448. Diffuse alveolar haemorrhage secondary to biopsy-proven anti-GBM disease with negative circulating antibodies by standard ELISA

Presentation of Case: A 21-year old white British female presented to local hospital with acute shortness of breath requiring admission to intensive care for respiratory support. She had no significant past medical history, was an active smoker and had recently used intranasal cocaine recreationally. She denied haemoptysis, fever or contact with unwell persons. Haemoglobin was found to be 55 g/L with raised CRP and normal creatinine. Urine dip was negative for blood and protein. Chest X-ray and subsequent CT chest showed bilateral lung infiltrates in keeping with possible pulmonary haemorrhage. She was commenced on pulsed Methylprednisolone and transferred to our unit for plasma exchange. Serology including ANA, ANCA, complements and anti-GBM antibody were negative on numerous occasions. Bronchoscopy and subsegmental biopsy confirmed diffuse alveolar haemorrhage with linear alveolar staining for IgG supporting the diagnosis of anti-GBM disease. She received 7 sessions of plasma exchange and 4 doses of intravenous Cyclophosphamide with gradual weaning of corticosteroids. She made an excellent response and was strongly advised to stop smoking. Diagnostic Testing: Bronchoscopy - diffuse alveolar haemorrhage and linear alveolar staining for IgG with immunoperoxidase and immunofluorescence (fig. 1). Differential & Final Diagnosis: At presentation, important differentials included crack cocaine lung, atypical pulmonary infections and seronegative pulmonary syndromes including ANCA-associated vasculitis and anti-GBM disease. Bronchoscopy confirmed the diagnosis as anti-GBM disease. Discussion of Management: We present an unusual case of anti-GBM disease diagnosed by lung biopsy, in the absence of detectable circulating anti-GBM antibodies or urinary abnormalities. In clinical practice, we rely on ELISA to detect circulating anti-GBM antibodies; however, there are reports of renal biopsy proven anti-GBM disease in absence of these antibodies. Lung biopsies are seldom used to diagnose anti-GBM disease where detection of linear IgG staining pattern is less reliable than in glomeruli. There are several possible explanations for negative anti-GBM testing using standard ELISA. The half-life of binding antibodies could be longer than those in circulation thus circulating antibodies could have disappeared when serum sample is collected. Salama et al1 were able to detect circulating antibodies in 2 cases using a biosensor technique despite both ELISA and Western blot being negative. Anti-GBM antibodies are usually IgG1, however other IgG subclasses can be detected. Ohlsson et al2 reported 4 young women with severe alveolar haemorrhage and IgG4 anti-GBM antibodies who showed low or negative result on regular anti-GBM ELISA testing; although in our case lung biopsies were negative for IgG4 staining. Other possibilities include presence of IgA/IgM anti-GBM antibodies or antibodies reacting to an atypical antigen or epitope on type IV collagen. Conclusions: Anti-GBM disease without circulating autoantibodies is rare but should be considered in patients with unexplained pulmonary haemorrhage. This case emphasizes the importance of obtaining a tissue diagnosis in these settings and that patients can present with isolated lung involvement. Disclosures: None