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.
What Is ANCA-Associated Vasculitis? AAV Overview Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is not a single condition but a group of autoimmune diseases that causes inflammation in small- to medium-size blood vessels throughout the body. An autoimmune disorder is one in which your immune system mistakenly attacks the healthy cells in your body.e60dc2a1-f33c-4a05-9b50-8e3e8e5976291e5d57b1-30a1-42c2-af71-066e633064ec Antibodies are important blood proteins that help neutralize and eliminate foreign invaders (like bacteria or viruses) that cause infections. In contrast, ANCAs are autoantibodies, which are antibodies that attack your own cells — specifically, a type of white blood cell called neutrophils, which eventually leads to inflammation. Over time, inflammation can damage blood vessels and reduce normal blood flow. Since small blood vessels are present everywhere in your body, AAV causes a variety of symptoms and can affect a broad range of organs, including the kidneys, lungs, and sinuses.e60dc2a1-f33c-4a05-9b50-8e3e8e597629fb5112a3-9e96-4f84-b8d0-c2dc7213e34ce60dc2a1-f33c-4a05-9b50-8e3e8e59762969064e8c-9e5d-4537-92c4-2fccf7d649c2 “When we think about forms of systemic vasculitis, typically we categorize the different types of vasculitis by the size of the vessel involved — small, medium, and large,” says Lindsay S. Lally, MD , an assistant attending physician in the division of rheumatology at the Hospital for Special Surgery in New York City.
The Subtypes Subtypes Explained There are three main forms of AAV:e60dc2a1-f33c-4a05-9b50-8e3e8e597629f25e90e1-a507-4ce3-a156-190a6c883703 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) Formerly known as Wegener’s granulomatosis, GPA is the most common AAV subtype. It primarily affects blood vessels in the kidneys, lungs, ears, nose, throat, and sinuses. A key feature of GPA is the presence of granulomas (clusters of white blood cells that form around an infection or foreign object) in blood vessels and organs, and inflammation in different types of blood vessels.e60dc2a1-f33c-4a05-9b50-8e3e8e597629983ed4d9-885e-4431-98e1-0082138ef888 The initial symptoms of GPA are usually respiratory and can seem like a severe cold. Some early symptoms include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a82ceebe-fb69-4f99-95f1-4be5cbab0c6a Cough Earache Nasal congestion Sinus headache Runny nose More serious symptoms may eventually develop, such as:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a82ceebe-fb69-4f99-95f1-4be5cbab0c6ae60dc2a1-f33c-4a05-9b50-8e3e8e597629d4d70e35-7d58-4359-93bd-7d8184625c7e 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) MPA is the second most common subtype. It shares many clinical features with GPA, but one of the main differences is that MPA typically does not cause granulomas to form.e60dc2a1-f33c-4a05-9b50-8e3e8e597629216b0063-c127-4e35-b95d-96a7ba4845c5 As with GPA, it can affect a wide range of organs, but most commonly affects the kidneys, nerves, skin, joints, and lungs. MPA almost always affects your kidneys, with about 80 percent of patients experiencing kidney inflammation.e60dc2a1-f33c-4a05-9b50-8e3e8e597629216b0063-c127-4e35-b95d-96a7ba4845c5 Common symptoms include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976297766fa4a-4fe2-42dd-bf5b-22adfbcd719a 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) EGPA is the rarest of the three AAV types, and was formerly called Churg-Strauss syndrome, named after the two physicians who first described it, back in 1951. Similar to the two other subtypes, EGPA can affect multiple organ systems, including the lungs, kidneys, gastrointestinal tract, and heart.e60dc2a1-f33c-4a05-9b50-8e3e8e597629be13f06f-0e1a-4eba-9405-a8aa8ddc2ff0 “EGPA is like the ‘step-sibling’ to GPA/MPA,” says Dr. Lally. “The ‘E’ in EGPA refers to ‘eosinophilic’ and the eosinophilic manifestations [of the disease].” EGPA is characterized by excessive numbers of eosinophils, a type of white blood cell, that accumulate in the blood and tissues. Eosinophils normally make up 5 percent or less of your total white blood cells, but in EGPA, the percentage of eosinophils can be as high as 60 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82 Inflammation in your respiratory system is another key feature of EGPA. “ Asthma and sinusitis with nasal polyps distinguish EGPA from other forms of AAV,” says Lally. Asthma may develop long before there are any other noticeable signs or symptoms of EGPA. It can even be years between the onset of respiratory symptoms and a diagnosis of EGPA. Allergic rhinitis (also known as hay fever) is also an early symptom. And similar to GPA, granulomas may also develop.e60dc2a1-f33c-4a05-9b50-8e3e8e597629be13f06f-0e1a-4eba-9405-a8aa8ddc2ff0e60dc2a1-f33c-4a05-9b50-8e3e8e597629e9985ff4-f936-4306-bc31-64e73d780dc3 EGPA can be divided into three phases:e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82 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 These stages may not occur in everyone or even follow a strict sequence.e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82
Diagnosis: Solving the Alphabet Soup Subtype Diagnosis AAV can be challenging to diagnose because it affects multiple systems throughout the body. A thorough physical evaluation and several different types of tests are required to make a diagnosis. While testing may vary depending on the patient and symptoms, it usually includes blood tests, urinalysis, and imaging. A biopsy (a small sample of tissue taken from the affected area to examine in the lab) is also generally required for making a definitive diagnosis, although not always.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c121f2a-e4e8-400f-bf7c-56aee788450ce60dc2a1-f33c-4a05-9b50-8e3e8e597629acd9215f-da8b-4dce-b37d-ef09e5098bcb “While biopsy can be a valuable tool in confirming the diagnosis of ANCA-associated vasculitis, it is not always a required step,” 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. “When a patient presents with typical clinical features and laboratory findings that support the diagnosis, clinicians may proceed without performing a biopsy. But it remains crucial to rule out other conditions that can mimic ANCA-associated vasculitis, such as infections, before finalizing the diagnosis,” he says. Your doctor may include the following tests to make a diagnosis:e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c121f2a-e4e8-400f-bf7c-56aee788450ce60dc2a1-f33c-4a05-9b50-8e3e8e597629fdaab8ec-5c09-4059-aba6-96f5eb3f33f8 Initial Assessment Your doctor will take a full medical history and ask about your symptoms, other health conditions, and any medications you are currently taking, since AAV can be drug induced.e60dc2a1-f33c-4a05-9b50-8e3e8e59762950383744-6314-47a1-b52f-70ed6cf979dd A physical examination will also be done to look for any signs of vasculitis, such as joint pain, muscle aches, or skin rashes. Blood Tests Various blood tests are used to make a diagnosis. One test looks for the presence of ANCAs in your blood. “Each subtype can have associations with different ANCA antibodies,” says Dr. Dua. Other blood tests evaluate levels of inflammation in the body. Urinalysis A urinalysis is a simple way to assess whether vasculitis has affected the kidneys. It tests for the presence of protein, red blood cells, or clumps of red blood cells in the urine, which are indicators of inflammation in the kidneys. Biopsy When symptoms and tests suggest AAV, a biopsy is usually done to help confirm the diagnosis. A tissue sample will be taken from the part of the body that is being affected, such as the skin, kidneys, lungs, or nerves. The sample is then viewed under a microscope, where it is examined by a pathologist for signs of disease or other changes in the cells. Imaging The use of imaging devices including X-ray , ultrasound , MRI (magnetic resonance imaging) , and CT (computed tomography) scans can be helpful for diagnosis. For example, a CT scan can reveal detailed images of internal organs and is frequently used for suspected involvement in the abdomen. An MRI, which uses magnetic waves and computers to create two- or three-dimensional images, can help view the walls of blood vessels. In vasculitis, blood vessel walls may become thicker, which can reduce blood flow and cause damage to tissues.
How Your Subtype Dictates Treatment Treatments AAV treatment is focused on preventing organ damage, managing inflammation, and suppressing parts of the immune system. The goal is to put the vasculitis into remission (where there are no more signs and symptoms), and then to maintain remission.e60dc2a1-f33c-4a05-9b50-8e3e8e5976290c20c263-5490-4c1f-9fa1-5e1ae2638a3e The choice of treatment depends on the AAV subtype, the severity of your symptoms, and the type of ANCA found on blood tests. There are two main types of ANCA, and you may have one, none, or both:e60dc2a1-f33c-4a05-9b50-8e3e8e5976299992ae1f-0b85-4b0e-ad2a-01f387bcb11b 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 Dr. Warrington. “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 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.” The most commonly prescribed medications, used across subtypes, include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976290c20c263-5490-4c1f-9fa1-5e1ae2638a3ee60dc2a1-f33c-4a05-9b50-8e3e8e5976290f2527e0-b528-4adc-9474-1c6644457a75 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.e60dc2a1-f33c-4a05-9b50-8e3e8e59762973b922f0-fc22-4201-827b-de9fb3d10af0 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.e60dc2a1-f33c-4a05-9b50-8e3e8e59762908aecfdb-46c6-45de-8831-092477bc7acc Treatment of GPA and MPA In severe GPA and MPA, high doses of steroids are used in addition to immunosuppression with rituximab or cyclophosphamide as first-line. Additional therapy with avacopan, a relatively new immunosuppressant drug, may also be considered.e60dc2a1-f33c-4a05-9b50-8e3e8e59762984c4e2b9-f45e-4d26-8e4e-cb4beb302b60 “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.” Both mepolizumab and benralizumab received approval from the U.S. Food and Drug Administration (FDA) specifically for EGPA to target eosinophils. These agents are not used for standard GPA/MPA treatment.e60dc2a1-f33c-4a05-9b50-8e3e8e597629fd74e766-2a64-41af-9510-0d4a28a716b5e60dc2a1-f33c-4a05-9b50-8e3e8e5976298bdc8403-9d6c-44bd-98f6-642913106fb0 “As we continue to use these types of medications and study them further, I believe we will continue to find more roles for them to help control multiple aspects of active EGPA,” says Dua. For severe cases of EGPA, treatment still includes corticosteroids combined with cyclophosphamide or rituximab.e60dc2a1-f33c-4a05-9b50-8e3e8e5976290a75daf1-83c7-4dab-94cf-08a81037d6a0
The Takeaway 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.
Resources We Trust Cleveland Clinic: ANCA-Associated VasculitisMayo Clinic: VasculitisJohns Hopkins Vasculitis Center: What Is Vasculitis?Vasculitis UK: What Is ANCA?National Organization for Rare Disorders: Eosinophilic Granulomatosis With Polyangiitis
What Is ANCA-Associated Vasculitis? AAV Overview Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is not a single condition but a group of autoimmune diseases that causes inflammation in small- to medium-size blood vessels throughout the body. An autoimmune disorder is one in which your immune system mistakenly attacks the healthy cells in your body.e60dc2a1-f33c-4a05-9b50-8e3e8e5976291e5d57b1-30a1-42c2-af71-066e633064ec Antibodies are important blood proteins that help neutralize and eliminate foreign invaders (like bacteria or viruses) that cause infections. In contrast, ANCAs are autoantibodies, which are antibodies that attack your own cells — specifically, a type of white blood cell called neutrophils, which eventually leads to inflammation. Over time, inflammation can damage blood vessels and reduce normal blood flow. Since small blood vessels are present everywhere in your body, AAV causes a variety of symptoms and can affect a broad range of organs, including the kidneys, lungs, and sinuses.e60dc2a1-f33c-4a05-9b50-8e3e8e597629fb5112a3-9e96-4f84-b8d0-c2dc7213e34ce60dc2a1-f33c-4a05-9b50-8e3e8e59762969064e8c-9e5d-4537-92c4-2fccf7d649c2 “When we think about forms of systemic vasculitis, typically we categorize the different types of vasculitis by the size of the vessel involved — small, medium, and large,” says Lindsay S. Lally, MD , an assistant attending physician in the division of rheumatology at the Hospital for Special Surgery in New York City.
The Subtypes Subtypes Explained There are three main forms of AAV:e60dc2a1-f33c-4a05-9b50-8e3e8e597629f25e90e1-a507-4ce3-a156-190a6c883703 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) Formerly known as Wegener’s granulomatosis, GPA is the most common AAV subtype. It primarily affects blood vessels in the kidneys, lungs, ears, nose, throat, and sinuses. A key feature of GPA is the presence of granulomas (clusters of white blood cells that form around an infection or foreign object) in blood vessels and organs, and inflammation in different types of blood vessels.e60dc2a1-f33c-4a05-9b50-8e3e8e597629983ed4d9-885e-4431-98e1-0082138ef888 The initial symptoms of GPA are usually respiratory and can seem like a severe cold. Some early symptoms include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a82ceebe-fb69-4f99-95f1-4be5cbab0c6a Cough Earache Nasal congestion Sinus headache Runny nose More serious symptoms may eventually develop, such as:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a82ceebe-fb69-4f99-95f1-4be5cbab0c6ae60dc2a1-f33c-4a05-9b50-8e3e8e597629d4d70e35-7d58-4359-93bd-7d8184625c7e 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) MPA is the second most common subtype. It shares many clinical features with GPA, but one of the main differences is that MPA typically does not cause granulomas to form.e60dc2a1-f33c-4a05-9b50-8e3e8e597629216b0063-c127-4e35-b95d-96a7ba4845c5 As with GPA, it can affect a wide range of organs, but most commonly affects the kidneys, nerves, skin, joints, and lungs. MPA almost always affects your kidneys, with about 80 percent of patients experiencing kidney inflammation.e60dc2a1-f33c-4a05-9b50-8e3e8e597629216b0063-c127-4e35-b95d-96a7ba4845c5 Common symptoms include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976297766fa4a-4fe2-42dd-bf5b-22adfbcd719a 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) EGPA is the rarest of the three AAV types, and was formerly called Churg-Strauss syndrome, named after the two physicians who first described it, back in 1951. Similar to the two other subtypes, EGPA can affect multiple organ systems, including the lungs, kidneys, gastrointestinal tract, and heart.e60dc2a1-f33c-4a05-9b50-8e3e8e597629be13f06f-0e1a-4eba-9405-a8aa8ddc2ff0 “EGPA is like the ‘step-sibling’ to GPA/MPA,” says Dr. Lally. “The ‘E’ in EGPA refers to ‘eosinophilic’ and the eosinophilic manifestations [of the disease].” EGPA is characterized by excessive numbers of eosinophils, a type of white blood cell, that accumulate in the blood and tissues. Eosinophils normally make up 5 percent or less of your total white blood cells, but in EGPA, the percentage of eosinophils can be as high as 60 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82 Inflammation in your respiratory system is another key feature of EGPA. “ Asthma and sinusitis with nasal polyps distinguish EGPA from other forms of AAV,” says Lally. Asthma may develop long before there are any other noticeable signs or symptoms of EGPA. It can even be years between the onset of respiratory symptoms and a diagnosis of EGPA. Allergic rhinitis (also known as hay fever) is also an early symptom. And similar to GPA, granulomas may also develop.e60dc2a1-f33c-4a05-9b50-8e3e8e597629be13f06f-0e1a-4eba-9405-a8aa8ddc2ff0e60dc2a1-f33c-4a05-9b50-8e3e8e597629e9985ff4-f936-4306-bc31-64e73d780dc3 EGPA can be divided into three phases:e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82 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 These stages may not occur in everyone or even follow a strict sequence.e60dc2a1-f33c-4a05-9b50-8e3e8e5976294ef121b3-e836-44c6-b976-919010142f82
Diagnosis: Solving the Alphabet Soup Subtype Diagnosis AAV can be challenging to diagnose because it affects multiple systems throughout the body. A thorough physical evaluation and several different types of tests are required to make a diagnosis. While testing may vary depending on the patient and symptoms, it usually includes blood tests, urinalysis, and imaging. A biopsy (a small sample of tissue taken from the affected area to examine in the lab) is also generally required for making a definitive diagnosis, although not always.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c121f2a-e4e8-400f-bf7c-56aee788450ce60dc2a1-f33c-4a05-9b50-8e3e8e597629acd9215f-da8b-4dce-b37d-ef09e5098bcb “While biopsy can be a valuable tool in confirming the diagnosis of ANCA-associated vasculitis, it is not always a required step,” 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. “When a patient presents with typical clinical features and laboratory findings that support the diagnosis, clinicians may proceed without performing a biopsy. But it remains crucial to rule out other conditions that can mimic ANCA-associated vasculitis, such as infections, before finalizing the diagnosis,” he says. Your doctor may include the following tests to make a diagnosis:e60dc2a1-f33c-4a05-9b50-8e3e8e5976292c121f2a-e4e8-400f-bf7c-56aee788450ce60dc2a1-f33c-4a05-9b50-8e3e8e597629fdaab8ec-5c09-4059-aba6-96f5eb3f33f8 Initial Assessment Your doctor will take a full medical history and ask about your symptoms, other health conditions, and any medications you are currently taking, since AAV can be drug induced.e60dc2a1-f33c-4a05-9b50-8e3e8e59762950383744-6314-47a1-b52f-70ed6cf979dd A physical examination will also be done to look for any signs of vasculitis, such as joint pain, muscle aches, or skin rashes. Blood Tests Various blood tests are used to make a diagnosis. One test looks for the presence of ANCAs in your blood. “Each subtype can have associations with different ANCA antibodies,” says Dr. Dua. Other blood tests evaluate levels of inflammation in the body. Urinalysis A urinalysis is a simple way to assess whether vasculitis has affected the kidneys. It tests for the presence of protein, red blood cells, or clumps of red blood cells in the urine, which are indicators of inflammation in the kidneys. Biopsy When symptoms and tests suggest AAV, a biopsy is usually done to help confirm the diagnosis. A tissue sample will be taken from the part of the body that is being affected, such as the skin, kidneys, lungs, or nerves. The sample is then viewed under a microscope, where it is examined by a pathologist for signs of disease or other changes in the cells. Imaging The use of imaging devices including X-ray , ultrasound , MRI (magnetic resonance imaging) , and CT (computed tomography) scans can be helpful for diagnosis. For example, a CT scan can reveal detailed images of internal organs and is frequently used for suspected involvement in the abdomen. An MRI, which uses magnetic waves and computers to create two- or three-dimensional images, can help view the walls of blood vessels. In vasculitis, blood vessel walls may become thicker, which can reduce blood flow and cause damage to tissues.
How Your Subtype Dictates Treatment Treatments AAV treatment is focused on preventing organ damage, managing inflammation, and suppressing parts of the immune system. The goal is to put the vasculitis into remission (where there are no more signs and symptoms), and then to maintain remission.e60dc2a1-f33c-4a05-9b50-8e3e8e5976290c20c263-5490-4c1f-9fa1-5e1ae2638a3e The choice of treatment depends on the AAV subtype, the severity of your symptoms, and the type of ANCA found on blood tests. There are two main types of ANCA, and you may have one, none, or both:e60dc2a1-f33c-4a05-9b50-8e3e8e5976299992ae1f-0b85-4b0e-ad2a-01f387bcb11b 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 Dr. Warrington. “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 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.” The most commonly prescribed medications, used across subtypes, include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976290c20c263-5490-4c1f-9fa1-5e1ae2638a3ee60dc2a1-f33c-4a05-9b50-8e3e8e5976290f2527e0-b528-4adc-9474-1c6644457a75 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.e60dc2a1-f33c-4a05-9b50-8e3e8e59762973b922f0-fc22-4201-827b-de9fb3d10af0 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.e60dc2a1-f33c-4a05-9b50-8e3e8e59762908aecfdb-46c6-45de-8831-092477bc7acc Treatment of GPA and MPA In severe GPA and MPA, high doses of steroids are used in addition to immunosuppression with rituximab or cyclophosphamide as first-line. Additional therapy with avacopan, a relatively new immunosuppressant drug, may also be considered.e60dc2a1-f33c-4a05-9b50-8e3e8e59762984c4e2b9-f45e-4d26-8e4e-cb4beb302b60 “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.” Both mepolizumab and benralizumab received approval from the U.S. Food and Drug Administration (FDA) specifically for EGPA to target eosinophils. These agents are not used for standard GPA/MPA treatment.e60dc2a1-f33c-4a05-9b50-8e3e8e597629fd74e766-2a64-41af-9510-0d4a28a716b5e60dc2a1-f33c-4a05-9b50-8e3e8e5976298bdc8403-9d6c-44bd-98f6-642913106fb0 “As we continue to use these types of medications and study them further, I believe we will continue to find more roles for them to help control multiple aspects of active EGPA,” says Dua. For severe cases of EGPA, treatment still includes corticosteroids combined with cyclophosphamide or rituximab.e60dc2a1-f33c-4a05-9b50-8e3e8e5976290a75daf1-83c7-4dab-94cf-08a81037d6a0
The Takeaway 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.
Resources We Trust Cleveland Clinic: ANCA-Associated VasculitisMayo Clinic: VasculitisJohns Hopkins Vasculitis Center: What Is Vasculitis?Vasculitis UK: What Is ANCA?National Organization for Rare Disorders: Eosinophilic Granulomatosis With Polyangiitis