Case Editor - Jeremy Falk
Reviewed By Behavioral Science Assembly
Submitted by
Martha E. Billings, MD
Senior Fellow Pulmonary Critical Care Medicine
University of Washington
Seattle, Washington
Christopher Goss, MD, MPH
Associate Professor Division of Pulmonary Critical Care
University of Washington
Seattle, Washington
Submit your comments to the author(s).
History
The patient is a 28-year-old pregnant woman who presented to the emergency room with a several-week history of cough and progressive shortness of breath. The patient initially thought she was suffering from an upper respiratory infection, as her 4-year-old son had some cough and rhinitis symptoms. However, her symptoms progressed and persisted over 2 weeks. She subsequently developed severe sinus pain and congestion and progressive hoarseness. A few days prior to her presentation to the emergency room, she began coughing up bloody, mucoid sputum, and had marked dyspnea. She noted low-grade fevers but no weight loss. She also had developed new nodular rashes over her elbows and knees. She had no chest pain, asymmetric lower extremity swelling, or arthritis. She denied frank hematuria or vaginal bleeding. She had no recent travel, no prolonged immobility, and has lived only in Southern California. She has never smoked. She worked in the home caring for her son and has no exposure history. She took only prenatal vitamins and denied illicit drug use.
Medical History
G2P1: 19 weeks pregnant
Pre-eclampsia with prior pregnancy
Lab
- Complete Blood Count: WBC 9,300/mm3, hemoglobin 7.1g/dL, hematocrit 23%, platelets 331,000/mm3, MCV 101 fL
- Electrolytes and liver function tests were within normal limits, including creatinine of 0.7 mg/dL
- Arterial Blood Gas: pH 7.46, PaCO2 30 mm Hg, PaO2 78 mm Hg on 15L face mask
- Coagulation: PTT 23 s, INR 1.0
- Urine Analysis: 1+ protein, 2+ blood, 6-10 RBC, no WBC
- HIV test negative
Figures
Chest Radiograph
C. Wegener’s granulomatosis: The patient has the suggestion of diffuse alveolar hemorrhage (DAH) clinically with diffuse patchy infiltrates, hypoxemia, and hemoptysis. She also has a rash and signs of glomerular nephritis, with an active urine sediment. This suggests a pulmonary-renal syndrome and systemic vasculitis. The presences of upper airway disease with sinusitis, vocal cord, and subglottal crusting lesions make Wegener’s granulomatosis (WG) the most likely diagnosis. It is rare to have Wegener’s during child-bearing years; it is more common in middle-aged men.
Goodpasture’s syndrome and lupus, both causes of diffuse alveolar hemorrhage and glomerular nephritis, do not involve the upper airway. Antiphospholipid syndrome is another known cause of DAH due to diffuse microthrombi but again does not cause upper airway lesions. Pulmonary embolism, a common cause of hemoptysis in pregnant women, usually does not lead to diffuse infiltrates. PE would also not explain the upper-airway lesions, nephritis, and rash.
The patient’s C-ANCA was 1:1280, her P-ANCA was negative as well as ANA, anti-GBM Ab, dsDNA Ab and RF. The clinical presentation is most consistent with Wegener’s confirmed by laboratory data.
B. Methylpredisolone: high-dose intravenous steroids are the most appropriate immunosuppressant in this pregnant woman. Intravenous cyclophosphamide is likely more efficacious for WG - induced diffuse alveolar hemorrhage but is highly teratogenic. Cyclophosphamide has a 16-22% likelihood of being teratogenic to the fetus, especially at this early stage. It would be an appropriate second-line agent if she failed to respond to steroids and continued to have life-threatening DAH and glottal disease. Plasmapharesis is the treatment of choice for Goodpasture’s syndrome with circulating antibodies causing the disease, but this has no known efficacy in Wegener’s. Termination of the pregnancy will not lead to resolution of her WG; this is only effective for pre-eclampsia and
HELLP syndrome, (hemolysis elevated liver enzymes and low platelets). Heparin would likely worsen her alveolar hemorrhage.
A. Wegener’s granulomatosis typically causes a necrotizing granulomatous inflammation. Capillaritis is present in 35-45% of all WG cases. Wegener’s is a pauci-immune necrotizing vasculitis without circulating immune complexes. Lupus also causes capillaritis, but due to immune complex deposition. Goodpasture’s syndrome has classic linear IgG deposition of anti-basement membrane antibodies. Microvascular thrombosis is typical of antiphospholipid antibody syndrome. Diffuse alveolar damage is the pathologic correlate of adult respiratory distress syndrome (ARDS).
B. Caplan’s syndrome is associated with rheumatoid arthritis (not lupus) and other pneumoconiosis with inhaled mining dusts (coal, silica, etc.). Wegener’s granulomatosis typically causes lung nodules which cavitate due to necrosis, vasculitis-mediated small vessel microinfarction and diffuse alveolar hemorrhage more rarely. Rheumatoid arthritis causes a fixed upper-airway obstruction due to cricoarytenoid ankylosis. Vanishing lung syndrome seen in SLE is a process of progressive restriction and loss of lung volume of unknown mechanism. Chest computed tomography does not show parenchymal or pleural abnormalities. Patients complain of dyspnea and pleuritic chest pain.
The patient was treated with 1 g methylprednisolone as well as empiric antibiotics. She had a rapid response with resolution of her hemoptysis, diminished crackles within 2 days; she was weaned off of oxygen in just 3 days and discharged home.
A. Vasculitis typically worsens during pregnancy. In case series, pregnancy is associated with higher activity in Wegener’s granulomatosis, lupus, Churg-Strauss, and other systemic vasculitis. The best outcomes occur when pregnancy is initiated during periods of disease inactivity. Flares of collagen-vascular disease can endanger the life of the mother and fetus and lead to worse outcomes. Most drugs used to control pulmonary vasculitis are teratogenic. Methotrexate, a folate antagonist, causes “aminopterin syndrome” marked by unusual facies, skull anomalies, and skeletal defects and fetal bone marrow toxicity. Azathioprine is less teratogenic but also less efficacious.
References
- Auzary C, et al. Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women. Ann Rheum Dis 2000;59(10):800-4.
- Geterud A, et al. Severe airway obstruction caused by laryngeal rheumatoid arthritis. J Rheumatol 1986;13(5):948-51.1.
- Karim MY, et al. Presentation and prognosis of the shrinking lung syndrome in systemic lupus erythematosus. Semin Arthritis Rheum 2002;31(5):289-98.
- Specks U. Diffuse alveolar hemorrhage syndromes. Curr Opin in Rheum 2001 13:12-17.
- Green RJ, et al. Pulmonary capillaritis and alveolar hemorrhage: update on diagnosis and management. Chest 1996;110(5):1305-16.
