A 10-month-old boy was admitted to our hospital for 2 weeks with intermittent fever. His disease started with a low-grade fever, which peaked at 40 C the next day, occurring one to three times per day. Then, the patient visited the local hospital, and laboratory findings showed a white blood cell (WBC) count of 7.75 x 109/L (reference range: 5.00-15.00 x 109/L), with a neutrophils percentage of 30.6% (reference range: 10.0-56.9%). Hemoglobin and platelet levels were 11.8 g/dL (reference range: 10.0-14.0 g/dL) and 280 x 109/L (reference range: 150-450 x 109/L), respectively. The C-reactive protein (CRP) level was normal. After being given symptomatic treatment, the boy had no fever for 2 days. However, the fever reappeared subsequently, accompanied by scattered red rashes all over the body, diarrhea, and a mild cough. Full blood count (FBC) testing was then repeated, and the WBC count was 5.22 x 109/L with a neutrophil ratio of 60.6%. The CRP level increased to 81.3 mg/L (reference range: <0.5 mg/L) and the procalcitonin level was also significantly elevated (8.02 ng/ml, reference range: <0.05 ng/ml), indicating severe infection. Alanine aminotransferase and aspartate aminotransferase levels were 58 (reference range: <=41 U/L) and 76 U/L (reference range: <=40 U/L), respectively, suggesting a mild liver injury. The patient was treated with intravenous antibiotics (mezlocillin sodium, 100 mg/kg/d and cefoperazone/ sulbactam sodium, 100 mg/kg/d), corticosteroid, and intravenous immunoglobulin (IVIG) (0.25 g/kg/day over 3 days). After the aforementioned treatments were given, the levels of CRP and procalcitonin returned almost to normal, but the boy's temperature was not well-controlled.
For further diagnosis and treatment, the boy was admitted to our hospital 2 weeks after the onset of symptoms. An initial physical examination revealed small red rashes scattered throughout the body, pharynx congestion, and swollen lymph nodes in the neck. Laboratory investigations were performed subsequently. FBC testing showed leukocytosis (WBC count of 24.02 x 109/L with a neutrophil ratio of 48.5%), anemia (hemoglobin 8.9 g/dL), and thrombocytosis (platelet count of 507 x 109/L). The CRP (65.02 mg/L) and procalcitonin (1.99 ng/ml) levels were elevated once more. Hypoalbuminemia (albumin 30.0 g/L, reference range: 38.0-54.0 g/L) and a high erythrocyte sedimentation rate (ESR, 57 mm/h, reference range: 0-15 mm/h) were also noted. Aminotransferase, albumin, creatine kinase, b-type natriuretic peptide, and coagulation tests were normal.
The child was treated with antibiotics (cefotaxime and sulbactam, 100 mg/kg/d). To better screen for infectious diseases, autoimmune rheumatic diseases, and blood disorders, further laboratory tests were carried out. Cultures for blood, urine, and stool were negative. Acute infections of common respiratory tract pathogens, viruses, Mycobacterium tuberculosis, and fungi were excluded (Table 1). Assays of circulating cytokines showed a mildly raised IL-6 level. Lymphocyte subset analysis and levels of immunoglobulin and complement were both normal, indicating that the patient had normal immunity. In addition, autoantibodies for systemic autoimmune diseases were all negative. Bone marrow aspiration was performed, and the pathological findings showed hyperplasia of granulocytes, decreased erythroid hyperplasia, and a significant increase of platelets, which did not indicate any hematologic disease. In terms of imaging tests, renal ultrasound showed normal kidney, ureters, and bladder structures. An echocardiography examination showed mild mitral and tricuspid regurgitation with no dilation of the coronary artery.
The diagnosis of incomplete KD was initially considered depending on the duration of the fever, clinical features, the ineffectiveness of antibiotic treatment, and laboratory results before and after admission. Based on the diagnosis, high-dose IVIG (2 g/kg) and aspirin (5 mg/kg/day) were administered on day 4 post-admission. Thirty-six hours after the first infusion of high-dose IVIG, the boy's fever was persistent and a repeated infusion of IVIG (2 g/kg) was given. However, two doses of IVIG were still unable to relieve the fever. In addition, the hemoglobin level of the patient declined to 7.6 g/dL, and the platelet count rose to 885 x 109/L, while the albumin level dropped to 28.1 g/L, which indicated resistance to IVIG. Then, corticosteroid (intravenous methylprednisolone, 2 mg/kg/day) was added as adjunctive therapy for KD. The antiplatelet medicine clopidogrel was also provided to prevent blood clots, and human albumin was given to increase the albumin level of the patient. After the aforementioned treatments were given, the patient's fever subsided, and periungual desquamation of fingers and toes occurred simultaneously. Repeated FBC testing showed a WBC count of 8.29 x 109/L, and the CRP level decreased to normal. Following 4 days of intravenous methylprednisolone, steroid therapy was continued with oral prednisone, starting at a dose of 2 mg/kg/day, and tapering in the next few days.
On the 5th day after the fever retreat, the boy developed slight swelling of the right knee with decreased joint mobility and a palpable skin temperature increase. MRI (Figure 1) and ultrasound (Figure 2A) tests were then performed to evaluate the condition of the right knee. The results demonstrated that infectious lesions existed in the right knee joint and its surrounding soft tissue, and there was massive effusion in the suprapatellar capsule and joint cavity. A final diagnosis of SA was considered in combination with the laboratory results (high CRP and ESR levels), signs, and imaging findings of the right knee. Thereafter, empiric antibiotics therapy was adjusted and teicoplanin was used to enhance the coverage of gram-positive bacteria.
Four days after the antibiotic adjustment, the patient developed a low-grade fever again. FBC testing showed a WBC count of 16.67 x 109/L with a neutrophil ratio of 36.4%. The CRP level increased once more to 41.69 mg/L, which indicated the ineffectiveness of antibiotic therapy. To better eradicate the infection and to obtain samples for culture and pathology tests, the boy was then transferred to the pediatric surgery department for subsequent treatment. Soon after, arthroscopy-assisted synovial debridement and joint cavity drainage of the right knee were performed. Samples collected during the surgery were sent for microbiological and pathological analyses. The synovial fluid culture was negative for bacteria. The pathological findings of the synovial tissue showed a large amount of neutrophil exudate and small pieces of inflammatory granulation tissue, which were consistent with the changes in purulent inflammation.
However, after surgery, the patient still had an intermittent low fever. The levels of CRP and ESR continued to rise to 97.7 mg/L and 105 mm/h, respectively. To determine the organisms involved and to carry out targeted treatment, metagenomics next-generation sequencing (mNGS, using the BGISEQ-50/MGISEQ-2000 Sequencing Platform, BGI/MGI Tech, Shenzhen, China) of joint draining fluid for pathogen detection was done. The result showed that A. baumannii was positive with a stringent mapped reads number of 14,209. In addition, bacterial antibiotic resistance genes detection showed that the resistance genes of beta-lactamase (CTX-M1), metallo-beta-lactamase (IMP, VIM, NDM, SIM, DIM), and carbapenemase (KPC) were negative. Thereafter, meropenem (started at 60 mg/kg/day and tapering) was added immediately to strengthen antibiotics treatment. After antibiotic adjustment, his fever was relieved completely, and the WBC count and CRP levels gradually returned to normal. A rehabilitation approach was provided subsequently to improve his knee extension. The patient eventually recovered after 23 days of treatment and was discharged from the hospital. Thereafter, the boy received rehabilitation training outside the hospital. In the half-year follow-up of the patient, the range of motion of the right knee had returned to normal, and no obvious abnormality was found in the repeated X-ray examination (Figure 2B). A timeline, with relevant data from the patient's episode of care, is shown in Figure 3.