Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare immune system disorder that causes inflammation in blood vessels and tissues, particularly affecting people who have asthma or allergies. This condition, once known as Churg-Strauss syndrome, can impact many parts of the body and develops gradually over time, often starting with respiratory symptoms before progressing to more widespread complications.
Understanding Eosinophilic Granulomatosis with Polyangiitis
Eosinophilic granulomatosis with polyangiitis is a condition where the body’s immune system becomes overactive and begins attacking its own blood vessels and tissues. The long name describes three key features of the disease. Eosinophilic refers to an unusually high number of eosinophils, which are white blood cells that normally help fight infections and play a role in allergic reactions. In people with EGPA, eosinophil levels often double the normal amount. Granulomatosis describes the formation of granulomas, which are small clusters of immune cells that develop when tissues become inflamed. These granulomas are meant to help wall off infections or threats, but in EGPA they form inappropriately. Polyangiitis means inflammation affecting many small to medium-sized blood vessels throughout the body, rather than just a few large ones.[1]
This disease belongs to a group of conditions called vasculitides, which are disorders characterized by inflammation of blood vessels. When blood vessels become inflamed over a long period, their walls can weaken, potentially leading to an aneurysm (where the vessel stretches and bulges) or internal bleeding if the vessel breaks. Inflammation also causes swelling and scarring that can narrow blood vessels, restricting or stopping blood flow to tissues and organs. Because small blood vessels travel throughout the entire body, EGPA can cause symptoms in multiple organ systems, though it most commonly affects the respiratory system, including the lungs and sinuses.[1]
The disease was first described in 1951 by doctors Jacob Churg and Lotte Strauss, who examined autopsy findings from thirteen patients who all showed a similar pattern of severe asthma, fever, high numbers of eosinophils in the blood, and evidence of blood vessel inflammation affecting various organ systems. At that time, they called the condition “allergic granulomatosis.” The name was later changed to remove the doctors’ names from the diagnosis, following a trend in medicine to use more descriptive terminology.[3][15]
How Common Is EGPA and Who Gets It?
Eosinophilic granulomatosis with polyangiitis is extremely rare. The disease affects between half a person and just over four people per million individuals each year worldwide. The total number of people living with the condition at any given time ranges from ten to fourteen cases per million people globally. In the United States, this means there are roughly five thousand people with EGPA, though the actual number may be higher because some cases go undiagnosed or are not properly reported. One reason for underdiagnosis is that symptoms may be masked when patients receive corticosteroid treatment for what doctors believe is just severe asthma, without recognizing the underlying vasculitis.[5][9]
The disease affects men and women in approximately equal numbers. While EGPA can occur at any age, most people are diagnosed in middle age, with the average age at diagnosis being around fifty years old. Some sources indicate that the typical patient is between thirty-five and fifty years old when diagnosed. Cases in children are extremely rare. EGPA is almost never seen in two members of the same family, suggesting that while genetics may play a small role, the disease is not strongly inherited.[5][7][9][15][18]
What Causes Eosinophilic Granulomatosis with Polyangiitis?
The exact cause of EGPA remains unknown, but researchers believe it probably results from a combination of factors rather than a single trigger. The disease appears to involve an interaction between a person’s genetic makeup, environmental exposures, and an overactive immune system. Because all patients with EGPA have high levels of eosinophils at some point during their disease, scientists think there may be some problem with how the body produces, develops, or controls these white blood cells.[5][18]
Many patients with EGPA have certain antibodies in their blood called anti-neutrophil cytoplasmic antibodies, or ANCA for short. These antibodies are present in about thirty to forty percent of EGPA patients. While their exact role is unclear, it is thought that when ANCA binds to the walls of blood vessels, this contributes to inflammation and injury of the vessels, as well as attracting more inflammatory cells to the area. Interestingly, EGPA is classified as an ANCA-associated vasculitis even though ANCA is positive in less than half of cases, which can make diagnosis challenging.[3][5]
Environmental factors may play a role in who develops EGPA. Exposure to certain substances such as industrial solvents has been suggested as a possible risk factor, though this remains largely speculative and unproven. Some researchers have also theorized that infections might trigger the disease in susceptible individuals, but to date there is no definitive evidence supporting this idea. Drug sensitivities to certain medications, including penicillin, penicillamine, iodides, leukotriene modifiers, or mesalazine, have been identified as potential risk factors, as has environmental exposure to inhaled allergens such as silica dust.[7][18]
Risk Factors for Developing EGPA
The strongest and most consistent risk factor for developing eosinophilic granulomatosis with polyangiitis is having a history of asthma or severe allergies. Almost all patients with EGPA have asthma, and the typical patient is someone who has developed new asthma or has experienced worsening of existing asthma in adulthood. This respiratory component is so fundamental to the disease that asthma is considered one of the cardinal features of EGPA and helps distinguish it from other types of vasculitis.[7][15]
Other risk factors include having allergic rhinitis (an allergic condition affecting the nose) or nasal polyps, which are noncancerous growths inside the nose. People with a history of chronic or recurring sinus infections are also at increased risk. Essentially, EGPA develops in the context of pre-existing airway inflammation and allergic conditions, suggesting that chronic activation of the immune system in response to allergens may set the stage for the disease to develop.[7]
Symptoms of Eosinophilic Granulomatosis with Polyangiitis
EGPA develops gradually, and symptoms tend to appear in phases that can unfold over several years. Not everyone experiences all three phases, and some people may progress through the stages in a different order. The symptoms a person experiences can vary greatly depending on which organs are affected and how severe the inflammation is. Some people have relatively mild symptoms, while others develop serious or even life-threatening complications.[1][4][8]
Phase 1: Allergic or Prodromal Stage
The first stage of EGPA often lasts for several years and is characterized by respiratory symptoms. This phase is called the allergic or prodromal phase because it sets the stage for later disease development. The hallmark symptom during this phase is asthma, which may be new-onset (meaning it appears for the first time in adulthood) or represents a worsening of pre-existing asthma. People typically experience coughing, wheezing, and shortness of breath.[1][4]
Other common symptoms during the first phase include chronic hay fever with sneezing, nasal itching, and nasal congestion. Many people develop chronic sinusitis, which is inflammation of the sinuses that causes pressure and discomfort in the face. Nasal polyps, which are soft, painless growths on the lining of the nasal passages or sinuses, are also common. Some people experience more general symptoms such as joint pain, muscle pain, fever, a general feeling of being unwell (called malaise), and fatigue.[1][4]
Phase 2: Eosinophilic Stage
In the second stage, the body produces too many eosinophils, and these white blood cells begin to build up in tissues and organs, causing damage. This is when blood tests would show markedly elevated eosinophil counts. During this phase, eosinophils can infiltrate the lungs, causing symptoms such as chest pain and difficulty breathing. The eosinophils may also affect the digestive system, leading to stomach pain, nausea, vomiting, diarrhea, or gastrointestinal bleeding.[1][4]
Other symptoms that may appear during the eosinophilic stage include heart palpitations (a feeling that the heart is racing or pounding) and skin problems such as rashes or lesions. People may continue to experience the respiratory symptoms that began in the first phase, and these may worsen. Rapid and unintentional weight loss is common during this stage, as are ongoing fever and fatigue.[7]
Phase 3: Vasculitic Stage
The third and final stage of EGPA is characterized by vasculitis, the inflammation of blood vessels throughout the body. This stage can be the most serious because the inflammation reduces blood flow to various organs and tissues, potentially causing permanent damage. Symptoms during this phase depend on which organs are affected by the vasculitis.[4][8]
One of the most devastating complications during the vasculitic stage is nerve involvement, called mononeuritis multiplex. This condition causes inflammation of peripheral nerves and leads to severe tingling, numbness, shooting pains, and significant muscle wasting or loss of strength in the hands or feet. The skin may develop various rashes, including purpura (small red or purple spots caused by bleeding under the skin), skin nodules (bumps that may appear above or below the skin surface, often at pressure points like the elbows), or recurrent hives.[7][15][18]
The heart can be affected during the vasculitic phase, with inflammation potentially leading to congestive heart failure or heart attack. The kidneys may develop glomerulonephritis, which is inflammation of the small filtering units in the kidneys, possibly leading to high blood pressure and kidney damage. The lungs may show infiltrates (areas where eosinophils have accumulated), and occasionally people experience bleeding into the lungs. The gastrointestinal tract can be affected by vasculitic lesions, and the spleen may develop granulomas. Inflammation of veins (phlebitis) or pulmonary embolism (blood clots in the lungs) can also occur.[7][15][18]
Prevention Strategies
Because the exact cause of eosinophilic granulomatosis with polyangiitis is unknown, there are no proven strategies to prevent the disease from developing in the first place. However, for people who already have asthma or severe allergies, which are the main risk factors, proper management of these conditions is important. Following prescribed treatment plans for asthma and allergies, avoiding known triggers, and maintaining regular contact with healthcare providers can help keep respiratory inflammation under control.[1]
For people who have been diagnosed with EGPA, prevention focuses on preventing disease flares and complications. This includes taking medications exactly as prescribed, even when feeling well, since stopping treatment prematurely can lead to relapse. Regular monitoring by healthcare providers allows for early detection of disease activity and adjustment of treatment before serious complications develop. Managing overall health through adequate sleep, stress reduction, and avoiding infections when possible may also help support immune system balance.[1]
How EGPA Changes Normal Body Function
Understanding the pathophysiology of EGPA means looking at how the disease changes the normal way the body works. In healthy people, eosinophils make up only about five percent or less of the total white blood cell count. These cells normally help defend against parasitic infections and play a role in allergic reactions. When activated, eosinophils release substances that are toxic to parasites, but these same substances can damage the body’s own tissues when released inappropriately or in excessive amounts.[15][18][20]
In EGPA, the percentage of eosinophils in the blood can reach as high as sixty percent of all white blood cells, far exceeding the normal range. This extreme elevation, called hypereosinophilia, leads to eosinophils infiltrating tissues throughout the body. When large numbers of eosinophils accumulate in organs like the lungs, digestive tract, heart, or nerves, they release their toxic contents, causing tissue damage and inflammation. This eosinophil-mediated damage is one of the two main ways EGPA harms the body.[15][18]
The second major mechanism of damage is the vasculitis itself. The walls of small and medium-sized blood vessels become chronically inflamed, which weakens them structurally and causes them to function abnormally. Inflammation triggers swelling of the vessel walls, which narrows the space through which blood can flow. Over time, inflammation also leads to scarring and further narrowing. When blood flow to an organ or tissue is reduced or blocked completely, that area cannot receive the oxygen and nutrients it needs, leading to tissue damage or death. This is why people with EGPA can develop problems in so many different organ systems—wherever the affected blood vessels are located, the downstream tissues suffer.[1]
The presence of granulomas is another pathological feature of EGPA. Granulomas are organized collections of immune cells that form when the immune system is trying to wall off something it perceives as a threat. In EGPA, these granulomas are rich in eosinophils and can be found in various tissues, particularly in the respiratory system. While granulomas are meant to be protective, in EGPA they contribute to tissue damage and organ dysfunction.[1][9]
The immune system dysfunction in EGPA appears to involve both the innate immune system (the body’s first line of defense) and the adaptive immune system (which involves antibodies and specialized immune cells). The production of ANCA antibodies in some patients suggests that the adaptive immune system has mistakenly begun targeting the body’s own cells, specifically neutrophils (another type of white blood cell). When ANCA binds to neutrophils in blood vessel walls, it triggers an inflammatory cascade that damages the vessels. This autoimmune component adds another layer to the disease process.[3][5]
The fact that EGPA typically develops in people with pre-existing allergic conditions suggests that chronic activation of the immune system in response to allergens may somehow lead to this more serious vasculitic disease. The progression from allergies to asthma to vasculitis implies a gradual escalation of immune dysfunction, though the exact mechanisms that drive this progression remain under investigation.[9]
