Articulation Infection in Patient with Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is a rare congenital immunodeficiency disorder that significantly impacts the body’s ability to fight off bacterial and fungal infections. This condition arises from a defect in the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which is crucial for the production of superoxide anions necessary for microbial killing. The case of a 7-year-old boy with CGD, who developed an articulation infection in his left ankle, provides a comprehensive illustration of the challenges associated with diagnosing and managing this rare disease.
The patient initially presented with a mass in his left distal forearm, which had developed over the course of a month. A biopsy performed during surgery led to a diagnosis of histiocytosis, with suspected yellow granulomas. Postoperatively, the patient experienced poor wound healing accompanied by purulent secretions. Two months after the surgery, he was readmitted to the hospital due to a painful swelling in his left ankle that had persisted for 10 days. A color Doppler ultrasound revealed synovitis in the left ankle joint and fasciitis in the left posterior tibialis.
The patient’s medical history was significant for recurrent respiratory infections since infancy, for which he had received anti-tuberculosis therapy. However, there was no evidence of acid-fast bacilli isolated from the patient, and no family history of similar illnesses. Additionally, the patient had undergone open drainage of abscesses in the posterior ears, posterior cervical lymph nodes at the age of 5, and perianus at the age of 6. He had frequently been prescribed multiple antibiotics, such as oxycefazid, vancomycin, and imipenem, due to recurring multi-site infectious lesions.
Upon readmission, the patient’s vital signs included a temperature of 38°C, blood pressure of 128/83 mmHg, pulse rate of 132 beats per minute, and respiratory rate of 22 per minute. Laboratory findings showed a white blood cell count of 11,200 mL, platelet count of 287,000 mL, erythrocyte sedimentation rate of 85 mm/h at the end of the first hour, serum pro-calcitonin level of 0.38 ng/mL, and serum C-reactive protein level of 118 mg/L. Chest computed tomography revealed fibrotic lesions in both lungs and an enlarged liver. X-ray radiography of the left ankle joint showed massive swelling in the left ankle and left plantar soft tissue.
Pathology examination of the distal left radius and left ankle joint synovial membrane revealed granulomatitis with focal necrosis. Notably, no Mycobacterium tuberculosis was found in the acid-fast staining, and no M. tuberculosis DNA fragments were detected through quantitative polymerase chain reaction analysis. Diagnostic puncture detected pus, which was identified as being caused by Serratia marcescens. The pus was surgically drained to prevent further infection.
Given the patient’s history of multiple infections, congenital immunodeficiency diseases or malignant histiocytosis were considered. The patient underwent genetic screening for gene-deficient diseases and related immune system tests. Peripheral blood was extracted after obtaining informed consent from the patient’s parents. DNA extraction was followed by protein-coding exome enrichment using 429,826 individually synthesized and quality-controlled probes, targeting 39 Mb of protein-coding regions (19,396 genes) of the human genome and covering 51 Mb of end-to-end tiled probe space. High-throughput sequencing was performed, with >99% of the target sequences sequenced before bioinformatics analysis.
The trio whole-exome sequencing test revealed a CYBB chrX: 37653064 c.483 + 1 (IV S5) G > T mutation. This splice site variant in the CYBB gene had been previously reported in association with CGD. The c.483 + 1 G > T variant destroys the canonical splice donor site in intron 5, resulting in a frameshift of codon 112 to codon 133. Based on these genetic test results, the patient was diagnosed with X-linked CGD (XL-CGD). His current treatment regimen includes anti-infective treatment, and he is awaiting stem cell transplantation.
CGD is characterized by severe and recurring bacterial and fungal infections in various parts of the body, including the lungs, skin, soft tissues, liver, and lymph nodes. The condition can also affect the skeletal system, although cases of osteomyelitis arising from CGD are rare, and infectious arthritis is even less commonly reported. This case is particularly notable for the diagnosis of XL-CGD using whole-exon sequencing and the presentation of infectious arthritis in the left ankle.
Infectious arthritis can be categorized as acute or chronic based on a combination of microbial and host factors. Acute infectious arthritis is typically caused by purulent bacteria and viruses, while chronic arthritis is often due to mycobacteria and fungi. In this patient, the infectious arthritis was bacterial, and the underlying cause was a genetic mutation in the CYBB gene. This case underscores the importance of considering infectious arthritis in children with a history of unexplained repeated infections and joint swelling. It also highlights the need for thorough examinations to rule out CGD, particularly in cases where skeletal system infections might be misdiagnosed as bone tumors.
To diagnose CGD, it is essential to measure residual NADPH oxidase activity by examining oxygen consumption and superoxide or hydrogen peroxide production. However, in some cases, the etiology can only be discovered through gene sequencing. Knowledge of genetic mutations is invaluable for diagnosing carriers, providing genetic counseling, and conducting prenatal screening. Although genetic testing is an expensive procedure, it is crucial for guiding the patient’s and his parents’ future procreation and should be recommended clinically.
This case also emphasizes the importance of a multidisciplinary approach in managing CGD. The patient’s treatment involved collaboration between departments of endocrinology, pediatric surgery, and rheumatology and immunology. The comprehensive care provided to the patient highlights the need for specialized centers that can address the complex needs of individuals with rare diseases.
In conclusion, the case of this 7-year-old boy with XL-CGD and infectious arthritis in the left ankle illustrates the challenges associated with diagnosing and managing CGD. The use of whole-exon sequencing was pivotal in identifying the genetic mutation responsible for the disease. This case underscores the importance of considering genetic mutations in patients with a history of recurrent infections and joint swelling and highlights the need for thorough diagnostic evaluations to ensure accurate diagnoses and appropriate treatment plans.
doi.org/10.1097/CM9.0000000000001385
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