The Complexities of Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Introduction

EGPA is a condition in which the inflammation of certain blood cells and tissues can be observed. The inflammation may lead to organ damage, including heart and kidney damage. EGPA is considered eosinophil-rich and granulomatous inflammation, causing necrotizing vasculitis, especially in medium—to small-sized vessels. This condition was previously known as Churg-Strauss syndrome (CSS).

What Is EGPA?

EGPA is a rare systemic condition that occurs among those with asthma. It causes inflammation of the small blood vessels, leading to vasculitis. It was estimated to affect less than two out of a million people yearly. About half the individuals with EGPA are considered to have a systemic autoimmune disorder involving blood vessels. It is called antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. This condition may be responsible for affecting many organs of the body. It is always linked with asthma and eosinophilia or allergy.

EGPA is associated with increased eosinophils (allergic-type blood cells). Eosinophils are white blood cells that makeup five percent or less of white blood cells. In EGPA, eosinophils are ten percent of the white blood cells. Along with this, most of the biopsies were observed to contain granulomas which are clusters of cells. These may or may not involve blood vessels.

Vasculitis means the inflammation of the blood vessels. When vasculitis occurs, there are certain changes. These include:

• The blood vessels may become weak and stretch, leading to aneurysms (abnormal blood-filled blood vessel enlargement).

• The walls of the blood vessels become thinner, causing rupture. This may cause blood leakage into tissues.

• The blood vessels may become narrowed to the point of closing, and organ damage occurs due to the loss of the supply of nutrients and oxygen to the organs.

The organs that are affected by EGPA include:

• Nose.

• Sinuses.

• Lungs.

• Skin.

• Joints.

• Nerves.

• Intestinal tract.

• Heart.

• Kidneys.

The brain is rarely affected by EGPA. EGPA may happen to anyone from children to the elderly. The average age being affected by EGPA is 35 years and 50 years. It affects males and females equally.

The cause of EGPA is not known. The immune system plays a role in this condition. The immune system generally protects against infections from the outside. In this condition, the immune system becomes overactive and can cause inflammation.

It was estimated that the disease may occur among 10.7 to 14 per million adults worldwide. The disease may begin among those in between the age group of 38 to 54 years. The gender difference was not found in this condition.

What Are the Symptoms of EGPA?

EGPA can affect many organs and hence exhibit more symptoms. These include:

• Affected individuals exhibit weakness, illness, and fever.

• Loss of appetite and weight may be observed.

• Shortness of breath due to asthma can be seen.

• Inflammation of the air sacs and blood vessels of the lungs may be observed.

• Chest pain caused may affect the lungs and heart.

• Rashes on the skin are observed.

• Experience muscle or joint pain.

• Enhanced nasal discharge and facial pain due to sinusitis may occur.

• Abdominal pain or blood in stools due to the involvement of the intestine may be observed.

• Experience abnormal feelings, and numbness or loss of strength and feeling may occur due to nerve involvement.

These symptoms may be observed in combinations. Kidney disease caused due to EGPA may not be observed until the kidneys stop working. Hence if a person has vasculitis, that individual should be checked for urinalysis.

The pathogenesis and clinical phenotypes follow a dichotomy of eosinophilic-mediated damage or ANCA-induced endothelial injury.

The clinical features of the disease follow either eosinophilic tissue infiltration or small and medium vessel vasculitis. The clinical course occurs in three phases. These include:

• Initial Phase: In this phase, nonspecific symptoms like malaise, fever, migrating polyarthralgia (pain in several joints), and weight loss were found to be common. These symptoms accompany severe adult-onset asthma. Upper respiratory symptoms were found to be common with chronic rhinosinusitis and nasal polyps.

• Second Phase: This phase involves eosinophilic infiltration in end organs with peripheral eosinophilia. Patchy peripheral nodular pulmonary infiltrates, eosinophilic gastroenteritis, and serosal effusion were found to be common.

• Third Phase: The onset of vasculitis may be found in this phase. Neurological symptoms are important symptoms of this phase.

What Are the Complexities of Eosinophilic Granulomatosis With Polyangiitis (EGPA)?

Complexities of EGPA involve many organs. These include:

• Respiratory and Pulmonary Manifestations: Including respiratory disease asthma. Asthma precedes vasculitis by three to nine years. It was thought that some of the asthma medications, like leukotriene receptor antagonists and montelukast, may be responsible for the onset of the CSS. Asthma is progressive and becomes steroid-dependent asthma. Even after systemic therapy, the asthma remains uncontrolled and affects the quality of life. Apart from these, pulmonary manifestations are related to parenchymal eosinophilic infiltration and vasculitic process. Alveolar hemorrhage was found to occur among those with ANCA positive.

• Cardiac Disease: Cardiac manifestations can be observed in 62 percent of cases. These are caused due to mediators released from activated eosinophils and vasculitis in the myocardium and coronary arteries. This is responsible for myocarditis and this further causes post-inflammatory fibrosis and restrictive cardiomyopathy (a disorder affecting the heart muscle) leading to congestive cardiac failure. Cardiac changes are related to poor prognosis and high mortality.

• Gastrointestinal Manifestations: These manifestations include abdominal pain, nausea, vomiting, diarrhea, and more severe symptoms like bleeding or intestinal obstruction caused by submucosal nodular masses. Mesenteric vasculitis may lead to ischemic bowel, mucosal ulceration, and perforation needing exploratory laparotomy. Serosal involvement may cause eosinophilic ascites and peritonitis. A few rare manifestations, like necrotizing acalculous cholecystitis, pancreatitis, and eosinophilic liver disease, may also be observed.

• Renal Manifestations: Renal involvement may be observed in 25 percent of cases. Manifestations include necrotizing crescentic glomerulonephritis (extensive glomerular inflammation), focal sclerosing disease (frequently encountered cause of nephrotic syndrome), IgA nephropathy (disease of the kidney and immune system), or eosinophilic interstitial nephritis (allergic type of reaction that occurs due to corticosteroid therapy). Hypertension was observed among 10 to 30 percent of patients with EGPA. This reflects the involvement of the renal system.

• Neurological Manifestations: A wrist or a foot drop may be observed due to mononeuritis multiplex or mixed sensorimotor peripheral neuropathy. Peripheral neuropathy can be observed in 70 to 80 percent of cases. Out of these, 10 to 39 percent of neurological manifestations occur in the form of cerebral infarctions or hemorrhages.

• Other Organs Manifestations: Skin manifestations can be observed in half to one-third of cases. Extravascular granulomas can be observed in the skin, and these are the changes observed with leukocytoclastic vasculitis. Other skin manifestations include nonthrombocytopenic palpable purpura (lesion of cutaneous leukocytoclastic vasculitis), scalp nodules (occurs in response to irritation to the skin), urticarial rashes (raised itchy rash), skin infarcts (focal necrosis due to vasculitis), and livedo reticularis (occurs due to the spasm of blood vessels near the skin surface).

Less common involvement of organs includes central retinal artery and venous occlusion, thromboembolic disease, salivary gland, or vasculitis of breasts.

Conclusion

EGPA is a multisystem disease related to the immune system. Whenever there is poorly controlled asthma for many months and an increased eosinophilic count, this condition may be searched for. EGPA may have many manifestations involving many organ systems of the body. Hence, it is important to know about EGPA and its cause, symptoms, pathogenesis, and complexities. Knowing the condition in detail helps in the early detection of the disease. This leads to effective treatment and helps an affected individual achieve a good quality of life.