D2.156 - Defining the Systemic Boundary Between N-ERD and EGPA: Avoiding Misclassification of Eosinophilic Diseases

Current classification criteria for EGPA, including the ACR 1990 and the ACR/EULAR 2022 criteria, are designed for disease classification rather than diagnosis and require confirmation of vasculitis as a prerequisite. In clinical practice, however, these criteria are frequently applied without sufficient evaluation of vasculitic organ involvement. As a result, nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD), a non-vasculitic eosinophilic airway disease, may fulfill EGPA classification criteria due to shared features such as asthma, eosinophilia, and chronic rhinosinusitis with nasal polyps. This overlap can lead to misclassification and misdiagnosis of N-ERD as EGPA.Despite the clinical importance of this issue, the systemic differences between strictly defined N-ERD and definite EGPA have not been systematically compared.

We retrospectively analyzed patients with N-ERD (n=111) and EGPA (n=95) who visited our institution from 1995 onward and whose clinical manifestations at disease onset could be confirmed. All patients with N-ERD had aspirin hypersensitivity confirmed by a positive aspirin challenge test.Patients with EGPA were limited to definite cases fulfilling both the Lanham criteria and the 1990 ACR classification criteria, ensuring the presence of vasculitic disease. Patients with coexisting N-ERD and EGPA (n=5) were identified and excluded from the analysis to allow a clear comparison between non-vasculitic and vasculitic eosinophilic diseases. The prevalence of respiratory, dermatological, gastrointestinal, neurological, cardiac, renal, and serological manifestations was compared between the two groups using Fisher’s exact test.

Chronic rhinosinusitis with nasal polyps was significantly more prevalent in N-ERD than in EGPA (97.3% vs 78.9%, p<0.001). Notably, patients with N-ERD frequently exhibited systemic manifestations beyond asthma, including eosinophilic pneumonia (25.2%), recurrent abdominal pain (27.9%), non-purpuric skin manifestations (53.2%), and angina-like chest pain (16.2%), partly overlapping with those observed in EGPA. However, hallmark features of vasculitic organ involvement were exclusively observed in EGPA. These included eosinophilic bronchiolitis (36.8%), mononeuritis multiplex (91.6%), cardiac involvement with heart failure or cardiomegaly (28.4%), renal impairment (24.2%), purpura (22.1%), gastrointestinal bleeding (11.6%), and ANCA positivity (28.4%), whereas none of these manifestations were observed in N-ERD (all p<0.001). Among these features, peripheral neuropathy showed the most striking discriminatory value between the two diseases.

Patients with N-ERD may present with systemic symptoms beyond asthma, including eosinophilic pneumonia, abdominal pain, and chest pain, partly overlapping with EGPA. However, N-ERD lacks vasculitic organ involvement such as peripheral neuropathy, cardiac failure, renal impairment, and ANCA positivity. Therefore, in patients with severe eosinophilic airway inflammation without peripheral neuropathy, careful differentiation between N-ERD and EGPA is essential to avoid misdiagnosis based on classification criteria.