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Idiopathic pulmonary hemosiderosis

Author
Nils Milman, MD
Section Editor
Talmadge E King, Jr, MD
Deputy Editor
Helen Hollingsworth, MD

INTRODUCTION

Idiopathic pulmonary hemosiderosis is a rare disease found primarily in children that causes recurrent episodes of diffuse alveolar hemorrhage. Recurrent alveolar bleeding may eventually produce pulmonary hemosiderosis and fibrosis. Diffuse alveolar hemorrhage is characterized by hemoptysis, dyspnea, alveolar opacities on chest radiographs, and anemia and can result from a variety of underlying conditions (table 1). When no underlying cause for repeated episodes of diffuse alveolar hemorrhage is apparent, the entity is referred to as idiopathic pulmonary hemosiderosis (IPH) [1].

The clinical features, treatment, and prognosis of IPH will be reviewed here. A general discussion of the diffuse alveolar hemorrhage syndromes is provided separately. (See "The diffuse alveolar hemorrhage syndromes".)

PATHOGENESIS

The etiology of IPH is unknown. However, the response to immunosuppressive therapy suggests that immune processes may be involved. It appears that a structural defect in the alveolar capillaries, either in the alveolar basement membrane or in the alveolar endothelial cell, may predispose to the condition [1-5]. The accumulation of neutrophils in the alveoli also may play a role [6].

Immunologic abnormalities — The degree to which immunologic injury to the lung contributes to the development of IPH remains unclear. Immune complexes have been demonstrated in plasma in several patients; however, immunohistochemical examination of lung tissue generally has not supported an immunologic pathogenesis [2,3,7-10]. The possibility that autoimmune mechanisms play a role in IPH is suggested by the observation that approximately 25 percent of patients with the condition who survive for more than 10 years subsequently develop autoimmune disorders [11].

Links between IPH and ingested protein antigens have also been hypothesized, based upon the following observations:

                      

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Literature review current through: Nov 2016. | This topic last updated: Wed Jul 31 00:00:00 GMT+00:00 2013.
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References
Top
  1. Ioachimescu OC, Sieber S, Kotch A. Idiopathic pulmonary haemosiderosis revisited. Eur Respir J 2004; 24:162.
  2. Corrin B, Jagusch M, Dewar A, et al. Fine structural changes in idiopathic pulmonary haemosiderosis. J Pathol 1987; 153:249.
  3. Donald KJ, Edwards RL, McEvoy JD. Alveolar capillary basement membrane lesions in Goodpasture's syndrome and idiopathic pulmonary hemosiderosis. Am J Med 1975; 59:642.
  4. Yeager H Jr, Powell D, Weinberg RM, et al. Idiopathic pulmonary hemosiderosis: ultrastructural studies and responses to azathioprine. Arch Intern Med 1976; 136:1145.
  5. Hyatt RW, Adelstein ER, Halazun JF, Lukens JN. Ultrastructure of the lung in idiopthic pulmonary hemosiderosis. Am J Med 1972; 52:822.
  6. Cohen S. Idiopathic pulmonary hemosiderosis. Am J Med Sci 1999; 317:67.
  7. Blanco A, Solís P, Gómez S, et al. C1q-binding immune complexes and other immunological studies in children with pulmonary hemosiderosis. Allergol Immunopathol (Madr) 1984; 12:37.
  8. Ali, AM, Milman, N, Clausen, PP, et al. Idiopathic pulmonary haemosiderosis. Favourable effect of corticosteroids in two women aged 16 and 55 years. Eur Respir Topic 1998; 4:53.
  9. Dolan CJ Jr, Srodes CH, Duffy FD. Idiopathic pulmonary hemosiderosis. Electron microscopic, immunofluorescent, and iron kinetic studies. Chest 1975; 68:577.
  10. Irwin RS, Cottrell TS, Hsu KC, et al. Idiopathic pulmonary hemosiderosis: an electron microscopic and immunofluorescent study. Chest 1974; 65:41.
  11. Le Clainche L, Le Bourgeois M, Fauroux B, et al. Long-term outcome of idiopathic pulmonary hemosiderosis in children. Medicine (Baltimore) 2000; 79:318.
  12. Milman N, Pedersen FM. Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis. Respir Med 1998; 92:902.
  13. Boat TF, Polmar SH, Whitman V, et al. Hyperreactivity to cow milk in young children with pulmonary hemosiderosis and cor pulmonale secondary to nasopharyngeal obstruction. J Pediatr 1975; 87:23.
  14. Torres MJ, Girón MD, Corzo JL, et al. Release of inflammatory mediators after cow's milk intake in a newborn with idiopathic pulmonary hemosiderosis. J Allergy Clin Immunol 1996; 98:1120.
  15. Wright PH, Menzies IS, Pounder RE, Keeling PW. Adult idiopathic pulmonary haemosiderosis and coeliac disease. Q J Med 1981; 50:95.
  16. Pacheco A, Casanova C, Fogue L, Sueiro A. Long-term clinical follow-up of adult idiopathic pulmonary hemosiderosis and celiac disease. Chest 1991; 99:1525.
  17. Hemoptysis, pulmonary infiltrates, and diarrhea in a 36-year-old man. Am J Med 1986; 80:930.
  18. Reading R, Watson JG, Platt JW, Bird AG. Pulmonary haemosiderosis and gluten. Arch Dis Child 1987; 62:513.
  19. Bouros D, Panagou P, Rokkas T, Siafakas NM. Bronchoalveolar lavage findings in a young adult with idiopathic pulmonary haemosiderosis and coeliac disease. Eur Respir J 1994; 7:1009.
  20. Agarwal R, Aggarwal AN, Gupta D. Lane-Hamilton syndrome: simultaneous occurrence of coeliac disease and idiopathic pulmonary haemosiderosis. Intern Med J 2007; 37:65.
  21. Khemiri M, Ouederni M, Khaldi F, Barsaoui S. Screening for celiac disease in idiopathic pulmonary hemosiderosis. Gastroenterol Clin Biol 2008; 32:745.
  22. Lane DJ, Hamilton WS. Idiopathic steatorrhoea and idiopathic pulmonary haemosiderosis. Br Med J 1971; 2:89.
  23. Sethi GR, Singhal KK, Puri AS, Mantan M. Benefit of gluten-free diet in idiopathic pulmonary hemosiderosis in association with celiac disease. Pediatr Pulmonol 2011; 46:302.
  24. Custer G, Balcerzak S, Rinehart J. Human macrophage hemoglobin-iron metabolism in vitro. Am J Hematol 1982; 13:23.
  25. DeGowin RL, Sorensen LB, Charleston DB, et al. Retention of radioiron in the lungs of a woman with idiopathic pulmonary hemosiderosis. Ann Intern Med 1968; 69:1213.
  26. Fillet G, Beguin Y, Baldelli L. Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation. Blood 1989; 74:844.
  27. Persson HL, Vainikka LK, Eriksson HB, Wennerström U. Lane-Hamilton syndrome: ferritin protects lung macrophages against iron and oxidation. Chest 2011; 139:361.
  28. Dearborn DG, Yike I, Sorenson WG, et al. Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect 1999; 107 Suppl 3:495.
  29. Hossain MA, Ahmed MS, Ghannoum MA. Attributes of Stachybotrys chartarum and its association with human disease. J Allergy Clin Immunol 2004; 113:200.
  30. Brown CM, Redd SC, Damon SA, Centers for Disease Control and Prevention (CDC). Acute idiopathic pulmonary hemorrhage among infants. Recommendations from the Working Group for Investigation and Surveillance. MMWR Recomm Rep 2004; 53:1.
  31. Dearborn DG, Smith PG, Dahms BB, et al. Clinical profile of 30 infants with acute pulmonary hemorrhage in Cleveland. Pediatrics 2002; 110:627.
  32. Soergel, KH, Sommers, SC. The alveolar epithelial lesion of idiopathic pulmonary hemosiderosis. Am Rev Respir Dis 1962; 85:540.
  33. Green RJ, Ruoss SJ, Kraft SA, et al. Pulmonary capillaritis and alveolar hemorrhage. Update on diagnosis and management. Chest 1996; 110:1305.
  34. Jennings CA, King TE Jr, Tuder R, et al. Diffuse alveolar hemorrhage with underlying isolated, pauciimmune pulmonary capillaritis. Am J Respir Crit Care Med 1997; 155:1101.
  35. Kjellman B, Elinder G, Garwicz S, Svan H. Idiopathic pulmonary haemosiderosis in Swedish children. Acta Paediatr Scand 1984; 73:584.
  36. Yao TC, Hung IJ, Wong KS, et al. Idiopathic pulmonary haemosiderosis: an Oriental experience. J Paediatr Child Health 2003; 39:27.
  37. Soergel, KH, Sommers, SC. Idiopathic pulmonary hemosiderosis and related syndromes. Am J Med 1962; 32:499.
  38. Morgan PG, Turner-Warwick M. Pulmonary haemosiderosis and pulmonary haemorrhage. Br J Dis Chest 1981; 75:225.
  39. Beckerman RC, Taussig LM, Pinnas JL. Familial idiopathic pulmonary hemosiderosis. Am J Dis Child 1979; 133:609.
  40. Thaell JF, Greipp PR, Stubbs SE, Siegal GP. Idiopathic pulmonary hemosiderosis: two cases in a family. Mayo Clin Proc 1978; 53:113.
  41. Cassimos CD, Chryssanthopoulos C, Panagiotidou C. Epidemiologic observations in idiopathic pulmonary hemosiderosis. J Pediatr 1983; 102:698.
  42. Chen RL, Chuang SS. Silent idiopathic pulmonary hemosiderosis with iron-deficiency anemia but normal serum ferritin. J Pediatr Hematol Oncol 2007; 29:509.
  43. Walters GO, Miller FM, Worwood M. Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol 1973; 26:770.
  44. Milman N, Pedersen NS, Visfeldt J. Serum ferritin in healthy Danes: relation to marrow haemosiderin iron stores. Dan Med Bull 1983; 30:115.
  45. Harte S, McNicholas WT, Donnelly SC, Dodd JD. Honeycomb cysts in idiopathic pulmonary haemosiderosis: high-resolution CT appearances in two adults. Br J Radiol 2008; 81:e295.
  46. Miller T, Tanaka T. Nuclear scan of pulmonary hemorrhage in idiopathic pulmonary hemosiderosis. AJR Am J Roentgenol 1979; 132:120.
  47. Allue X, Wise MB, Beaudry PH. Pulmonary function studies in idiopathic pulmonary hemosiderosis in children. Am Rev Respir Dis 1973; 107:410.
  48. Ewan PW, Jones HA, Rhodes CG, Hughes JM. Detection of intrapulmonary hemorrhage with carbon monoxide uptake. Application in goodpasture's syndrome. N Engl J Med 1976; 295:1391.
  49. Kocakoc E, Kiris A, Sen Y, Bozgeyik Z. Pediatric idiopathic pulmonary hemosiderosis diagnosed by sputum analysis: plain radiography and computed tomography findings. Med Princ Pract 2003; 12:129.
  50. Yao TC, Hung IJ, Jaing TH, Yang CP. Pitfalls in the diagnosis of idiopathic pulmonary haemosiderosis. Arch Dis Child 2002; 86:436.
  51. Kabra SK, Bhargava S, Lodha R, et al. Idiopathic pulmonary hemosiderosis: clinical profile and follow up of 26 children. Indian Pediatr 2007; 44:333.
  52. Nielsen VR, Valerius NH. [Idiopathic pulmonary hemosiderosis. A cause of severe iron deficiency anemia in childhood]. Ugeskr Laeger 1995; 157:176.
  53. Kiper N, Göçmen A, Ozçelik U, et al. Long-term clinical course of patients with idiopathic pulmonary hemosiderosis (1979-1994): prolonged survival with low-dose corticosteroid therapy. Pediatr Pulmonol 1999; 27:180.
  54. Ohga S, Nomura A, Suga N, et al. Liposteroid against refractory pulmonary haemorrhage in idiopathic pulmonary haemosiderosis. Eur J Pediatr 1994; 153:687.
  55. Saeed MM, Woo MS, MacLaughlin EF, et al. Prognosis in pediatric idiopathic pulmonary hemosiderosis. Chest 1999; 116:721.
  56. Doi T, Ohga S, Ishimura M, et al. Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis. Eur J Pediatr 2013; 172:1475.
  57. Elinder G. Budesonide inhalation to treat idiopathic pulmonary haemosiderosis. Lancet 1985; 1:981.
  58. Tutor JD, Eid NS. Treatment of idiopathic pulmonary hemosiderosis with inhaled flunisolide. South Med J 1995; 88:984.
  59. Watson AM, Boyce TG, Wylam ME. Legionella pneumonia: infection during immunosuppressive therapy for idiopathic pulmonary hemosiderosis. Pediatr Infect Dis J 2004; 23:82.
  60. Helman DL, Sullivan A, Kariya ST, et al. Management of idiopathic pulmonary haemosiderosis in pregnancy: report of two cases. Respirology 2003; 8:398.
  61. Rossi GA, Balzano E, Battistini E, et al. Long-term prednisone and azathioprine treatment of a patient with idiopathic pulmonary hemosiderosis. Pediatr Pulmonol 1992; 13:176.
  62. Byrd RB, Gracey DR. Immunosuppressive treatment of idiopathic pulmonary hemosiderosis. JAMA 1973; 226:458.
  63. Airaghi L, Ciceri L, Giannini S, et al. Idiopathic pulmonary hemosiderosis in an adult. Favourable response to azathioprine. Monaldi Arch Chest Dis 2001; 56:211.
  64. Huang SH, Lee PY, Niu CK. Treatment of pediatric idiopathic pulmonary hemosiderosis with low-dose cyclophosphamide. Ann Pharmacother 2003; 37:1618.
  65. Naithani R, Chandra J, Singh V, et al. Life threatening exacerbation in idiopathic pulmonary hemosiderosis salvaged by cyclophosphamide infusion. Indian J Chest Dis Allied Sci 2006; 48:287.
  66. Luo XQ, Ke ZY, Huang LB, et al. Maintenance therapy with dose-adjusted 6-mercaptopurine in idiopathic pulmonary hemosiderosis. Pediatr Pulmonol 2008; 43:1067.
  67. Sun LC, Tseng YR, Huang SC, et al. Extracorporeal membrane oxygenation to rescue profound pulmonary hemorrhage due to idiopathic pulmonary hemosiderosis in a child. Pediatr Pulmonol 2006; 41:900.
  68. Wroblewski BM, Stefanovic CR, McDonough VM, Kidik PJ. The challenges of idiopathic pulmonary hemosiderosis and lung transplantation. Crit Care Nurse 1997; 17:39.
  69. Calabrese F, Giacometti C, Rea F, et al. Recurrence of idiopathic pulmonary hemosiderosis in a young adult patient after bilateral single-lung transplantation. Transplantation 2002; 74:1643.