Case Illustrates the Difficulty Diagnosing Granulomatosis with Polyangiitis

Once the diagnosis has been confirmed and disease activity analyzed, treatment is initiated. The use of cyclophosphamide and rituximab, in addition to glucocorticoids, changed the fate of these diseases from fatal to chronic conditions. The treatment is a two-phase approach: induction and maintenance. The induction phase includes a combination of high-dose glucocorticoids and immunosuppressants (either cyclophosphamide or rituximab). However, in the recent years, rituximab was shown not to be inferior to cyclophosphamide and has been favored because it seems to have favorable outcomes in disease remission.¹²

Several studies have shown that rituximab may be superior to cyclophosphamide under some circumstances. Rituximab has also been shown to be superior to cyclophosphamide to achieve immunosuppression in patients with PR3-positive ANCA-vasculitis.¹³ Analysis from the RAVE and RITUXVAS trials have suggested that rituximab may be more effective than cyclophosphamide in refractory disease.¹²

Once remission is achieved, the patient can be transitioned to maintenance therapy with azathioprine or methotrexate. A recent study showed that patients treated with a low dose of rituximab had a lower relapse rate at 28 months compared with patients treated with azathioprine.¹⁴ Glucocorticoids have been shown to decrease disease relapse at six months and, currently, several studies are underway to establish formal glucocorticoid guidelines.¹⁵ After remission has been achieved, patients need to be monitored closely to assess for relapsing disease.

Just recently, Rhee et al. showed that persistent hematuria (but not proteinuria), after induction therapy, was associated with a four times higher risk of disease relapse.¹⁶ In ANCA vasculitis, the risks of relapsing disease continue to remain a major concern in the disease process. The risk factors for relapsing disease include the diagnosis of GPA, previous relapse and positive PR3-antibodies.¹² In a small study, a CTLA4-Ig inhibitor drug (abatacept) that affects T cell activation, was proposed for treatment of non-severe relapsing GPA disease. Of the 20 patients included in the study, 90% had disease improvement, and 80% achieved remission. Many of these patients were able to rapidly discontinue prednisone.¹⁷

In patients with severe disease, such as rapidly progressive glomerulonephritis and/or alveolar hemorrhage, plasma exchange has been proposed in combination with other remission induction agents.¹⁸

Conclusion

Increasing awareness and the ability to early recognize, diagnose and treat GPA will save a patient’s life. In the past 20 years, major advances in treatment have been made that dramatically improved long-term survival and quality of life for these patients.

Diana Girnita, MD, PhD, is an attending rheumatologist and faculty for the internal medicine residency program at Trihealth Good Samaritan Hospital in Cincinnati.

Vishnuteja Devalla, MD, is an internal medicine resident at Trihealth Good Samaritan Hospital in Cincinnati, with an interest in rheumatology.

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