As a child the patient had suffered from repeated bouts of otitis media, and already as a 6-year-old had suffered from pneumonia confirmed by X-ray imaging. His history included the classic AD-HIES characteristic of retention of primary teeth and typical facies including a wide nose. He had also suffered from fungal nail infections but never fungal infections in any of his mucous linings. He did not suffer from asthma.
In terms of presenting symptoms, the patient had experienced mild productive clear coloured sputum in the mornings for a few years. He had, however, no dyspnoea, weight loss or fever. Pulmonary function tests showed normal dynamic volumes, static volumes and diffusion capacity. A bronchoalveolar lavage (BAL) was performed and the culture was positive for Streptococcus pneumoniae, sensitive for penicillin. Cultures also grew Achromobacter sp. And polymerase chain reaction (PCR) was positive for Pneumocystis jirovecii, which was treated with Sulfatrim. However, BAL was negative for Aspergillus sp. and other fungal moulds. PCR and microscopy for Aspergillus sp. were negative as well. Biochemically the titre for Aspergillus IgG antibody was 0.0 arbitrary unit/mL and therefore negative. Immunological studies showed normal IgG and IgM, but elevated IgA = 6.22 g/L and reduced IgG2 = 1.53 g/L. The Galactomannan antigen test was negative. Furthermore, the BAL showed negative microscopy for Mycobacterium sp. The BAL culture for Mycobacterium sp. was negative as well. The interferon gamma release assay (IGRA) test was also negative. The value of total serum IgE was slightly elevated at 158 international units (IU)/mL (reference < 115 IU/mL).
The patient was treated with phenoxymethylpenicillin for 10 days because of the BAL findings of S. pneumoniae and Achromobacter sp. Because of the high suspicion of pulmonary Aspergillosis, empiric Voriconazole treatment was prescribed for 11 months (Figure 2). No tissue biopsy was obtained before initiating treatment. The level of plasma-Voriconazole was monitored throughout the treatment period and found to be within therapeutic levels. A control CT/positron emission tomography (PET) (Figure 3) 2 months later showed increased fluorodeoxyglucose (FDG) uptake at the level of the cavity; 8 months later a high-resolution computed tomography (HRCT) scan (Figure 4) showed further progression of cavitating lesion in the right upper lobe and new infiltrates caudally. A new BAL was performed where Pseudomonas aeruginosa was cultured. The second BAL fluid was negative for Aspergillus sp., Mycobacterium sp. and Pneumocystis sp. Blood test was again negative for Galactomannan antigen. The patient was given 2 weeks of intravenous (IV) Tazobactam and Ciprofloxacin to eradicate the P. aeruginosa. A PET/CT scan was done 3 months later. The pulmonary cavity was unchanged with no PET activity in the perceived fungal ball. However, new pulmonary infiltrates were visible in the right upper lobe. After this, a superdimension-bronchoscopy with brush biopsies was performed. It came out with normal cells. A CT-guided transthoracic coarse needle biopsy showed chronic inflammation with no evidence of malignancy or any fungal infection.
Finally, as the clinic and all examinations performed did not point towards fungal infection as only signs of chronic inflammation were present and because the radiological findings progressed despite Voriconazole treatment, a new strategy was agreed upon. The patient would now be treated for non-infectious inflammation. The patient was started on prednisolone 25 mg/day (2.5 mg/kg). A control CT thorax (Figure 5) after 1 month of this treatment regimen showed some regression of the infiltrate. A further follow-up CT thorax (Figure 6) 12 months later showed further regression of the infiltrate. The Prednisolone treatment was subsequently stopped (Figure 7). The patient has been followed in the infectious disease clinic ever since, and his condition has been stable. He now runs 5 km a few times a week without any issues. He continues to be treated prophylactically with Sulfatrim and Itraconazole. A follow-up CT thorax in 2021 showed no progression of infiltrate. During the 4 years of follow-up the cavity with a fungal ball looking appearance in the right lung had only regressed from 21 mm in 2017 to 19 mm in 2021. A follow-up IGRA test in 2022 was negative for Mycobacterium tuberculosis with a positive control (mitogen-nil = 10.00 kIU/L and nil = 0.10 kIU/L).
Apr 2017 BAL: positive cultures for Pneumococcus sp., Achromobacter sp., Pneumocystis sp.; negative for Aspergillus sp. Cytology showed inflammation with macrocytosis and granulocytosis. No tumour cells were seen.
Apr 2017 BAL: negative microscopy for Mycobacterium sp., negative cultures for Mycobacterium sp.
Feb 2018 BAL: negative cultures. Negative for Aspergillus sp. Cytology unchanged from April 2017.
Apr 2018: superdimension-bronchoscopy with brush biopsies: normal cells.
May 2018: CT-guided transthoracic coarse needle biopsy: chronic inflammation, no malignant cells. No fungal cells.
Mar 2017: HRCT: multiple cavitating lesions in the right upper lobe.
May 2017: PET/CT: multiple cavitating processes in the right upper lobe with high FDG uptake. New infiltrative changes posteriorly and caudally to the known cavity, possible progression of known lesion.
Dec 2017: HRCT: discrete regression of cavitary lesion in right upper lobe. Regression of scattered areas of ground glass opacity.
May 2018: CT: multiple cavitating as well as solid and semisolid changes in the right upper lobe with increased FDG uptake.
May 2019: HRCT: regression of known right-side infiltrate.
May 2020 (HRCT) and May 2021 (CT): unchanged status.
June 2021: lymphocyte-population investigation (Th17-assay): Reduced amount of Th17-helper cells (<0.1% of all T-helper cells).