The most sensitive serologic test is anti-GBM antibodies (95% sensitive for GS). These antibodies are directed against type IV collagen—the major component of basement membranes—and their presence in the setting of hemoptysis and/or glomerulonephritis is enough to make the diagnosis of GS. ANCA testing is still warranted because although ANCA positivity certainly suggests GPA/MPA/EGPA, between 10% and 40% of GS patients are also ANCA positive (particularly p-ANCA).6,7 Thus, it’s possible, although not common, for a patient with GS to be anti-GBM negative and ANCA positive. By the same token, 10–20% of patients with GPA/MPA/EGPA can be ANCA negative, making the clinical features and biopsy more important for diagnosis.7
Among the ANCA-associated vasculitides, GPA and MPA have the most similarities in presentation. MPA does not affect the upper airways, but is more likely to cause DAH, and it lacks ocular involvement. EGPA has more distinct features—asthma, peripheral eosinophilia and gastrointestinal involvement—that allow it to be differentiated from the other diseases.
Unlike the other entities, GS does not usually present with systemic symptoms such as fever, fatigue, weight loss, arthralgias and rash. It should be noted that it is also rare for GS to have a predominantly pulmonary involvement. GS is rarer than the other diseases, although it is the most likely of the aforementioned diseases to affect a young patient such as ours.6
Because eye involvement occurs with the AAV (particularly GPA) and SLE, our patient’s conjunctivitis made Goodpasture’s less likely. Reduced complement levels are unique to SLE in our differential, but because complement levels reflect a balance of complement production and consumption, normal levels cannot always exclude SLE.
Treatment Options
The approach to all ANCA-associated vasculitides relies on corticosteroids in combination with other immunosuppressants or, rarely, plasmapheresis. Treatment can be divided into induction therapy and maintenance therapy. The aggressiveness of induction therapy depends on disease severity. Patients receiving both induction and maintenance therapy are immunosuppressed and, thus, are at risk for opportunistic infections. Prophylaxis against Pneumocystis jiroveci is advised for those patients receiving greater than 15 mg prednisone per day (or equivalent). Nasal irrigation with 2% mupirocin can help prevent sinus infections.
Induction therapy (see Table 1): For localized or early-systemic disease without imminent organ failure, daily prednisone with the addition of weekly methotrexate is an effective option that offers the least number of side effects. If methotrexate is contraindicated, rituximab can be used instead. These patients typically do very well, and although a steroid taper is warranted, caution must be used during the first month given the high risk of relapse.
