A 24-year-old African-American woman presented with nausea, flank pain, and hematuria recurring over several months. Review of symptoms and past medical history were negative. She was a current smoker. Family history was noncontributory. Physical exam was significant for bilateral flank pain. Laboratory testing, serology, and kidney biopsy led to the diagnosis of rapidly progressive glomerulonephritis (Goodpasture syndrome) with mildly elevated levels of anti-GBM antibody. The patient was treated and discharged home with appropriate medications and follow up.
She remained seronegative and clinically stable until 8 months later when she presented with hemoptysis and developed acute respiratory failure requiring invasive mechanical ventilation. She recently used marijuana. Chest xray showed diffuse patchy opacities of both lungs. Anti-GBM antibody level was undetectable. Bronchoscopy showed alveolar hemorrhage. She was diagnosed with antibody-negative relapse of Goodpasture syndrome with pulmonary hemorrhage. She was treated, extubated, and discharged home on medications.
Discussion:
Goodpasture syndrome is a rare autoimmune disease with an estimated incidence of one case per million per year. It is mediated by anti-GBM antibody deposition on the alveolar and glomerular basement membrane detectable by immunofluorescence. Most patients present with a combination of acute renal failure due to RPGN and hemoptysis due to pulmonary hemorrhage, while 30-40% present with an isolated renal involvement. Goodpasture syndrome is more common in white populations and is very rare in those of African descent. Most patients with Goodpasture syndrome have circulating anti-GBM antibodies detectable by ELISA, which is highly sensitive (>95%) and specific (>97%), and confirmed by Western blot.
Interestingly, although she was mildly positive for anti-GBM antibody on initial diagnosis, serology was undetectable during relapse with pulmonary hemorrhage. Rare cases of antibody-negative Goodpasture syndrome have been reported. In this case, prior administration of immunosuppressives may explain the negative serology at relapse. It is possible that the antibody levels fell below the detection limits of the assays. It is also worth noting that antibody titers do not correlate well with the severity of disease or clinical course. Relapses resulting in pulmonary disease strongly correlate with volatile hydrocarbon exposure such as cigarette or marijuana use causing inhalation injury leading to alveolar damage, which occurred in this case. Perhaps subjects with very low levels of anti-GBM antibodies develop pulmonary hemorrhage when exposed to the right precipitant.
Conclusions:
As this case highlights, isolated pulmonary hemorrhage can occur as the sole manifestation of relapse in Goodpasture syndrome, and this can occur in the absence of detectable antibody levels. Clinicians should have enhanced awareness of this atypical presentation of a rare disease.