The authors present a case in which the initial manifestation of systemic lupus erythematosus (SLE) was diffuse alveolar hemorrhage (DAH), which is a rare presentation that carries a high risk of death. The patient failed to respond to standard therapy but was successfully treated with plasmapheresis.
A 65-year-old woman with a history of hypertension, positive lupus anticoagulant, and unspecified arthritis presented with massive hemoptysis of 1 day's duration and respiratory failure. She denied chest pain, fever, recent upper respiratory tract symptoms, and GI or urinary problems. There was no history of substance use, travel, or any clinical manifestations of SLE. She had 2 healthy children and no history of spontaneous abortions.
The physical examination was significant for severe respiratory distress and hemoptysis, with diffuse crepitations on auscultation of the right side of the chest. Results of the remainder of the physical examination were normal.
Laboratory results were remarkable for severe anemia (hemoglobin level, 6 g/dL; baseline, 11 g/dL 5 months earlier) and acute renal failure (creatinine level, 7.2 mg/dL; baseline, 1.1 mg/dL). A chest radiograph (Figure 1) and CT scan showed diffuse alveolar infiltrates in the right lung. Results of nuclear perfusion scanning and echocardiography were normal.
Serologic tests were positive for antinuclear antibody (titer of 1:320) and double-stranded DNA (titer of 134). Results were nega-tive for antineutrophil cytoplasmic antibodies (c-ANCA), perinuclear ANCA (p-ANCA), antiglomerular basement membrane antibodies, and anticardiolipin antibodies. Serum complement levels were in the low-normal range (C3 of 78 mg/dL and C4 of 18 mg/dL).
The patient underwent endotracheal intubation and mechanical ventilation, and treatment with broad-spectrum antibiotics was started. A flexible fiberoptic bronchoscopy revealed blood in all segments of the right tracheobronchial tree, with no visible evidence of active bleeding.
Bronchoalveolar lavage (BAL) return was persistently bloodstained, strongly suggesting alveolar hemorrhage. Hemosiderin-laden macrophages were seen in the BAL fluid. Results of routine bacterial and fungal cultures of blood, sputum, and BAL fluid were negative. Kidney biopsy was not performed, because of the critical condition of the patient.
A diagnosis of SLE associated with DAH was made on the basis of the hemoptysis, alveolar infiltrates, decrease in hemoglobin level, bronchoscopic evidence of alveolar hemorrhage, positive serologic results, and acute renal failure.
Pulse corticosteroids, cyclophosphamide, and hemodialysis were initiated within 24 hours of admission. The patient's condition improved, with resolution of hemoptysis. There was also significant improvement of hypoxemia and lung infiltrates. Her hemoglobin level increased to 10 g/dL.
Five days later, the patient had a recurrence of symptoms, with hemoptysis, hypoxemia, and new left lung infiltrates (Figure 2). Her hemoglobin level dropped from 10 g/dL to 8 g/dL. She received 3 cycles of plasmapheresis, which resulted in prompt resolution of hemoptysis and infiltrates (Figure 3). She was successfully extubated and transferred out of the ICU and was given maintenance doses of corticosteroids and cyclophosphamide.
Hemodialysis was continued until renal function returned to baseline. There was no further recurrence of hemoptysis. However, the patient's hospital course was complicated by sepsis with multiorgan failure, leading to death 3 months after admission.
DAH can be a complication of coagulation disorders, inhalation of toxins, infections, and autoimmune diseases. Most cases are caused by capillaritis associated with systemic autoimmune diseases, including ANCA-associated vasculitis, anti-glomerular basement membrane disease, and SLE.1
DAH is a rare and catastrophic complication of SLE, with an incidence of 2% to 5.4% and a mortality rate that ranges from 23% to 92%.2 Among the rheumatologic diseases, DAH is most frequently seen in patients with SLE and systemic vasculitides.2-4
In 1904, Osler5 reported the first case of hemoptysis, bilateral alveolar consolidations, rash, anemia, and nephritis. DAH has been reported to be the initial manifestation of SLE in 20% of these cases and is commonly seen in young women. Most patients presenting with DAH have carried the diagnosis of SLE for several years.3,6
The classic triad of hemoptysis, abrupt fall in hemoglobin level, and new pulmonary infiltrates can be seen in 25% to 100% of cases.2,7 Up to 10% of patients have recurrent hemoptysis, as seen with our patient. Renal involvement is the most common extrapulmonary manifestation of DAH associated with SLE.
Patients with lupus nephritis are at greater risk for DAH (64%) than are SLE patients without DAH (28%).6,7 The most common radiographic pattern in lupus-associated DAH is bilateral interstitial and alveolar infiltrates (80%) followed by lobar or unilateral infiltrates (20%). Pleural effusion is evident in 30% of cases.7
Early flexible fiberoptic bronchoscopy may be useful; BAL fluid that is progressively bloodier from aliquot to aliquot confirms the diagnosis. The presence of hemosiderin-laden macrophages in BAL fluid and of capillaritis in the transbronchial biopsy specimen and the exclusion of infection support the diagnosis. Carbon monoxide-diffusing capacity, which can be used as an adjunctive test, is increased in 91% of cases.
An aggressive immunosuppressant is the mainstay of treatment. Pulse-dose corticosteroids and cyclophosphamide are the recommended therapy.8 Plasmapheresis has been used in a few cases, with no proven survival benefit.6 Concerns associated with the use of plasmapheresis alone include the theoretical risk of increased autoantibody synthesis as a rebound phenomenon and line-associated sepsis.7
Euler and Guillevin9 reported the synchronized use of plasmapheresis and cyclophosphamide; however, this regimen has been unsuccessful in the prevention of renal failure in patients with lu- pus nephritis. Anecdotal case reports suggest a beneficial role for intravenous immunoglobulin and tacrolimus in refractory cases of DAH.10
Our patient represented an interesting diagnostic challenge. She was an elderly woman who had predominantly unilateral radiographic abnormalities, which to our knowledge is unlike previously reported cases. Her initial manifestation of SLE was alveolar hemorrhage with renal insufficiency. Pulmonary embolism, cardiogenic or noncardiogenic pulmonary edema, and bleeding from coagulopathies were excluded.
Other entities that may mimic the clinical presentation of DAH in SLE include acute lupus pneumonitis, which is usually not associated with renal failure. The various pulmonary manifestations of SLE include lupus pneumonitis, lymphocytic interstitial pneumonia, pulmonary hypertension, pulmonary hemorrhage, pulmonary embolism associated with circulating lupus anticoagulant, lu- pus pleuritis, and weakness of the diaphragm.11
DAH is a serious manifestation of pulmonary SLE that may occur early or late in disease evolution; it should be a part of the differential diagnosis in all patients presenting with hemoptysis and diffuse lung infiltrates. An aggressive diagnostic approach with early bronchoscopy to confirm the diagnosis and exclude the presence of infection is indicated.
Prompt immunosuppressive treatment is essential for improving survival rates. It is important to be aware that DAH may recur despite ongoing immunosuppressive therapy, as with our case.
Plasmapheresis should be considered in refractory cases, although a survival benefit has not been proved. Larger studies are needed to investigate the benefit of plasmapheresis in patients who have DAH secondary to SLE.
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