Our patient presented with asthma, paranasal sinus abnormalities, hypereosinophilia, and extravascular eosinophils, and therefore met four of six criteria needed for the diagnosis of Churg-Strauss syndrome [
2]. Of interest, she did not present with any neuropathy or pulmonary infiltrates, which are the two other criteria used to classify EGPA and are some of the more common manifestations of this disease [
2,
3]. Instead, she exhibited left periorbital swelling, probably representing a so-called orbital inflammatory pseudotumor formed by a localized mixed inflammatory cell infiltrate which, in our case, would be expected to also include numerous tissue eosinophils [
4]. Very few cases of orbital inflammatory pseudotumors associated with EGPA have ever been described and may only present in less than 1% of all patients with the disease [
4‐
6]. In addition, her cardiac tamponade was another unusual clinical presentation, reported in only ten other cases of EGPA [
3,
7,
8]. Three of those studies were also able to confirm eosinophilic infiltration in the pericardium with biopsy, as we have demonstrated (Fig.
1e) [
8]. Since the cause of EGPA is unknown and is difficult to study due to low disease prevalence (less than 1.4 per 100,000 adults), unusual case presentations like ours are an important step in helping to elucidate how different clinical phenotypes correlate with disease pathophysiology [
3].
One hypothesis for why our patient had such an uncommon clinical presentation of her disease was because she lacked ANCA. Of interest, while EGPA is considered an ANCA-associated systemic vasculitis, only ~ 40 to 60% of patients with EGPA are ANCA-positive, as compared to up to 95% of patients with other small vessel vasculitides [
3,
7,
9]. This is why the presence of ANCA is not a requirement for EGPA diagnosis. One study which stratified the clinical symptoms of patients with EGPA according to their ANCA status showed that ANCA-negative patients with EGPA are more likely to have fever and cardiac anomalies (more likely pericarditis and cardiomyopathy, less likely tamponade), whereas ANCA-positive patients more often had peripheral neuropathy, vasculitis, and renal involvement [
7]. These findings have led several groups to hypothesize that the pathophysiology of ANCA-positive and ANCA-negative EGPA may be different. To generalize, it has been observed that ANCA-positive EGPA may have a more “vasculitic” phenotype, characterized by small vessel vasculitis, whereas ANCA-negative EGPA could be considered a more “eosinophilic” phenotype in which eosinophilic infiltration causes significant organ damage [
7,
10]. This hypothesis will need further modeling and testing, but our unusual case would certainly lend support to this theory.