GPA vs. MPA vs. EGPA: A Guide to Your Specific ANCA Vasculitis Subtype

A diagnosis of ANCA-associated vasculitis (AAV) can sound like "alphabet soup," as it comes with an assortment of similar-sounding acronyms: AAV, ANCA, GPA, MPA, EGPA, etc. This jumble of letters can seem overwhelming, especially when you’re dealing with a potentially serious diagnosis.

The three main subtypes of ANCA-associated vasculitis — GPA, MPA, and EGPA — have similarities but all affect your body in different ways. Knowing your subtype provides the roadmap your doctor uses to select your treatment.

• Granulomatosis with polyangiitis (GPA)
• Microscopic polyangiitis (MPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)

“Knowing your subtype is important because each subtype has distinct clinical patterns as well as pathologic findings,” says Anisha Dua, MD, MPH, a professor of medicine and the director of the Vasculitis Center at Northwestern University Feinberg School of Medicine in Chicago. “The subtype of ANCA vasculitis that you have can influence prognosis, relapse risk, and therapeutic management, as well as the types of screenings that need to be done during the course of the disease,” she says.

Granulomatosis With Polyangiitis (GPA)

• Cough
• Earache
• Nasal congestion
• Sinus headache
• Runny nose

• Coughing up blood
• Hearing loss or vertigo
• Hoarseness
• Kidney failure
• Muscle weakness
• Nasal swelling or ulcerations
• Nerve pain
• Splotchy patches on skin

Microscopic Polyangiitis (MPA)

• Abdominal pain
• Cough or coughing up blood
• Eye pain or vision changes
• Fatigue
• Fever
• Loss of appetite or unexplained weight loss
• Muscle or joint pain
• Shortness of breath
• Skin rashes, especially on the legs
• Tingling, weakness, or numbness

Eosinophilic Granulomatosis With Polyangiitis (EGPA)

• First phase: asthma and respiratory symptoms
• Second phase: eosinophilia, when an excessive number of eosinophils are found in the blood or in tissues
• Third phase: vasculitis, or inflammation of blood vessels, which may involve the skin, lungs, nerves, kidneys, along with other organs

• cANCA, which targets a protein called proteinase 3 (PR3)
• pANCA, which targets a protein called myeloperoxidase (MPO)

“GPA is more commonly associated with c-ANCA, or PR3 positivity, whereas MPA is associated with p-ANCA, or MPO positivity. EGPA can be ANCA-negative, but when it’s positive, it’s usually associated with p-ANCA (MPO positivity),” says Dua.

“Generally, at the time of diagnosis, distinguishing between GPA and MPA is not essential, as treatment is identical for the 2 conditions,” says Kenneth J. Warrington, MD, the director of the vasculitis clinic and the chair of the division of rheumatology at Mayo Clinic in Rochester, Minnesota. “On the other hand, EGPA may require a different treatment regimen targeting the eosinophil.

Treatment Across Subtypes

In ANCA-associated vasculitis, disease severity helps guide treatment decisions, says Dr. Warrington. “For instance, when a patient with GPA presents with only sinonasal disease, this scenario is categorized as non-severe disease due to the limited organ involvement,” he says. “But if a patient with EGPA develops what is called mononeuritis multiplex — a condition characterized by damage to multiple nerves — this situation is classified as severe disease.”

• Corticosteroids These are anti-inflammatory medications that may also suppress the immune system.
• Monoclonal Antibodies These medications are used to treat certain types of autoimmune disorders and cancer, and are often prescribed together with corticosteroids. Rituximab is a type of monoclonal antibody used as a first-line therapy to induce remission, and also for maintaining remission in patients with severe GPA and MPA.
• Chemotherapy Cyclophosphamide is a type of chemotherapy medication that is used to treat certain cancers and autoimmune conditions. Its use is similar to that of rituximab, and is used together with corticosteroids to achieve remission. But rituximab generally has fewer and less-serious side effects, and professional guidelines recommend it over cyclophosphamide for remission induction in many cases.

  [16]

• Other Immunosuppressants Methotrexate is used in non-severe GPA, while azathioprine is used as a standard maintenance agent. Mycophenolate mofetil is often used as a third-line or alternative maintenance option.

  [17]

Treatment of GPA and MPA

“Rituximab is then typically used as a maintenance therapy, with serial infusions every 6 months for a period of time to keep patients in remission,” says Lally. “In EGPA, patients often need longer courses of steroids than GPA/MPA and this is partially due to a dearth of studies in EGPA looking at different doses of steroids.”

Treatment of EGPA

EGPA treatment also follows a two-stage approach: inducing remission and maintaining it. But EGPA treatment generally requires a different strategy, as the focus is on managing asthma and high eosinophil levels. Recently, there have been significant developments and studies targeting the pathophysiology of EGPA, leading to new approvals for medications specific to EGPA, says Dua.

“In EGPA, we have come a long way … with approvals for mepolizumab and benralizumab for patients with non-severe EGPA,” says Dua. “There is clear evidence demonstrating the ability of [these drugs] to help decrease glucocorticoid use and effectively control many manifestations of EGPA, including persistent asthma, rhinosinusitis, nasal polyposis, nerve involvement, and various other features of the disease.”

• ANCA-associated vasculitis (AAV) is an autoimmune disorder with three subtypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
• The three subtypes share some similar symptoms, including fever, joint pain, muscle aches, and skin rashes — but they differ in terms of the organs affected and the presence of granulomas
• Treatment for all subtypes involves induction therapy, which puts the patient into remission, and then maintenance therapy to maintain remission. The types of treatments given depend mostly on the AAV subtype and the severity of symptoms.