Page 17 / March 07
Pulmonary Hemorrhage
Background to pulmonary hemorrhage
Pulmonary hemorrhage can be focal or diffuse.1 Focal bleeding occurs most commonly in the context of chronic disease with the bleeding originating from the bronchial arteries. Cystic fibrosis accounts for the majority of focal bleeding with congenital heart disease as the second leading cause.2
Diffuse alveolar hemorrhage is a rare but potentially life threatening condition due to bleeding from the microvasculature that typically occurs in young children. Diffuse hemorrhage may occur as an isolated phenomenon or as part of a systemic disease. Diffuse bleeding is also classified into immune mediated or non immune mediated disease.
The conditions categorized as pulmonary renal syndromes that are associated with systemic immune disorders are Goodpasture's Syndrome, Systemic Lupus Erythematosus (SLE), Wegener's granulomatosis and microscopic polyangiitis. Antibodies typically associate with certain conditions although there is much overlap.3 Anti-glomerular basement membrane antibodies are more found in Goodpasture's, anti-nuclear antibodies and anti-double stranded DNA in SLE, c-anti-neutrophilic antibody(c-ANCA) in wegener's granulomatosis and p-ANCA in microscopic polyangiiitis.
Isolated diffuse alveolar hemorrhage without an identifiable cause is referred to as Idiopathic Pulmonary Hemosiderosis (IPH).1 IPH is further subdivided into those accompanied by pulmonary capillary inflammation known as Pulmonary Capillaritis and those without such inflammation.
Pulmonary capillaritis
The epidemiology of this condition is not well defined with the available evidence based mainly on case reports. The first description is from the 1950s and apparently it is more recognized among adults. Within the pediatric population, a recent case series of patients seen between 1989 and 2003 has attempted to better characterize this condition.4 The case definition was of lung biopsy confirmed pulmonary hemorrhage with subsequent review and analysis of the clinical presentation, investigations and treatment strategies.
The features of Pulmonary Capillaritis on histopathology are neutrophilic invasion of the interstitium with fibrinoid necrosis of the alveolar capillary walls.1;4 Small thrombi may be seen in the capillaries and venules. Intra-alveolar hemorrhage results from the injury to the alveolar capillary interface.
In the case series the biopsies were divided into those with Pulmonary Capillaritis, those with a diagnosis of Idiopathic Pulmonary Hemorrhage without capillaritis and a group with neither of these features.
Among 23 patients on whom lung biopsy was performed they were able to identify 8 cases of pulmonary capillaritis. In the remainder there were 4 with IPH and 11 with non-PC, non-IPH.
Children with PC had an age distribution of 1.5 to 12 years. The majority presented unwell and hypoxic but only 2 with hemoptysis. All of them had a pattern of alveolar infiltrates on chest imaging with fewer also showing interstitial infiltrates. They were anaemic, had low hematocrits and raised inflammatory markers. In only two cases was pulmonary hemorrhage confirmed on bronchoalveolar lavage by the presence of hemosiderin laden macrophages. Apart from a lower hematocrit and slightly higher erythrocyte sedimentation rates (ESR) there were no distinguishing features in the investigation of PC compared to IPH and non-IPH, non-PC group.
PC in this series was associated with several other conditions including myocarditis, SLE, microscopic polyangitis, prune belly syndrome transplanted for end stage renal failure, crohn's disease and autoimmune hepatitis. Only one case had isolated PC.
In this case series high dose steroids proved effective in controlling hemorrhage though additional treatments in individual cases included; intravenous immunoglobulin, cyclophosphamide, hydroxychoriquine, pentasa and azathioprine. Response meant resolution of pulmonary symptoms though there was co-morbidity from associated conditions. Mortality appeared to less in the children with PC but the numbers were limited and it is hard to draw firm conclusions.
To biopsy or not?
The identification of pulmonary hemorrhage as a separate entity has a long tradition with the first description by Virchow in the mid 18th century. It is a testimony of the observational acumen of clinicians of previous eras that Goodpasture's syndrome was first described in an male adolescent at the turn of the 19th century. By the mid 20th century anti-glomerular basement membrane had been reported and towards the latter part of the century anti-neutrophilic antibodies.
There has been a debate as to the necessity of lung biopsy for the management of pulmonary hemorrhage. This is reflected in following statement:
"Open lung biopsy is rarely needed to arrive at the most likely diagnosis, which can almost always be reached by less invasive procedures"
"To make a definitive diagnosis of IPH lung and/or renal biopsy are necessary"
Though these statements appear to be contradictory when read merely in an abstract sense they may be relevant in different circumstances and be appropriate in the context of a particular clinical service. The causes of pulmonary hemorrhage vary according to the base population, the nature of referral patterns and the type of allied professional sub-specialities. With a major referral centre that has a large catchment area receiving patients with increasing complexity there may be a predominance of more unusual causes for pulmonary hemorrhage. Over time there is a growing demand to be able to reach a more definitive diagnosis so as to improve treatment and prognosis. Accompanying this shift in workload and expectations there is also change in the availability of investigations. With the novel surgical techniques and improved technology it is now more feasible to undertake lung biopsies. These secular trends favor a more investigative approach with the aim of improving our understanding of these rare disorders. Although there are risks associated with biopsy the risks of chronic empirical treatment without knowing the pathophysiology are not inconsequential.
References /
Pulmonary Hemorrhage
Background to pulmonary hemorrhage
Pulmonary hemorrhage can be focal or diffuse.1 Focal bleeding occurs most commonly in the context of chronic disease with the bleeding originating from the bronchial arteries. Cystic fibrosis accounts for the majority of focal bleeding with congenital heart disease as the second leading cause.2
Diffuse alveolar hemorrhage is a rare but potentially life threatening condition due to bleeding from the microvasculature that typically occurs in young children. Diffuse hemorrhage may occur as an isolated phenomenon or as part of a systemic disease. Diffuse bleeding is also classified into immune mediated or non immune mediated disease.
The conditions categorized as pulmonary renal syndromes that are associated with systemic immune disorders are Goodpasture's Syndrome, Systemic Lupus Erythematosus (SLE), Wegener's granulomatosis and microscopic polyangiitis. Antibodies typically associate with certain conditions although there is much overlap.3 Anti-glomerular basement membrane antibodies are more found in Goodpasture's, anti-nuclear antibodies and anti-double stranded DNA in SLE, c-anti-neutrophilic antibody(c-ANCA) in wegener's granulomatosis and p-ANCA in microscopic polyangiiitis.
Isolated diffuse alveolar hemorrhage without an identifiable cause is referred to as Idiopathic Pulmonary Hemosiderosis (IPH).1 IPH is further subdivided into those accompanied by pulmonary capillary inflammation known as Pulmonary Capillaritis and those without such inflammation.
Pulmonary capillaritis
The epidemiology of this condition is not well defined with the available evidence based mainly on case reports. The first description is from the 1950s and apparently it is more recognized among adults. Within the pediatric population, a recent case series of patients seen between 1989 and 2003 has attempted to better characterize this condition.4 The case definition was of lung biopsy confirmed pulmonary hemorrhage with subsequent review and analysis of the clinical presentation, investigations and treatment strategies.
The features of Pulmonary Capillaritis on histopathology are neutrophilic invasion of the interstitium with fibrinoid necrosis of the alveolar capillary walls.1;4 Small thrombi may be seen in the capillaries and venules. Intra-alveolar hemorrhage results from the injury to the alveolar capillary interface.
In the case series the biopsies were divided into those with Pulmonary Capillaritis, those with a diagnosis of Idiopathic Pulmonary Hemorrhage without capillaritis and a group with neither of these features.
Among 23 patients on whom lung biopsy was performed they were able to identify 8 cases of pulmonary capillaritis. In the remainder there were 4 with IPH and 11 with non-PC, non-IPH.
Children with PC had an age distribution of 1.5 to 12 years. The majority presented unwell and hypoxic but only 2 with hemoptysis. All of them had a pattern of alveolar infiltrates on chest imaging with fewer also showing interstitial infiltrates. They were anaemic, had low hematocrits and raised inflammatory markers. In only two cases was pulmonary hemorrhage confirmed on bronchoalveolar lavage by the presence of hemosiderin laden macrophages. Apart from a lower hematocrit and slightly higher erythrocyte sedimentation rates (ESR) there were no distinguishing features in the investigation of PC compared to IPH and non-IPH, non-PC group.
PC in this series was associated with several other conditions including myocarditis, SLE, microscopic polyangitis, prune belly syndrome transplanted for end stage renal failure, crohn's disease and autoimmune hepatitis. Only one case had isolated PC.
In this case series high dose steroids proved effective in controlling hemorrhage though additional treatments in individual cases included; intravenous immunoglobulin, cyclophosphamide, hydroxychoriquine, pentasa and azathioprine. Response meant resolution of pulmonary symptoms though there was co-morbidity from associated conditions. Mortality appeared to less in the children with PC but the numbers were limited and it is hard to draw firm conclusions.
To biopsy or not?
The identification of pulmonary hemorrhage as a separate entity has a long tradition with the first description by Virchow in the mid 18th century. It is a testimony of the observational acumen of clinicians of previous eras that Goodpasture's syndrome was first described in an male adolescent at the turn of the 19th century. By the mid 20th century anti-glomerular basement membrane had been reported and towards the latter part of the century anti-neutrophilic antibodies.
There has been a debate as to the necessity of lung biopsy for the management of pulmonary hemorrhage. This is reflected in following statement:
"Open lung biopsy is rarely needed to arrive at the most likely diagnosis, which can almost always be reached by less invasive procedures"
"To make a definitive diagnosis of IPH lung and/or renal biopsy are necessary"
Though these statements appear to be contradictory when read merely in an abstract sense they may be relevant in different circumstances and be appropriate in the context of a particular clinical service. The causes of pulmonary hemorrhage vary according to the base population, the nature of referral patterns and the type of allied professional sub-specialities. With a major referral centre that has a large catchment area receiving patients with increasing complexity there may be a predominance of more unusual causes for pulmonary hemorrhage. Over time there is a growing demand to be able to reach a more definitive diagnosis so as to improve treatment and prognosis. Accompanying this shift in workload and expectations there is also change in the availability of investigations. With the novel surgical techniques and improved technology it is now more feasible to undertake lung biopsies. These secular trends favor a more investigative approach with the aim of improving our understanding of these rare disorders. Although there are risks associated with biopsy the risks of chronic empirical treatment without knowing the pathophysiology are not inconsequential.
References /