Alveolar Hemorrhage in Anti-Basement Membrane Antibody Disease

Abstract

Anti-basement membrane antibody disease is a rare disorder characterized by the presence of autoantibodies binding to the alveolar and glomerular basement membranes, and mediating both alveolar hemorrhage and acute glomerulonephritis. We retrospectively analyzed 28 cases of anti-basement membrane antibody disease with alveolar hemorrhage proven by bronchoalveolar lavage. The median age of patients at diagnosis was 23 years; 68% were male, 89% were active smokers, and 36% were exposed to some other inhaled agent. At diagnosis, 46% had predominant pulmonary involvement with normal initial serum creatinine. Lung function tests disclosed a restrictive ventilatory defect in 28% (n = 11) and hypoxemia (moderate in 29% and severe in 29%, n = 21). Carbon monoxide transfer factor was elevated in only 25% (n = 12). Bronchoalveolar lavage was more sensitive than any other criterion for detecting alveolar hemorrhage. After onset of treatment, new hemoptysis or transient worsening of hypoxemia occurred in 29% but did not affect pulmonary outcome. In contrast, worsening of renal function occurred in 33% and adversely affected renal outcome. At last follow-up (median, 2.6 yr; n = 24), all patients were alive and a complete cure was achieved in 50%. Long-term dialysis or renal transplantation was required in 42%, and 8% had mild chronic renal insufficiency. Last chest X-ray was normal in all cases, and no patient had respiratory insufficiency. All patients with predominant pulmonary involvement at presentation maintained independent renal function. In summary, this cohort was characterized by frequent exposure to tobacco smoking and other inhaled agents, and a constantly favorable pulmonary outcome contrasting with frequent chronic renal failure. Renal outcome was excellent in the subgroup of patients with predominant pulmonary involvement.

Circulating Anti–Glomerular Basement Membrane Antibodies With Predominance of Subclass IgG4 and False-Negative Immunoassay Test Results in Anti–Glomerular Basement Membrane Disease

“…In our Swedish series we found overt hemoptysis in only 23 % 2 , but other studies report higher figures 3,21,22 . Smoking has repeatedly been linked to pulmonary engagement in anti-GBM disease 23 and three of our patients were current smokers, but the severity of the lung disease in the current cases is intriguing. activates the lectin pathway of complement due to defects in glycosylation 27 .…”

“…This was the case in only 20 % of our Swedish series and even less in the studies from Beijing 2,28 . Interestingly the case with IgG4 anti-GBM reported by Cui also had mild kidney disease 16 ; and in a French study 23 5 of 13 cases with alveolar hemorrhage and normal kidney function had no detectable anti-GBM in the circulation. It is possible that differences in epitope specificity and/or in engagement of inflammatory effector systems account for the differences in phenotype between our patients with IgG4 anti-GBM and patients with "regular" IgG1 anti-GBM.…”

Anti-Glomerular Basement Membrane Disease

“…There are limited data on how frequently artificial ventilation is required, although one small series estimated that this occurred in 11% of patients with lung hemorrhage (70). There are case reports of successful use of extracorporeal membrane oxygenation in patients with very severe lung disease (71)(72)(73).…”

65-Year-Old Woman With Shortness of Breath and Dark Urine

“…Most patients present with the combination of rapidly progressive glomerulonephritis and pulmonary hemorrhage, although 30% to 40% of patients present with isolated renal involvement, as in our patient. 4 Rarely, pulmonary involvement predominates in the setting of a normal initial level of serum creatinine, 5 reminding the clinician that anti-GBM disease should also be considered in any patient presenting with alveolar hemorrhage.…”