On 21 November 2018, an 11-year-old preadolescent boy presented to our hospital with a productive cough, fever, and weight loss for four weeks. 1.5 months before the current illness, the patient was admitted to a local hospital with left neck lymphadenitis and underwent surgical drainage. The bacterial culture of the drained pus grew MRSA and received ten days of vancomycin and clindamycin. He was sent home in good condition. Symptoms started two weeks after discharge with a daily high-grade fever and productive cough. He had lost around 5 kg since his illness began with a poor appetite. There was no history of contact with tuberculous-infected patients. His older sister died six years ago due to severe pneumonia, and there was no clear underlying diagnosis. Parents are second-degree consanguineous with no family history of inherited lung disease.
On admission, he was dyspneic and febrile with an oral temperature of 39 C. His blood pressure was 110/60 mmHg, his heart rate was 120/min, his oxygen saturation was 85% on room air, and his respiratory rate was 20/min. Physical examination revealed left neck enlarged lymph nodes with healed scars (Figure 1). The chest revealed bilateral diminished air entry with bilateral coarse crackles. Peripheral blood leukocyte count was 28.260/muL with 84% neutrophil, 11% lymphocyte, and 4.4% monocyte; hemoglobin and platelet counts were 9.5 mg/dL and 550 x 109 per liter. The erythrocyte sedimentation rate was 150 mm/h. All the results of biochemical tests were normal. A chest CT scan showed bilateral diffuse air space disease (Figure 2). A direct smear of sputum for acid-fast bacilli and tuberculous mycobacteria PCR was negative.
Upon admission (21 November 2018), the patient was started on broad-spectrum antibiotics linezolid, gentamycin, and meropenem. After five days of therapy, the fever continued with worsening chest X ray findings. So, the infectious team decided to start antituberculosis treatment empirically, given the rapid deterioration in his condition, which was later discontinued after getting the negative PCR and AFB smear results.
On 29 November 2018, the demonstration of yeast in a smear made from sputum and the appearance of pseudohyphae and budding yeast cells (Figure 3(a)) dictated the need for fungal culture. Fungal cultures were performed on Sabouraud dextrose agar (SDA) and blood agar plates. Inoculated plates were incubated at 30 C and 37 C, respectively. Plates were examined daily for microbial growth. Initial identification of the grown organism was carried out using routine growth and colonial morphology criteria -confirmation of identification of Candida spp. by the VITEK 2 system. The VITEK 2 automated system was used to confirm the identities of Candida species following protocols described by the manufacturer (bioMerieux Inc., Durham, NC 27712, USA). Candida tropicalis were isolated from a sputum specimen's culture (Figures 3(b) and 3(c)), which raised the possibility of invasive mycosis due to underlying primary immunodeficiency. Amphotericin was added at 1 mg/kg/day for two weeks, and he also received IV methylprednisolone (1 mg/kg/day twice daily for seven days), which was later tapered over two weeks. The patient improved and was weaned off oxygen with no fever.
On 15 December 2018, he was referred to higher centers for further workup. The bronchoscopy was done at the higher center, which showed diffuse bronchitis with necrotic involving mainstem bronchi (Figure 2). The patient's immune system was assessed. The ranges of the immunoglobulins (Ig) were normal, which include IgG 10.4 g/l (reference 7-16 g/l), IgA 2.81 g/l (reference 0.7-4 g/l), IgM 0.675 g/l (reference 0.4-2.3 g/l), and IgE 26.3 IU/ml (reference less than 200 IU/ml). The total protein level was 8.1 g/dl (reference 6.6-8.3 g/dl) and the albumin level was 2.4 g/dl (reference 3.5-5.2 g/dl). The oxidative burst measurement with flow cytometry using the dihydrorhodamine 123 assays was performed and confirmed the diagnosis of CGD through the comparison between control (reference range 98-100%) and the patient results (0.3%). The patient was started on daily prophylaxis withTrimethoprim-sulfamethoxazole (5 mg/kg/d, based upon the Trimethoprim) and itraconazole (5 mg/kg/day). The patient was then sent for HLA-identical bone marrow transplantation (BMT).