Taiwan Crit. Care Med.2009;10:268-274
Kuan-Chun Lin et al.
IDIOPATHIC PULMONARY HEMOSIDEROSIS IN ADULT: A CASE
REPORT
Kuan-Chun Lin1, Chu-Tau Lee2, Ping- Chen Yu2
Abstract
Diffuse pulmonary hemorrhage is a rare but potentially catastrophic event.
It manifests radiographically by the rapid development of diffuse bilateral infiltrates,
which, although they resemble pulmonary edema. There are over 45 known causes
for diffuse pulmonary hemorrhage. Here, we report a case of idiopathic pulmonary
hemosiderosis who presented to emergency room complaining of severe dyspnea
and cough with blood-tinged sputum for several months. The chest radiography
revealed bilateral unevenly distribution of alveolar opacities. A computed tomography
scan of the chest showed consolidation lesion over bilateral lung parenchymal.
Bronchoscopy was performed. Trans-bronchial lung biopsy and bronchial lavage
were done. Pathologically, it showed hemorrhage with hemosiderin-laden macrophages deposition. Vasculitis, collagen vascular disorders and immune complex diseases
were excluded. The chest radiography improved greatly after 4 days of admission.
We should keep a high index of suspicion of the diagnosis and it should be included
as a differential diagnosis in the case of diffuse radiographic bilateral infiltrates
with a history hemoptysis.
Key words: Idiopathic pulmonary hemosiderosis, Pulmonary hemorrhage, Hemoptysis
Introduction
(DAD), or other miscellaneous abnormalities.
Capillaritis is recognized to be the most common
histologic finding in patients with DPH. In patients
with bone marrow transplantation or DAD, the
pathogenesis of DPH is often multifactorial,
commonly a mixture of coagulopathy/thromobocytopenia with pulmonary infection. DPH is
rarely seen in AIDS.5,6 Other associations with
DPH include DAD, mitral stenosis, venooccclusive
disease,7 leptospirosis,8 fat embolism, and hemorrhagic pulmonary edema of renal failure.
Bleeding into the lung parenchymal is common
in a lot of disorders. A triad of symptoms suggests
diffuse pulmonary hemorrhage (DPH); hemoptysis , anemia, and airspace opacities on the chest
radiography.1 Occasionally, the bleeding is covert
and hemoptysis is absent. The clinicians always
miss the diagnosis. There are over 45 known
causes for diffuse pulmonary hemorrhage.2-4 The
underlying lung parenchymal may be normal, or
may show capillaritis, diffuse alveolar damage
Correspondence: Ping-Chen Yu
Divison of Pulmonary, Chia-Yi Hospital; No. 312, Beigang Rd., West District, Chiayi City 600, Taiwan
Phone: +886-5-231-9090 ext.2128; E-mail: [email protected]
Division of Critical Care Medicine, Department of Internal Medicine, Chia-Yi Hospital1
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Case presentation
Here, we report a case of 39-year-old
Taiwanese male who presented to emergency
room complaining of severe dyspnea and fever
for 2 days. Tracing back his medical history, he
suffered from cough with occasional blood-tinged
sputum for several months, but he did not pay
attention to it until progressive short of breath,
fever happened 2 days ago. He ever visited other
local hospital for help, where chest radiography
showed bilateral alveolar and reticular infiltrates.
Acute pulmonary edema and suspected pneumonia were told. There was no systemic disease
or cardiovascular disease about the past history.
He has smoking history one pack per day for
several years. He has been also a policeman for
more than 10 years.
On admission, his body temperature was
38°C, blood pressure was 138/77 mmHg, pulse
rate was 118 beats/min, and respiratory rates was
28 cycles/min. On examination, the pulse oximeter is 77% under room air. The breathing sound
was moist rales and wheezing. There is no evidence
of fluid overload such as increased water intake
or lower limbs pitting edema. The laboratory tests
showed elevated white blood cell (13770/uL), a
hemoglobin level of 15.7.g/dL and normal
coagulopathy. The chest radiography revealed
bilateral unevenly distribution of alveolar opacities (Fig. 1). A computed tomography scan of
the chest was done later. It showed consolidation
lesion over bilateral lung parenchymal (Fig. 2).
There is no engorged pulmonary vessel or enlarged
lymph nodes over hilum and mediastinum.
Empirical antibiotic was prescribed for suspected
community-acquired pneumonia due to fever and
leukocytosis. Rapid deterioration of the respiratory pattern and oxygen saturation prompted transfer
to intensive care unit on day 1 admission (Fig.
3). Bi-level positive airway pressure was given
and helps the patient to feel less discomfort and
short of breath. Bronchoscopy was performed.
Trans-bronchial lung biopsy and bronchial lavage
were done after respiratory pattern recovered
and oxygen pressure was above 60 mmHg.
Fig 1. Chest radiography revealed bilateral
unevenly distribution of alveolar opacities.
Fig 2. Computed tomography scan of the chest
showed consolidation lesion over bilateral lung parenchymal.
Pathologically, it showed hemorrhage with hemosiderin-laden macrophages deposition and associated acute inflammation and mild alveolar
cell hyperplastic change. The fluid of bronchial
lavage was found mostly red blood cells microscopically. Neither antinuclear antibody, antidouble-stranded DNA antibody, nor rheumatoid
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Kuan-Chun Lin et al.
Fig. 3. Chest radiography showed homogenous
opacity in bilateral hilum.
Fig 4. Chest radiography became improved a
lot.
factor was documented. Both antineutrophil
cytoplasmic antibody (ANCA) and urine analysis
were negative. The complement levels (C3, C4),
IgG, IgM were normal. Other miscellaneous
examinations such as HIV-titer and RPR, VDRL
were checked to exclude the presence of
pneumocystis jiroveci pneumonia. Finally, cardiac sonography was performed and it showed
no valvular heart disease. The chest radiography
improved greatly and fever subsided after 4 days
of admission (Fig. 4). The patient was discharged
and made appointment with out-patient department follow-up.
stitial thickening which can lead to prominent
lung fibrosis in long-standing cases.11 Late in the
disease, alveolar septal fibrosis develops. 1
Theoretically, IPH is a disease of childhood.
The onset typically is from 1 to 7 years of age
with exact a fifth of patients presenting in the
late teens and 20s.12 On the contrary, this case
was a middle-aged male patient without hemoptysis history in his childhood. The sex incidence
in child is equal, but in adults, there is a twofold
preponderance in males. The severity of hemoptysis varies greatly. Bleeding into the lung is
evidenced by consolidation on the chest radiography and the presence of iron deficiency anemia
with low iron stores. Diagnosis is by exclusion
and has been recently reviewed.11 The outcome
is variable with a better prognosis in adults than
children.11 Death is due to pulmonary arterial
hypertension and cor pulmonale, respiratory failure
and bleeding. Treatment is supportive. Steroids
and immunosuppressive drugs may be used without
clear efficacy, though there is little evidence that
steroid therapy in adults particularly helps in
acute situations.11 In childreen and adolescents
Discussion
Idiopathic pulmonary hemosiderosis (IPH)
is a disease of unknown etiology featured by
episodic alveolar hemorrhage that finally leads
to lung fibrosis.9 Autoimmune associations are
found such as hyper- and hypo-thyroidism,
hemolytic anemia and IgA gammopathy. 10
Histologically, alveolar hemorrhage, hemosiderin laden macrophage in the alveoli and inter270
Taiwan Crit. Care Med.2009;10:268-274
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were checked to exclude the presence of
pneumocystis jiroveci pneumonia. No opportunistic infection was documented. Finally, cardiac
sonography was performed and it showed no
valvular heart disease. Surprisingly, a hemoglobin level of 15.7.g/dL was found on laboratory
examination. There was no iron-deficiency anemia on admission. The acute onset of hemoptysis
may explain the reason for normal hemoglobin.
By the way, the patient has been a smoker
for several years. Chronic obstructive pulmonary
disease was diagnosed clinically and graded stage
III via spirometry according to Global Initiative
for Chronic Obstructive Lung Disease (GOLD)
guideline on this admission. Seretide (salmeterol
and fluticasone) accuhaler (50/250) 1 puff bid
has been used since the period of admission.
Accidently, no more episode of hemoptysis attacks
after discharge. The follow-up chest radiography
showed a lot of improvement. The role of inhaled
corticosteroid may be worth further studying.
the long term treatment can be problematic 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 date13. Other immunosuppressants including azathioprine, hydroxyxhloroquine, cyclophosphamide, and methotrexate, have been tried with variable results. 14,15
Among these, azathioprine in combination of
steroids may be the best therapeutic regimen,
especially in preventing IPH exacerbations.
Focusing on our admission course, we have
tried everything we can to make better differential
diagnosis of diffuse pulmonary hemorrhage.
Goodpasture syndrome manifests diffuse pulmonary hemorrhage, glomerulonephritis and antiglomerular basement membrane antibodies.
Knowing vasculitis disorder was a potential cause
of pulmonary hemorrhage, urinary analysis and
renal function were checked. Normal result was
found. Neither proteinuria nor hematuria was
complained. Anti-glomerular basement membrane
disease (Good-pasture syndrome) was excluded
initially. The majority of patients presenting with
the pulmonary renal syndrome are antineutrophil
cytoplasmic antibody (ANCA) positive. MPOANCA is associated with microscopic polyangitis
and Churg-Strauss syndrome, whereas PR3-ANCA
is more strongly associated with Wegener
granulomatosis. Both two types of ANCA were
negative in this patient. Compatibly, clinical features
also excluded the ANCA-related diseases.
Several collagen vascular disorders and
immune complex disease also are involved with
diffuse pulmonary hemorrhage. Systemic lupus
erythematosus are most common seen.16,17 DPH
is well documented in patients with SLE usually
occurring in the context of established disease
with extra-pulmonary features including glomerulonephritis.3 On physical examination, there is
no skin rash, arthralgia, deformity of joints was
found. Neither antinuclear antibody, anti-doublestranded DNA antibody, nor rheumatoid factor
was documented. The complement levels (C3,
C4), IgG, IgM were normal. Other miscellaneous
examinations such as HIV-titer and RPR, VDRL
Conclusion
Idiopathic pulmonary hemosiderosis (IPH)
are rare and are sometimes not discovery until
frequent episodes of hemoptysis. Correct diagnosis is often missed or delayed until during
bronchoscopy. The diagnosis of idiopathic pulmonary hemosiderosis may be difficult and mostly
depend on clinical suspicion and exclusion of
collagen vascular disorders, immune complex
disease, vasculitis and coagulopathy. Triad of
features including hemoptysis, anemia and airspace opacities on the chest film suggest idiopathic pulmonary hemosiderosis. It is well recognized that, because alveolar hemorrhage occurs
distal to the mucociliary escalator, hemoptysis
may be absent Additionally, blood which does
reach the upper airway may be swallowed and
produce a misleading positive stool blood test.
Radiographic signs are not particularly helpful
in distinguishing between IPH and various other
causes of consolidation and reticular pattern.
Bronchoscopy and pulmonary lavage is usually
diagnostic, and help exclude associated infection.
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Taiwan Crit. Care Med.2009;10:268-274
Kuan-Chun Lin et al.
07. Cohn RC, Wong R, Spohn WA, et al. Death due
to diffuse alveolar hemorrhage in a child with pulmonary veno-occlusive disease. Chest 1991;100:14561458.
08. Im JG, Yeon KM, Han MC, et al. Leptispirosis of
the lung: radiographic findings in 58 patients. Am
J Roentgenol 1989;152:955-959.
09. Turner-Warwick M, Dewar A. Pulmonary hemorrhage and pulmonary hemosiderosis. Clin Radiol
1982;33:361-370.
10. Bouros D, Panagou P, Arseniou P, et al. Idiopathic
pulmonary hemosiderosis and autoimmune hypothyroidism: bronchoalveolar lavage findings after
cimetidine treatment. Respir Med 1995;89:307-309.
11. Milman N, Pederson FM. Idiopathic pulmonary
hemosiderosis. Epidemiology, pathogenic aspects and
diagnosis. Respir Med 1998;92:902-907.
12. Soergel K, Sommers S. Idiopathic pulmonary hemosiderosis and related syndromes. Am J Med 1962;
32:499-511.
13. Elinder G. Budesonide inhalation to treat idiopathic
pulmonary hemosiderosis. Lancet 1985;1:981-982.
14. Ohga S, Takahashi K, Miyazaki S, et al. Idiopathic
pulmonary hemosiderosis in Japan: 39 possible cases
from a survey questionnaire. Eur J Pediatr 1995;154:
994-995.
15. Baz MA, Ghio AJ, Roggli VL, et al. Iron accumulation in lung allografts after transplantation. Chest
1997;112:435-439.
16. Zamora MR, Warner ML, Tuder R, et al. Diffuse
alveolar hemorrhage and systemic lupus erythematosus.
Clinical presentation, histology, survival, and outcome.
Medicine(Baltimore) 1997;76:192-202.
17. Onomura K, Nakata H, Tanaka Y, et al. Pulmonary
hemorrhage in patients with systemic lupus
erythematosus. J Thorac Imaging 1991;6:57-61.
Hemosiderin-laden macrophage in sputum or
alveolar lavage indicates bleeding within the
recent past.
Serological studies should include tests for
anti-GBM antibodies, ANCA, antinuclear antibodies (ANA), anti-double-stranded DNA antibodies, cryoglobulins, rheumatoid factor, and
complement levels. With current methods of
serological diagnosis, lung biopsy is rarely needed,
and should it be necessary, open lung biopsy is
to be preferred to trans-bronchial biopsy. Finally,
we should keep a high index of suspicion of the
diagnosis and it should be included as a differential diagnosis in the case of diffuse radiographic bilateral infiltrates with or without a
history hemoptysis.
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05. Koziel H, Haley K, Nasser I, et al. Pulmonary
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Taiwan Crit. Care Med.2009;10:268-274
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Fig. 1. It shows prominent hemorrhage in lung tissue
Fig. 2. Hemosiderin-laden macrophages deposition were found (yellow arrow).
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Taiwan Crit. Care Med.2009;10:268-274
Kuan-Chun Lin et al.
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