ABPM is an allergic disease involving hyper-reactivity to environmental fungi, the most common being Aspergillus, which induced to ABPA. In addition to Aspergillus, other etiologic agents including Candida albicans, Schizophyllum commune, species of Alternaria, Bipolaris, Cladosporium, Curvularia, Fusarium, Penicillium, Pseudallescheria, Rhizopus, Saccharomyces, Stemphylium and Trichosporon(1), can also cause clinical manifestations similar to ABPA, which refer to ABPM. EGPA is a systemic disorder related to eosinophilic necrotizing vasculitis. It is categorized as a primary ANCA-associated vasculitides but also shares features of hypereosinophilic syndrome. The two diseases have several common diagnostic criteria, including asthma, peripheral blood eosinophilia, eosinophilic pneumonia, and elevated serum IgE. Considering long-term exposure to allergens may activate the immune response and lead to systemic eosinophilic vasculitis, some scholars believe that both ABPM and EGPA belong to adult-onset eosinophilic respiratory diseases and share common immune and pathological processes(2). There were several cases of coexistence of ABPM and EGPA have been reported(3-9), in some cases ABPM was diagnosed prior to EGPA, in some cases EGPA was diagnosed prior to ABPM, and in some cases diagnosed simultaneously.
This case is a rare case diagnosed of ABPM and EGPA simultaneously. The patient is a young female with a history of asthma, peripheral blood eosinophilia, increased total IgE, Aspergillus fumigatus specific IgE, reversible mild bronchiectasis, sinusitis, bronchial mucus plugs and cultivation of Aspergillus from BALF. And glucocorticoids therapy is effective. Our patient was diagnosed with EGPA and ABPM based on the ACR 1990 criteria for EGPA and Rosenberg’s criteria for ABPA. The IgE level of this case is relatively low. According to statistics, 20% -50% of East Asian ABPA patients have a total serum IgE<1000 IU/ml(10). About 40% of EGPA patients can detect MPO-ANCA(11), so negative ANCA in this patient cannot exclude EGPA diagnosis.
Table 1 summarizes the clinical and investigation features of previously reported 9 patients and our patient combined with ABPM and EGPA. There were 9 cases allergic by Aspergillus and 1 case allergic by Candida. In 5 of these 10 cases, ABPM was diagnosed prior to EGPA, though the interval varied, in 3 cases EGPA diagnosed prior to ABPM, and in 2 cases diagnosed simultaneously. Among the 3 cases EGPA diagnosed prior to ABPM, there were 2 cases had already showed bronchial mucus plugs when EGPA was first diagnosed. In cases which ABPM precedes EGPA, the abnormal Th2 response induced by long-term colonization of Aspergillus in the respiratory tract may lead to systemic eosinophilia and eosinophilic vasculitis. Many Aspergillus fumigatus antigens can stimulate humoral and cellular immune responses, directly or indirectly mediated by allergens that bind to IgE/IgG and stimulate CD4+Th2 cell subpopulations(7). Aspergillus may stimulate the production of eosinophilic chemokine-3, a specific marker of EGPA, thereby promoting excessive aggregation and damage of eosinophils(12). In cases where EGPA precedes ABPM, it may be due to the treatment of EGPA causing host immune damage and susceptibility to colonization of fungi.
The treatment for ABPM and EGPA have similarities, so the treatment of one disease may often cause delays in the diagnosis of the other disease. ABPM should avoid contact with environmental allergens(13). The medication of ABPM includes glucocorticoids, antifungal drugs and omazumab(10). Glucocorticoids is the basis of treatment by suppressing excessive immune responses. Anti-fungal treatment can reduce fungal colonization(14). Omazzumab can reduce glucocorticoid use(15). In addition to Omazzumab, there are also other effective biological agents used for the ABPM, such as Duprizumab, Mepagzumab and Bellazumab(16-18). Meanwhile, clearing bronchial mucus plugs is also crucial, as persistent inflammation caused by protease products released by fungi in the mucus can lead to central bronchiectasis(19). For EGPA, the first step of treatment is to induce disease remission and the glucocorticoids should be used as the initial treatment. For severe patients, high-dose glucocorticoids therapy should be considered, and immunosuppressants or rituximab and mepolizumab can be applied to induce and maintain remission(11). For EGPA patients with acute episode of asthma or sinus involvement, inhaled and local corticosteroids should be optimized. Omazzumab is effective in treating respiratory symptoms of EGPA, but its effect on vascular inflammation is still unclear. Invasive pulmonary mycosis should be alerted(20). There were reports of fungal pneumonia in patients with ABPM combined with EGPA during immunosuppressants and glucocorticoids therapy(4). Therefore, anti-fungal therapy should be applied in patients combined with ABPM and EGPA.