Abstract
Tuberculosis (TB) primarily involves the respiratory tract, but any
organ in the body can be affected. In recent years, extrapulmonary TB
cases have significantly increased due to the prevalence of
immunocompromised patients. Here, we report a case of unilateral ankle
arthritis due to Mycobacterium tuberculosis infection.
Keywords: Tuberculosis, Arthritis, Infection
Introduction
Tuberculosis (TB) primarily involves the respiratory tract, but any
organ in the body can be affected [1]. In recent years, due to the
prevalence of human immunodeficiency virus (HIV) infection and the
widespread use of immunosuppressants in various settings, the prevalence
of extrapulmonary TB manifestations has significantly increased [2],
which may or may not be accompanied by active pulmonary involvement
[3]. Bone and joint involvement comprise up to 10% of
extrapulmonary TB, approximately half of which are accompanied by
pulmonary involvement [4, 5]. In addition, bone and joint TB is
divided into spinal and arthritic (synovial) diseases. Tuberculosis
spondylitis has a significantly high prevalence, particularly in endemic
areas. However, peripheral arthritic involvement has been rarely
reported [6]. Here, we report a case of unilateral ankle arthritis
due to Mycobacterium tuberculosis infection.
Case Report
A 90-year-old man presented to the infectious disease clinic with a
draining ulcer on his left ankle. He complained about this problem for
the past 2 years, causing him to undergo various courses of
antimicrobial treatment, with no complete resolution. His past medical
history was not significant, except for hypertension. On physical
examination, tenderness, and induration, in addition, a fistulized ulcer
with the discharge was detected on the affected ankle. Moreover, an
obvious limitation of motion was evident in the joint. Abnormalities in
her laboratory tests included an elevated erythrocyte sedimentation rate
(ESR) (103 mm/h, reference value: < 30 mm/h) and C-reactive
protein (CRP) (28 mg/L, reference value: < 10 mg/L) levels,
moderate anemia (hemoglobin = 10 g/dL, reference value: 13-17 g/dL),
mild azotemia (creatinine = 1.5 mg/dL, reference value: < 1.2
mg/dL), and an active urine analysis (U/A) (WBC = 15-20, bacteria: many,
nitrite: positive). The serologic evaluation was negative for
brucellosis and viral markers, including HIV and hepatitis B (HBV) and C
(HCV) viruses. The plain radiography showed severe subchondral erosions
and extensive destructive lesions in the left ankle, intertarsal, and
tarsometatarsal joints, in addition to diffuse osteoporosis and
periarticular soft tissue swelling.
After an orthopedic surgery consultation, magnetic resonance imaging
(MRI) of the affected foot and articular biopsy under an ultrasound
guide were recommended. Although MRI was not performed as the patient
did not consent, she gave his consent to undergo tissue sampling. After
taking the biopsy, a chest high-resolution computed tomography (HRCT)
scan was performed, demonstrating hyperdense mediastinal lymph nodes,
diffuse nodules, with a tree-in-bud pattern, almost in the right upper
lobe, along with cicatricial atelectasis and fissure thickening in the
right lung. All the mentioned findings were compatible with pulmonary
tuberculosis (TB). Therefore, his sputum sample was drawn and sent for
acid-fast staining, culture, and Xpert MTB/RIF assay. Furthermore, the
patient was started on quadruple antituberculosis treatment (isoniazid
300 mg daily, rifampin 600 mg daily, ethambutol 15 mg daily, and
pyrazinamide 20 mg daily) with dose adjustment due to his mildly
increased creatinine. The histopathology was indicative of granuloma
formation compatible with tuberculosis. His polymerase chain reaction
(PCR) test indicated rifampin-sensitive Mycobacterium
tuberculosis . Therefore, we continued anti-TB treatment. His pain and
swelling had improved significantly at one-month follow-up, and the
discharge had stopped.
Discussion
Tuberculosis arthritis occurs either as an infection spread from the
adjacent bone or due to hematogenous spread from a distant organ, such
as the lungs [7]. In non-endemic areas, extrapulmonary TB usually
occurs in the context of an immunosuppression state, such as HIV,
chronic diseases like diabetes mellitus, alcoholism, and cancer, or
being treated by corticosteroids or immunomodulators. Moreover, local
injury, such as trauma, surgery, or intravenous drug use, can
precipitate TB reactivation in the adjacent joints. However, none of the
mentioned conditions might be present in endemic areas [8-10], and
our patient did not have any of those risk factors.
The process of arthritic involvement by Mycobacterium
tuberculosis is indolent and insidious that initially begins with
simple synovitis, depicted by increased joint space in the imaging
modalities. Then, granulation tissue formation, effusion, pannus
formation, and cartilage destruction ensue. In the next stage, the
underlying bone might be affected, or para-articular cold abscesses
form, which result in fistulae formation and draining sinus tract
[11]. Tuberculosis arthritis usually presents with a monoarticular
pattern. Large and medium weight-bearing joints like the hip, and the
knee, are the most common sites of involvement in peripheral TB
arthritis [12]. Nonetheless, a proportion present with foot or ankle
joint involvements [13]. In any sub-acute to chronic arthritis, we
should consider tuberculosis as a potential differential diagnosis. This
is especially true for those cases of arthritic involvement with a
draining sinus tract to the overlying skin [14, 15].
As happened for our patient, the diagnosis of TB arthritis is often
delayed since it is repeatedly misdiagnosed as septic or reactive
arthritis and treated accordingly [15]. Therefore, a high index of
suspicion is needed for timely detection. In order to confirm the
diagnosis, the synovial fluid should be stained for acid-fast bacteria
(AFB), and a synovial biopsy should be drawn [16]. Demonstration of
granulomatous synovitis can indicate TB [16], as happened in our
patient. However, since the diagnosis of TB arthritis is mainly based on
clinical suspicion, and our patient had concomitant pulmonary findings
indicative of TB, he was immediately started on antituberculosis
treatment rather than waiting for the synovial biopsy results. Hence,
detecting a simultaneous pulmonary TB can be a clue for tuberculosis as
the cause of extrapulmonary involvement [17]. The concomitant
pulmonary involvement can be easily identified with imaging modalities
like chest X-ray (CXR) or lung CT scan. However, sending sputum culture
for PCR is mandated since some cases of pulmonary TB have normal
pulmonary patterns on the imaging modalities [18]. Moreover, culture
and Xpert MTB/RIF assay are specific tools for identifying the isolate’s
antibiotic susceptibility [19]. Fortunately, our patient had both
imaging abnormalities indicative of TB and positive sputum Xpert MTB/RIF
assay results, indicating a rifampin-sensitive isolate. Moreover, the
histopathologic findings of his joint further confirmed our diagnosis.
Imaging modalities can also be beneficial in confirming TB arthritis
suspicion. Plain radiography cannot aid the clinician in detecting the
articular involvement early since the so-called Phemister triad,
including juxta-articular osteoporosis, peripheral osseous erosions, and
gradual joint space narrowing, is evident in later stages of TB
arthritis [20]. Nonetheless, due to the delayed diagnosis, our
patient did have these findings on his plain radiography. It is of note
that MRI is a better choice in showing the associated abnormalities,
such as joint effusion, loose bodies, and calcifications, but
unfortunately, our patient did not consent for it [12].
Finally, the treatment strategy for TB arthritis includes
pharmacological therapy and surgical options in certain conditions.
Medical therapy consists of the conventional four-drug regimen for at
least 9 months [21].
Conclusion
Although TB is rarely seen in developed countries, it is still an
important public health issue in developing countries. This infection
primarily manifests with pulmonary involvements, but extrapulmonary TB
signs and symptoms are also widely reported, such as TB arthritis. When
suspected, different imaging modalities (e.g., CXR) could help diagnose
this condition, but further confirmation with molecular methods, such as
PCR, is mandated. Moreover, culture and Xpert MTB/RIF assay could be
beneficial in identifying the isolate’s susceptibility to antibiotics.
Then, a conventional four-drug regimen for at least 9 months should be
initiated for the patients, with further pharmacological and surgical
options if indicated.