Radiology Cases in Pediatric Emergency Medicine Volume 3, Case 7 Craig T. Nakamura, MD

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.

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 radgraph (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).

Copyrighted:Radiology Cases in Pediatric Emergency Medicine Volume 3, Case 7
Loren Yamamoto, MD, MPH
Associate Professor of Pediatrics
University of Hawaii John A. Burns School of Medicine