Case Report
Idiopathic Pulmonary Haemosiderosis: Complete Remission with Steroids T. Sen, D. Patel and Z.F. Udwadia Department of Pulmonary Medicine, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
ABSTRACT A 13-year-old boy was diagnosed as a case of idiopathic pulmonary haemosiderosis on the basis of clinical presentation, radiological assessment and open lung biopsy. The patient had a complete clinical and radiological remissions with oral corticosteroids. [Indian J Chest Dis Allied Sci 2008; 50: 289-291] Key words: Idiopathic pulmonary haemosiderosis, Recurrent haemoptysis, Corticosteroid.
INTRODUCTION Diffuse alveolar haemorrhage (DAH) is characterised by haemoptysis, dyspnoea, alveolar infiltrates on chest radiograph, and various degrees of anaemia. Following a bleeding episode the alveolar macrophages convert the haemoglobin’s iron into haemosiderin within 36-72 hours, 1,2 hence the term haemosiderosis. Since the haemosiderin – laden macrophages reside for up to 4-8 weeks in the lungs, 1-3 the term pulmonary hemosiderosis should be reserved for persistent or recurrent intra-alveolar bleeding. In some patients the work-up for a specific aetiology is negative and a diagnosis of idiopathic pulmonary haemosiderosis (IPH) is rendered. The entity of IPH was initially described by Virchow4 in 1864 as “brown lung induration”. A more in-depth characterisation of IPH was made in 1931, by Ceelen,5 who published the autopsy findings in two children who were found with large amounts of haemosiderin in the lungs. Waldenstrom established the first ante mortem diagnosis in 1944.6,7 The clinical triad of haemoptysis, pulmonary infiltrates and anaemia with no other identified cause is considered diagnostic8 if the lung biopsy excludes vasculitis/capillaritis, granulomas, or immune depositions.9 We report a case of IPH that was followed up and there was a resolution of symptoms after corticosteroid treatment.
evening rise of temperature for the last five months. There was no history of skin rash, joint pains, exertional dyspnoea, chest pain or wheeze. Though his sputum for acid-fast bacilli (AFB) was negative, chest radiograph revealed patchy shadows in the right upper and lower zones and he was started empirically on antituberculosis therapy by the physician. After six months of anti-tuberculosis drugs his fever subsided and he gained 12 kg of weight but haemoptysis increased in quantity and frequency in the last one and a half months, with a drop of haemoglobin to 8 gm%. Laboratory investigations revealed normal routine urine analysis, creatinine, coagulation profile and erythrocyte sedimentation rate. Antinuclear antibody was weakly positive at 1:100, while serum rheumatoid factor, pantinuclear cytoplasmic antibody and anti-glomerular basement membrane antibody were negative. Serial chest radiographs revealed a homogeneous opacity in the right middle and lower zones (Figure 1). Computed
CASE REPORT A 13-year-old school boy presented with a history of minimal recurrent streaky haemoptysis for the last nine months. The haemoptysis was intermittent, occurring two to three times a week. He also had a low grade
Figure 1. Chest radiograph revealed homogeneous opacity in the right middle and lower zones.
[Received: June 19, 2006; accepted after revision: December 12, 2006]
Correspondence and reprint requests: Dr Z.F. Udwadia, PFT Department, P.D. Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai-400 016, India; Fax: 91-22-24449115/91-22-24447361.
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tomographic (CT) scan of the chest revealed multiple diffuse poorly circumscribed, micronodular shadows (Figure 2). Pulmonary function test revealed moderately severe restriction. Bronchoscopy was done and the bronchoalveolar lavage was negative for AFB and fungus culture. Video-assisted thoracoscopic lung biopsy (VATS) revealed fresh and old intra-alveolar haemorrhage. There were clusters of haemosiderin pigment laden macrophages in many of the alveolar lumina.
Figure 2. Computed tomography of the chest revealed multiple diffuse poorly-circumscribed micronodular shadows.
There was no evidence of granulomas, capillaritis, or vasculitis. The features were suggestive of IPH. The patient was commenced on 30 mg of oral prednisolone that was tapered over the next six months. There was a dramatic improvement in haemoptysis that settled completely. Chest radiograph and CT scan of the chest on follow-up (Figure 3) were normal. The lung function improved, haemoglobin normalised and at follow-up, he was back to normal on a maintenance dose of oral prednisolone of 5 mg per day.
Figure 3. Computed tomography of the chest after steroids were started became normal with resolution of the micronodular shadows.
T. Sen et al
DISCUSSION Idiopathic pulmonary haemosiderosis is a rare condition with an unknown incidence and prevalence in the population. To date, there are 500 reported cases in literature, either as isolated cases or as case series. The rarity of the disease makes prospective studies almost impossible. A Swedish study published in 1984, and based on records reviewed between 1950-1979, estimated an incidence of 0.24 per million children per year, 10 while a Japanese retrospective study, 11 that estimated around 1.23 cases per million yearly. The aetiology of IPH remains unknown. There are a few aetiologic hypotheses including the genetic theory, the allergic theory, the environmental theory, the metabolic theory, the common delineator being postulated structural lesions of the alveolar-endothelial membrane.12-17 The clinical course of IPH includes two phases. First, an acute phase “IPH exacerbation”, corresponds to intra-alveolar bleeding episodes, manifested by cough, dyspnoea, anemia, haemoptysis and sometimes respiratory failure. Secondly, the chronic phase is characterised by a slow resolution of the previous symptoms, with or without treatment. The complete blood count will reveal variable degrees of anaemia. Bone marrow biopsy typically shows hyperplastic erythropoiesis, and low intramedullary iron store.9,18 Sputum examination, although not very sensitive, can demonstrate intraalveolar bleeding (erythrocytes and haemosiderrinladen macrophages), by haematoxylin-eosin and Prussian blue (Perl’s) stains. If the patient is not spontaneously producing sputum, inducing it can be dangerous. Bronchoalveolar lavage (BAL) from involved areas has a higher diagnostic yield than the sputum examination. 19-21 The predominant cellular types are the alveolar macrophages, filled with haemosiderin, intact erythrocytes and occasionally neutrophils. Lung function tests show in general a ventilatory restrictive pattern of variable severity.18 The DLCO can be low or normal during the chronic phase or elevated during the acute phase, as a manifestation of DAH. During the acute phase of IPH exacerbations, the chest radiographs show diffuse alveolar type infiltrates, predominantly in the lower lung fields, with corresponding ground glass attenuation on the high resolution computed tomographic (HRCT) scan.22 During remission, the alveolar infiltrates tend to be reabsorbed and interstitial reticular and micronodular patterns of opacities ensue in the same areas, with variable degree of fibrosis.22 A number of treatments have been tried, most commonly systemic glucocorticoids. Corticosteroids and immunosuppressive drugs do not appear to affect the long term prognosis but either may be of value
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during acute episodes of alveolar haemorrhage, as in goodpasture’s syndrome. 23,25 In children and adolescents the long term treatment can be problemetic because of side-effects and a higher rate of recurrence on trial to taper or discontinue the steroids. Inhaled steroids also have been tried but insufficient experience exists to date. 23 Other immuno suppressants including azathioprine, hydroxychloroquine, cyclophosphamide, and methotrexate, have been tried with variable results.11, 21 Among these, azathioprine in combination of steroids may be the best therapeutic regimen, especially in preventing IPH exacerbations. Few studies have shown that, glucocorticoids when started in the acute phase of IPH, show apparent good control of symptoms, particularly haemoptysis, and have an impact on the mortality9,12,18 but with unclear effects on the chronic phase. The recommended starting dose of prednisolone is < 1 mg per kg per day for a couple of months, until the alveolar infiltrates resolve, and then taper off during the next few months if symptoms do not recur. The majority of patients with IPH seem to respond favourably to chronic oral corticosteroids, with a decreased number of IPH exacerbations and possibly, a decline in fibrogenesis.18 Long-term follow-up should take into account the number and severity of haemorrhagic episodes and the progression of interstitial lung disease (the decline of DLCO). Our patient had a dramatic response to a modest dose of oral steroids with clinical and radiological remision. He remains free of further bleeding episodes on a small maintenance dose of oral prednisolone of 5 mg per day after six months of follow-up. The most frequent cause of death is acute respiratory failure secondary to massive DAH, and chronic respiratory failure and cor pulmonale due to severe pulmonary fibrosis. In one case series of 68 patients with a mean follow-up of four years, 20 patients died, 17 had recurrent IPH exacerbations 12 had chronic active disease with persisting dyspnoea and anaemia, and 19 remained asymptomatic.19 In that study, the average survival after the onset of symptoms was 2.5 years. Chryssanthopoulos et al24 studied the outcome of 30 children for an average of five years. The mean mortality rate was 60% and the mean survival was ~ three years (range, 3 months to 10.5 years). Almost 87% of the patients were on steroids at some point in time; while none were treated with azathioprine. It appears that children and adolescents have a more severe course and prognosis, while the adults have a more protracted course, with milder symptoms and a more favourable prognosis. The lack of prospective studies or large Registries makes the evaluation of short-and long- term prognosis difficult to assess.
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