Joint tuberculosis (TB) is an uncommon manifestation of TB that typically presents with subacute or chronic atraumatic inflammatory symptoms in single, large, weight-bearing joints.
In Canada, epidemiological risk factors for TB include extended time spent in countries with high burden of TB, known exposure to TB or being part of a population disproportionately affected by TB (e.g., people born outside of Canada, those of Indigenous ethnicity or those with a history of homelessness or incarceration).
Synovial thickening, joint effusions, juxta-articular osteopenia, peripheral osseous erosions and gradual joint space narrowing on magnetic resonance imaging or computed tomography are suggestive of joint TB.
Specialized mycobacterial culture is the gold standard for diagnosis of TB, but nucleic acid amplification tests are increasingly accessible and allow for rapid diagnosis of joint TB.
Treatment for joint TB should be started promptly for preservation of joint function and prevention of irreversible destruction.
A 47-year-old man presented to the emergency department with 2 weeks of acute-on-chronic pain in his right knee. He described a 5-year history of chronic pain in his right knee, with 1 flare-up 3 years before presentation, which had resolved after a few weeks of ibuprofen use. He had not previously sought care for this problem. He was otherwise healthy, with no chronic medical conditions or previous surgeries, and he tested negative for HIV. He had smoked crystal methamphetamine daily for the last 10 years and had no history of intravenous drug use. He had immigrated from the Philippines 16 years before and had not returned.
When examined, the patient was afebrile with normal vital signs. His right knee was swollen with limited flexion and extension. He did not have any overlying erythema or tenderness to palpation of the bursa or the joint line. He had no other inflamed joints. Initial laboratory results showed a leukocyte count of 8.4 (normal 4–11) × 109/L and an elevated C-reactive protein level of 34.4 (normal < 3.1) mg/L. A radiograph of the patient’s right knee showed bony destruction of the knee joint and an irregular lucency of the medial tibial plateau (Figure 1). A computed tomography (CT) scan showed cortical destruction with peripheral osseous erosions and juxta-articular osteopenia (Figure 2). The patient was admitted to the internal medicine service and the initial treating physicians were concerned that he may have had a malignant disease; they ordered a CT scan of the chest, abdomen and pelvis, which showed mild, biapical lung scarring (Figure 3).
<a href=”https://www.cmaj.ca/content/cmaj/195/22/E782/F1.large.jpg?width=800&height=600&carousel=1″ title=”Radiograph of the right knee joint of a 47-year-old man with joint tuberculosis, showing peripheral osseous erosions (red arrow), irregular lucency of the medial tibial plateau (yellow arrow) and joint space narrowing (white arrow).” class=”highwire-fragment fragment-images colorbox-load” rel=”gallery-fragment-images-1137217360″ data-figure-caption=”
Radiograph of the right knee joint of a 47-year-old man with joint tuberculosis, showing peripheral osseous erosions (red arrow), irregular lucency of the medial tibial plateau (yellow arrow) and joint space narrowing (white arrow).
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Figure 1:
Radiograph of the right knee joint of a 47-year-old man with joint tuberculosis, showing peripheral osseous erosions (red arrow), irregular lucency of the medial tibial plateau (yellow arrow) and joint space narrowing (white arrow).
<a href=”https://www.cmaj.ca/content/cmaj/195/22/E782/F2.large.jpg?width=800&height=600&carousel=1″ title=”Serial computed tomography scans (coronal view) of the right knee of a 47-year-old man with joint tuberculosis, showing the Phemister triad of tuberculosis arthropathy including juxta-articular osteopenia (yellow arrows), peripheral osseous erosions (red arrows) and joint space narrowing (white arrow, panel A).” class=”highwire-fragment fragment-images colorbox-load” rel=”gallery-fragment-images-1137217360″ data-figure-caption=”
Serial computed tomography scans (coronal view) of the right knee of a 47-year-old man with joint tuberculosis, showing the Phemister triad of tuberculosis arthropathy including juxta-articular osteopenia (yellow arrows), peripheral osseous erosions (red arrows) and joint space narrowing (white arrow, panel A).
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Figure 2:
Serial computed tomography scans (coronal view) of the right knee of a 47-year-old man with joint tuberculosis, showing the Phemister triad of tuberculosis arthropathy including juxta-articular osteopenia (yellow arrows), peripheral osseous erosions (red arrows) and joint space narrowing (white arrow, panel A).
<a href=”https://www.cmaj.ca/content/cmaj/195/22/E782/F3.large.jpg?width=800&height=600&carousel=1″ title=”Computed tomography scans of the lungs of a 47-year-old man with joint tuberculosis, showing mild biapical scarring (arrows), suspected to be secondary to previous tuberculosis infection. (A) and (B) are serial axial images; (C) and (D) are serial coronal images.” class=”highwire-fragment fragment-images colorbox-load” rel=”gallery-fragment-images-1137217360″ data-figure-caption=”
Computed tomography scans of the lungs of a 47-year-old man with joint tuberculosis, showing mild biapical scarring (arrows), suspected to be secondary to previous tuberculosis infection. (A) and (B) are serial axial images; (C) and (D) are serial coronal images.
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Figure 3:
Computed tomography scans of the lungs of a 47-year-old man with joint tuberculosis, showing mild biapical scarring (arrows), suspected to be secondary to previous tuberculosis infection. (A) and (B) are serial axial images; (C) and (D) are serial coronal images.
Bloody synovial fluid was aspirated from the patient’s right knee joint, with a leukocyte count of 36.7 × 109/L (79% neutrophils, 15% lymphocytes, 6% monomacrophages) and an erythrocyte count of 150 × 109/L, and no crystals or organisms on Gram stain. Cultures for mycobacteria were negative on acid-fast bacilli staining. Given these findings, bacterial septic arthritis was suspected and he was treated with empirical antibiotic therapy (intravenous [IV] ceftriaxone 2 g daily, and IV vancomycin with a target trough of 10–20 mg/L). After 6 days, the patient’s knee had not improved and bacterial cultures from synovial fluid remained negative. The internal medicine team consulted our infectious diseases team.
We suspected tuberculosis (TB) based on 3 factors, namely the chronic nature of the monoarthritis, the pulmonary apical scarring on chest imaging and that the patient had emigrated from the Philippines — designated as a country with a high burden of TB by the World Health Organization (WHO), with the fourth highest national incidence of TB globally.1 We identified no other identifiable risk factors for TB, such as previous incarceration, homelessness or known close contact with someone with TB.
Nucleic acid amplification testing (NAAT) for TB using the GeneXpert MTB/RIF Ultra assay (Cephied) was performed on samples of synovial fluid, which confirmed the presence of Mycobacterium tuberculosis. Smear testing of sputum samples were negative for acid-fast bacilli. We prescribed standard weight-based dosages of rifampin (10 mg/kg/d), isoniazid (5 mg/kg/d) with pyridoxine (25 mg/d), pyrazinamide (25 mg/kg/d) and ethambutol (15 mg/kg/d) and discharged him to continue this therapy under care of the provincial TB program.
Four weeks later, samples of the patient’s synovial fluid showed growth of M. tuberculosis that was susceptible to the first-line anti-TB medications he was receiving. Mycobacterial cultures from sputum samples were negative, suggesting that he did not have pulmonary TB. At follow-up after the 9-month course of treatment, the patient had considerable improvement of his knee pain (pain only with extended use), periarticular and lower leg swelling and range of motion (full flexion and extension). He had returned to work and was ambulating without need for a mobility aid. Given the extensive destruction of the knee joint, we had planned to refer him to an orthopedic surgeon for consideration of knee arthroplasty. However, he was lost to follow-up, and subsequent knee imaging and surgical referral could not be completed.
Discussion
In 2020, the incidence of TB in Canada was 4.7 per 100 000 people, consistent with the previous 10 years.2 However, people born outside of Canada and Canadian-born Indigenous peoples are disproportionately affected.2 Bone and joint TB, including both vertebral and extra-axial joint disease, is an uncommon manifestation of extrapulmonary TB. In Canada, this form of TB accounts for about 2.5% of all TB cases per year, and around half of these cases have vertebral disease.3 In low-income regions, bone and joint TB is more commonly seen among children, usually developing shortly after primary infection. In high-income countries, however, it is most commonly seen among adults, resulting from TB reactivation, as we suspected with our patient.3 Extra-axial disease usually presents as a monoarthritis that affects the knee or hip.
Diagnosis may be difficult and is often delayed by many months, particularly in countries where TB is not endemic.4,5 Key features of TB include the presence of risk factors, the long duration of symptoms and constitutional symptoms. Unlike in bacterial septic arthritis, systemic infectious symptoms such as fevers and chills, rigors or elevated heart rate are usually absent in tuberculous arthritis. Other differential diagnoses include bacterial septic arthritis, crystal arthropathy, systemic rheumatic disease (such as rheumatoid arthritis) and osteoarthritis. Poncet disease, a reactive polyarthritis associated with extra-articular TB disease, should also be considered if several joints are involved and the patient has evidence of nonerosive arthritis.6 Findings from physical examination are nonspecific and include restricted range of motion, swelling and joint effusion.7 Joint erythema, warmth and tenderness may be absent, unlike in crystal arthropathy or bacterial septic arthritis.
Typical radiologic findings in early disease show thickening of the synovium and joint effusions — similar to other causes of monoarthritis such as septic arthritis or crystal arthropathy.8 Early TB arthritis may also be misdiagnosed as osteoarthritis if imaging shows only joint space narrowing.8 Later-stage disease has features of juxta-articular osteopenia, peripheral osseous erosions and joint space narrowing, known as the Phemister triad.9 Some chronic cases may have sinus tract formation.8
Plain radiographs may show the Phemister triad in later-stage disease, but magnetic resonance imaging (MRI) and CT are the best imaging modalities for disease characterization. In particular, MRI offers the most specificity for TB arthritis, but timely availability is often limited; therefore, CT may be used as it offers more specific disease characterization than plain radiographs. 8 However, because joint TB has no pathognomonic imaging findings, particularly early in the disease course, the diagnosis cannot be made based on imaging alone and requires microbiological confirmation.
Diagnosis is typically achieved by synovial fluid analysis or synovial biopsy with microscopy for acid-fast bacilli and mycobacterial culture. However, testing synovial fluid for acid-fast bacilli has a low sensitivity of about 30% and cultures take weeks to detect growth. Mycobacterial cultures also require specialized laboratories that are certified for biosafety containment level 3 and have clinical mycobacteriology accreditation to ensure quality assurance.3 Joint fluid analysis often finds a leukocyte count in the inflammatory range, typically 10–20 × 109/L, but may be higher.7
Newer methods for molecular detection of M. tuberculosis such as NAAT are rapid, more geographically accessible and do not require specialized laboratories. The most studied and widely available NAAT assay recommended by WHO is the automated, cartridge-based GeneXpert MTB/RIF and the newer generation, GeneXpert MTB/RIF Ultra. A recent review of the diagnosis of extrapulmonary TB with the GeneXpert assay found a sensitivity of 60%–100%, depending on specimen type, and a specificity of 87.5%–100% for bone and joint specimens.10 We did not diagnose TB in our patient until 5 years after symptom onset, by which time he had considerable destruction of the knee joint. Despite the presence of joint destruction, TB arthritis typically responds well to medical therapy and is usually treated for 6–12 months. Treatment duration should be extended for patients with increased risk of relapse, such as those with extensive disease at presentation.3 Unlike other causes of septic arthritis, TB arthritis does not require acute surgical management; surgery is reserved for treatment of complications related to joint destruction after completion of TB treatment.3
Conclusion
Clinicians should consider joint TB in patients who present with subacute joint pain and swelling with joint fluid analysis suggestive of an inflammatory arthritis, and in patients who do not respond to standard therapy for inflammatory or septic arthritis. In addition to mycobacterial cultures, NAAT may aid timely diagnosis and management.
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Footnotes
Competing interests: None declared.
This article has been peer reviewed.
The authors have obtained patient consent.
Contributors: All of the authors contributed to the conception and design of the work. Adrianna Gunton drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.
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The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.
It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.
Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”
Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.
Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.
A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.
On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.
Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”
But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”
“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.
Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.
Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.
Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.
“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.
“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”
This report by The Canadian Press was first published Sept. 13, 2024.
Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.
Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.
Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.
Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.
The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.
“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.
Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.
Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.
Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.
A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.
This report by The Canadian Press was first published Sept. 10, 2024.
