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|Year : 2011 | Volume
| Issue : 1 | Page : 57-60
Idiopathic pulmonary hemosiderosis: Alveoli are an answer to anemia
S Bhatia1, MS Tullu1, P Vaideeswar2, KR Lahiri1
1 Department of Pediatrics, Pediatric Chest Clinic, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Pathology, Cardiovascular and Thoracic Division, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India
|Date of Submission||21-Mar-2010|
|Date of Decision||25-Aug-2010|
|Date of Acceptance||28-Sep-2010|
|Date of Web Publication||31-Jan-2011|
M S Tullu
Department of Pediatrics, Pediatric Chest Clinic, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra
Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder (triad of iron-deficiency anemia, hemoptysis, and alveolar infiltrates). 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). 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. There were transient increases in the hemoglobin and normalization of red cell morphology with blood transfusions. Serum iron, G6PD enzyme assay, hemoglobin electrophoresis, the sickling test, Coomb's test, stool and urine analysis, and a Meckel's scan were normal. HIV antibody and dsDNA were negative. The chest radiograph revealed symmetrical patchy infiltrates sparing lung apices (confirmed on high-resolution computed tomography). Lung biopsy diagnosed pulmonary hemosiderosis (interstitial lung disease with hemosiderin-laden macrophages scattered in the alveoli and areas of fibrosis in the alveolar septa). The patient showed marked clinical improvement in 10 days of therapy with prednisolone. IPH should be listed in the differential diagnosis of a child presenting with unexplained hypochromic, microcytic anemia and respiratory symptoms.
Keywords: Anemia, alveoli, biopsy, blood, child, hemosiderosis, lung, respiratory
|How to cite this article:|
Bhatia S, Tullu M S, Vaideeswar P, Lahiri K R. Idiopathic pulmonary hemosiderosis: Alveoli are an answer to anemia. J Postgrad Med 2011;57:57-60
|How to cite this URL:|
Bhatia S, Tullu M S, Vaideeswar P, Lahiri K R. Idiopathic pulmonary hemosiderosis: Alveoli are an answer to anemia. J Postgrad Med [serial online] 2011 [cited 2013 Jun 18];57:57-60. Available from: http://www.jpgmonline.com/text.asp?2011/57/1/57/74290
| :: Case Details|| |
A 3-year-old male child was admitted to our institution on July 1, 2009, with chief complaints of mild-grade fever, breathlessness, dry cough, and bluish discoloration of nails for 8-day duration prior to admission. The child was diagnosed to have a lower respiratory tract infection and received antibiotics for 1 day in a private hospital in a district place after which he was referred to our hospital. There was neither a past history of recurrent respiratory tract infections, tuberculosis, or tuberculous contact nor was there any history suggestive of an underlying cardiac disorder. 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. His birth history and developmental milestones were normal.
On examination, at the time of admission, the child was afebrile with a heart rate of 124/min and a respiratory rate of 58/min with respiratory distress. His blood pressure was 94/60 mmHg. He was cyanosed with grade III clubbing. He weighed 12 kg with a height of 89 cm. Apart from the presence of bilateral angular stomatitis, the rest of the general and the systemic examination was normal.
In the current admission, the investigations done showed a hemoglobin of 12.7 g/dl, total leukocyte count of 13,000/mm 3 , platelets of 3.5 lakhs/mm 3 with a normocytic and a normochromic peripheral smear. He was, however, extensively investigated for anemia in the past. These laboratory test results are shown in [Table 1].
Transient increases in the hemoglobin levels and changes in the red blood cell morphology on peripheral smear to normocytic- normochromic picture [Table 1] coincided with the intermittent blood transfusions given to the child. Additional investigations for the cause of anemia such as G6PD enzyme levels, parvovirus B19 IgG levels, hemoglobin electrophoresis, unstable hemoglobin assay, the sickling test, direct and indirect Coomb's test, bone marrow examination, routine stool and urine analysis, and a Meckel's scan were normal. Methemoglobin levels were normal. Liver and renal function tests and electrocardiogram were normal. The antibody test for HIV, serum antinuclear antibody, and dsDNA were negative. Studies for complement levels were normal. The Mantoux test and sputum analysis for acid-fast bacilli were negative. Serum lactate dehydrogenase levels were 578 U/l (normal range: 100-190 U/l). The coagulation profile was normal (prothrombin time, activated partial thromboplastin time, and INR [International Normalized Ratio]).
The chest radiograph revealed typically symmetrical patchy infiltrates sparing the lung apices [Figure 1]. High-resolution computed tomography (HRCT) of chest was reported to have pulmonary edema with mediastinal lymphadenopathy and the radiologist suggested to rule out the possibility of tuberculosis or lymphoma [Figure 2]. CT-guided lung biopsy [Figure 3] showed mild thickening of the alveolar septa with a striking presence of many hemosiderin-laden macrophages that filled most of the alveolar spaces. In addition, a small-sized artery showed calcific incrustation of its media. These findings clinched the diagnosis of idiopathic pulmonary hemosiderosis. Inflammatory markers, antiglomerular basement antibody, and serum immunoglobulins could not be performed due to nonaffordability.
|Figure 1: Chest radiograph - showing bilateral symmetrical infiltrates sparing the lung apices|
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|Figure 2: HRCT chest - bilateral symmetrical infiltrates involving the bases and sparing the lung apices with mediastinal lymphadenopathy|
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Treatment was initiated with oral prednisolone at 2 mg/kg/day and there was a marked clinical improvement within 10 days of therapy. At present, he is being regularly followed up on tapering doses of steroids and is presently asymptomatic.
|Figure 3: (a) Refractile, coarse brown pigment fills the cytoplasm of the alveolar macrophages. Note the mild septal thickening. (b) Calcific incrustation of the small-sized pulmonary artery (H and E, ×250).|
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| :: Differential Diagnosis|| |
On admission to our institute, various differential diagnoses were considered in this child. 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. A normal methemoglobin level ruled out methemoglobinemia which was considered in the presence of cyanosis without respiratory signs. An acute infectious interstitial pneumonia was another working diagnosis due to the acuteness of the respiratory symptoms and the chest radiographic findings. However, a poor clinical response to antibiotic therapy made this diagnosis unlikely. Antituberculosis therapy was started in view of the HRCT findings of mediastinal lymphadenopathy.
However, the chest radiograph findings of symmetrical patchy infiltrates which spared the lung apices along with the previous documentation of microcytic, hypochromic anemia requiring repeated blood transfusions was strongly suggestive of a pulmonary hemorrhage syndrome as was the case reported by Minkov et al.  The chest HRCT in our patient was reported as pulmonary edema with mediastinal lympadenopathy raising the possibility of an infective etiology like tuberculosis or a neoplastic process such as an lymphoma. The HRCT findings in suspected cases of pulmonary hemorrhage syndromes can be nonspecific because pulmonary edema and alveolar hemorrhage display similar CT changes.  Mediastinal lymphadenopathy on chest HRCT can be seen in various pulmonary infiltrative diseases;  in a child with suspected alveolar hemorrhage, it only indicates the chronicity of the disease process.  Nevertheless, the child was started on antituberculous drugs for a period of 6 months. We performed a lung biopsy on our patient as it the gold standard investigation to confirm the diagnosis of pulmonary hemorrhage/hemosiderosis.  The biopsy was suggestive of a chronic interstitial lung disease with hemosiderin-laden macrophages scattered in the alveoli and areas of fibrosis in the alveolar septum, an indicator of the chronicity of the disease.
After confirmation of the diagnosis of pulmonary hemosiderosis by the lung biopsy, the child was further investigated to rule out secondary causes of alveolar hemorrhage leading to pulmonary hemosiderosis. Urinanalysis and renal function tests (for Goodpasture's syndrome) were normal. Underlying bacterial, mycobacterial, and HIV infections were excluded. 2D echocardiography was normal. Antibodies against dsDNA were negative and complement levels were within normal limits (for autoimmune disorders). As these laboratory results did not yield any discernible cause for the pulmonary hemorrhage, we made the diagnosis of idiopathic pulmonary hemosiderosis (IPH) in our patient.
| :: Discussion|| |
Pulmonary hemosiderosis is a rare pediatric chronic respiratory disorder, with a diffuse alveolar involvement and clinically manifesting as a classical triad of iron-deficiency anemia, hemoptysis, and alveolar infiltrates on chest radiographs.  When diffuse alveolar hemorrhage occurs in isolation and an exhaustive evaluation for underlying disease is found to be negative, the patient is said to have IPH. 
Retrospective case analyses from Sweden and Japan place an estimated prevalence rate of IPH ranging from 0.24 to 1.23 cases per million. , Nearly 80% of the cases manifest before the age of 10 years without any sex predilection in childhood.  Various etiological theories have been proposed of which autoimmune mechanism is the most widely accepted theory, but the cause of IPH largely remains unknown. 
The classical clinical triad of IPH consisting of anemia, hemoptysis, and infiltrates on chest radiograph is rare in children.  Although the clinical presentation of this condition can be quite variable - anemia, cough, and pulmonary infiltrates on chest radiographs are found in majority of the patients. Fever, low oxygen saturation (SpO 2 < 95%), respiratory distress, clubbing, hemoptysis, and pallor are the less frequently presenting features.  Anemia can be the solitary manifestation in children as described in a case report by Minkov et al. and was the forthcoming complaint in our patient also, for which he underwent an exhaustive evaluation before presenting to us, thus delaying the definitive diagnosis.  Spontaneous remission may explain the absence of reticulocytosis in our patient. The child was transfusion free for 4 months before coming to our institute.
Apart from the routine investigations in a child with anemia, a chest radiograph forms an important diagnostic tool.  Typically, symmetrical lung infiltrates sparing the apices on a chest radiograph in a child with anemia are an indicator of an underlying alveolar hemorrhage syndrome.  A chest radiograph gave a vital cue to the definitive diagnosis in our patient as well. Though the HRCT observations in our patient were nonspecific and a sputum analysis for hemosiderin-laden macrophages noncontributory, the clinical picture of microcytic, hypochromic anemia in the presence of pulmonary infiltrates justified a lung biopsy, which is the gold standard diagnostic tool in pulmonary hemosiderosis.  A look at the alveoli on the lung biopsy specimen showing scattered hemosiderin-laden macrophages provided the answer to anemia in our patient, and, confirmed the diagnosis of pulmonary hemosiderosis. A diagnosis of IPH was made as a diagnosis of exclusion after we ruled out the various secondary causes of pulmonary hemorrhage in our patient.
Systemic corticosteroids are the mainstay of therapy in IPH. Corticosteroids not only decrease episodes of alveolar hemorrhage during the acute stage of the disease (thus contributing to a reduction in the mortality of IPH) but also by virtue of their anti-inflammatory properties, decrease the progression toward a fibrotic disease and hence the long-term morbidity in children.  Our patient was started on oral prednisolone at 2 mg/kg/day and demonstrated a remarkable symptomatic improvement within 10 days of therapy.
In conclusion, a chest radiograph is imperative in a child with an unexplained anemia along with respiratory symptoms. The presence of pulmonary infiltrates sparing the apices should be a strong hint toward an underlying pulmonary hemorrhage syndrome. Should this be the case, a lung biopsy is the gold standard to confirm the diagnosis of pulmonary hemosiderosis. A patient should be labeled as having IPH after an extensive workup fails to yield a secondary cause for the alveolar hemorrhage. It is necessary that the general pediatrician and the hematologist, who very often deal with unexplained anemia in children, be aware of this rare entity of IPH. Recent reviews have documented a 5-year survival rate of around 86% in cases with IPH as also spontaneous remissions.  A look at the alveoli in the lung biopsy specimen by an experienced pathologist provides an early diagnostic answer so that immunosuppressive therapy with corticosteroids can be started in time which drastically decreases the mortality and morbidity of this condition.
| :: Acknowledgment|| |
The authors thank Dr. Sanjay N Oak, Director, Medical Education and Major Hospitals of Municipal Corporation of Greater Mumbai, and Dean, Seth GS Medical College and KEM Hospital, Mumbai, for granting permission to publish this article.
| :: References|| |
|1.||Minkov M, Kovacs J, Wiesbauer P, Dekan G, Gadner H. Severe anemia owing to occult pulmonary hemorrhage - A diagnostic pitfall. J Pediatr Hematol Oncol 2006;28:467-70. |
|2.||Akyar S, Ozbek SS. Computed tomography findings in idiopathic pulmonary hemosiderosis. Respiration 1993;60:63-4. |
|3.||Vrielynck S, Mamou-Mani T, Emond S, Scheinmann P, Brunelle F, de Blic J. Diagnostic value of high-resolution CT in the evaluation of chronic infiltrative lung disease in children. AJR Am J Roentgenol 2008;191:914-20. |
|4.||Nevin MA. Pulmonary hemosiderosis. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 18th ed. London: WB Saunders Company Publishers; 2000. p. 1825. |
|5.||Kjellman B, Elinder G, Garwicz S, Svan H. Idiopathic pulmonary hemosiderosis in Swedish children. Acta Paediatr Scand 1984;73:584-8. |
|6.||Ohga S, Takahashi K, Miyazaki S, Kato H, Ueda K. Idiopathic pulmonary haemosiderosis in Japan: 39 possible cases from a survey questionnaire. Eur J Pediatr 1995;154:994-8. |
|7.||Soergel KH, Sornmers SC. Idiopathic pulmonary hernosiderosis and related syndromes. Am J Med 1962;32:499-511. |
|8.||Yao TC, Hung IJ, Wong KS, Huang JL, Niu CK. Idiopathic pulmonary haemosiderosis: An Oriental experience. J Paediatr Child Health 2003;39:27-30. |
|9.||Saeed MM, Woo MS, MacLaughlin EF, Margetis MF, Keens TG. Prognosis in pediatric idiopathic pulmonary hemosiderosis. Chest 1999;116:721-5. |
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