On July 28, 2020, a boy aged 3 years and 8 months was admitted to pediatric intensive care unit with a complaint of lip swelling with fever for half a month and neck abscess for 11 days. Physical examination revealed hyperthermia (38.7℃), tachycardia (165 bpm), tachypnea (60 bpm) and normal blood pressure (102/74 mmHg) on the day of admission. His jaw to right upper lip was swollen, with tenderness and elevated skin temperature. Palpation suggested hepatomegaly and splenomegaly. Five anal fistulas could be seen and there were ulceration and scabs of the perianal skin.
Laboratory findings revealed elevated white blood cell count of 39.79 × 109/L, percentage of neutrophils 87%, procalcitonin 3.48 ng/mL, C-reactive protein 221.6 mg/L, erythrocyte sedimentation rate 44.00 mm/h, 1,3-β-D-glucan118.40 pg/mL, and galactomannan 1.06 ug/L. While the hemoglobin 95.8 g/L, percent of lymphocytes 7.7%, serum potassium 2.88 mmol/L, serum sodium 128.0 mmol/L, and albumin 23.8 g/L were reduced. Arterial blood gas analysis showed hypoxemia of 51 mmHg. Other indicators, including neutrophil oxidative burst test, T-SPOT, blood culture, bone marrow aspiration cytology, bone marrow culture, mycoplasma titer, human parvovirus, antistreptolysin “O”, and anti-neutrophil cytoplasmic antibody were negative.
Computed tomography (CT) scan indicated multiple clusters and nodular high-density shadows in both lung fields (Fig. 1), which were considered as bilateral lung infection. Besides, cystic density shadows were seen in the right maxillofacial region and submaxillary. Ultrasound found multiple enlarged lymph nodes on the bilateral neck, the larger ones were 12 mm × 6 mm on the right and 11 mm × 7 mm on the left. The right submaxillary region detected a hypoechoic area of about 35 mm × 22.5 mm, and the submental continuation to the left submaxillary region probed a range of about 79 mm × 15 mm hypoechoic.
Severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. The child received empirical anti-infective treatment with intravenous meropenem, vancomycin, and fluconazole. However, in the early morning of the second day of admission, the child developed breathlessness and decreased oxygen saturation. Continuous positive airway pressure (CPAP) noninvasive ventilator was applied with the informed consent of the family. The following day, he was administered nasotracheal intubation and ventilator support due to hypoxic saturation (93%) and severe carbon dioxide retention (98 mmHg).
The child’s condition didn’t improve after initial therapy and an infrequent pathogen was doubted. On day 3 post admission, submandibular pus puncture was performed and the pus was tested through metagenomic next-generation sequencing (mNGS). Within 24 h, it revealed 87 sequence readings of Nocardia farcinica genome (Table 1). The child was given oral compound sulfamethoxazole tablets. Besides, vancomycin was switched to linezolid and meropenem was changed to imipenem. 48 h later, special bacterial smear of pus indicated that weak acid-fast staining was positive, which was suspected of Nocardia. Moreover, the pus was cultured and the N. farcinica was identified after 5 days, further proving the pathogen detected by mNGS.
On day 5 of admission, bronchoalveolar lavage fluid (BALF) was detected by mNGS and the results showed 64 sequence readings of N. farcinica genome and 5 sequence readings of Aspergillus fumigatus genome (Table 1). While the galactomannan value reported from BALF was ≤ 0.25. The child was considered an overlapping infection of N. farcinica and A. fumigatus. Moreover, special bacterial smear of BALF found positive weak acid-fast staining, which was suspected Nocardia. The antibiotics were adjusted to imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, the child’s condition improved.
Pursuing his medical history uncovered that he developed a fever 21 days after birth and was diagnosed with pulmonary Aspergillus infection. Perianal abscess appeared when he was 8 months old. It’s necessary to be alert to immunodeficiency diseases. Thus, on the 8th day of admission, peripheral blood of the children and his parents were collected for whole-exome sequencing (WES). Twelve days later, WES reported c.121 locus T deletion mutation in the CYBB gene of the child (Fig. 2), which is related to X-linked chronic granulomatous disease (X-CGD). And his mother was found a carrier of X-CGD with the inherited c.121 locus T deletion mutation.
Combined with medical history, physical signs, auxiliary examinations, pathogen detection and genetic sequencing results, the child was diagnosed as X-CGD caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation (HSCT) was a potential sanative approach and his family expressed willingness to have a try. On September 19, the child’s father and elder brother were administered human leukocyte antigen (HLA) typing test. On September 30, HLA typing results showed the child was 5/10 HLA-matched with his father or brother. There were no available HLA-compatible donors for the child. On October 1, the family requested to transfer to a superior hospital for further treatment. After informing them of the precautions in detail, the child was discharged. Two months later, we followed up with the child’s family. Unfortunately, the child had expired due to severe infection. The detailed diagnosis and treatment process are shown in Fig. 3.