Recurrent Arthritis Caused by Brucella melitensis in a Chinese Adult: A Case Report

Background

From 2013 to 2018, a total of 282,264 cases of brucellosis were reported in China, and more than 95% of the cases were reported by northern Hospitals, Chinese Center for Disease Control (CDC) and other institutions.¹ Brucellosis, also known as waveform fever or Maltese fever, is a zoonotic disease.² Human brucellosis is a systemic infection that can affect any organ or system. Musculoskeletal involvement is one of the most common sites, and brucellosis involves bones and joints (osteojoints) between 10% and 85% of the time. Osteoarticular involvement includes spondylitis, sacroiliitis, and peripheral arthritis. The most common bone joint in children is mono-articular arthritis, mainly in the knee and hip. However, in adults, spondylitis and sacroiliitis are the most common.³ Ankle arthritis in adults is extremely rare, and its main clinical manifestations are ankle pain and limited movement, no significant difference from other bacterial ankle arthritis clinical symptoms. This often leads to clinical misdiagnosis or missed diagnosis. We present a rare case of Brucella ankle arthritis.

Case Presentation

A 50-year-old Chinese male presented to a local hospital with right ankle pain and limited mobility 23 months ago and underwent a synovectomy of the ankle. Specimen culture revealed brucellosis infection in sheep. The patient came to the department of Orthopaedics of our hospital 18 months ago because his symptoms did not improve. His case history indicated that he had worked in a Sheep farm for 9 months. We, therefore, suspected that he might have acquired Brucella infection through ingestion or contact with injured skin. A 37°C temperature, no sweating, weight loss, and no personal or family history of tuberculosis were all present on admission. Physical examination showed significant tenderness on the lateral side of the right ankle without fever. Blood flow to right toe is good, right ankle varus pressure test is positive. Laboratory tests were as follows: Hemoglobin (Hb) 136 g/L, Red blood cell count (RBC) 4.25×1012/L, White blood cell (WBC) 10.09×109/L accompanied by neutrophil elevation, Platelet 363×109/ L, Erythrocyte sedimentation rate (ESR) 31 mm/h, C-reactive protein (CRP) 32 mg/L. Rose-Bengal Plate Agglutination Test (RBPT) was positive.

Anteroposterior and lateral X-ray of the right ankle showed arrowed joint spaces (Figure 1A and B). CT showed multiple cysts were noted below the articular surface of the right ankle, and the articular surface of the talus collapsed (Figure 2A–D). MRI showed the right ankle joint space was significantly narrowed, the articular surface was coarse, the articular cartilage was thinned, the talus articular surface collapsed, and multiple cysts were found in the subchondral bone (Figure 3A–D). Joint synovial fluid of right ankle was extracted by joint aspiration and sent to the laboratory for Real-time PCR examination, and the results showed that there was B. melitensis in the synovial fluid (Figure 4). The HE staining of ankle fluid revealed inflammatory cell infiltration, while acid-fast staining was negative (Figure 5A and B). We concluded that the patient had recurrent Brucella ankle arthritis and was treated with doxycycline (0.1 g po bid), rifampicin (0.6 g po qd) and cefotaxime-sulbactam (2.25 g ivgtt q8h) for six weeks during hospitalization. ESR and CRP levels declined significantly after drug treatment, returning to normal levels of 17.00 mm/h and 7.88 mg/L, respectively.

Figure 1 X-Ray examination of the patient on admission. (A and B) Coronal and sagittal radiographs demonstrated collapsed articular surfaces and narrowed joint spaces in the talus bone.

Figure 2 CT examination of the patient on admission. (A and B) Coronal CT showed bone destruction at the lower part of the right tibia, and the articular surface of the right talus collapsed). (C and D) Axial CT showed multiple cystic bone destruction below the articular surface of the right ankle, with obvious destruction of the medial malleolus.

Figure 3 MRI examination of the patient on admission. (A and B) Sagittal T1T2-weighted image shows an abnormal signal, a narrowing of the right ankle joint, and coarse articular surfaces. (C and D) Axial image shows erosion and destruction of the medial and medial malleolus of the talus, with multiple cystic changes.

Figure 4 Brucella melitensis was detected by real-time PCR, real-time PCR showed that the DNA content of Brucella melitensis (Dotted red line) increased in 27 cycles.

Figure 5 Pathological staining of right ankle joint effusion and inflammatory tissue. (A) Inflammatory cell infiltration was seen by HE staining. (B) Acid-fast staining was negative.

The right ankle movement of the patient was basically normal at discharge, and the pain was significantly reduced. Laboratory tests after drug treatment showed erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels of 17.00 mm/h and 7.88 mg/L, respectively, significantly decreased and returned to normal. At following-up 18 months later, the patient had no discomfort in the right ankle and all inflammatory markers were normal. RBPT was negative.

Discussion and Conclusions

The most common cause of Brucella arthritis is blood transmission.⁴ Between 18% and 60% of patients with brucellosis develop osteoarthritis.⁵ The type of bone and joint involvement in brucellosis mainly depends on the age of the patient, with sacroiliac joint and spinal disease predominating in adults, and knee and ankle joint infection in children and minors.⁶

Brucella ankle arthritis were more commonly affected in children and young adults, while middle-aged and elderly patients are rarely affected.^7–9 In Turkey, Iran, and other regions, studies have shown, Iran and other regions, the most common bone and joint manifestation of brucellosis in adults is sacroiliac arthritis, and the most common manifestation in children is single joint arthritis (usually hips and knees).¹⁰ Brucellosis spondylitis is the most common bone and joint complication of adult brucellosis patients in China.¹¹ It has not been reported in China that Brucella ankle arthritis occurs.

Pain and limited ankle movement are common symptoms of Brucella ankle arthritis. Since Brucella ankle arthritis is rare, its clinical symptoms are non-specific, and negative laboratory results have been reported in chronic cases, it is difficult to diagnose.¹² In patients with histories of exposure to cattle and sheep or from areas where Brucella is endemic, clinicians should be highly suspicious of Brucella infection. In imaging, Brucella ankle arthritis does not appear characteristic, making diagnosis more challenging. Inflammation of the joints associated with brucellosis ranges from acute to subacute, usually less severe than in acute suppurative arthritis.¹³ Early joint imaging did not reveal any pathological findings because the disease is synovial in nature. In spite of this, MRI results alone cannot predict the cause of infection, since they are not specific for Brucella ankle arthritis. Soft tissue swelling and narrowing of joint spaces were seen on X-ray in advanced cases.¹⁰ There is a low incidence of destructive arthritis in brucellosis, and treatment may not stop further bone destruction, possibly because irreversible cartilage damage has occurred.¹⁴ In patients with brucellosis, ESR and CRP levels are often elevated, but they are nonspecific. Brucellosis is diagnosed with B.Melitensis cultured from blood or tissue specimens, but the positive rate is low.¹⁵ As a screening method for Brucella infection, RBPT is often used to identify B. Melitensis infection.¹⁶ Brucellosis can be diagnosed using Real-time PCR, which has relatively high sensitivity.¹⁷

The recommended drug treatment for brucellosis includes a combination of two or three antibiotics. These are prescribed according to whether the disease is complex or not. The appropriate combination of antibiotics should be selected according to the patient’s condition. The triple therapy recommended by the World Health Organization (WHO), doxycycline (0.1 g bid), rifampicin (0.6 g qd) and streptomycin (1 g qd) may be most effective if given within 6 months of disease onset.¹⁸ To prevent Brucella osteoarthritis from occurring or recurring, the sustained treatment of 2–3 courses of 2 weeks each is recommended; however, blood tests and liver and kidney function should be monitored during the course of treatment.¹⁹ Aside from medication, surgical goals include disinfecting and decompressing the joint as soon as possible to maximize function after healing. In order to treat Brucella ankle arthritis surgically, necrotic bone, synovial membrane, and joint space need to be cured. It is generally considered to be a good choice to treat infectious ankle arthritis with ankle arthrodesis.^20,21 In some cases, ankle arthrodesis may not be the first choice.

In our case, the patient had recurrent Brucella ankle arthritis after necrotic bone removal. After irrigating the joint space and receiving antibiotic treatment, the patient’s symptoms were significantly relieved, the inflammatory markers returned to normal, and the patient was able to walk after discharge. After 18 months of follow-up, there was no obvious discomfort and the function returned to normal. Our case is characterized by the following points: 1. Middle-aged and elderly patients rarely suffer from Brucella ankle arthritis; 2. It has not been reported in China that Brucella ankle arthritis occurs; 3. Arthritis caused by brucellosis is rarely destructive; 4. In this case, the patient did not undergo an ankle arthrodesis; however, medications helped him regain normal function.

Brucella ankle arthritis complicated is a rare but serious complication of brucellosis in adults. There are no obvious specific features on clinical and imaging examination. Early diagnosis and treatment can prevent the occurrence of knee joint deformity or pathological fracture. In our opinion, the key to treating osteoarthritis is to scrape away necrotic bone, synovium, and clear the joint space. Patients can return to normal function with the help of postoperative anti-infection therapy. If necessary, ankle arthrodesis may be performed.