Allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis: diagnostic criteria when the IgE level is less than 500 IU/mL

Abstract

Recently, the Cystic Fibrosis Foundation developed a consensus report recommending diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis that includes a serum IgE level greater than 500 IU/mL as the "minimal diagnostic criterion." To describe a 7-year-old girl with ABPA whose serum IgE level increased to only 398 IU/mL. Total IgE and anti-Aspergillus serologic measurements were performed using enzyme-linked immunosorbent assay and standard laboratory techniques; HLA analysis was performed; interleukin 4 receptor alpha single nucleotide polymorphisms were performed using polymerase chain reaction and DNA sequencing; CD23+ B cells were measured using flow cytometry; and cytokine synthesis to Aspergillus purified antigens was assessed using flow cytometry. A 7-year-old girl with cystic fibrosis who had mild pulmonary disease and well-controlled asthma developed pulmonary infiltrates, increased wheezing, and decreased pulmonary function. Additional studies demonstrated peripheral blood eosinophilia (eosinophil count, 1807 cells/mm3 [19%]) and an increase in IgE and IgG anti-Aspergillus serology; bronchoalveolar lavage revealed septate hyphae with 45 degrees branching subsequently identified as A fumigatus and pulmonary eosinophilia. Previous HLA typing revealed that the patient was HLA-DR2+, DRB*1501, HLA-DQ2-, a pattern associated with increased risk of ABPA. In addition, there was increased up-regulation of CD23 molecules by interleukin 4 stimulation on the patient's B cells, as observed in ABPA. The patient was treated with corticosteroids and itraconazole with resolution of symptoms and pulmonary infiltrates. Examination of the pulmonary inflammatory response using bronchoalveolar lavage, genetic risk with HLA-DR2+DQ2- typing, and increased interleukin 4 sensitivity are useful adjunctive studies in the diagnosis of ABPA.