SERIES: RARE LUNG DISEASES
Pulmonary haemosiderosis in infants and children

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Summary

Pulmonary haemosiderosis (PH) results from recurrent bleeding into alveolar spaces and interstitial lung tissue. If untreated, fibrosis and restrictive lung disease will develop and may lead to death. A distinction can be made between primary and secondary pulmonary haemosiderosis as a manifestation of auto-immune small vessel vasculitides, coagulation disorders or diseases with increased venous pressure. Interestingly, in some cases of ‘idiopathic’ PH, exposure to moulds and van Willebrand's disease may contribute to the pathogenesis. Haemosiderosis usually begins with haematemesis. Anaemia, alveolar infiltrates on chest x ray and siderophages in broncho-alveolar lavage fluid are diagnostic factors. Immunosuppressive treatment has improved the prognosis in recent years.

Section snippets

INTRODUCTION

Pulmonary haemosiderosis (PH) is a serious and potentially fatal disease that occurs predominantly in infants and children. PH is rare but small endemics have occurred, e.g. in Greece1 and in the USA.2 The disease was first described by Virchow in 1864. It is now seen as a primary disorder or in association with rheumatic and cardiovascular disorders. The group of primary haemosideroses is made up of Goodpasture's syndrome, PH with cow's milk hypersensitivity (Heiner's syndrome) and idiopathic

EPIDEMIOLOGY

In Sweden, an incidence of 0.24 new patients/million/year has been calculated for the paediatric age group,3 if children with renal symptoms are excluded. In Japan, 1.23 patients per million children were diagnosed with PH.4 Local epidemics have been reported in Greece,1 in Cleveland, Ohio2 and in Boston, Massachusetts.5 There is a case report of two brothers who were both affected by IPH.6 The authors concluded that IPH may have a genetic basis in some cases.

PATHOPHYSIOLOGY

When bleeding occurs from alveolar capillaries into pulmonary tissue, haemoglobin will be transformed to haemosiderin. This is ingested by macrophages, which will then produce pro-inflammatory molecules leading to chronic inflammation and fibrosis if bleeding occurs repeatedly. An indirect sign of bleeding into alveolar spaces may be haematemesis. Loss of blood and deposition of iron in the lungs lead to iron-deficiency anaemia.

CLINICAL MANIFESTATIONS

PH typically becomes evident during infancy and early childhood.20 In the Cleveland outbreak of acute pulmonary haemorrhage, most infants started with haematemesis and progressed rapidly to respiratory distress requiring intensive care.2 The onset may also be subtle with haematemesis occurring at night and being mistaken for nose bleeding. Lung involvement may be so mild that anaemia is the first presenting sign.21 Respiratory symptoms due to decreased lung compliance are characterised by

DIAGNOSIS

The typical chest x ray is often described as showing a ‘butterfly’ or ‘batwing’ pattern, i.e. symmetrical alveolar infiltrates slanting upwards towards the lateral chest walls. Infiltrates may be unilateral or asymmetrical. The computer tomogram shows ground-glass changes and is more sensitive than the routine chest x ray. On laboratory investigation, inflammatory markers are only slightly increased. Anaemia due to blood loss and eventually due to iron deficiency is most suggestive.

Antibodies

TREATMENT

The association between mould exposure and IPH is considered to be strong enough to justify moving the patient to a new environment or remediating the damage. Furthermore, the patient should also be tentatively taken off cow's milk, independent of the concentrations of antibodies to milk. A gliadin-free diet improves pulmonary disease in patients with coeliac disease.

Immunosuppressive treatment of the acute episode with steroids (2 mg/kg/day of prednisolone) is effective in most patients.

PROGNOSIS

There is no prospective study on long-term survival in Heiner's syndrome or IPH. An older retrospective study suggested a median survival of 3–5 years.35 In one study, 15 patients with IPH were followed for a mean of 17.2 years.36 Fourteen of them had received long-term steroids. Three developed rheumatoid diseases, one developed coeliac disease and respiratory problems were seen in three of the 15 patients. Most authors feel that early diagnosis and aggressive immunosuppressive treatment have

PRACTICE POINTS

  • Diagnosis of PH is based on the triad of haematemesis, anaemia and pulmonary infiltrates.

  • Diagnosis of PH is secured by the finding of haemosiderin-laden macrophages (siderophages) in broncho-alveolar lavage fluid.

  • Trigger factors such as gliadin, moulds and cow's milk proteins have to be considered.

  • Immunosuppressive treatment improves the prognosis.

  • Measurement of CO diffusion has been proven for monitoring disease activity with an increase of diffusion capacity during and after bleeding episodes.

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