Why Are Eosinophils Important in Churg-Strauss Syndrome?

Eosinophils play a central role in the pathogenesis of Churg-Strauss Syndrome (CSS), now known as Eosinophilic Granulomatosis with Polyangiitis (EGPA). Understanding how these cells contribute to the development and progression of CSS is key to diagnosing and managing the disease effectively. Eosinophils, a type of white blood cell, are typically involved in the body's response to allergens and infections, particularly parasitic infections. However, in Churg-Strauss Syndrome, eosinophils become overactive, leading to inflammation and damage in various tissues and organs.

What Are Eosinophils?

Eosinophils are one of the several types of white blood cells that make up the immune system. While they represent a small percentage of the total white blood cells in circulation, they perform specific functions that are crucial in protecting the body from harm, particularly in defense against parasitic infections and involvement in allergic reactions.

• Normal Function: Under normal circumstances, eosinophils help control immune responses by releasing proteins that can attack pathogens. They are primarily found in tissues like the skin, lungs, and gastrointestinal tract, where they guard against allergens and parasitic threats. When the body encounters an allergen or parasite, eosinophils respond by releasing cytotoxic proteins and enzymes that help neutralize the threat.

• Eosinophilia: In certain conditions, including CSS, the number of eosinophils can increase significantly, a state known as eosinophilia. When eosinophils become overactive, instead of targeting foreign invaders, they attack the body's own tissues, leading to inflammation, tissue damage, and ultimately, the symptoms associated with CSS.

Eosinophils and the Three Phases of Churg-Strauss Syndrome

Churg-Strauss Syndrome is typically divided into three stages or phases, each of which is closely associated with the activity of eosinophils in the body. The phases do not always occur in a specific order, and not all patients experience all three phases.

1. Prodromal Phase:

   • The initial phase, known as the prodromal phase, is marked by the onset of allergic symptoms such as asthma, rhinitis, and sinusitis. Eosinophils are involved in this phase through their role in allergic reactions, especially in the lungs and nasal passages. Asthma, in particular, is common in patients with CSS, and eosinophils contribute to the airway inflammation that makes breathing difficult.

2. Eosinophilic Phase:

   • The second phase is characterized by eosinophilia, where the number of eosinophils in the blood rises abnormally high. Eosinophils start to infiltrate various tissues and organs, such as the lungs, gastrointestinal tract, and skin. This can result in pulmonary infiltrates, abdominal pain, and rashes. During this phase, tissue damage occurs as eosinophils release toxic granules, which are intended to destroy parasites but end up causing harm to the body's own tissues instead.

3. Vasculitic Phase:

   • In the final phase, vasculitis, or inflammation of the blood vessels, develops as eosinophils and other immune cells attack the vascular system. This can affect small- to medium-sized arteries and veins, leading to reduced blood flow to organs and tissue damage. Organ systems most commonly affected during this phase include the heart, lungs, kidneys, and nervous system.

Eosinophil-Induced Damage in Churg-Strauss Syndrome

The excessive accumulation of eosinophils in CSS is not just a marker of the disease—it is directly responsible for many of the symptoms and complications experienced by patients. Understanding how eosinophils contribute to the damage helps explain the severity of the condition.

• Pulmonary Involvement:

  • The lungs are one of the most commonly affected organs in CSS. Eosinophils contribute to lung inflammation and can lead to eosinophilic pneumonia, which is characterized by cough, wheezing, and shortness of breath. The accumulation of eosinophils in lung tissue can also cause pulmonary infiltrates visible on imaging, a common feature in patients with CSS.

• Gastrointestinal Tract:

  • Eosinophils can infiltrate the gastrointestinal tract, causing abdominal pain, diarrhea, nausea, and vomiting. In severe cases, eosinophils may cause ulcers or perforations in the gastrointestinal tract due to the release of toxic proteins.

• Cardiac Involvement:

  • Heart involvement is one of the most serious complications of CSS, and it is often linked to eosinophilic infiltration. When eosinophils invade the heart muscle, they can cause myocarditis, pericarditis, or heart failure. Cardiac complications are a leading cause of mortality in patients with Churg-Strauss Syndrome.

• Neurological Symptoms:

  • Peripheral neuropathy is common in CSS and is often a result of eosinophil-induced vasculitis. This inflammation of the blood vessels that supply the nerves can lead to numbness, tingling, pain, or even paralysis in affected areas.

Diagnostic Role of Eosinophils in Churg-Strauss Syndrome

The presence of elevated eosinophil levels in the blood is one of the key diagnostic markers for Churg-Strauss Syndrome. A complete blood count (CBC) test often reveals eosinophilia, and physicians use this information alongside clinical features to diagnose CSS. Eosinophil counts exceeding 1,500 cells per microliter of blood are a red flag, prompting further investigations such as imaging or biopsies.

1. Eosinophil Count:

   • A high eosinophil count, or eosinophilia, is typically one of the first signs that suggests the presence of Churg-Strauss Syndrome. Regular monitoring of eosinophil levels helps assess disease activity and the effectiveness of treatment.

2. Tissue Biopsy:

   • In addition to blood tests, tissue biopsies can reveal eosinophilic infiltration in organs such as the lungs, skin, or nerves. These biopsies confirm the presence of eosinophils and help determine the extent of organ damage.

3. Imaging:

   • Imaging studies like chest X-rays or CT scans may show pulmonary infiltrates or cardiac involvement associated with eosinophilic inflammation. In some cases, a bronchoscopy with a lung biopsy may be needed to identify eosinophils in lung tissue.

The Role of Eosinophil Targeted Therapies

Given the critical role that eosinophils play in Churg-Strauss Syndrome, targeted therapies have been developed to reduce the activity of eosinophils and manage the disease more effectively.

• Corticosteroids:

  • Corticosteroids like prednisone are the cornerstone of treatment for CSS, as they effectively reduce inflammation by suppressing the immune system, including the activity of eosinophils. For many patients, corticosteroids can bring about rapid symptom relief, especially during flare-ups.

• Biologic Therapies:

  • More recently, biologic therapies have emerged as a promising treatment option for CSS. These drugs specifically target the immune mechanisms responsible for the overproduction and activation of eosinophils. One such biologic, mepolizumab, targets interleukin-5 (IL-5), a cytokine responsible for the growth and activation of eosinophils. By inhibiting IL-5, mepolizumab helps reduce eosinophil levels in the blood and tissues, resulting in less inflammation and tissue damage.

  • Other biologics targeting eosinophil-associated cytokines or immune pathways are currently under investigation and may offer additional options for patients who do not respond well to corticosteroids or traditional immunosuppressive therapies.

Monitoring Eosinophil Levels in Treatment

For patients with Churg-Strauss Syndrome, monitoring eosinophil levels is an essential part of disease management. Regular blood tests to assess eosinophil counts help healthcare providers track disease activity and adjust treatment as needed.

• Response to Treatment: As eosinophil levels decline with effective treatment, patients typically experience an improvement in symptoms. If eosinophil levels remain elevated despite treatment, this may indicate a need for stronger immunosuppressive therapy or the addition of biologics.

• Predicting Flare-Ups: Rising eosinophil counts can signal an impending flare-up of the disease. In such cases, physicians may preemptively increase corticosteroid doses or adjust other treatments to prevent the worsening of symptoms.