Eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis

Other Names: CSS; Allergic granulomatous and angiitis; Allergic angiitis and granulomatosis; Allergic granulomatosis; Churg-Strauss vasculitis; Granulomatous allergic angiitis; Churg-Strauss syndrome; EGPA

Eosinophilic granulomatosis with polyangiitis (EGPA), also called Churg Strauss syndrome, is a rare, chronic disorder and a form of primary systemic autoimmune vasculitis characterized by inflammation of blood vessels. In EGPA, vasculitis is associated with asthma and eosinophilia. EGPA is also known as Churg-Strauss syndrome (CSS), and affected individuals may have perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) directed against myeloperoxidase (MPO). These autoantibodies are more common in patients with more vasculitic manifestations, such as glomerulonephritis. EGPA affects about 5,000 people in the United States.

This disease was first described in 1951 by Drs. Jacob Churg and Lotte Strauss as a condition consisting of “asthma, eosinophilia [an excessive number of eosinophils in the blood], fever, and accompanying vasculitis of various organ systems.” EGPA shares many of the clinical and pathological features of polyarteritis nodosa (“PAN”, another type of vasculitis) and granulomatosis with polyangiitis (GPA). However, Drs. Churg and Strauss found that the presence of granulomas as well as the abundance of eosinophils distinguished this disease from PAN and GPA.

Although the cause of EGPA is unknown, an allergic mechanism, with tissue directly injured by eosinophils and neutrophil degranulation products, may be involved. Activation of T lymphocytes seems to help maintain eosinophilic inflammation. The syndrome occurs in patients who have adult-onset asthma, allergic rhinitis, nasal polyposis, or a combination. Antineutrophil cytoplasmic autoantibodies (ANCA) are present in about 40% of cases.

EGPA has 3 phases, which may overlap:

  1. Alergic: This phase may persist for years. Patients have allergic rhinitis, nasal polyposis, asthma, or a combination.
  2. Eosinophilic: Peripheral blood and tissue eosinophilia is typical. Clinical presentation, which may resemble Löffler syndrome, includes chronic eosinophilic pneumonia and eosinophilic gastroenteritis.
  3. Vasculitic: Potentially life-threatening vasculitis develops in this third phase. Systemic symptoms (eg, fever, malaise, weight loss, fatigue) are common.

These phases do not necessarily follow one another consecutively, and the time interval between them varies greatly.

Another important aspect of EGPA which leads to challenges in properly diagnosing the disease is that various organs and systems may be affected. This leads to multiple specialties coming into contact with the disorder before a proper diagnosis is made. Patient’s symptoms depend on which parts of the body are being affected:

  • Respiratory: Asthma, often with onset during adulthood, occurs in most patients and tends to be severe and corticosteroid-dependent. Sinusitis is common, but not destructive, without severe necrotizing inflammation. Patients may be short of breath.
  • Musculoskeletal: Arthralgias, myalgias, or even arthritis can occur, usually during the vasculitic phase.
  • Renal: The kidneys are affected less often than in other vasculitic disorders associated with ANCA. Typically, pauci-immune (few if any immune complexes), focal segmental necrotizing glomerulonephritis with crescent formation is present; eosinophilic or granulomatous inflammation of the kidneys is rare.
  • GI: Up to one third of patients present with GI symptoms (eg, abdominal pain, diarrhea, bleeding, acalculous cholecystitis) due to eosinophilic gastroenteritis or mesenteric ischemia due to vasculitis.
  • Neurologic: Neurologic manifestations are very common. Multiple mononeuropathy (mononeuritis multiplex) occurs in up to three fourths of patients. CNS involvement is rare but can include hemiparesis, confusion, seizures, and coma, with or without cranial nerve palsies or evidence of cerebral infarction.
  • Cutaneous: The skin is affected in about one half of patients. Nodules and papules appear on extensor surfaces of extremities. They are caused by extravascular palisading granulomatous lesions with central necrosis. Purpura or erythematous papules, due to leukocytoclastic vasculitis with or without prominent eosinophilic infiltration, may develop.
  • Cardiac: Cardiac involvement, a major cause of mortality, includes heart failure due to myocarditis and endomyocardial fibrosis, coronary artery vasculitis (possibly with MI), valvular disorders, and pericarditis. The predominant histopathologic finding is eosinophilic myocarditis.

The symptoms of EGPA differ from person to person, depending on its severity and which organs are affected. The majority of patients have asthma, nasal polyps and/or blood eosinophilia. Other symptoms include:

  • Fever
  • Fatigue
  • Rapid and unintentional weight loss
  • Muscle and joint pain
  • Skin rash, such as purpura (punctuated red lesions) skin nodules or recurrent hives
  • Numbness, tingling or sudden loss of strength in the hands or feet
  • Chest pain, palpitations or arrhythmias (irregular heartbeat)
  • Shortness of breathor coughing
  • Phlebitis (vein inflammation) or pulmonary embolism
  • Abdominal pain
  • Gastrointestinal bleeding

The current treatment of EGPA is systemic corticosteroids. However, corticosteroids alone often do not maintain remission, even if there are no poor prognostic factors. Other immunosuppressants (eg, cyclophosphamide, methotrexate, azathioprine) may be added, depending on the severity and the type of organ involvement, using the same general criteria for treatment of granulomatosis with polyangiitis or microscopic polyangiitis.

Most individuals with EGPA are first treated with corticosteroids, such as prednisone. Some of these patients are able to achieve remission, but some may experience relapses and require additional medicines to treat their EGPA.

In December of 2017, The U.S. Food and Drug Administration expanded the approved use of mepolizumab to treat adult patients with EGPA. This new indication provides the first FDA-approved therapy specifically to treat EGPA. Before this FDA approval, patients with EGPA did not have an FDA-approved treatment option. According to the FDA press release announcing mepolizumab’s approval (December 11, 2017), “The expanded indication of Nucala meets a critical, unmet need for EGPA patients. It’s notable that patients taking Nucala in clinical trials reported a significant improvement in their symptoms.”

No cure for Churg-Strauss syndrome exists. But certain medications may help manage your symptoms. Medications used to treat Churg-Strauss syndrome include:

  • Prednisone is the most commonly prescribed drug for Churg-Strauss syndrome. Your doctor may prescribe a high dose of corticosteroids or a boost in your current dose of corticosteroids to get your symptoms under control as soon as possible.

But because high doses of corticosteroids can cause serious side effects, your doctor will decrease the dose gradually until you’re taking the smallest amount that will keep your disease under control. Even lower doses taken for extended periods can cause side effects.

Side effects of corticosteroids include bone loss, high blood sugar, weight gain, cataracts and hard-to-treat infections.

  • Other immunosuppressive drugs. For people with mild symptoms, a corticosteroid alone may be enough. Other people may require another immunosuppressive drug, such as cyclophosphamide, azathioprine (Azasan, Imuran) or methotrexate (Trexall), to reduce the body’s immune reaction still further.

Because these drugs impair your body’s ability to fight off infection and can cause other serious side effects, your condition will be closely monitored while you’re taking them.

  • Immune globulin. Given as a monthly infusion, immune globulin is generally given to people who haven’t responded to other treatments. The most common side effects are flu-like symptoms that usually last just a day or so. Immune globulin has two major drawbacks: It’s very expensive, and it doesn’t work for everyone.
  • Biologic medications. Drugs such as rituximab (Rituxan) that alter the immune system’s response seem to improve symptoms and decrease the number of eosinophils.

These medications have only been studied in small trials, and their long-term safety and efficacy is still unknown. They may be suggested for those who haven’t responded to other treatments.