This is a 12 year-old female who presented to the 
emergency department with pallor and hemoptysis.  
Seven days ago she presented to her pediatrician with 
a complaint of fever, cough, and rhinorrhea.  She was 
evaluated and diagnosed with a viral upper respiratory 
tract infection.  Over the next six days, the cough 
persisted and she noticed that her sputum was 
streaked with blood.  She continued to cough up bloody 
secretions, which eventually became coffee-ground in 
nature.  Her mother was concerned that she "looked 
pale" and brought her to the emergency department.
     She denies any sore throat.  She was seen one 
month ago for impetigo and was treated with topical 
antibiotics.  This resolved and she was well until her 
recent onset of symptoms.  She has also noticed coffee 
colored urine over the past three days.  There is no 
history of ill contacts or gastroenteritis.  She has been 
afebrile for four days.
     Exam:  VS  T37.0, P120, R28, BP 145/78, oxygen 
saturation 93% in room air.  Her oxygen saturation 
increases to 100% on some oxygen by nasal prongs.  
She is awake, but tired appearing.  No acute distress.  
Skin:  Pallor is noted.  No bruising or petechiae.  
Normal turgor. Pupils equal and reactive.  EOM's full.  
Conjunctiva pale.  Sharp optic discs.  Moist mucous 
membranes.  No oral erythema or exudates.  Neck 
supple without adenopathy.  Lungs:  Good aeration 
bilaterally.  Bibasilar inspiratory crackles.  No wheezing.  
Abdomen:  Benign.  Extremities:  No rash or lesions.  
Neurologic:  Normal.  Pulses are good.
     Her laboratory workup revealed a CBC with a 
normocytic, normochromic anemia.  Her hemoglobin 
was 4.0, hematocrit 12.2, and reticulocyte count 6.0%.  
Her platelets were 300,000.  Her WBC was 8,400 with 
no left shift.  Electrolytes were normal, however, her 
BUN was 32 and her creatinine 2.3.  Her urinalysis is 
significant for many red blood cells.  SG 1.011, pH 6.0, 
6-10 WBC's, >100 RBC's, 3-5 granular casts per HPF.
     A chest radiograph is obtained.

View chest radiograph.

     Her chest radiograph shows bilateral diffuse hazy 
infiltrates with a fine nodular appearance.  The lateral 
view showed a small amount of fluid or thickening in the 
fissures of the right lung.  This type of radiographic 
finding in conjunction with hemoptysis suggests the 
presence of a pulmonary hemorrhage.  Pulmonary 
hemosiderosis is generally confirmed by finding 
hemosiderin laden macrophages in the sputum.  Just 
based on the CXR alone, the differential includes viral 
pneumonia, mycoplasma pneumonia, fungal 
pneumonia, pulmonary edema, pulmonary 
lymphagiectasia, hemangiomatosis, pulmonary 
hemosiderosis, and pulmonary fibrosis (lymphoma, 
sarcoidosis, leukemia, tuberous sclerosis, chronic 
aspiration, and cystic fibrosis).
     After the initial admission, stabilization, and 
treatment, further laboratory studies were drawn.  Her 
anti-basement membrane serology was positive.  Her 
ANA was 5,120 (high), but her other lupus serologies 
were all negative.  Anti-streptolysin and Coombs were 
both negative.  C3, C4, and CH50 were all normal.  In 
light of her pulmonary hemorrhage, glomerulonephritis, 
and positive anti-basement membrane serology, a 
presumptive diagnosis of Goodpasture's syndrome is 
made.

     In 1919, Ernest Goodpasture, a Harvard pathologist, 
analyzed autopsy cases during an influenza epidemic.  
He described a case of an 18 year-old male with 
hemoptysis and renal insufficiency after having 
influenza (1).  The syndrome of pulmonary hemorrhage 
and glomerulonephritis became known as 
Goodpasture's syndrome.  In 1967, it was noted that 
anti-glomerular basement membrane antibodies were 
found in cases of the disease (1).  Goopasture's 
syndrome is now defined as a triad of:  a) pulmonary or 
alveolar hemorrhage (defined as hemoptysis, 
unexplained anemia, and diffuse alveolar infiltrates on 
chest x-ray) (2), b) glomerulonephritis (cresentic or 
rapidly progressive), and c) serum anti-basement 
membrane antibodies or linear immunofluorescence of 
IgG on basement membranes.
     Goodpasture's syndrome (GS) affects persons of all 
ages and races, with an average age of onset of 27 (3).  
Men are affected more commonly than women (about 7 
to 1) (3).  Although it may occur at any time of the year, 
seasonal patterns have been reported (winter and early 
summer).  The etiology remains unclear, however, 
numerous genetic and environmental relationships have 
been described.  The pathologic mechanism of GS is 
thought to stem from antibody mediated injury of type 
IV collagen (the backbone basement membranes) (4).  
Alveolar and glomerular basement membranes are 
thought to be affected more than other type IV collagen 
containing organs (ie. skin, eye, and choroid plexus) 
because of increased accessibility of epitopes due to an 
increased expression of alpha-3 collagen chains in 
these basement membranes (4), allowing access and 
formation of antibodies.   In addition, disease states 
such as infection, fluid overload, and increased O2 
requirement causes capillary leakage and further 
accessibility of the basement membranes.
     In GS, the pulmonary symptoms and signs always 
precede the renal symptoms.  The initial manifestations 
are usually a cough, mild shortness of breath, and 
hemoptysis.  Hypoxia may occur.  There are decreased 
alveolar gas volumes, and subsequently decreased 
total lung and vital capacities (5).  The renal 
involvement follows the pulmonary symptoms.  This 
may range from nearly normal to a focal proliferative or 
necrotizing glomerulonephritis.  Other systemic 
symptoms are fever and arthralgias.  Pallor may occur 
as an iron-deficiency anemia develops secondary to 
blood loss.
     The differential diagnoses of GS includes all other 
pulmonary-renal syndromes, most of which are 
vasculitic (Wegener's granulomatosis, polyarteritis 
nodosa, systemic lupus erythematosis, lymphomatoid 
granulomatosis, Henoch-Schonlein purpura, hemolytic 
uremic syndrome, scleroderma, rheumatoid arthritis, 
mixed connective tissue disease, drug-induced 
vasculitis, giant-cell arteritis, and idiopathic rapidly 
progressive glomerulonephritis) (5).
     The diagnosis of GS should be made expeditiously, 
for it can progress rapidly to fatal pulmonary or renal 
failure.  Diagnostic studies should consist of a complete 
blood count, creatinine, sedimentation rate, serum 
antibodies, and urine creatinine and protein.  A chest 
radiograph should be performed.  The acute air space 
involvement may have a patchy, diffuse, or perihilar 
appearance.  The infiltrates are usually bilateral with 
apical sparing.  Air bronchograms may be present (6).  
Two to three days later, the blood begins to be 
reabsorbed and the chest radiograph now takes on an 
interstitial reticular appearance.  With continual 
hemorrhage there may be fibrosis.  Several studies 
have shown that a CT may detect minor parenchymal 
involvement despite a normal chest radiograph (6).  The 
use of MRI in pulmonary hemorrhage has also been 
described (increased signal density on T1 and 
decreased on T2 secondary to the physical 
characteristics of pulmonary hemosiderin deposits) (6).

     On bronchoscopy, blood is often visualized in the 
tracheobronchial tree.  Although this is nondiagnostic, a 
positive bronchoalveolar lavage with Prussian blue 
staining (iron containing alveolar macrophages) is 
diagnostic of pulmonary hemosiderosis (7).  Biopsy 
shows intra-alveolar hemorrhage with hemosiderin 
laden macrophages.  Electron microscopy shows a 
thickened basement membrane with hyperplasia of type 
I and II pneumocytes (4).  The renal basement 
membrane is also widened.  There is hypertrophy of the 
cells with loss of foot processes and IgG deposits.
     Once the diagnosis is made, treatment should be 
initiated.  The patient may need an initial RBC 
transfusion if clinically unstable.  Hypertension may also 
need to be treated.  In addition, other factors which may 
cause further alveolar damage (ie. infection or 
pulmonary edema) must be treated.  Once stabilized, 
there are two objectives of therapy:  1) remove all 
anti-GBM antibodies and 2) prevent their resynthesis by 
immunosuppression with steroids and cytotoxic drugs 
(3).  The first objective is accomplished by 
plasmapheresis.  The second objective is met by 
treatment with corticosteroids and cyclophosphamide.  
Its dosage is titrated to the WBC count (1, 4).  The 
success of therapy can be monitored by serial 
anti-GBM titers (3).  The response to treatment and 
course of GS is quite variable and may range from 
long-term remissions to chronic pulmonary hemorrhage 
with fibrosis and renal failure requiring hemodialysis or 
transplantation (3).
    
References:
     1)  Jones DA, Jennette JC, Falk RJ.  
Goodpasture's syndrome revisited.  North Carolina 
Medical Journal 1990;51(8):411-415.
     2)  Rezkalla MA, Simmons JL.  Idiopathic 
pulmonary hemosiderosis and alveolar hemorrhage 
syndrome:  case report and review of the literature.  
South Dakota Medical Journal.  March 1995:79-84.
     3)  Glassock RJ, Brenner BM.  Immunopathogenic 
Mechanisms of Renal Injury.  In:  Braunwald E, 
Isselbacher KJ, Petersdorf RG,  Wilson JD, Martin JB, 
Fauci AS (eds).  Harrison's Principles of Internal 
Medicine, eleventh edition, New York, McGraw-Hill, 
Inc., 1987, pp. 1185-1186.
     4)  Kelly PT, Haponik EF.  Goodpasture 
syndrome:  molecular and clinical advances.  Medicine  
1994;73(4):171-183.
     5)  Prakash UBS.  Renal Diseases.  In:  Baum GL, 
Wolinsky E (eds).  Textbook of Pulmonary Diseases,  
fifth edition.  Boston, Little Brown & Company, 1984, 
pp. 1600-1609.
     6)  Muller NL, Miller RR.  Diffuse pulmonary 
hemorrhage.  Radiology Clinics of North America 
1991;29(5):965-970.
     7)  Duffy TP.  The Red Baron.  New England 
Journal of Medicine 1992;327(6):408-411.