Idiopathic pulmonary haemosiderosis
Idiopathic pulmonary haemosiderosis (IPH) is a lung disease of unknown cause that is characterized by alveolar capillary bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence between 0.24 and 1.23 cases per million people.
|Idiopathic pulmonary haemosiderosis|
|Other names||Idiopathic pulmonary hemosiderosis|
Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease. The lung bleeding causes accumulation of iron, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cells which carry oxygen to body tissues for cellular respiration.
Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.
- PH1 involves PH with circulating anti-GBM antibodies.
- PH2 involves PH with immune complex disease such as systemic lupus erythematosus, SLE.
- PH3 involves no demonstrable immune system involvement.
A distinct subset of patients with pulmonary hemosiderosis has hypersensitivity to cow's milk which result in formation of IgG antibodies against basement membrane. This is called Heiner syndrome. Mechanism of haemorrhage is similar to that observed in Goodpasture syndrome.
Related or similar conditions
There are many pulmonary problems that may seem to mimic haemosiderosis but do not necessarily include the deposits of iron into the lung. The deposition of iron in the lungs, occurring in the form of haemosiderin, is the defining characteristic of this illness. These other conditions may occur separately or together with haemosiderosis.
Clinically, IPH manifests as a triad of haemoptysis, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia. It is diagnosed at an average age of 4.5 plus or minus 3.5 years, and it is twice as common in females. The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure.
Corticosteroids are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour. They are thought to decrease the frequency of haemorrhage, while other studies suggest that they do not have any effect on the course or prognosis of this disease. In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine, azathioprine, and cyclophosphamide. 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage. A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.
Death may occur rapidly with acute, massive pulmonary bleeding or over longer periods as the result of continued pulmonary failure and right heart failure. Historically, patients had an average survival of 2.5 years after diagnosis, but today 86% may survive beyond five years.
The condition was first described as "brown lung induration" by Rudolf Virchow in 1864 in patients after their death. Wilhelm Ceelen later correlated his findings to the clinical symptoms of two children who died of IPH in 1931. The first living patient was diagnosed by Jan Waldenström in 1944. It has been given several names, including:
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- Gonzalez-Crussi F, Hull MT, Grosefeld JL (1976). "Idiopathic pulmonary hemosiderosis: evidence of capillary basement membrane abnormality". Am Rev Respir Dis. 114 (4): 689–698. doi:10.1164/arrd.19188.8.131.529 (inactive 2019-12-03). PMID 970745.
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- Matsaniotis N, Karpouzas J, Apostolopoulou E, et al. (1968). "Idiopathic pulmonary hemosiderosis in children". Arch Dis Child. 43 (229): 307–309. doi:10.1136/adc.43.229.307. PMC 2019947. PMID 5652705.
- Beckerman RC, Taussig LM, Pinnas JL (June 1979). "Familial idiopathic pulmonary hemosiderosis". Am. J. Dis. Child. 133 (6): 609–11. doi:10.1001/archpedi.1979.02130060049010. PMID 375718.
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- Boat, TF (1998). "Idiopathic pulmonary hemosiderosis". In Chernick V, Boat T (eds.). Kendig's disorders of the respiratory tract in children. Philadelphia PA: WB Saunders. pp. 628–9.
- Bush A, Sheppard MN, Warner JO (1992). "Chloroquine in idiopathic pulmonary hemosiderosis". Arch Dis Child. 67 (5): 625–627. doi:10.1136/adc.67.5.625. PMC 1793713. PMID 1599302.
- Zaki M, Al Saleh Q, Al Mutari G (1995). "Effectiveness of chloroquine therapy in idiopathic pulmonary hemosiderosis". Pediatric Pulmonology. 20 (2): 125–126. doi:10.1002/ppul.1950200213. PMID 8570303.
- Byrd RB, Gracey DR (1973). "Immunosuppressive treatment of idiopathic pulmonary hemosiderosis". JAMA. 226 (4): 458–9. doi:10.1001/jama.226.4.458. PMID 4800237.
- Rossi GA, Balzano E, Battistini E (1992). "Long-term prednisone and azathioprine treatment of a patient with idiopathic pulmonary hemosiderosis". Pediatr Pulmonol. 13 (3): 176–180. doi:10.1002/ppul.1950130310. PMID 1437333.
- Colombo JR, Stolz SM (1992). "Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide". Chest. 102 (3): 959–960. doi:10.1378/chest.102.3.959. PMID 1516434.
- Luo XQ, Ke ZY, Huang LB, Guan XQ, Zhang XL, Zhu J, Zhang YC (Nov 2008). "Maintenance therapy with dose-adjusted 6-mercaptopurine in idiopathic pulmonary hemosiderosis". Pediatric Pulmonology. 43 (11): 1067–71. doi:10.1002/ppul.20894. PMID 18972408.
- "Idiopathic Pulmonary Haemosiderosis - World 1st Medical Treatment By Researchers At Queen Mary University London And University Of Leicester". Medical New Today. 2 June 2007.
- Ceelen, W. (1931). "Die Kreislaufstörungen der Lungen". In Henke, F.; Lubarsch, O. (eds.). Handbuch der speziellen pathologischen Anatomie und Histologie (in German). 3. Berlin: Springer. p. 10.
- Heiner, DC (1990). "Pulmonary hemosiderosis". In Chernick V, Kendig EL Jr (eds.). Disorders of the respiratory tract in children. Philadelphia PA: WB Saunders. pp. 498–509.
- Ceelen-Gellerstedt syndrome at Who Named It?