A 67-year-old lady with a background of Chronic Sero-negative Arthritis being treated as Rheumatoid Arthritis, and Systemic Hypertension was referred to our hospital with progressive deterioration of sensorium over the past two months, and a high-grade fever since two weeks prior with a diagnosis of a urinary tract infection. An extensive workup was done, with PET-CT proving useful, and subsequent knee biopsy culture growing Mycobacterium Tuberculosis (TB), with other lesions suggestive of TB in her spine and meninges, and an abscess in her left elbow joint. A modified regimen of anti tubercular treatment was started, which arrested further deterioration. We wish to highlight the diagnostic dilemma we had, and the treatment hurdles we faced in this patient, even with a multidisciplinary approach and the best of resources. We also wish to highlight the differential of Tuberculosis in a patient with chronic sero-negative arthritis, especially in the Indian subcontinent.
Tuberculosis (TB) is a leading cause of mortality as it stems from a pandemic infectious agent. Osteoarticular TB represents 1-5% of all cases of TB disease and 10-18% of extrapulmonary involvement with the spine being the most commonly affected followed by major weight bearing joints. It often affects multiple organs through the hematogenous spread of Mycobacterium tuberculosis, but knee-joint involvement is extremely rare, comprising approximately 0.1% of all forms of tuberculosis.  In this manuscript, we present the case of a patient diagnosed to have disseminated TB with active synovial TB of her knee having been the source, which went undetected for a considerable period of time.
A 67-year-old lady with a background of Chronic Sero- negative Arthritis being treated as Rheumatoid Arthritis, Systemic Hypertension was referred to our hospital with progressive deterioration of sensorium from the past two months, and high grade fever since two weeks, with a diagnosis of a Urinary Tract Infection (UTI). She also has history of decreased appetite and weight loss for the last two months. In the past, she had a history of anemia, high CRP and high ESR for 2 years, with seronegative arthritis after extensive testing. She was being treated with Methotrexate as having probable Rheumatoid arthritis. On examination, she was drowsy, appeared cachexic and anemic. She was also tachycardic, tachypneic and had an elevated blood pressure. Neurological examination revealed her to be drowsy and disoriented. A Computerized Tomography (CT) scan of the brain was completed in view of her delirious state, and it was normal. Blood investigations showed elevated total white blood cell count, CRP, ESR, deranged renal function test and hypercalcemia. Routine urine tests revealed numerous pus cells. Considering the arthritis history, and extensive involvement of left knee joint, right elbow, Magnetic Resonance (MR) of the knee joint was taken, which showed chronic inflammatory and active arthritis (Fig 1.& Fig 2).
An arthroscopic biopsy from knee joint was taken, which revealed chronic granulomatous synovitis. A Tuberculosis (TB) diagnostic panel comprising of Ziel-Nielson stain smear, Card based nucleic acid amplification test (CBNAAT) and TB culture was done on the Knee biopsy sample. The smear and CBNAAT were negative. A Gamma interferon assay for TB was also negative. Blood culture was of no growth, while the urine culture grew E. coli, and she was started on IV Meropenem for the same. She then underwent a (18) F-FDG PET/CT scan, which showed FDG avid lytic areas in L3 & L4 vertebrae and necrotic areas in the left Psoas muscle, FDG avid bilateral elbow joints. (Fig 3). MR brain and spine showed signs of multiple infarcts, secondary to vasculitis, Arachnoiditis and an abscess between L3 & L4. In the meantime, she was worked up for Multiple myeloma, with Serum electrophoresis revealing no M band, but elevated serum Kappa of 51.80 mg/L (3.3-19.4 mg/L) and serum Lambda of 50.80 mg/L (5.71-26.30 mg/L). In view of persistent drowsiness and fever, a lumbar puncture was done, which showed elevated protein, with normal level of ADA and culture having no growth. An Infectious disease opinion was taken and in view of high possibility of Disseminated TB, a modified regimen of ATT (Isoniazid, Rifampicin, Pyrazinamide and Ethambutol with linezolid & Levofloxacin) was started. She was also treated with I.V antibiotics, antipyretics, proton pump inhibitors and other supportive measures. After about a week, her TB diagnostic panel culture grew Mycobacterium tuberculosis complex. A diagnosis of Tuberculosis was confirmed. As her relatives wanted to take her to a nearby local medical facility, she was discharged on request to a smaller center for further care.
This case proved a diagnostic as well as therapeutic challenge. Diagnosis can be difficult, and delay can cause harm, but most people with Extrapulmonary-Tuberculosis Complex can be cured if they have access to diagnosis and treatment with anti-TB drugs in time.  In our patient, she possibly had active synovial Tuberculosis of her knee, which went undetected for a period spanning 2 years. It then disseminated, and she presented with an acute deterioration in mental status and fever. She did have a super-imposed UTI, which was treated with culture sensitive antibiotics, but her symptoms persisted in spite of this. This led to the workup for a more sinister pathology, and after extensive workup, she was found to have TB, with the primary focus in her knee, with other foci in the elbow, spine and para-spinal muscles, which was responsible for her chronic seronegative granulomatous arthritis. The nonspecific, often indolent, clinical presentation of osteoarticular TB, together with its low prevalence and the low index of suspicion among clinicians, may result in delay in its diagnosis. We also wish to highlight the effectiveness of a (18) F-FDG PET/CT in the early diagnosis of such a case of Inflammation of unknown origin (IUO). In IUO. (18) F-FDG PET/CT has the potential to become a cost- effective routine imaging technique indicating the direction for further diagnostic decisions thereby allowing unnecessary, invasive and expensive diagnostic investigations to be avoided and possibly the duration of hospitalization to be reduced. Tuberculosis should be high on the index of suspicion for a patient with seronegative chronic inflam-matory arthritis, especially in the Indian Subcontinent. In suspected TB cases, early biopsy and appropriate testing for TB in addition to the routine investigation, is key. Our patient went undiagnosed for a period of 2 years, until the disease was disseminated and this posed a therapeutic challenge. We feel that, if the disease is diagnosed in a timely fashion, early initiation of treatment could potentially reduce the overall morbidity and improve the outcome in similar patients.
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