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Indonesian Journal of Rheumatology Vol 15 Issue 1 20231. Introduction
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis.1 It remains a significant health care burden, especially in developing countries.
Tuberculosis infection can affect pulmonary and extra pulmonary organs. Most of the newly diagnosed tuberculosis cases are pulmonary tuberculosis, however tuberculosis infection may also involve other organs such as bones and joints. Tuberculosis often presents diagnostic challenges as it frequently mimics other diseases, especially in cases of extra pulmonary tuberculosis.2 Skeletal tuberculosis accounts for 10%
to 35% of all extrapulmonary tuberculosis cases, with the knee joint being the most commonly affected site after the spine and hip.3 However, currently there is no data regarding the prevalence of tuberculosis arthritis in Indonesia.
The spread of tuberculosis to bone structures may occur through several modes of transmission, namely
hematogenous, lymphogenous, and per continuitatum routes.4 Symptoms of bone and joint tuberculosis are generally non-specific with a slow clinical course, often leading to a delay in diagnosis.1 Herein, we report a patient with chronic monoarthritis of the knee with a history of repeated operative procedures, which eventually led to a diagnosis of tuberculosis arthritis of the knee.
2. Case Presentation
A 23-year-old female patient presented with a complaint of pain in the right knee which progressively worsened over the last 1 month. The pain was accompanied by swelling and limited joint movement which made it difficult for the patient to walk. The patient had a history of similar complaints in 2018 and 2021 and had undergone two operative procedures.
Additionally, the patient also reported discomfort in her abdomen since the previous 1 week. Coughing,
Tuberculosis Arthritis: A Diagnostic Challenges
Desak Putu Gayatri Saraswati Seputra1*, Pande Ketut Kurniari1
1Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia
ARTICLE INFO Keywords:
Arthritis Knee Tuberculosis
*Corresponding author:
Desak Putu Gayatri Saraswati Seputra
E-mail address:
All authors have reviewed and approved the final version of the manuscript.
https://doi.org/10.37275/IJR.v15i1.237
A B S T R A C T
Background: Tuberculosis infection still poses a significant health problem, especially in developing countries. While most of tuberculosis cases affect the pulmonary organ, this infection may also involve other organs such as bones and joints. Case presentation: We reported a case of 23-year-old female patient with a history of recurrent pain and swelling in the right knee.
On physical examination of the right knee, bulging sign was found, accompanied by tenderness, warmth on palpation, and limited active and passive movement. Radiographic examination was suggestive for septic arthritis in the right knee. Debridement and biopsy were performed, and TB PCR examination of the debridement tissue was found to be positive for Mycobacterium tuberculosis. The histopathological finding was also consistent with tuberculosis infection. The patient was subsequently treated with antituberculosis drugs and underwent rehabilitation therapy, resulting in a satisfying response. Conclusion: Diagnosis of tuberculosis arthritis in this case was established based on the presence of clinical symptoms, radiological findings, tissue TB PCR, and histopathological findings. Both surgical and pharmacological interventions were performed, which yielded favorable results. Tuberculosis arthritis was often misdiagnosed as arthritis for other causes, resulting in delays in providing medical intervention.
Therefore, increased understanding of tuberculosis arthritis is necessary to facilitate early diagnosis and improve therapeutic outcome.
Indonesian Journal of Rheumatology
Journal Homepage: https://journalrheumatology.or.id/index.php/IJR
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shortness of breath, fever, night sweats, or weight loss were denied. There were no manifestations of hair loss, facial redness upon sun exposures, mouth sores or skin lesions, and pain in other joints. She denied having any systemic diseases or a history of drug use.
Furthermore, there was no personal or family history of autoimmune disorders, and she had no known contact with tuberculosis or suspected tuberculosis patients.
Upon physical examination, the patient appeared moderately ill, with a blood pressure of 100/70 mmHg, pulse rate of 84 beats per minutes, respiratory rate of 18 breaths per minute, temperature of 36.5 ⁰C, and a Visual Analogue Scale (VAS) pain score of 6/10.
Abdominal examination revealed ascites with a positive shifting dullness examination. Other general physical examination findings were unremarkable. On physical examination of the right knee joint, bulging sign was found, accompanied by tenderness and warmth upon palpation. The patient experienced limited active and passive movement of the right knee joint due to pain and swelling, with a restricted range of motion limited to 70° on flexion and 0° on extension.
No redness, mass, or deformity was observed in the right knee (Figure 1).
Complete blood count revealed the following results: white blood cell count of 10.79 x103/µL, hemoglobin level of 11.6 g/dL, hematocrit of 38.5%,
and platelet count of 313 x103/µL. Markers of inflammation and infection were elevated, with procalcitonin at 0.04 ng/ml, erythrocyte sedimentation rate (ESR) at 35 mm/hour and C- reactive protein (CRP) at 6.4 mg/dl. Rheumatoid factor and antinuclear antibody indirect immunofluorescence (ANA IF) tests showed negative results.
Chest x-ray examination revealed that the pulmonary organ was within normal limits. However, anteroposterior (AP)/lateral x-ray of the right knee revealed periarticular osteopenia in the subchondral bone of the right tibia, accompanied by joint effusion in the right knee region and swelling of the surrounding soft tissue, suggestive of septic arthritis (Figure 2).
Synovial fluid aspiration showed a xanthochromic color. However, tuberculosis polymerase chain reaction (PCR) examination of the synovial fluid was negative for Mycobacterium tuberculosis. Sputum gene expert examination also showed no Mycobacterium tuberculosis. Ascitic fluid aspiration was performed on the patient, with negative TB PCR result.
Debridement and biopsy were also performed on the patient for both diagnostic and therapeutic purposes. Cytological examination of the joint fluid indicated a non-specific chronic inflammation.
Figure 1. Clinical picture of the knee joint before and during operative procedure.
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Histopathological examination of the joint tissue showed connective tissue containing several foci of granulomas, which consisted of proliferating epithelioid macrophages and a few peripheral lymphocytes, mostly with areas of caseous necrosis at the center. Additionally, multinucleated giant cells of the Langhan's type were observed in several foci at the edge of the necrosis. This histopathological finding was suggestive for tuberculosis (Figure 3). TB PCR
examination of the debridement tissue was positive for Mycobacterium tuberculosis. The patient was given the first category of antituberculosis drugs for 9 months.
After 3 months of therapy, improvement was noted in the swelling and pain of the right knee, along with improvement in joint movement. The patient has started to regain the ability to perform low intensity activities.
Figure 2. AP/lateral x-ray view of the right knee joint of the patient.
Figure 3. Histopathology examination shows A. caseating necrosis B. granuloma C. multinucleated giant cell Langhans.
3. Discussion
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis which can affect pulmonary or extra pulmonary organs. Skeletal tuberculosis may infect individuals of all age groups
and gender, although most cases are found in the first three decades of life, with equal distribution between women and men.5 This reported patient was in her second decade of life, which aligns with the epidemiological findings of tuberculosis arthritis.
A B C
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Tuberculosis arthritis is generally monoarticular, but can also be multifocal.1,6,7 Large, weight-bearing joints such as the hip and knee are the most common sites of involvement.6 Symptoms of tuberculosis arthritis are generally non-specific with slow or chronic disease course, which may lead to a delay in diagnosis.1,7 In the early stage of disease, tuberculosis of the knee joint usually presents with signs of inflammation. Infection may be accompanied by cold abscesses, tenosynovitis, muscle spasms and muscle weakness resembling paralysis. In advanced and severe cases, patients may experience joint movement disability.1
Tuberculosis arthritis patients may present with or without systemic symptoms.7 Classic constitutional symptoms associated with tuberculosis infection include subfebrile fever, weight loss, malaise, night sweats, and anorexia.1,7,8 These systemic symptoms are found in less than a third of cases.5 In the reported case, the patient presented with complaints of monoarticular joint pain and swelling, affecting a weight-bearing joint. The symptoms were chronic with a slow disease course. No systemic manifestations were found in the patient.
On physical examination, loss of muscle mass, local pain, enlarged regional lymph nodes and limited joint movement can be found. In advanced stages, other destructive findings such as abscesses, fistulas and deformities may be present.5 In the reported case, we observed signs of inflammation in the right knee in the form of swelling, tenderness, and warmth upon palpation, with limitation of active and passive movement. There was no regional lymphadenopathy or joint deformity.
The spread of tuberculosis to bone structures may occur through several mechanisms, namely through the hematogenous dissemination, lymphatic spread or per continuitatum.4 The mode of transmission of knee tuberculosis infection in this patient still requires further exploration. The patient did not have clinical manifestations consistent for pulmonary tuberculosis.
Investigations had also been carried out with the aim of confirming the absence of pulmonary tuberculosis
involvement. Chest radiography revealed a normal lung appearance, ruling out pulmonary tuberculosis.
Additionally, sputum gene expert examination was also performed with negative results. Previous studies have found that only half of bone and joint tuberculosis cases are accompanied by pulmonary involvement.6
The presence of ascites may indicate possible tuberculous involvement of gastrointestinal organ.
Peritoneal tuberculosis may manifest as the exudative type, adhesive type, or fibrotic-fixed type. The exudative type usually presents as ascites.9 In this patient, aspiration of ascitic fluid was performed, and TB PCR examination was done with negative result, thereby ruling out peritoneal tuberculosis infection.
In non-endemic areas, extra pulmonary tuberculosis generally occurs in immunosuppressed conditions, such as in individuals with Human Immunodeficiency Virus (HIV) infection, diabetes mellitus, alcoholism, malignancy, or in patients receiving immunosuppressant therapy. In addition, local injuries such as trauma, surgery or the use of intravenous drugs can be a precipitating factor for skeletal tuberculosis.6 However, in this patient there were no known risk factors that could have triggered skeletal tuberculosis infection. Prior history of systemic disease, use of immunosuppressant drugs and history of trauma around the right knee were not found. Literature stated that the previously mentioned systemic and local tuberculosis risk factors may not be found in endemic areas of tuberculosis such as Indonesia.6
Synovial fluid examination is one of the diagnostic methods of tuberculosis arthritis. Findings include increased volume of synovial fluid, which is non- hemorrhagic and cloudy in color, containing fibrin, with cell count ranging from 10,000 to 20,000 cells/µl and a predominance of mononuclear cells.1 In this patient, synovial fluid aspiration was performed, but unfortunately only a minimum amount of synovial fluid was obtained, hence a complete analysis of synovial fluid could not be carried out.
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Identification of Mycobacterium tuberculosis is essential for the definitive diagnosis of tuberculosis arthritis. Traditionally, the diagnosis of tuberculosis is made through microscopic examination of Acid-fast Bacteria or culture of bodily fluids and tissues.
Currently, molecular tests for the diagnosis of tuberculosis have been developed and are widely available. PCR examination is one of the most commonly used molecular tests for the diagnosis of tuberculosis.7
TB PCR examination of the patient's synovial fluid was found to be negative for Mycobacterium tuberculosis, while the debridement tissue samples showed positive results. There are several possible causes of TB PCR low sensitivity of synovial fluid, which include paucibacillary disease, degradation of the organism by phagocytosis or other components of the immune system, initiation of tuberculosis therapy prior to examination, degradation of samples during transfer or storage, or uneven distribution of Mycobacterium tuberculosis in the sample.7,9 In this case, the minimal amount of synovial fluid sample obtained may have contributed to the negative TB PCR results, as previous literature states that too little specimen may cause inadequate target DNA extraction, leading to false negatives.
Imaging can be useful in confirming suspected tuberculosis arthritis. Conventional radiography is generally used as initial imaging for the evaluation of tuberculosis despite its limitations in detecting articular involvement in the early stage of disease.1,6 Initial radiological examination shows soft tissue swelling which can eventually develop into osteopenia, periosteal thickening and periarticular bone destruction.7 In the appendicular skeleton, the presence of Phemister's Triad which consists of juxta- articular osteopenia/osteoporosis, peripheral osseous erosion, and gradual joint space narrowing, is suggestive for tuberculosis arthritis but is not specific and is generally only seen in the advanced phase of arthritis.5 In this patient, periarticular osteopenia was found in the subchondral bone of the right tibia accompanied by joint effusion in the right knee region
and swelling of the surrounding soft tissue. These radiological findings are suggestive of septic arthritis, but is not specific for tuberculosis infection.
Computed Tomography (CT) scans and Magnetic Resonance Imaging (MRI) of bones and joints are useful for evaluating the extent of bone damage, soft tissue abscesses and soft tissue swelling around the lesion. However, there are no pathognomonic radiological findings for bone and joint tuberculosis.1
The gold standard for diagnosis of tuberculosis arthritis is through synovial biopsy.1 Histopathological examination plays an important role in the diagnosis of extra pulmonary tuberculosis.2 The pathological lesion in tuberculosis infection is tuberculoma, characterized by central necrosis surrounded by epithelioid cells, giant cells, and mononuclear cells.5 In this patient, debridement and synovial biopsy were performed, followed by cytological and histopathological examination. Cytological examination revealed non-specific chronic inflammation. Histopathological examination showed some of the typical features of tuberculosis infection, including granulomas with areas of caseous necrosis, multinucleated giant cells of Langhan's type, and mononuclear cell infiltration.
The main principle of tuberculosis infection management is through administration of effective and appropriate anti-tuberculosis therapy regimen.1 Based on National Guideline of Tuberculosis Management from the Indonesian Ministry of Health, treatment for bone and joint tuberculosis should be given for 9-12 months. Therapy may be extended to 18 months in certain cases, especially if there is no clinical improvement. The standard treatment regimen comprises of a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months followed by isoniazid and rifampicin for 10 to 16 months (2RHZE/10-16RH). The longer duration of the therapeutic regimen compared to pulmonary tuberculosis infection is necessary considering the weak drug penetration into bone and fibrous tissue and the difficulty in monitoring treatment response.10
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Surgical therapy is generally performed for diagnostic purposes, drainage of abscess in case of minimal response to oral therapy, or in large abscesses to reduce intraarticular pressure. Medical rehabilitation is required following bone and joint surgery.1 This patient underwent debridement followed by antituberculosis drug therapy for 9 months with the 2HRZE/7HR regimen according to recommendations from the Indonesian Ministry of Health. Response to therapy was assessed through clinical indicators such as pain, constitutional symptoms, mobility, and neurological signs.
Improperly treated tuberculosis arthritis carries the risk of joint space destruction, ankylosis, secondary osteoarthritis, and disseminated tuberculosis, which further increase morbidity and mortality.7 Therefore, it is necessary to ensure the administration of appropriate medical therapy and physiotherapy in patients with tuberculosis arthritis to achieve favorable clinical outcomes. In most cases, continuous medical monitoring is required to evaluate potential complications of the disease.2
4. Conclusion
This report presents a case of 23-year-old female with a diagnosis of tuberculosis arthritis. The diagnosis was established by the presence of clinical symptoms of arthritis accompanied by radiological evidence suggestive of septic arthritis, positive tissue TB PCR results, and histopathological findings. The patient underwent debridement and was given antituberculosis drug therapy, resulting in a favorable response. Early recognition of tuberculosis arthritis and the provision of appropriate therapy are crucial to prevent functional disability that may affect the patient's quality of life.
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