    term:
      id: HP:0002091
      label: Restrictive ventilatory defect
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002091 | Restrictive ventilatory defect | Occasional (29-5%)"
    explanation: Orphanet records restrictive ventilatory defect as occasional.
- category: Pulmonary
  name: Dyspnea
  frequency: OCCASIONAL
  description: Dyspnea reflects impaired gas exchange during alveolar hemorrhage or chronic lung disease.
  phenotype_term:
    preferred_term: dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002094 | Dyspnea | Occasional (29-5%)"
    explanation: Orphanet records dyspnea as occasional.
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "dyspnea (n = 17, 68%)"
    explanation: The French cohort recorded dyspnea at diagnosis in 17 of 25 children.
- category: Pulmonary
  name: Pulmonary fibrosis
  frequency: OCCASIONAL
  description: Severe or relapsing disease can progress to pulmonary fibrosis.
  phenotype_term:
    preferred_term: pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002206 | Pulmonary fibrosis | Occasional (29-5%)"
    explanation: Orphanet records pulmonary fibrosis as occasional.
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One patient developed severe pulmonary fibrosis"
    explanation: The French cohort documents pulmonary fibrosis as a severe complication.
- category: Abdominal
  name: Hepatomegaly
  frequency: OCCASIONAL
  description: Hepatomegaly is reported as an occasional systemic finding.
  phenotype_term:
    preferred_term: hepatomegaly
    term:
      id: HP:0002240
      label: Hepatomegaly
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002240 | Hepatomegaly | Occasional (29-5%)"
    explanation: Orphanet records hepatomegaly as occasional.
- category: Pulmonary
  name: Respiratory failure
  frequency: OCCASIONAL
  description: Acute massive hemorrhage or chronic respiratory insufficiency can cause respiratory failure.
  phenotype_term:
    preferred_term: respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002878 | Respiratory failure | Occasional (29-5%)"
    explanation: Orphanet records respiratory failure as occasional.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "three died from massive pulmonary hemorrhage and respiratory failure"
    explanation: The pediatric cohort documents respiratory failure in fatal severe presentations.
- category: Comorbidity
  name: Down syndrome
  frequency: OCCASIONAL
  description: >
    Down syndrome is an associated comorbidity reported in pediatric idiopathic
    pulmonary hemosiderosis cohorts, not a defining feature of all cases.
  phenotype_term:
    preferred_term: Down syndrome
    term:
      id: MONDO:0008608
      label: Down syndrome
  evidence:
  - reference: PMID:24125570
    reference_title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome."
    explanation: The French pediatric cohort documents Down syndrome in 5 of 25 IPH cases, supporting an occasional comorbidity association.
- category: Laboratory
  name: Rheumatoid factor positive
  frequency: OCCASIONAL
  description: Rheumatoid factor positivity is one of the reported autoimmune serologic abnormalities.
  phenotype_term:
    preferred_term: rheumatoid factor positive
    term:
      id: HP:0002923
      label: Rheumatoid factor positive
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002923 | Rheumatoid factor positive | Occasional (29-5%)"
    explanation: Orphanet records rheumatoid factor positivity as occasional.
- category: Laboratory
  name: Smooth muscle antibody positivity
  frequency: OCCASIONAL
  description: Smooth muscle antibody positivity is one of the reported autoimmune serologic abnormalities.
  phenotype_term:
    preferred_term: smooth muscle antibody positivity
    term:
      id: HP:0003262
      label: Anti-smooth muscle antibody positivity
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003262 | Smooth muscle antibody positivity | Occasional (29-5%)"
    explanation: Orphanet records smooth muscle antibody positivity as occasional.
- category: Laboratory
  name: Antineutrophil antibody positivity
  frequency: OCCASIONAL
  description: Antineutrophil antibody positivity is one of the reported autoimmune serologic abnormalities.
  phenotype_term:
    preferred_term: antineutrophil antibody positivity
    term:
      id: HP:0003453
      label: Antineutrophil antibody positivity
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003453 | Antineutrophil antibody positivity | Occasional (29-5%)"
    explanation: Orphanet records antineutrophil antibody positivity as occasional.
- category: Laboratory
  name: Antinuclear antibody positivity
  frequency: OCCASIONAL
  description: Antinuclear antibody positivity is one of the reported autoimmune serologic abnormalities.
  phenotype_term:
    preferred_term: antinuclear antibody positivity
    term:
      id: HP:0003493
      label: Antinuclear antibody positivity
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003493 | Antinuclear antibody positivity | Occasional (29-5%)"
    explanation: Orphanet records antinuclear antibody positivity as occasional.
- category: Immune
  name: Allergy
  frequency: OCCASIONAL
  description: Allergy is reported in a subset and is one hypothesized contributor rather than a proven cause.
  phenotype_term:
    preferred_term: allergy
    term:
      id: HP:0012393
      label: Allergy
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012393 | Allergy | Occasional (29-5%)"
    explanation: Orphanet records allergy as occasional.
- category: Imaging
  name: Reticular pattern on pulmonary HRCT
  frequency: OCCASIONAL
  description: Reticular pulmonary HRCT changes may reflect chronic interstitial injury.
  phenotype_term:
    preferred_term: reticular pattern on pulmonary HRCT
    term:
      id: HP:0025390
      label: Reticular pattern on pulmonary HRCT
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025390 | Reticular pattern on pulmonary HRCT | Occasional (29-5%)"
    explanation: Orphanet records reticular pattern on pulmonary HRCT as occasional.
- category: Imaging
  name: Nodular pattern on pulmonary HRCT
  frequency: OCCASIONAL
  description: Nodular pulmonary HRCT changes are reported in a subset.
  phenotype_term:
    preferred_term: nodular pattern on pulmonary HRCT
    term:
      id: HP:0025392
      label: Nodular pattern on pulmonary HRCT
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025392 | Nodular pattern on pulmonary HRCT | Occasional (29-5%)"
    explanation: Orphanet records nodular pattern on pulmonary HRCT as occasional.
- category: Pulmonary
  name: Diffuse alveolar hemorrhage
  frequency: OCCASIONAL
  description: Diffuse alveolar hemorrhage is the core lesion of IPH and can be recurrent.
  phenotype_term:
    preferred_term: diffuse alveolar hemorrhage
    term:
      id: HP:0025420
      label: Diffuse alveolar hemorrhage
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025420 | Diffuse alveolar hemorrhage | Occasional (29-5%)"
    explanation: Orphanet records diffuse alveolar hemorrhage as occasional.
  - reference: PMID:15293620
    reference_title: "Idiopathic pulmonary haemosiderosis revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "repetitive episodes of diffuse alveolar haemorrhage"
    explanation: The clinical review supports recurrent diffuse alveolar hemorrhage as central to IPH.
- category: Laboratory
  name: Autoimmune antibody positivity
  frequency: OCCASIONAL
  description: Autoimmune serologic abnormalities support immune involvement in a subset.
  phenotype_term:
    preferred_term: autoimmune antibody positivity
    term:
      id: HP:0030057
      label: Autoimmune antibody positivity
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030057 | Autoimmune antibody positivity | Occasional (29-5%)"
    explanation: Orphanet records autoimmune antibody positivity as occasional.
- category: Cardiac
  name: Heart murmur
  frequency: OCCASIONAL
  description: Heart murmur is an occasional clinical finding.
  phenotype_term:
    preferred_term: heart murmur
    term:
      id: HP:0030148
      label: Heart murmur
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030148 | Heart murmur | Occasional (29-5%)"
    explanation: Orphanet records heart murmur as occasional.
- category: Pulmonary
  name: Crackles
  frequency: OCCASIONAL
  description: Crackles can occur with alveolar filling and parenchymal involvement.
  phenotype_term:
    preferred_term: crackles
    term:
      id: HP:0030830
      label: Crackles
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030830 | Crackles | Occasional (29-5%)"
    explanation: Orphanet records crackles as occasional.
- category: Immune
  name: Cow milk allergy
  frequency: VERY_RARE
  description: Cow milk allergy is a rare reported associated finding and should not be treated as the primary IPH mechanism.
  phenotype_term:
    preferred_term: cow milk allergy
    term:
      id: HP:0100327
      label: Cow milk allergy
  evidence:
  - reference: ORPHA:99931
    reference_title: Idiopathic pulmonary hemosiderosis (Orphanet structured-database record)
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100327 | Cow milk allergy | Very rare (<4-1%)"
    explanation: Orphanet records cow milk allergy as very rare.
diagnosis:
- name: Chest radiography and computed tomography
  description: >
    Chest radiographs or CT are used to identify infiltrates, ground-glass
    opacity, nodular changes, cardiomegaly, or reticular interstitial changes
    compatible with alveolar hemorrhage and chronic injury.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: MAXO:0000003
      label: diagnostic procedure
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All of the patients showed abnormal chest X-rays or computed tomography scans."
    explanation: The pediatric cohort supports chest imaging as a routine diagnostic component.
- name: Hemosiderin-laden macrophage testing
  description: >
    Sputum, gastric lavage fluid, or bronchoalveolar lavage fluid can be tested
    for hemosiderin-laden macrophages; repeated gastric lavage or BAL can improve
    detection in children who cannot expectorate.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: MAXO:0000003
      label: diagnostic procedure
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The positive rates of hemosiderin-laden macrophages in sputum, gastric lavage fluid, and bronchoalveolar lavage fluid were 91.66%, 98.21%, and 100%, respectively."
    explanation: The cohort supports cytologic testing for hemosiderin-laden macrophages across respiratory and gastric samples.
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chest imaging combined with repeated examinations for hemosiderin-laden macrophages in sputum, gastric lavage fluid, or bronchoalveolar lavage fluid are helpful for diagnosing IPH."
    explanation: The cohort conclusion supports combined imaging and repeated siderophage testing.
- name: Exclusion of secondary diffuse alveolar hemorrhage causes
  description: >
    IPH is diagnosed only after excluding secondary causes such as infection,
    bronchiectasis, interstitial pneumonia, neoplasm, cardiovascular disease,
    coagulation disorders, connective-tissue disease, celiac disease, and
    systemic vasculitis.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: MAXO:0000003
      label: diagnostic procedure
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "exclusion of other diseases, which are associated with diffuse alveolar hemorrhage, such as bronchiectasis, interstitial pneumonia, neoplasms, cardiovascular disease, coagulation disorders, infections, connective tissue diseases, celiac disease, and systemic vasculitis."
    explanation: The cohort's case definition supports exclusion of secondary DAH causes.
treatments:
- name: Systemic corticosteroid therapy
  description: >
    Systemic corticosteroids are first-line therapy for acute episodes and are
    commonly used for initial control and maintenance, though recurrence during
    tapering is frequent.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: MAXO:0000640
      label: corticosteroid agent therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
    - preferred_term: prednisone
      term:
        id: CHEBI:8382
        label: prednisone
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glucocorticoids and immunosuppressive agents are the first choice for treating IPH."
    explanation: The pediatric cohort review supports glucocorticoids as first-choice treatment.
  - reference: PMID:26289251
    reference_title: "A physician survey reveals differences in management of idiopathic pulmonary hemosiderosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Common medications respondents used for treatment at initial presentation and chronic maintenance therapy were corticosteroids (98.7 and 84.0 %, initial and chronic therapy respectively)"
    explanation: The international physician survey supports common corticosteroid use for initial and chronic therapy.
  - reference: PMID:33184706
    reference_title: "Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticosteroid therapy represents the first line of treatment"
    explanation: The treatment review supports corticosteroids as first-line therapy.
- name: Steroid-sparing immunosuppressive therapy
  description: >
    Hydroxychloroquine, azathioprine, cyclophosphamide, mycophenolate mofetil,
    and other immunomodulatory agents have been used when disease is severe,
    recurrent, steroid-refractory, or steroid-toxic.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: MAXO:0000297
      label: immune suppressant agent therapy
    therapeutic_agent:
    - preferred_term: hydroxychloroquine
      term:
        id: CHEBI:5801
        label: hydroxychloroquine
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
    - preferred_term: cyclophosphamide
      term:
        id: CHEBI:4027
        label: cyclophosphamide
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
  evidence:
  - reference: PMID:33184706
    reference_title: "Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Additional immunomodulatory/immunosuppressive medications have been used with varying success, especially in the setting of steroid-refractory disease."
    explanation: The treatment review supports steroid-sparing immunosuppression for steroid-refractory IPH.
  - reference: PMID:30806370
    reference_title: "Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We initiated hydroxy-chloroquine and azathioprine early in treatment along with steroids in seven children with idiopathic pulmonary hemosiderosis"
    explanation: The pediatric series supports hydroxychloroquine and azathioprine as steroid-sparing options used with corticosteroids.
  - reference: PMID:30806370
    reference_title: "Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "early introduction of second line immunosuppressants helped in reducing disease flare and steroid toxicity without serious adverse effects."
    explanation: The series supports benefit of early steroid-sparing immunosuppression in seven children.
  - reference: PMID:33184706
    reference_title: "Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cyclophosphamide, azathioprine, hydroxychloroquine, mycophenolate mofetil, and mesenchymal cell transplantation have been attempted to improve outcome and reduce side effects."
    explanation: The treatment review specifically names cyclophosphamide and mycophenolate mofetil among attempted steroid-sparing options.
- name: Supportive care for acute anemia and respiratory compromise
  description: >
    Supportive management includes acute stabilization, oxygen or respiratory
    support when needed, and transfusion for severe anemia while disease-directed
    immunosuppression is initiated.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:30278795
    reference_title: "Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All of the 107 patients were provided symptomatic treatments before diagnosis, and 29 received blood transfusions."
    explanation: The pediatric cohort documents symptomatic care and transfusion in a subset before definitive diagnosis.
notes: >
  Pulmonary hemosiderosis in this entry follows the idiopathic pulmonary
  hemosiderosis concept mapped by ORPHA:99931 and MONDO:0008346. Celiac disease
  with pulmonary hemosiderosis is represented separately as Lane-Hamilton
  syndrome; IPH should be evaluated for that association but is not itself
  defined by gluten sensitivity. Etiologic hypotheses include environmental,
  allergic, autoimmune, and genetic contributors, but none is established enough
  to curate as a single upstream causal node.
references:
- reference: ORPHA:99931
  title: Idiopathic pulmonary hemosiderosis
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:15293620
  title: Idiopathic pulmonary haemosiderosis revisited.
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:24125570
  title: "New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort."
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:26289251
  title: A physician survey reveals differences in management of idiopathic pulmonary hemosiderosis.
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:30278795
  title: Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients.
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:30806370
  title: Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis.
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
- reference: PMID:33184706
  title: "Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions."
  found_in:
  - Pulmonary_Hemosiderosis-deep-research-fallback.md
  findings: []
📚

References & Deep Research

References

7
ORPHA:99931
Idiopathic pulmonary hemosiderosis
No top-level findings curated for this source.
PMID:15293620
Idiopathic pulmonary haemosiderosis revisited.
No top-level findings curated for this source.
PMID:24125570
New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort.
No top-level findings curated for this source.
PMID:26289251
A physician survey reveals differences in management of idiopathic pulmonary hemosiderosis.
No top-level findings curated for this source.
PMID:30278795
Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients.
No top-level findings curated for this source.
PMID:30806370
Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis.
No top-level findings curated for this source.
PMID:33184706
Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions.
No top-level findings curated for this source.

Deep Research

1
Pulmonary Hemosiderosis Deep-Research Fallback ▸

Pulmonary Hemosiderosis Deep-Research Fallback

Automated deep-research providers were attempted after local evidence-backed curation, but both stayed silent and were stopped by bounded timeouts:

  • timeout 120s just research-disorder falcon Pulmonary_Hemosiderosis returned 124 / signal 15.
  • timeout 60s just research-disorder openai Pulmonary_Hemosiderosis returned 124 / signal 15.

Because provider runs were unavailable, the curation used generated local caches and the disease-specific literature already fetched into references_cache/. The reviewed scope is idiopathic pulmonary hemosiderosis as represented by ORPHA:99931 and MONDO:0008346, with secondary diffuse alveolar hemorrhage causes and Lane-Hamilton syndrome kept outside the core disease definition.

Scope Confirmation

  • ORPHA:99931 supplied the disease definition, childhood onset, epidemiology, cross-references, and HPO phenotype rows.
  • PMID:30278795 supplied the large 107-patient pediatric cohort, clinical frequencies, diagnosis, prognosis, and glucocorticoid treatment evidence.
  • PMID:24125570 supplied the French RespiRare pediatric cohort, autoimmunity signals, Down syndrome comorbidity signal, diagnosis, fibrosis, and severe hemorrhage outcomes.
  • PMID:15293620 supplied recurrent diffuse alveolar hemorrhage, siderophages, alveolar hemosiderin deposition, and biopsy exclusion of vasculitis.
  • PMID:26289251 supplied physician-practice treatment patterns.
  • PMID:33184706 and PMID:30806370 supplied corticosteroid and steroid-sparing immunosuppressive treatment scope.

Review Follow-Up

The provider fallback was explicitly cross-checked for obvious curation gaps. PMID:24125570 supports autoimmune contribution in a subset through ANCA, ANA, and coeliac antibody positivity and through the authors' conclusion that autoimmunity contributes to disease development. The YAML now models this as an atomic modifier node rather than replacing the idiopathic upstream trigger.

The same cohort reported Down syndrome in 5 of 25 pediatric IPH cases. Because the current disease schema has no top-level comorbidities slot, the YAML represents this as a Comorbidity phenotype entry with a MONDO term binding and an exact cohort snippet.

PMID:33184706 names cyclophosphamide and mycophenolate mofetil among attempted steroid-sparing therapies. The YAML treatment entry now includes those therapeutic-agent bindings alongside hydroxychloroquine and azathioprine.