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].

• 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]

• 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]

• 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]

  Figure 1 A three-year-old girl with a declining growth rate and recurrent iron-deficiency anemia presented with a five-day history of nonproductive cough, fever, and anorexia. [nejm.org]

  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. [merckmanuals.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]

  Ceelen-Gellerstedt syndrome - repeated sudden attacks of dyspnea and hemoptysis leading to diffuse pulmonary hemosiderosis. Synonym(s): idiopathic pulmonary hemosiderosis [medical-dictionary.thefreedictionary.com]

  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]

• 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]

• Pulmonary Disorder

  February 2017; http://www.merckmanuals.com/professional/pulmonary-disorders/diffuse-alveolar-hemorrhage-and-pulmonary-renal-syndrome/idiopathic-pulmonary-hemosiderosis. Pulmonary Hemosiderosis. Online Mendelian Inheritance in Man. [rarediseases.info.nih.gov]

• Heart Block

  A young woman with idiopathic pulmonary hemosiderosis (IPH) and advanced heart block below the atrioventricular node requiring pacemaker therapy is discussed. [ncbi.nlm.nih.gov]

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]

• Ventricular Hypertrophy

  Cardiac involvement in the form of myocarditis and right ventricular hypertrophy have been reported to occur in association with IPH, although findings on echocardiography have not been described. [ncbi.nlm.nih.gov]

METHODS: Charts of patients diagnosed as IPH were reviewed for clinical features and treatment regimen. [ncbi.nlm.nih.gov]

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

Charts of patients diagnosed as IPH were reviewed for clinical features and treatment regimen. [popline.org]

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]

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]

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

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]

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

[…] 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]

Abstract An epidemiologic survey was undertaken of 30 children in whom idiopathic pulmonary hemosiderosis (IPH) had been identified. In determining the prognostic significance of various parameters, a clinical severity score was used. [ncbi.nlm.nih.gov]

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 Age: occurs mainly in children, but 20% of cases occur in adults (mainly in >30 y/o group) Age Range for Onset: 4 months-62 y/o Sex: M:F ratio is 2:1 (in adults) Familial Clustering: has been reported Associated with: Celiac Disease HLA-B8 [mdnxs.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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