Idiopathic pulmonary hemosiderosis patients present with symptoms associated with pulmonary suffering and signs of anemia, usually before reaching the age of 10 years [1]. Respiratory complaints, often recurrent or chronic, include coughing (dry or productive), wheezing, dyspnea, tachypnea, and hemoptysis, sometimes being wrongly diagnosed with lower respiratory infections [2]. However, hemoptysis is sometimes absent in children due to the fact that they swallow their sputum [3], but this does not exclude the presence of the disease. Symptoms may occur in an insidious or acute manner and initial presentation may be dramatic, with cyanosis, hypoxemia, respiratory failure, tachycardia, and fever. Clinical diagnosis is difficult in these cases, especially since pulmonary auscultation reveals crackles (caused by fibrosis [4] [5]) and pneumonia is easily suspected. Chronic but limited lung bleeding leads to more non-specific findings, like pallor, asthenia, exercise intolerance, failure to thrive, unsatisfactory ponderal and statural curves and finger clubbing.

Idiopathic pulmonary hemosiderosis may be accompanied by other illnesses, such as celiac disease [6] or von Willebrand disease. These associations induce more severe anemia, as the first one is a bleeding disorder per se, and the second one leads to enteral blood loss. Celiac disease may also cause flatulence, steatorrhea, and diarrhea, but the presence of these findings is not compulsory. Other associations include chronic granulomatous disease [7], idiopathic [8] and rheumatoid arthritis [9].

• Splenomegaly

  Clubbing, hepatomegaly and splenomegaly was seen in 16 (62%), 15 (58%) and 10 (38%) children, respectively. Hemosiderin laden macrophages were documented in BAL and gastric aspirate in 92% and 30% patients, respectively. [ncbi.nlm.nih.gov]

  […] after significant bleed May be streaky or life-threatening Chest Pain Crackles Interstitial Lung Disease (see [[ILD-Etiology]]) Other Manifestations Fever Fatigue Clubbing: may occur over time as interstitial lung disease develops Lympadenopathy and Splenomegaly [mdnxs.com]

  There was no hepatomegaly or splenomegaly. Arterial blood gas objectified a PaO2: 52, 1 mmHg, PaCO2: 25, 7mmHg, SaO2: 90, 8 %. [latunisiemedicale.com]

• Fatigue

  A 14-year-old girl was admitted to the pediatric emergency department with complaints of cough, dyspnea, fatigue and bloody sputum for 6 months. She had been hospitalized 3 times during this period and received antibiotics and blood transfusion. [ncbi.nlm.nih.gov]

  The most common symptoms in adults are exertional dyspnea and fatigue due to pulmonary hemorrhage and iron deficiency anemia. [msdmanuals.com]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019 [patientslikeme.com]

  Iron deficiency anemia causes fatigue, paleness, and weakness. The most common symptoms in adults are shortness of breath during activity and the symptoms of iron deficiency anemia. [merckmanuals.com]

• Pallor

  A 5-year-old male patient was admitted to our clinic with sudden-onset pallor during iron therapy given for anemia. While he was being investigated for clinical and laboratory signs mimicking hemolytic anemia, he developed cough and dyspnea. [ncbi.nlm.nih.gov]

  Chronic but limited lung bleeding leads to more non-specific findings, like pallor, asthenia, exercise intolerance, failure to thrive, unsatisfactory ponderal and statural curves and finger clubbing. [symptoma.com]

• Pathologist

  Pathologists newly developed techniques to make diagnoses more involved in day-to-day practice are expected to precise. Until recently, these new techniques have have knowledge of ongoing advances in their field. [books.google.com]

  Recent reviews have documented a 5-year survival rate of around 86% in cases with IPH as also spontaneous remissions. [4] A look at the alveoli in the lung biopsy specimen by an experienced pathologist provides an early diagnostic answer so that immunosuppressive [jpgmonline.com]

• Chills

  On review of systems, she admitted to fatigue and shortness of breath, but denied hemoptysis, fever, chills or gastro-intestinal and genitourinary symptoms. [omicsonline.org]

• Cough

  The first patient was 23 years of age, and had suffered from dry cough and progressive dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level was 900 U/mL and eosinophilia was 9%. [ncbi.nlm.nih.gov]

  Symptoms of idiopathic pulmonary hemosiderosis in children include repeated episodes of shortness of breath and cough. Cough is usually dry initially. Later, the person may cough up blood. [msdmanuals.com]

• Dyspnea

  The first patient was 23 years of age, and had suffered from dry cough and progressive dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level was 900 U/mL and eosinophilia was 9%. [ncbi.nlm.nih.gov]

  The most common symptoms in adults are exertional dyspnea and fatigue due to pulmonary hemorrhage and iron deficiency anemia. [msdmanuals.com]

• Respiratory Distress

  He had a respiratory rate of 58/min with respiratory distress, cyanosis, and grade III clubbing. Respiratory system examination was normal. Several previous reports of hemoglobin were as low as 3.6 g/dl with hypochromic and microcytic anemia. [ncbi.nlm.nih.gov]

  Criterion B: Severe presentation leading to acute respiratory distress or respiratory failure resulting in hospitalization in a PICU with intubation and mechanical ventilation. [cdc.gov]

  On examination, the boy was anxious, pale and cyanosed with marked respiratory distress. Vitals were deranged with pulse rate of 155 per minute, respiratory rate of 60 per minute and blood pressure of 103/75 mm Hg. [jpma.org.pk]

  Pulmonary Fibrosis Adult Respiratory Distress Syndrome (ARDS) Immune Complex Disease intra-alveolar bleeding Clinically, IPH manifests as a triad of haemoptysis, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia. [en.wikipedia.org]

  Corticosteroids have a proven beneficial role in asthma, croup (Laryngotracheobronchitis), decreasing the risk and severity of respiratory distress syndrome (RDS), allergic bronchopulmonary aspergillosis, interstitial lung disease, hemangioma of trachea [doi.org]

• Dry Cough

  The first patient was 23 years of age, and had suffered from dry cough and progressive dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level was 900 U/mL and eosinophilia was 9%. [ncbi.nlm.nih.gov]

  Dry cough and dyspnea were the principal symptoms of the functional respiratory syndrome in our cases (13 cases, respectively, 12 cases). [nature.com]

  A 3-year-old male presented with mild fever, breathlessness, dry cough, and bluish nail discoloration for 8 days. He had required five blood transfusions in the past 1 year (last transfusion was given 4 months ago). [jpgmonline.com]

  Case Report A 38-year-old female, presented to our emergency room with progressive breathlessness (MMRC grade 2- 4) and dry cough for three months. She had history of multiple blood transfusions elsewhere during the prior three months period. [ijcasereportsandimages.com]

• Tachypnea

  Respiratory complaints, often recurrent or chronic, include coughing (dry or productive), wheezing, dyspnea, tachypnea, and hemoptysis, sometimes being wrongly diagnosed with lower respiratory infections. [symptoma.com]

  Her tachypnea decreased and we were able to stop supplementary oxygen. The child was discharged. She was put on maintenance steroids and was symptom free for 15 months. [indianpediatrics.net]

  […] explained by parents and was mistaken for haematemesis, therefore, it is important to distinguish between the two in a clinical setting. 8,9 Other studies, however, have included different respiratory symptoms, such as recurrent cough, wheezing, and tachypnea [jpma.org.pk]

  Common findings are, tachypnea, tachycardia, cyanosis, clubbing, fine or coarse crackles, wheezing, and hypoxemia. [hawaii.edu]

• Failure to Thrive

  Its diagnosis should be considered in any child presenting with moderate to severe anemia and failure to thrive of unclear etiology. [ncbi.nlm.nih.gov]

  Children with idiopathic pulmonary hemosiderosis may instead have failure to thrive and iron deficiency anemia. Children with failure to thrive are extremely underweight. Iron deficiency anemia causes fatigue, paleness, and weakness. [msdmanuals.com]

• Hematemesis

  We report a 3-year-old girl who was presented with acute pale-looking appearance, hemoptysis, hematemesis and shortness of breath. [ncbi.nlm.nih.gov]

  We also had two cases of false hematemesis/occult gastrointestinal hemorrhages which has increased the incidence of haemoptysis in our study at 30,95%. [nature.com]

  Hematemesis may occur as a result of swallowed pulmonary blood. Other common features include pallor, poor weight gain and fatigue. [indianpediatrics.net]

  She had no history of hemoptysis, hematemesis, menorrhagia, bleeding per rectum or any other obvious focus of bleeding. There was no history of fever. She had no symptoms related to connective tissue disorder. [ijcasereportsandimages.com]

• Abdominal Pain

  Occasionally, recurrent fever and abdominal pain. Onset is sudden, usually in infancy or childhood. Equal sex distribution in children. The condition also occurs in adults where there is a sex difference (M:F = 2:1). [whonamedit.com]

  Chest X-ray showing bilateral interstitial infiltrates Case 2: A 2-year-8-month-old female child presented to us with fever of one month duration, rapid breathing and progressive pallor associated with abdominal pain of I week duration. [indianpediatrics.net]

• Jaundice

  Here, we present a case of a 15-month-old boy with IPH who presented with anemia, jaundice, and failure to thrive, as well as a history of hemoptysis that was not initially elicited. [ncbi.nlm.nih.gov]

  Older age, longer duration of illness, history of hemoptysis and jaundice were associated with poor response. Treatment with prednisolone and hydroxychloroquine followed by inhaled corticosteroids may improve survival in children with IPH. (author's) [popline.org]

  However, on further enquiry, there was a history of requiring multiple (five) blood transfusions over the first 8 months of past 1 year without any obvious history of blood loss or jaundice, though the child was transfusion free for the last 4 months. [jpgmonline.com]

• Heart Disease

  A possibility of a cyanotic congenital heart disease was considered in the presence of respiratory symptoms, cyanosis, and clubbing. However, a normal electrocardiography and normal 2D echocardiography eliminated this possibility. [jpgmonline.com]

• Asthenia

  Chronic but limited lung bleeding leads to more non-specific findings, like pallor, asthenia, exercise intolerance, failure to thrive, unsatisfactory ponderal and statural curves and finger clubbing. [symptoma.com]

  All patients had recurrent episodes of fever and anemia syndrome, with pallor and asthenia associated with respiratory symptoms of cough in nine patients, and hemoptysis and dyspnea in seven. [em-consulte.com]

• Hematuria

  Urinalysis may reveal proteinuria or hematuria. Coagulation disorders should also be investigated. [symptoma.com]

  Paueksakon, Pulmonary hemorrhage with hematuria: do not forget IgA nephropathy, Clinical Kidney Journal, 5, 5, (463), (2012). [doi.org]

  He developed hematuria on cyclophosphamide so he was put on azathioprine. Child was discharged on prednisolone and azathioprine. He was followed up in the clinic. He is thriving well with no further need of blood transfusion. [jpma.org.pk]

  Gross and microscopic urinary analysis was negative for hematuria, proteinuria or casts. Chest xray showed scattered infiltrates ( Figure 1 ). [omicsonline.org]

Idiopathic pulmonary hemosiderosis is a diagnosis of exclusion. Therefore cow milk protein allergy and autoimmune diseases, as well as other frequently associated illnesses like systemic lupus erythematosus, celiac disease, Goodpasture syndrome or Wegener granulomatosis must be ruled out. Towards this purpose, the physician may find it useful to order serum precipitins to casein and lactalbumin titers, anti-glomerular basal membrane, antinuclear antibodies, anti-DNA, anti-gliadin, anti-reticulin and anti-endomysial antibodies. The complete cell blood count will reveal the presence of anemia and possible eosinophilia. The anemia has iron deficiency characteristics (hypochromic and microcytic) [10]. Enteral blood loss is detected using guaiac tests. Keeping in mind that sputum is often swallowed by children, a gastric lavage analysis and bronchoalveolar lavage may prove useful, as they demonstrate the presence of presence of hemosiderin-bearing macrophages [4]. Despite the fact that pulmonary biopsy remains the gold standard for diagnosis [11], it can also be achieved using bronchoalveolar lavage [12] [13]. If sputum can be obtained, a cytological and bacteriologic analysis is necessary. Urinalysis may reveal proteinuria or hematuria. Coagulation disorders should also be investigated.

Chest radiography reveals bilateral alveolar infiltrates which are seen as opacities located in the basal and perihilar areas, that may be accompanied by edema [8]. After blood absorption, during remission phase, a reticular pattern remains. [4] Hilar adenopathy may be present in the acute phase. A more accurate diagnosis may be obtained with computed tomography, that also characterizes bronchial and vascular status, but pulmonary embolism is best excluded by ventilation/perfusion nuclear scanning.

Spirometry testing reveals a restrictive pattern between acute episodes and a mixed pattern during pulmonary hemorrhagic events.

• Microcytic Anemia

  IPH should be listed in the differential diagnosis of a child presenting with unexplained hypochromic, microcytic anemia and respiratory symptoms. [ncbi.nlm.nih.gov]

• Leukopenia

  Only one of eight patients with relative leukopenia on 6MP maintenance recurred while 5 of 7 others recurred (P < 0.05) during median 4.5-year follow-up. [ncbi.nlm.nih.gov]

  Only one of eight patients with relative leukopenia on 6MP maintenance recurred while 5 of 7 others recurred ( P Citing Literature Number of times cited according to CrossRef: 13 Lu-Hong Xu, Rong-Qiong Ou, Bao-Jing Wu, Hai-Yan Wang, Jian-Pei Fang and [doi.org]

Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). [ncbi.nlm.nih.gov]

All the patients exhibited response to the initial treatment. [doi.org]

CONCLUSION: Adult IPH patients showed good prognosis. However, the present patients are clinically slightly different from the previously characterized IPH. [ncbi.nlm.nih.gov]

Keens, Prognosis in Pediatric Idiopathic Pulmonary Hemosiderosis, Chest, 116, 3, (721), (1999). N. Milman and F.Møller Pedersen, Idiopathic pulmonary haemosiderosis. [doi.org]

Conclusion Adult IPH patients showed good prognosis. However, the present patients are clinically slightly different from the previously characterized IPH. [jstage.jst.go.jp]

in 75% of cases, mean survival is 3-5 years Lung Transplantation: controversial, as disease recurs after bilateral lung transplant Prognosis Adults have better prognosis than children 25% of adults remit after first episode 25% have persistent dyspnea [mdnxs.com]

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage with unknown etiology. [ncbi.nlm.nih.gov]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

TERMINOLOGY Abbreviations Idiopathic pulmonary hemosiderosis (IPH) Synonyms Idiopathic pulmonary hemorrhage Definitions Intrapulmonary hemorrhage of unknown etiology that is unassociated with other systemic manifestations ETIOLOGY/PATHOGENESIS Etiology [basicmedicalkey.com]

In ICD-10-CM, etiology codes must be coded first, followed by the manifestation codes. [icd.codes]

An epidemiologic history and genetic investigation should be included in the evaluation of patients with any disease when the cause is obscure. [ncbi.nlm.nih.gov]

[…] of unknown etiology that is unassociated with other systemic manifestations ETIOLOGY/PATHOGENESIS Etiology Unknown No immunologic mechanism has been identified Familial clustering has been reported, supporting genetic susceptibility CLINICAL ISSUES Epidemiology [basicmedicalkey.com]

Epidemiology Frequency United States Idiopathic pulmonary hemosiderosis is an uncommon yet well-recognized disorder. Exact figures regarding prevalence are lacking. Familial recurrence has been reported but is rare. [emedicine.medscape.com]

Epidemiology, pathogenic aspects and diagnosis, Respiratory Medicine, 92, 7, (902), (1998). [doi.org]

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. [ncbi.nlm.nih.gov]

Clinical, pathophysiologic, radiologic and therapeutic findings in idiopathic pulmonary hemosiderosis Pascalis L., Saba L., Sessini P. [minervamedica.it]

Following this classification, the pathophysiology of pulmonary hemosiderosis [1] can be divided into 3 groups. Group 1 pulmonary hemosiderosis is defined by pulmonary hemorrhage associated with circulating anti-GBM antibodies. [emedicine.medscape.com]

Pathophysiological aspects, prevention and management. A review. Panminerva Med 2006; 48: 231–239. Google Scholar 28. Ward M, Sinn J. Steroid therapy for meconium aspiration syndrome in newborn infants. [doi.org]

Early diagnosis and treatment with corticosteroids prevents further episodes of recurrent alveolar hemorrhage and improves the clinical outcome. [ncbi.nlm.nih.gov]

A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine. [en.wikipedia.org]

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