EGPA is a rheumatic condition with frequent lung involvement characterized by patchy parenchymal infiltrates. Such presentation may create a diagnostic challenge during the pandemic since similar lesions are frequently observed in COVID-19 pneumonia. Our aim was to call attention to this issue and define clinical features which may be helpful in the differential of these entities. Additionally, we investigated COVID-19 outcomes in EGPA patients.
There is no specific symptom defined for COVID-19 yet [2]. COVID-19 is generally diagnosed with a positive PCR and/or coherent imaging findings in patients with symptoms suggestive of the disease [8]. Sensitivity of thorax CT in diagnosis was reported to be superior to PCR (97.2% vs 83.3%) and imaging findings emerge especially in the diagnosis of PCR negative patients [8, 9]. Most common imaging findings were revealed to be ground-glass opacities (GGO) (83%), GGO with consolidations, pleural thickening, interlobular septal thickening and air bronchograms [10]. However, none of these findings are specific to COVID-19 and frequently observed in other infections, interstitial lung diseases and lung involvements of rheumatic conditions such as EGPA. Accordingly, in a study, among 40 PCR negative subjects with suspected COVID-19 infection who eventually diagnosed with other conditions, a 36-year-old female patient with a history of asthma having multiple GGO with consolidations and crazy-paving pattern in thorax CT was diagnosed with EGPA. EGPA diagnosis was reported to be confirmed with paranasal involvement in CT, arthritis, eosinophilia and elevated Ig E levels [11].
The COVID-19 mimicker group in our study involved 7 patients (6 with new onset EGPA and 1 with EGPA flare). All of the patients were observed to present with respiratory symptoms and COVID-19 was the preliminary diagnosis in all. GGO were present in all cases, however, none of them was PCR positive which was probably the main reason for consideration of other conditions [12,13,14]. Six of these cases had peripheral eosinophilia as a common feature contradictory to the fact that eosinopenia is more common in COVID-19, reaching a rate of 95% in some studies [15,16,17,18]. On the other hand, eosinophilia is a diagnostic criterion in EGPA and may present in 90% of cases [19, 20]. The only patient in our study without eosinophilia already had an EGPA diagnosis and was under steroid treatment which is known to suppress peripheral eosinophilia. Another common feature in our COVID-19 mimicker group was a history of asthma which is again a cardinal feature of EGPA. Other EGPA related findings in our study group were a history of allergic rhinitis and nasal polyps, coronary vasculitis, cutaneous eosinophilic erythema, drop-foot (which may be indicative of peripheral neuropathy) and hematuria (which may be indicative of renal involvement). These findings suggest not to overlook EGPA during the pandemic, particularly PCR negative patients should be evaluated thoroughly for accompanying symptoms.
ANCA positivity is generally useful in distinguishing ANCA-associated vasculitides (AAV) from other conditions with similar features. However, the rate of ANCA positivity is relatively low in EGPA when compared to other AAV and reported to vary from 38 to 60% [21,22,23]. In contrast to the vasculitic phenotype of EGPA with prominent manifestations of small-vessel vasculitis, rate of ANCA positivity is further reduced in the eosinophilic phenotype of EGPA which is characterized by eosinophilic infiltrates in organ systems [24]. Likewise, in our study ANCAs were positive in only one case (MPO-ANCA). Therefore, ANCA negativity may not be reliable in distinguishing COVID-19 from EGPA in suspected patients.
There were four EGPA patients with PCR confirmed COVID-19 in our study [25, 26]. COVID-19 related mortality was not observed in any of the patients. Similarly, COVID-19 Global Rheumatology Alliance physician-reported registry have already reported no significant increase in COVID-19 related mortality among vasculitis patients [27]. Laboratory data was available in two of the cases, neither of them had eosinophilia at the time of COVID-19 but both of them had lymphopenia. Absence of eosinophilia, presence of lymphopenia and/or eosinopenia in peripheral blood may be in favor of COVID-19 infection rather than an EGPA flare in such cases [15,16,17, 28,29,30].
Systemic glucocorticoids are proven to have beneficial effects on COVID-19 outcomes [31]. However, being under systemic glucocorticoid treatment with a dose ≥ 10 mg prednisolone equivalent at the onset of COVID-19 infection has been reported to be related to an increased risk of hospitalization [27]. In our study, 2 of the EGPA patients were under low-dose glucocorticoid treatment (4 mg methylprednisolone in both cases) and despite both of them observed to be hospitalized neither of them needed oxygen support. Rituximab therapy have also been related with poor prognosis in rheumatic patients with COVID-19 infection [27]. As a potent inhibitor of CD20 B lymphocytes, rituximab hampers antibody production and hence the humoral immune system which plays a key role against viral infections [32]. In a multicenter study on AAV patients, 7 deaths were reported in 58 AAV patients with COVID-19 and 4 of those 7 were under rituximab treatment [33]. In our study, 2 EGPA patients were under rituximab treatment at the time of COVID-19 and despite both of them revealed to be hospitalized and had oxygen support, neither of them died.
In the pandemic, in most patients who present with respiratory distress, COVID-19 infection is inevitably the preliminary diagnosis. Since none of the findings in COVID-19 are disease-specific, other conditions like EGPA should not be overlooked particularly in PCR negative patients and clinical, laboratory and imaging findings should be interpreted carefully. Small sample size was the major limitation of this study. Secondly, some clinical and laboratory parameters were missing in the literature cases. It is known that nasopharyngeal swab may be false negative in some COVID-19 patients. Sampling with invasive techniques such as bronchofiberoscopy may increase the sensitivity of PCR test. Lack of further sampling with bronchofiberoscopy in PCR negative patients was another limitation of our study. Nevertheless, our study provides clues regarding the EGPA / COVID-19 diagnostic challenge which may be useful in the current pandemic. Furthermore, we did not observe poor outcomes in EGPA patients who had COVID-19. Larger studies will provide further knowledge regarding the management of EGPA during the COVID-19 pandemic.