Indonesian Journal of Rheumatology Vol 15 Issue 1 2023

Indonesian Journal of
Rheumatology
Journal Homepage: https://journalrheumatology.or.id/index.php/IJR

Tuberculosis Arthritis: A Diagnostic Challenges

Desak Putu Gayatri Saraswati Seputra1*, Pande Ketut Kurniari1
1 Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia

ARTICLE INFO ABSTRACT

Keywords: Background: Tuberculosis infection still poses a significant health problem,
Arthritis especially in developing countries. While most of tuberculosis cases affect
Knee 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
Tuberculosis 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,
*Corresponding author: accompanied by tenderness, warmth on palpation, and limited active and
Desak Putu Gayatri Saraswati Seputra 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
E-mail address: Mycobacterium tuberculosis. The histopathological finding was also
consistent with tuberculosis infection. The patient was subsequently treated
gayatri_saraswati@yahoo.com with antituberculosis drugs and underwent rehabilitation therapy, resulting
in a satisfying response. Conclusion: Diagnosis of tuberculosis arthritis in
All authors have reviewed and approved the this case was established based on the presence of clinical symptoms,
final version of the manuscript. 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
https://doi.org/10.37275/IJR.v15i1.237 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.

1. Introduction hematogenous, lymphogenous, and per continuitatum

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
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,

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shortness of breath, fever, night sweats, or weight loss and platelet count of 313 x103/µL. Markers of
were denied. There were no manifestations of hair loss, inflammation and infection were elevated, with
facial redness upon sun exposures, mouth sores or procalcitonin at 0.04 ng/ml, erythrocyte
skin lesions, and pain in other joints. She denied sedimentation rate (ESR) at 35 mm/hour and C-
having any systemic diseases or a history of drug use. reactive protein (CRP) at 6.4 mg/dl. Rheumatoid factor
Furthermore, there was no personal or family history and antinuclear antibody indirect
of autoimmune disorders, and she had no known immunofluorescence (ANA IF) tests showed negative
contact with tuberculosis or suspected tuberculosis results.
patients. Chest x-ray examination revealed that the
Upon physical examination, the patient appeared pulmonary organ was within normal limits. However,
moderately ill, with a blood pressure of 100/70 mmHg, anteroposterior (AP)/lateral x-ray of the right knee
pulse rate of 84 beats per minutes, respiratory rate of revealed periarticular osteopenia in the subchondral
18 breaths per minute, temperature of 36.5 ⁰C, and a bone of the right tibia, accompanied by joint effusion
Visual Analogue Scale (VAS) pain score of 6/10. in the right knee region and swelling of the
Abdominal examination revealed ascites with a surrounding soft tissue, suggestive of septic arthritis
positive shifting dullness examination. Other general (Figure 2).
physical examination findings were unremarkable. On Synovial fluid aspiration showed a xanthochromic
physical examination of the right knee joint, bulging color. However, tuberculosis polymerase chain
sign was found, accompanied by tenderness and reaction (PCR) examination of the synovial fluid was
warmth upon palpation. The patient experienced negative for Mycobacterium tuberculosis. Sputum
limited active and passive movement of the right knee gene expert examination also showed no
joint due to pain and swelling, with a restricted range Mycobacterium tuberculosis. Ascitic fluid aspiration
of motion limited to 70° on flexion and 0° on extension. was performed on the patient, with negative TB PCR
No redness, mass, or deformity was observed in the result.
right knee (Figure 1). Debridement and biopsy were also performed on
Complete blood count revealed the following the patient for both diagnostic and therapeutic
results: white blood cell count of 10.79 x103/µL, purposes. Cytological examination of the joint fluid
hemoglobin level of 11.6 g/dL, hematocrit of 38.5%, 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 examination of the debridement tissue was positive for
showed connective tissue containing several foci of Mycobacterium tuberculosis. The patient was given the
granulomas, which consisted of proliferating first category of antituberculosis drugs for 9 months.
epithelioid macrophages and a few peripheral After 3 months of therapy, improvement was noted in
lymphocytes, mostly with areas of caseous necrosis at the swelling and pain of the right knee, along with
the center. Additionally, multinucleated giant cells of improvement in joint movement. The patient has
the Langhan's type were observed in several foci at the started to regain the ability to perform low intensity
edge of the necrosis. This histopathological finding was activities.
suggestive for tuberculosis (Figure 3). TB PCR

Figure 2. AP/lateral x-ray view of the right knee joint of the patient.

A B C

Figure 3. Histopathology examination shows A. caseating necrosis B. granuloma C. multinucleated giant cell
Langhans.

3. Discussion and gender, although most cases are found in the first
Tuberculosis is an infectious disease caused by three decades of life, with equal distribution between
Mycobacterium tuberculosis which can affect women and men.5 This reported patient was in her
pulmonary or extra pulmonary organs. Skeletal second decade of life, which aligns with the
tuberculosis may infect individuals of all age groups epidemiological findings of tuberculosis arthritis.

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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 and swelling of the surrounding soft tissue. These
essential for the definitive diagnosis of tuberculosis radiological findings are suggestive of septic arthritis,
arthritis. Traditionally, the diagnosis of tuberculosis is but is not specific for tuberculosis infection.
made through microscopic examination of Acid-fast Computed Tomography (CT) scans and Magnetic
Bacteria or culture of bodily fluids and tissues. Resonance Imaging (MRI) of bones and joints are
Currently, molecular tests for the diagnosis of useful for evaluating the extent of bone damage, soft
tuberculosis have been developed and are widely tissue abscesses and soft tissue swelling around the
available. PCR examination is one of the most lesion. However, there are no pathognomonic
commonly used molecular tests for the diagnosis of radiological findings for bone and joint tuberculosis.1
tuberculosis.7 The gold standard for diagnosis of tuberculosis
TB PCR examination of the patient's synovial fluid arthritis is through synovial biopsy.1 Histopathological
was found to be negative for Mycobacterium examination plays an important role in the diagnosis
tuberculosis, while the debridement tissue samples of extra pulmonary tuberculosis.2 The pathological
showed positive results. There are several possible lesion in tuberculosis infection is tuberculoma,
causes of TB PCR low sensitivity of synovial fluid, characterized by central necrosis surrounded by
which include paucibacillary disease, degradation of epithelioid cells, giant cells, and mononuclear cells.5
the organism by phagocytosis or other components of In this patient, debridement and synovial biopsy were
the immune system, initiation of tuberculosis therapy performed, followed by cytological and
prior to examination, degradation of samples during histopathological examination. Cytological
transfer or storage, or uneven distribution of examination revealed non-specific chronic
Mycobacterium tuberculosis in the sample.7,9 In this inflammation. Histopathological examination showed
case, the minimal amount of synovial fluid sample some of the typical features of tuberculosis infection,
obtained may have contributed to the negative TB PCR including granulomas with areas of caseous necrosis,
results, as previous literature states that too little multinucleated giant cells of Langhan's type, and
specimen may cause inadequate target DNA mononuclear cell infiltration.
extraction, leading to false negatives. The main principle of tuberculosis infection
Imaging can be useful in confirming suspected management is through administration of effective and
tuberculosis arthritis. Conventional radiography is appropriate anti-tuberculosis therapy regimen.1 Based
generally used as initial imaging for the evaluation of on National Guideline of Tuberculosis Management
tuberculosis despite its limitations in detecting from the Indonesian Ministry of Health, treatment for
articular involvement in the early stage of disease.1,6 bone and joint tuberculosis should be given for 9-12
Initial radiological examination shows soft tissue months. Therapy may be extended to 18 months in
swelling which can eventually develop into osteopenia, certain cases, especially if there is no clinical
periosteal thickening and periarticular bone improvement. The standard treatment regimen
destruction.7 In the appendicular skeleton, the comprises of a combination of isoniazid, rifampicin,
presence of Phemister's Triad which consists of juxta- pyrazinamide, and ethambutol for 2 months followed
articular osteopenia/osteoporosis, peripheral osseous by isoniazid and rifampicin for 10 to 16 months
erosion, and gradual joint space narrowing, is (2RHZE/10-16RH). The longer duration of the
suggestive for tuberculosis arthritis but is not specific therapeutic regimen compared to pulmonary
and is generally only seen in the advanced phase of tuberculosis infection is necessary considering the
arthritis.5 In this patient, periarticular osteopenia was weak drug penetration into bone and fibrous tissue
found in the subchondral bone of the right tibia and the difficulty in monitoring treatment response.10
accompanied by joint effusion in the right knee region

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 Surgical therapy is generally performed for therapy: a case report. Jurnal Respirasi. 2021;
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to reduce intraarticular pressure. Medical DD. Tuberculosis of the knee: A pitfalls in
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