An adult autosomal recessive chronic granulomatous disease patient with pulmonary Aspergillus terreus infection

Abstract

Background: Genetic mutations that reduce intracellular superoxide production by granulocytes causes chronic granulomatous disease (CGD). These patients suffer from frequent and severe bacterial and fungal infections throughout their early life. Diagnosis is usually made in the first 2 years of life but is sometimes only diagnosed when the patient is an adult although they may have suffered from symptoms since childhood.

Case presentation: A 26-year-old man was referred with weight loss, fever, hepatosplenomegaly and coughing. He had previously been diagnosed with lymphadenopathy in the neck at age 8 and prescribed anti-tuberculosis treatment. A chest radiograph revealed extensive right-sided consolidation along with smaller foci of consolidation in the left lung. On admission to hospital he had respiratory problems with fever. Laboratory investigations including dihydrorhodamine-123 (DHR) tests and mutational analysis indicated CGD. Stimulation of his isolated peripheral blood neutrophils (PMN) with phorbol 12-myristate 13-acetate (PMA) produced low, subnormal levels of reactive oxygen species (ROS). Aspergillus terreus was isolated from bronchoalveolar lavage (BAL) fluid and sequenced.

Conclusions: We describe, for the first time, the presence of pulmonary A. terreus infection in an adult autosomal CGD patient on long-term corticosteroid treatment. The combination of the molecular characterization of the inherited CGD and the sequencing of fungal DNA has allowed the identification of the disease-causing agent and the optimal treatment to be given as a consequence.

Keywords: Aspergillus terreus; CGD; Pulmonary infection.

Fig. 1

Lung imaging. a. There is extensive consolidation in the right lung (red arrow). Scattered patches of consolidation in the left lung are also seen (green arrow). Chest CT scans show the lung window at the level of the pulmonary artery (b) and heart (c). Note extensive consolidation in the right upper lobe (red arrow b). There are also smaller patches of consolidation in the right lower and middle lobes and in the left lung (green arrows b and c)

Fig. 2

Dihydrorhodamine-1,2,3 (DHR) analysis of reactive oxygen species generation by peripheral blood neutrophils. Patient and healthy control cells were incubated with DHR (375 ng/ml), with or without PMA (100 ng/ml), and ROS generation was assayed by FACS analysis. The mean fluorescent intensity (MFI) of the following groups are indicated in the figure: Red lines represent cells from unstimulated healthy controls and patient cells, blue line represents PMA-stimulated patient cells, and grey line represents and PMA-stimulated healthy control cells

Fig. 3

Microbiological culture of lung fungal species obtained by bronchoscopy. a 7-day-old culture on sabouraud dextrose agar at 30 °C shows light yellow to brownish colonies. b Fungal growth after 12 days sterile culture on potato dextrose agar (PDA) plates for sporulation and identification, and LPCB mounting slide showing details of hyphae and the accessory conidia. c Septate and hyaline hyphae with biseriate phialides extending from the upper portion of the vesicle and covering 2/3 of the plate

Fig. 4

a Partial sequence of the putative invertase gene from Aspergillus terreus isolated from the patient. This is compared to the sequence of the ‘standard’ A. terreus sp. (b)