Knowledge on rare diseases and orphan drugs

The prevalence ranges from 1/70,000-100,000 in Europe.

Onset of eosinophilic granulomatosis with polyangiitis (EGPA) usually occurs in adulthood but may occur anywhere between 15 and 70 years of age. EGPA may involve multiple organ systems. The onset of EGPA is often associated, in patients with preexisting asthma, with worsening of the asthma. Eosinophilic asthma and angiitis are the two hallmarks of the disease. EGPA has been divided into three distinct phases, which may or may not be sequential. The prodromal phase is characterized by asthma with or without allergic rhinitis. The second phase is marked by peripheral blood eosinophilia and eosinophilic tissue infiltration producing a picture similar to those of simple pulmonary eosinophilia (Loeffler syndrome), chronic eosinophilic pneumonia, or eosinophilic gastroenteritis. The third phase, i.e. vasculitic phase, usually develops within 3 years of onset and may involve any of the following organs: heart (myocarditis, pericarditis, failure), peripheral nervous system (mononeuritis multiplex in 78% of patients), paranasal sinuses, muscles, skin and less frequently kidney. Skin involvement (nodules, utricarial rash) occurs in two thirds of patients. Fever, flu-like symptoms, and weight loss are also observed. Anti-myeloperoxidase (MPO)-anti neutrophil cytoplasmic antibodies (ANCA) are found in 30 to 40% of patients and identify patients with a different clinical phenotype (e.g a higher prevalence of renal disease).

Etiology of EGPA is unknown.

Classification criteria of EGPA include, in the presence of evidence of vasculitis, four of the following six features: asthma, eosinophilia, neuropathy, pulmonary infiltrates, paranasal sinus abnormalities and eosinophilic vasculitis. Eosinophilia above 10% is the hallmark laboratory finding in patients with EGPA and may be as high as 75% of the peripheral blood cell count. Findings in chest X-ray (infiltrates, pneumonitis) are extremely common in EGPA. Tissue biopsies show eosinophilia, necrotizing vasculitis of small to medium vessels and, sometimes, small necrotizing granulomatous inflammation.

Differential diagnoses of EGPA include granulomatosis with polyangiitis, hypereosinophilic syndrome, microscopic polyangiitis, polyarteritis nodosa, drug reactions, bronchocentric granulomatosis, fungal and parasitic infections, and malignancy.

The treatment of patients with mild disease involves glucocorticoids (GC) monotherapy. Other immunosuppressive regimens, such as those using cyclophosphamide (CP), azathioprine or methotrexate, are used for patients with an aggressive disease. Other treatments, including rituximab or interferon-alpha, has been used in patients refractory to GC plus CP. Treatment with the anti-interleukin-5 antibody mepolizumab now represents a very effective treatment of GC-dependent eosinophilic asthma; however, its efficacy to treat vasculitis manifestations remains to be evaluated.

Cardiac involvement used to be the leading cause of death related to EGPA, followed by cerebral hemorrhage and stroke. GC-related toxicity is also a frequent cause of morbidity and mortality. Despite treatment, neurological sequelae rarely resolve completely.

Last update: October 2020 - Expert reviewer(s): Pr Xavier PUECHAL - Pr Benjamin TERRIER