Persistent lung infiltrates are a frequent challenge in clinical practice. Diagnosis is often difficult when multiple co-morbidities are present.
A 58 year-old African American woman, former smoker, with multiple previous admissions for exacerbation of congestive heart failure (CHF), history of mitral valve repair, hemolytic anemia of unknown etiology and chronic obstructive pulmonary disease (COPD) was admitted for fever and received treatment for pneumonia, CHF and COPD exacerbations. Echocardiogram showed left ventricle ejection fraction of 30%, decreased right ventricle function and mitral regurgitation. Two weeks later, she was re-admitted for worsening dyspnea and productive cough. Physical examination showed no fever, tachycardia, diffuse bilateral crackles and expiratory wheezes. Anemia, leukocytosis, elevated brain natriuretic peptide but normal cardiac enzymes and electrocardiogram were documented. Chest x-ray showed bilateral alveolar opacities. Initial treatment included non-invasive positive pressure ventilation, intravenous diuretics, vasodilators, angiotensin-converting enzyme inhibitors, oral steroids, bronchodilators and antibiotics. After 3 days, she did not show significant improvement. Repeat chest x-ray showed persistent alveolar infiltrates. High-flow oxygen was required despite adequate volume removal. High resolution computed tomography (HRCT) of the chest showed ground glass opacities and alveolar consolidations throughout both lungs (Graphic 1). Airways were normal by bronchoscopy and bronchoalveolar lavage was unremarkable. Histologic examination of trans-bronchial biopsies from the right middle lobe revealed intra-alveolar fibrin, hemosiderin laden macrophages in the alveolar spaces and the interstitium, and neutrophilic infiltrate surrounding capillaries (capillaritis) with sparing of larger blood vessels (Graphic 2). Serologic studies were all negative, included antinuclear antibodies, anti-double stranded deoxyribonucleic acid, rheumatoid factor, anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basal membrane antibodies (ABMA). Urinalysis and serum complement levels were normal. Prednisone was increased and cyclophosphamide was started. Patient was discharged on oxygen and followed-up as outpatient. After 3 doses of cyclophosphamide, there was clinical and radiologic improvement and patient was weaned off oxygen.
Our patient had idiopathic pauci-immune pulmonary capillaritis, a clinical entity of isolated pulmonary capillaritis without evidence of systemic vasculitis. A myriad of disorders present with similar symptoms to our patient. Systemic Lupus Erythematous can present with hemolytic anemia and pulmonary vasculitis; however, the absence of other systemic manifestations of the disease and the negative serologic studies make this diagnosis unlikely. There was no evidence of acute glomerulonephritis, thus Henoch-Schonlein Purpura, Essential Cryoglobulinemia and IgA Nephropathy are less possible. The same can be said for Goodpasture’s Syndrome, especially in the setting of negative ABMA. ANCA-associated vasculitides are clinical entities that can present with pulmonary involvement. Wegener’s Granulomatosis is associated with ANCA positive in more than 90% of the cases, with predominance of cytoplasmic staining ANCA positive in more than 75% of the cases. Our patient did not have the classical involvement of the upper airways, nor the presence of necrotizing granulomatous inflammation. Churg-Strauss Syndrome is a clinical entity associated with asthma, hypereosinophilia and necrotizing vasculitis, however, none of these were present in our patient. Our patient did not have the typical systemic presentation and ANCA positivity seen in MPA patients with lung involvement. Patients with Idiopathic pauci-immune pulmonary capillaritis are usually younger than MPA patients, frequently present with both upper and lower respiratory tract symptoms and can be p-ANCA positive or negative. Propylthiouracil, diphenylhydantoin and retinoic acid are all associated to pulmonary capillaritis, but our patient had not received any of these medications.
Idiopathic pauci-immune pulmonary capillaritis must be considered as part of the differential diagnosis for non-resolving pulmonary infiltrates. The multiple other comorbidities and treatments made diagnosis difficult. The previous treatments with steroids for both hemolytic anemia and presumed COPD likely attenuated the clinical and serological manifestation of the disease in our patient.
Alan Orellana, No Financial Disclosure Information; No Product/Research Disclosure Information