Multi-Pathogen Knee Infection, Including Treponema pallidum and Brucella: A Case Report

Introduction

Infectious arthritis is an infection of the joint and joint cavities, with Staphylococcus aureus as the common causative agent. However, other bacteria, viruses, fungi, and mycobacteria can also cause infectious arthritis [1]. The literature shows that Mycobacterium tuberculosis [2], Brucella spp. [3,4], and Treponema pallidum [5] infections can cause localized destruction of the joints, and Charcot arthropathy can accompany syphilis [6]. However, complex infections caused by multiple pathogens, especially Treponema pallidum and Brucella spp. are uncommon. Mixed infections caused by multiple pathogens exhibit a more complex pathologic process, characterized by atypical clinical manifestations that complicate diagnosis [7]. A rapid and accurate diagnosis is important for this rare and complex type of septic infection of the knee [8].

We reported a rare case of multi-pathogenic infectious arthritis involving T. pallidum and Brucella spp. in a veterinarian who was admitted to the hospital with a diagnosis of infectious knee arthritis in April 2024. Based on a comprehensive review of the patient’s medical history, complete blood count results, imaging studies, and pathological findings, it was determined that the lesion was the result of an infection caused by multiple pathogens. The bony structure of the affected knee and the soft-tissue structure of the joint were severely damaged. Subsequently, he underwent knee arthrodesis. The main aim of this case report is to review the characteristics of the case and provide a reference for the management of atypical joint diseases and zoonoses.

Case Report

LABORATORY TESTS:

We assessed the erythrocyte sedimentation rate (ESR), procalcitonin (PCT), interleukin- 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) evaluate the systemic inflammatory level. Serological testing, including rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA), was conducted to investigate syphilis. An interferon-gamma release assay (TB-IGRA) was utilized to screen for Mycobacterium tuberculosis infection. Next-generation sequencing (NGS) of joint fluid was employed for broad-spectrum pathogen detection, which identified Escherichia coli nucleic acids. No bacteria were cultured from the synovial fluid. Treponema pallidum antibodies were positive in serum and cerebrospinal fluid, Brucella IgG was positive, blood neutrophil count was within normal limits, and tests for HIV and hepatitis B virus were negative. The results of the laboratory tests are shown in Table 1.

RADIOGRAPHIC EXAMINATION:

The X-ray findings suggested infectious arthritis of the left knee joint (Figure 2).

Computed tomography (CT) of the left knee revealed degenerative changes in the knee joint. We observed deformation and collapse of the articular surface between the femur and patella, along with multiple irregular changes in the peri-arthritic region, indicating possible arthritic lesions. Compared to the previous examination, the patient’s condition was significantly deteriorated (Figure 2).

Left-knee magnetic resonance imaging (MRI) similarly demonstrated degenerative changes in the left knee joint, revealing deformation of the medial tibiofemoral joint and collapse of the articular surface. Additionally, intra-articular effusion was present supra-patellarly, with surrounding soft-tissue swelling, all suggesting an infectious process in the knee joint. Furthermore, there was a medial meniscus body defect, anterior cruciate ligament injury, and lateral collateral ligament injury (Figure 3). The patient did not experience marked pain despite extensive joint destruction.

DIAGNOSIS:

First, we observed purulent and bloody fluid within the joint cavity, accompanied by severe destruction of joint structures, which we consider evidence of suppurative arthritis. Peripheral blood tested positive for Treponema pallidum-specific antibodies (26.66 s/co), and immunohistochemical staining of sinus tract tissue demonstrated Treponema pallidum positivity, supporting the diagnosis of syphilitic arthritis. Furthermore, syphilis-specific antibodies were positive in cerebrospinal fluid (20.82 s/co). The presence of severe joint malalignment, articular surface destruction, and joint effusion without significant pain aligns with the characteristics of Charcot arthropathy. Additionally, the patient was a veterinarian with prolonged exposure to domestic animals and had IgG-positive peripheral blood for Brucella abortus and low peripheral blood leukocytes, and we suspected he was also infected with Brucella spp. Finally, although the tuberculin skin test (TB-IGRA) blood test was positive for tuberculosis infection and next-generation sequencing (NGS) of the joint fluid detected Escherichia coli nucleic acid, the clinical signs and imaging findings did not support infection by these 2 pathogens. Therefore, it was difficult to determine whether these pathogens played a role.

TREATMENT:

The patient underwent a knee arthrodesis surgery. He was positioned supine for surgery. A midline longitudinal incision was used as the surgical approach. At 6 degrees of abduction, a distal femoral osteotomy was performed on the left femur, removing 9 mm of distal femoral bone. Perpendicular to the tibial mechanical axis and with 5 degrees of posterior tilt, the tibial plateau was resected. After extensive saline irrigation, the femur and tibia at the knee joint were compressed and fixed using an external fixation frame. Radiographic confirmation demonstrated satisfactory alignment between the distal femur and proximal tibia. A drainage tube was then inserted, and the wound was closed in layers.

The surgical team’s intraoperative exploration revealed a large amount of necrotic tissue in the suprapatellar capsule of the left knee, thickened and dark synovial membrane, a large area of defect in the posterolateral condyle of the left knee and the medial tibial plateau, a large amount of synovial tissue proliferation in the medial and lateral sulcus, and the loss of anterior and posterior cruciate ligaments (Figure 4). After the operation, anti-infection, anti-coagulation, analgesia, and other symptomatic treatments were given (Sulperazon, 1.5 g, Q12h, IV drip, up to 3 weeks after surgery; rivaroxaban tablets, 20 mg, QD, PO, up to 4 weeks after surgery; Flurbiprofen Axetil, 75 mg, Q12h, IV drip, up to 1 week after surgery). At the same time, penicillin G sodium (1.6 million units) was given by intravenous drip every 6 hours, according to the expert consultation, to treat neurosyphilis.

OUTCOME:

Postoperative X-ray demonstrated satisfactory alignment between the femur and tibia (Figure 5). Subsequent return visits in the next 6 months showed that the patient’s symptoms were effectively controlled, with no more swelling of the joints and no pain, and he was able to perform daily activities. He believed that the sensory function of his knee joint had declined; however, as he had not undergone relevant sensory tests, there was insufficient evidence to evaluate the improvement in sensory deficits.

Discussion

:

Acquired syphilis caused by Treponema pallidum infection can involve the skin, mucosa, cardiovascular system, nervous system [10], joints [5,11], bones [12], eyes [13], and other tissues and organs. The onset of the disease usually occurs at age 20 to 40 years, and joint symptoms may also appear more than 10 years after the incubation period of Treponema pallidum infection. The appearance of plasma cells is one of the characteristics of this disease. In the present case, the localized pathology of the joints primarily supported syphilitic infection.

Pathological biopsy of the sinus tract and synovium was performed at the initial surgery in our hospital. The sinus tissue was grayish-white, and pathological staining showed many plasma cells and neutrophil infiltration in the tissue (Figure 6A). Immunohistochemical testing showed Treponema pallidum, and a small number of inflammatory cells were cytoplasmic punctate- positive (Figure 6B). The synovial tissues of the joints showed hyperplasia of membranous tissue with vitreous degeneration, calcification, ossification, and a small infiltration of chronic inflammatory cells (Figure 6C). The immunohistochemical test showed that Treponema pallidum was negative (Figure 6D). When undergoing arthrodesis surgery, the synovial membrane of the joint was grayish-white and pathological findings also consistent with Treponema pallidum infection (Figure 7A). The immunohistochemical test showed that Treponema pallidum was negative (Figure 7B). The pathological changes were consistent with the changes of a gummy swelling, but the immunohistochemical staining results did not fully support the diagnosis of syphilitic arthritis [14]. Treponema pallidum is not detectable in the synovium of the knee in all Treponema pallidum-infected patients [15]. It is possible that the typical location was not cut, as Treponema pallidum spirochetes are only visible in some sections of synovial tissue [15], which partly explains the inconsistent results of immunohistochemistry.

:

Brucella is a small, immotile aerobic bacterium with a high survival rate and can survive for 90 to 120 days in animal waste, dairy products, and frozen meat [16,17]. Brucellosis is a zoonotic infection that remains a serious global public health problem. It is transmitted to humans through contact with body fluids of infected animals, or contact with food products of infected animals [18], and is more common in men over 40 years of age [19]. In China, the incidence of brucellosis is about 0.02/100 000, and the western region is the highest-risk area [20,21]. Brucella infection presents with a range of clinical manifestations such as fever, diaphoresis, and musculoskeletal pain, and its most common complication is osteoarticular involvement [22], with an incidence of approximately 12.8% in the knee joint [19]. Brucella infection does not induce the activation of neutrophils [23], and our repeated blood routine results did not detect an increase in white blood cells (the white blood cell level was 3.10–8.60×109/L), which might be the result of Brucella infection suppressing the activation of neutrophils. In addition, the patient lived in Enshi region in the western part of China and was a veterinarian with long-term contact with livestock, which carries a high risk of infection. His serum brucellosis IgG was positive, suggesting a history of Brucella infection, and the course of the disease was more than half a year. Therefore, we suspected that his arthritis was caused by Brucella infection. Unfortunately, he had been exposed to many animals and we were unable to perform etiologic testing of animals to confirm our diagnosis.

:

Tuberculosis T cell detection (TB-IGRA) was positive, while the acid-fast staining of the synovial fluid and the fungal culture were negative, and the MRI scan did not show significant tissue erosion. There were no typical imaging results of Tuberculosis bacillus invasion of the knee joint, and there was no positive result of culturing tuberculosis bacillus from the joint fluid, which is the diagnostic standard [24], so there was insufficient evidence of tuberculosis infection of the knee.

Al though there was neutrophil infiltration in the joint area, the number of neutrophils in the peripheral blood was normal, and during the current visit, E. coli was detected by next-generation sequencing (NGS) of the knee joint puncture fluid; therefore, E. coli infection may have contributed to joint destruction in the affected knee. Compared with traditional Sanger sequencing methods, although the throughput of NGS reads increases, the read length is shorter and the error rate is higher [25]. We did not culture E. coli from the joint fluid, and we cannot rule out the effect of sample contamination. Given the insufficiency of numerous pieces of evidence, we believe that E. coli was not be the main pathogen causing the infection. This is also a limitation of this case report.

MULTIFACTORIAL INTERACTIONS:

Charcot arthropathy due to Treponema pallidum infection probably played a major role in the knee lesions in this patient. The positive Treponema pallidum antibody in the serum and the elevated Treponema pallidum-specific antibody in the cerebrospinal fluid suggested that the patient had neurosyphilis. In addition, the local destruction of the knee joint was obvious, the punctured synovial fluid showed bloody changes, and the pathological changes of the synovial membrane and sinus tract were very similar to the characteristics of syphilis reported by others [26], which provided strong support for our diagnosis. The insensitivity of the affected limb to pain also supported nerve destruction as one of the syphilitic changes. Therefore, we hypothesized that Charcot arthropathy caused by neurosyphilis [27] was the cause of the left knee lesion. Central nervous system syphilis caused the lack of pain, and the patient had repeated local trauma after the first cystectomy, which led to effusion in the joint capsule, ligament relaxation, and decreased joint stability, and further aggravated the degenerative changes of the joint. His previous infection with Brucella spp. could also have caused the local joint destruction, and the clinical manifestations are more consistent with each other, so it is most likely that these 2 infectious processes acted synergistically to damage the patient’s knee joint. The atypical response in the context of multiple pathogens also prevented us from completely ruling out a role for M. tuberculosis and E. coli, and we performed additional preoperative tests (Table 1) to establish the diagnosis. Ultimately, knee arthrodesis surgery was successfully performed, effectively controlling local symptoms and restoring joint stability without any postoperative complications.

LIMITATIONS OF THIS STUDY:

This case study remains subject to certain limitations. None of the pathogens we discussed, despite positive serological or molecular results, were isolated from synovial culture, which makes the diagnosis more challenging. Although the patient underwent surgery after the initial onset of joint pain, definitive medical records were lacking to clarify whether the knee infection originated preoperatively or postoperatively. Furthermore, we did not employ methods such as polymerase chain reaction (PCR) to confirm the potential infecting microorganism. Given the presence of multiple potential pathogens, including Treponema pallidum and Brucella, animal studies would be needed to elucidate the pathophysiological process involved for a deeper understanding of the multi-pathogen co-infection.

Conclusions

We reported a case of joint destruction caused by at least 2 pathogens. The presence of multiple pathogens made the patient’s pathological changes and clinical symptoms atypical, which complicated the diagnosis and treatment. Physical examination, imaging, peripheral blood, cerebrospinal fluid, joint fluid, NGS, and other laboratory results supported and justified each other, providing the basis for the diagnosis and treatment of this patient. This case provides a reference for the management of atypical joint diseases and zoonoses.