The global burden of tuberculosis (TB) has been overwhelmingly high throughout the last century and continues to pose a major public health threat, especially to the developing and underdeveloped nations. India being the second-most populous country houses one-quarter of the global TB burden. As per recent national statistics, extrapulmonary TB (EPTB) accounts for 15%–20% of all cases of TB, of which skeletal TB amounts up to one-third of EPTB. Articular TB predominantly affects large joints such as the hip and knee. The atypical presentations of EPTB and difficulty in procuring tissue specimens can pose diagnostic challenges. Therefore, the development of schematic approaches and education at the primary care level for the early diagnosis of joint TB will be extremely useful. We present this case study and propose an algorithmic approach to monoarthritis [Figure 1] to highlight the inordinate delay in the diagnosis of joint TB which could have been easily diagnosed by the judicious application of resources available through the Revised National TB Control Program (RNTCP).
A 40-year-old male presented to our tertiary care referral teaching hospital with pain and swelling of the right knee for the past 1½ years. He is a factory worker by occupation who lives more than 2000 km away. The symptoms were insidious in onset, progressed gradually and were accompanied by low-grade intermittent fever. Six months back, he was treated for respiratory tract infection with antibiotics. In addition, he had a significant weight loss of about 9 kg and loss of appetite in the past 6 months. He denied similar complaints in the left knee or any other joint. There was no history of inflammatory back pain, skin rash, orogenital ulcers, gastrointestinal, or urinary tract infection in the past or before the onset of symptoms. No past history of TB, exposure to TB, or inflammatory arthritis in the family.
On evaluation, there was evidence of right knee synovitis with terminal restriction of movement [Figure 2]. Rest of the musculoskeletal examination and systemic examination was noncontributory.
His prior set of laboratory evaluations was consistent with ongoing inflammation (erythrocyte sedimentation rate-66 mm/h and C-reactive protein (CRP)-5.29 mg/dl). Anti-citrullinated peptide antibody, rheumatoid factor, human leukocyte antigen B27, HIV, and the Mantoux test were negative. Bilateral knee X-ray was performed which showed right knee effusion and trabecular enhancement suggestive of mild juxta-articular osteopenia [Figure 3a and b] consistent with synovitis which was corroborated by ultrasound examination [Figure 4].
On synovial fluid analysis, the fluid appeared serosanguinous, total count (614 cells/cumm), neutrophils (90%), and lymphocytes (10%) suggestive of noninflammatory etiology. However, GeneXpert, a cartridge-based nucleic acid amplification test (CBNAAT), detected high titers of Mycobacterium tuberculosis (MTB), without any resistance to RIF. The patient was further evaluated to identify the primary focus of TB but was noncontributory
The patient was initiated on anti-tubercular treatment (DOTS regimen) as per RNTCP protocol. On reviewing the patient after a month, he is doing better, with decreased pain and swelling.
Diagnosis of osteoarticular TB continues to be troublesome. Traditionally, smear microscopy and cultures have been used as diagnostic modalities; however, smear microscopy has variable sensitivity (45%–80%), with poor detection in EPTB. GeneXpert for EPTB showed a sensitivity of 81.6% and a specificity of 78.9%, outperforming the conventional AFB microscopy that showed a sensitivity and specificity of 63.2% and 70.5%, respectively. Conventional solid culture as well as newer liquid culture techniques have a long turnaround time of 2–6 weeks and 21 days, respectively. CBNAAT was developed for rapid detection of TB and for the identification of drug resistance. This technology permits the identification of MTB not only in the sputum, but also in extrapulmonary samples including synovial fluid. As per India TB report (2019), CBNAAT facilities for rapid diagnosis of MTB have been established at district levels and subdistrict levels (n = 1180).
The Xpert MTB/RIF assay is a fully automated nucleic acid amplification test that uses a disposable cartridge with the GeneXpert Instrument System (CBNAAT). GeneXpert MTB/RIF can detect both the presence of the MTB complex genome in test specimens as well as the presence of genomic sequences of the main mutations responsible for rifampicin resistance (rpoB gene mutation). Other advantages of the Xpert MTB/RIF assay include rapidity of results (within 2 h) and minimal requirement for technical training to run the test. World Health Organization (WHO) has approved Xpert® MTB/Rif for the diagnosis of PTB, EPTB, HIV-associated TB, and TB meningitis in adults and children. In a meta-analysis performed by Wen et al., the pooled sensitivity and specificity of Xpert MTB/RIF for bone and joint TB were 81% (95% confidence interval [CI], 78–83) and 83% (95% CI, 80–86), respectively.
The negative predictive value (NPV) of GeneXpert MTB/RIF for extrapulmonary samples (97%) is of immense value in eliminating the diagnosis of TB. According to WHO, the NPV of GeneXpert MTB/RIF exceeds 99% regardless of the TB population prevalence rate making it possible to exclude with assurance the diagnosis of TB.
The gold standard for diagnosis of tubercular synovitis remains synovial histopathology. In comparison to histopathology, the Xpert MTB/RIF assay has a sensitivity and specificity of 79.3% (73.5–85.1%) and 73.7% (67.8–79.6%), respectively. Therefore, although arthroscopic synovial biopsy gives the definite diagnosis for osteoarticular TB, the easy availability, noninvasive technology, and rapid turnaround time make GeneXpert MTB/RIF the investigation of choice. Further, the synovial fluid is rather easy to aspirate from large joints either as a blind procedure or under ultrasound guidance in an outpatient setting. The synovial fluid perse, the detection rates for acid-fast bacilli are quite low 10%–20%, and cytological examinations are rather noninflammatory and unable to point toward a diagnosis or differentials. Further, the conventional radiologic or ultrasound examination or magnetic resonance imaging of affected joints also reveals rather nonspecific changes.
In our case report, the synovial fluid aspiration was noninflammatory; however, the Genexpert clinched the diagnosis. We have proposed an algorithmic approach and emphasized the application of modern diagnostic technologies such as Genexpert for an accurate diagnosis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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