INTRODUCTION: Diffuse alveolar hemorrhage (DAH) can be an acute, life threatening presentation of several diseases - of which, the most common cause is pulmonary vasculitis. Microscopic polyangitis (MPA) is the least common cause of pauci-immune pulmonary capillaritis presenting with DAH and is associated with perinuclear antineutrophil cytoplasmic autoantibodies (pANCA). We present an unusual case of MPA which was pANCA negative by indirect immunofluorescence assay (IFA) and was positive for myeloperoxidase (MPO) by enzyme immunoassay (EIA) and required a renal biopsy for establishing the diagnosis.
CASE PRESENTATION: A 31 year-old non-smoker caucasian female with a history of Type I diabetes mellitus and hypothyroidism presented with fever, dyspnea and hemoptysis. Initial O2 saturation was 82% on room air; patient required oxygen supplementation with 40% venturi mask at 10 L/min to increase O2 saturation to 98%. Hemoglobin upon admission was 10.7 g/dl with MCV of 87 fl (normocytic anemia) and urinalysis was positive for hematuria. Chest X-Ray revealed diffuse alveolar infiltrates with bronchograms in all lobes of the right lung. Chest CT scan demonstrated diffuse alveolar infiltrates in all lobes of the right lung and infiltrates in the left upper and lower lobes. Patient was intubated and bronchoalveolar lavage (BAL) was performed. Serial aliquots during BAL demonstrated progressively hemorrhagic fluid in three separate bronchopulmonary segments. BAL was positive for hemosiderin laden macrophages. Creatinine steadily increased from a baseline of 1.2 mg/dl to 1.9 mg/dl with decreasing urine output. Hemodialysis was started on day 5 of admission. Laboratory evaluation revealed positive anti-nuclear antibody (1:160), with negative serological work-up for anti-cyclic citrullinated peptide (Anti-CCP), anti-glomerular basement membrane antibodies (anti-GBM), Anti-Smith antibodies, double stranded DNA, anti-Ro and pANCA and cytoplasmic staining ANCA (cANCA). Patient underwent renal biopsy that revealed glomerulonephritis with cellular crescents and necrosis consistent with pauci-immune glomerulonephritis. MPO detection by enzyme linked immunosorbent assay (ELISA) was positive and confirmed the diagnosis of MPA. Patient was started on methylprednisone 1000 mg IV daily for 5 days with lack in improvement of respiratory failure. Cyclophosphamide was started and patient was extubated after 2 days of initiating cyclophosphamide. She was discharged twenty-two days after admission. Two months after discharge, patient has regained her renal function and there have been no further episodes of hemoptysis.
DISCUSSIONS: Our patient presented with respiratory insufficiency and acute renal failure. Differential diagnosis of pulmonary-renal syndrome includes Wegner's granulomatosis (WG), Goodpasture's disease, systemic lupus erythematosus (SLE), Churg Strauss syndrome (CSS), Henoch Schonlein Purpura, and MPA. WG is ANCA positive in more than 90% of the cases, with cANCA positivity in more than 75% of the cases. Our patient did not have the involvement of the upper airways or the presence of necrotizing granulomas on biopsy making WG less likely. Goodpasture's disease is typically seen in men with history of smoking and almost all patient have anti-GBM antibodies detectable by ELISA . Renal biopsy findings of pauci-immune vasculitis were not consistent with SLE and patient lacked a history of asthma and eosinophilia suggestive of CSS. HSP occurs more commonly in children and is associated with rash in the lower extremities - features not seen in our patient. MPA was diagnosed in the presence of a negative pANCA by IFA - feature seen in less than 10% of all cases. In patients with features suggestive of pauci-immune capillaritis and absence of granulomas, a negative ANCA should be confirmed with EIA using purified MPO as substrate.
CONCLUSION: This is a unique case of pauci-immune glomerulonephritis that was confirmed as MPA on the basis of a positive EIA for MPO. Despite the absence of pANCA by IFA, MPA must be considered as part of the differential diagnosis for pauci-immune pulmonary capillaritis.
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