Adult Pulmonary Core Curriculum
Written by:
Gary W. Hunninghake, M.D.
Edited by:
Michael W. Peterson, M.D.
Joel N. Kline, M.D.
Christine Blaski, M.D.
Peer Review Status:
On physical examination, the patient appeared apprehensive, cyanotic, and very short of breath. Her temperature was 39oC, her pulse was 120/min, her respirations were 35/min and her blood pressure was 100/65 in the supine position. She had a petechial rash over most of her body which appeared to be confluent over her face. HEENT exam was within normal limits, with the exception of what appeared to be "cold sores" in her mouth. There was some cervical adenopathy. Examination of her chest revealed diffuse rhonchi. In some areas of the bases of her lungs, there was a decrease in normal breath sounds and an increase in "E to A" changes. A friction rub was sometimes heard on inspiration. Auscultation of the heart revealed a rapid rate with a II/VI systolic murmur. There was no S3 or S4. Occasionally, a friction rub, that was different that the pleural friction rub was heard. Her abdominal exam was normal, except that the tip of her spleen was felt. She had some swelling and redness of her fingers, wrists and ankles. Breast and pelvic exams were within normal limits. Neurological exam was also within normal limits.
Initial laboratory studies revealed a Hct of 25, WBC of 15.6 x 103/mm3 with 50% polys, 14% bands, 24% lymphocytes, 14% monocytes, and 2% eosinophils, and platelets of 200,000. A general screen was within normal limits; ESR was 95, and a blood gas revealed a pH of 7.48, pCO2 of 32, and a pO2 of 35 on room air. On 100% oxygen by face mask, her pO2 increased to 55. A chest x-ray revealed bilateral small pleural effusions and multiple lobar and subsegmental infiltrates with air bronchograms.
Sputum, blood and the cervical cultures were sent to the laboratory. The mouth ulcers were scraped and a gram stain and silver stain were performed. Anti-GBM, ANCA, ANA and RA serologies were sent to the laboratory. Doppler studies of her legs revealed no evidence of clots. Echo revealed only a small pericardial effusion. Bronchoscopy was performed and revealed blood in all of the airways. Samples were sent for culture.
Based on this evidence, the tentative diagnosis was acute lupus pneumonitis with pulmonary hemorrhage. Pending the results of her cultures, the patient was also started on broad spectrum antibiotics. Because of the diagnosis of acute lupus pneumonitis, the patient was also started on IV cyclophosphamide and solu-medrol. Prior to starting the cyclophosphamide, the potential side effects of the medication were discussed with the patient, including its potential to decrease fertility and to cause genetic abnormalities. The patient noted that she already had two children and that she wished to receive this therapy. All cultures were negative. The only positive serology was a markedly elevated ANA.
The patient ultimately required mechanical ventilation for oxygenation. After 4 days of therapy, her oxygenation started to improve and by 5 days, she was weaned from mechanical ventilation. By two weeks, her chest x-ray had returned to normal, her rash had disappeared, and the swelling in her joints had disappeared. At no time, did she have evidence of abnormal renal function. Follow-up pulmonary function tests and arterial blood gas measurements were within normal limits. She is, currently, followed in the Rheumatology clinic for her SLE.
Discussion:
Incidence
The pulmonary complications of SLE usually occur in patients in whom the
diagnosis of SLE is already known. However, in 3-5% of patients, pulmonary
disease is the presenting features of this disorder. Although acute massive
pulmonary hemorrhage is a rare complication of SLE (<5% of patients), this
disorder it is a relatively common cause of acute pulmonary hemorrhage.
Initial Evaluation Pulmonary hemorrhage is an acute medical emergency that requires prompt diagnosis and treatment. Even with appropriate treatment the mortality is high (>20%), and mortality is much greater (up to 80%) if instituting appropriate treatment is delayed. The diagnosis of the disorder, in this patient, was aided by the typical clinical findings of acute SLE, significant anemia, and the knowledge that SLE can cause acute pulmonary hemorrhage. A common clinical observation is that the systemic manifestations of SLE acutely worsen just prior to the onset of pulmonary hemorrhage. A common misunderstanding is that patients with massive pulmonary hemorrhage must have hemoptysis. Many patients, including this one, do not develop hemoptysis. For patients in whom the diagnosis of acute pulmonary hemorrhage is suspected, a bronchoscopy is the most rapid means to make the diagnosis. It is unlikely that a patient has massive pulmonary hemorrhage if bronchial secretions or bronchoalveloar lavage is not “red tinged” or frankly bloody. It should be noted that acute pulmonary hemorrhage is often a manifestation of acute lupus pneumonitis. This latter syndrome is poorly characterized, histologically. However, it probably is a diffuse small vessel vasculitis of the lung.
Differential Diagnosis
The diagnosis of acute pulmonary hemorrhage in patients with SLE is one of
exclusion. There are many other causes of diffuse alveolar infiltrates and hypoxia
in these patients. Some of these disorders also cause bleeding into the lung.
One major concern is infection. It is often difficult to clinically determine if a patient with SLE has an infection because they may have other complications of their disease that can mimic infection. About 1/2 of patients with SLE who present with fever, pulmonary infiltrates and hypoxia will have an infection. The incidence of infection is high for two reasons: 1) the underlying disorder predisposes patients to infection and 2) the patients are often receiving immunosuppressive medications. Almost any type of infection that is characteristic of immunosuppressed patients may be present. It is imperative, therefore, to aggressively obtain specimens for culture, including sputum (or cultures from bronchoscopy), blood, or pleural fluid (if there is an effusion). Other sites may be cultured, as indicated. These specimens must be obtained quickly because the patients are often started on broad spectrum antibiotics pending the results of these cultures. Also, the diagnosis of an infection precludes initiating prolonged treatment with immunosuppessive agents that, ultimately, may harm the patient.
Another concern in febrile patients with SLE, hypoxia, and pulmonary infiltrates is pulmonary emboli. Some patients with SLE have a predisposition to develop pulmonary emboli as a part of their underlying disease. These patients can often be recognized because of an elevated PTT and the presence of a lupus anticoagulant. They may present with a sudden onset of massive pulmonary emboli or with recurrent pulmonary emboli. If this embolic disease causes pulmonary infarction, they may also present with pulmonary hemorrhage and/or hemoptysis. This diagnosis must be excluded because the therapy of this disorder is very different that the pulmonary hemorrhage due to vasculitis.
Other causes of pulmonary infiltrates in a febrile and hypoxic patient with SLE include aspiration and congestive failure. The treatment of these complications of SLE also differ from that of pulmonary hemorrhage due to vascultits.
The differential diagnosis of pulmonary hemorrhage in a patient who appears to have an immune mediated connective tissue disease includes:
Treatment
Specific therapy. There is some disagreement regarding the specific
therapy of
this disorder. Most clinicians would agree that intravenous corticosteroids are
indicated. Some would use doses of 1-1.5 mg/kg/day of methylprednisolone. Others
would use higher doses up to 250 mg every six hours. It is probably reasonable to
use the higher dosages of the medication for the first 48-96 hours and then to
drop the dose to the lower level. When the patient stabilizes, the medication can
be given orally as an equivalent amount of Prednisone. The dosage should be
reduced after the first 3 months of therapy to the lowest amount that will keep
the patient in remission. Many would also use intravenous cyclophosphamide at a
dosage of 15 mg/kg. This may be given as a single dose or in divided doses over
4-5 days. No additional cyclophosphamide is given for two weeks. At this point in
time, the patient is started on oral cytoxan at a dosage of 1.5 mg/kg/day if the
WBC is >5000. The dosage is evaluated weekly for 1 month to keep the WBC count
above 4000. After 3 months, the WBC counts can be performed on a monthly basis. If
cyclophosphamide is used, the dosage of prednisone should be reduced more rapidly
after the first 6 weeks of therapy to minimize the chances of infection.
Plasmapharesis has also been used to treat this disorder. There is no data,
however, to support the use of this modality as therapy for this disorder.
Other Therapy. There are other important measures to control bleeding in this disorder. First, if the patient has received a nonsteroidal antiinflammatory medication in the past week, it is likely that there is abnormal platelet function. If this is the case, the medication should be discontinued and consideration given to platelet transfusions until platelet function returns to normal and/or the bleeding stops. Second, the bleeding is exacerbated if the pulmonary capillary wedge pressure is high. In this case, consideration should be given to lowering the pressure. This will likely require hemodynamic monitoring because it would not be prudent to reduce the pulmonary capillary wedge pressure to a very low value in the setting of active bleeding.
If there is any evidence of infection, it should be treated because this often increases the bleeding into the lung.
Many of these patients require mechanical ventilation. If this is the case, it is important to remember that the effective lung volumes are smaller if there is significant amounts of blood in the alveolar spaces. For this reason, it is important to monitor airway pressures during ventilation to prevent barotrauma. It might be prudent to use pressure controlled ventilation, in this setting.
References
1. Bunn, WB and Hunninghake, GW. Immunologic Lung Disease. In. Critical Care
Medicine. 1995. ed. JE Parillo and RC Bone. pp. 867.
2. Desnoyers, MB, Bernstein, S, Cooper, AG, et al. Pulmonary hemorrhage in lupus erythematosis without evidence of immunologic disease. Arch. Intern. Med. 144: 1398, 1984.
3. Mintz, G, Gilindo, LF, Gernandez, DJ, et al. Acute massive pulmonary hemorrhage in systemic lupus erythematosis. J. Rheumatol 5(1): 39, 1978.
4. Myers, JL and Katzenstein, AA. Microangiitis in lupus-induced pulmonary hemorrhage. Am. J. Clin. Pathol. 85: 552, 1986.
5. Lynch, JP and Hunninghake, GW. Pulmonary Complications of Collagen Vascular Disease. In. Annual Review of Medicine. 1992. ed. WP Creger. pp 17.
6. Hunninghake, GW and Fauci, AS. State of the Art: Pulmonary Involvement in the Collagen Vascular Diseases. Am. Rev. Respir. Dis. 119: 471, 1979. Questions
Media for Acute Pulmonary Hemorrhage in Systemic Lupus Erythematosis
Test for Acute Pulmonary Hemmorhage in
Systemic Lupus Erythematosis
Practice Test for Acute Pulmonary Hemmorhage in Systemic Lupus Erythematosis
CXR
Chest CT Scan