ANCA testing in eosinophilic granulomatosis with polyangiitis (EGPA)

 

The American Journal of Respiratory and Critical Care Medicine published a consensus statement on the use of ANCA testing in patients with eosinophilic granulomatosis with polyangiitis  (EGPA,formerly Churg Strauss syndrome).  The article serves is a helpful update and review on some aspects of EGPA.

First some Basics about the ANCA test. The two main types have two different nomenclatures of designation depending on the assay used. In the ELISA test, which uses specific antigens, the two antibodies are proteinase three (pr3) and myeloperoxidase (MPO).  These correlate mainly (and there are some exceptions) with the immunofluorescent patterns of C and P ANCA respectively.

What about disease associations? Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) is generally associated with C ANCA. Microscopic polyangiitis (MPA) is generally associated with P ANCA. The same is true of pauci immune  renal limited vasculitis. These categories are not absolute.

When it comes to EGPA it's a little more complex. Only 40% or so of patients with EGPA are ANCA  positive and the predominant pattern is ANCA P.  Test characteristics of ANCA for GPA,  MPA and renal limited vasculitis are pretty good. This, as is evident from the above, is not the case for EGPA.

Now on to the paper.

Despite the poor test characteristics the consensus panel recommends testing on all patients or suspected EGPA patients because it may point to the correct diagnosis and has implications for disease phenotype. Here's the specific recommendation, from the abstract of the paper:

MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA–associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having “vasculitic” or “eosinophilic” EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab, or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

According to the paper there are some important clinical correlations. EGPA patients who are anca positive tend more to have a vasculitic  manifestations such as glomerulonephritis, neuropathy, pulmonary Hemorrhage and skin lesions. Those who are negative tend more toward the infiltrative aspects of the disease which translates into cardiac involvement and pulmonary granulomas.

Treatment decisions are made more on clinical grounds than on the basis of the ANCA test. Again, from the paper:

Glucocorticoids  are  the  cornerstone  of  therapy  for  EGPA.  Additional  immunosuppressive agents  (e.g.,  cyclophosphamide)  should  be  prescribed  for  patients  with  life-  and/or  organ-threatening manifestations, such as heart disease, glomerulonephritis, alveolar hemorrhage or mononeuritis  multiplex,  and  can  be  considered  for  selected  patients  with  glucocorticoid dependence  or  recurrent  disease  [51].