INTRODUCTION
Worldwide, the annual incidence of tuberculosis (TB) is recorded as 10 million, of which 2.7 million are reported in India.[1,2] Disseminated TB (dTB) generally involves elderly and immunocompromised patients. It is commonly associated with increased morbidity and mortality and accounts for 1%–5% of TB cases.[3] As the clinical presentation of dTB is protean in nature, it may have subacute or chronic constitutional symptoms such as fever, weight loss, and night sweats. The symptoms and signs may progress over days to weeks or sometimes over several months. Here, we present a case of dTB in an immunocompetent individual.
CASE REPORT
A 27-year-old female, with no prior comorbidities, came to the pulmonology outpatient department with a history of loss of weight of 18 kg in the last 6 months, loss of appetite, intermittent high-grade fever for 3 months, evening rise of temperature, and dry cough for 1 month. Clinical examination revealed that the patient was anaemic, with multiple firm cervical and axillary lymph nodes bilaterally. She is not a diabetic. On respiratory examination, the patient had normal vesicular breath sounds bilaterally. Investigations revealed white cell count - 13,100 cells/mm3, platelets - 120,000 cells/mm3, hemoglobin of 6.3 g/dl, erythrocyte sedimentation rate - 50 mm in 1/2 h, and 101 mm in 1 h. Liver and renal profile was normal. Hepatitis B surface antigen, hepatitis C virus and HIV antibodies, were negative. Chest X-ray revealed bilateral non-homogeneous infiltrates, predominantly in the lower zones. Computed tomography (CT) of the chest showed bilateral alveolar opacities and enlarged mediastinal, para-tracheal, hilar, and sub-carinal lymph nodes [Figure 1]. CT of the abdomen revealed enlarged para-aortic, mesenteric, and iliac lymph nodes, along with hepatosplenomegaly [Figure 2].
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Figure 1: Computed tomography chest: Bilateral alveolar nodular opacities with tree in bud appearance
Figure 2: Computed tomography abdomen: Enlarged para-aortic nodes
Right cervical lymph node excision biopsy was done and sent for histopathological examination (HPE) and microbiological investigations. HPE revealed extensive caseous necrosis, suggestive of tuberculous lymphadenitis [Figure 3]. Truenat detected Mycobacterium tuberculosis (MTB), with rifampicin (RIF) resistance from the lymph node [Figures 4 and 5]. Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) was performed with bronchoalveolar fluid (BAL) which detected MTB, but no RIF resistance [Figure 6]. Acid-fast bacillus (AFB) culture after 6 weeks did not grow MTB from the lymph node.
Figure 3: Histopathology-lymph node-caseating tuberculous lymphadenitis
Figure 4: Truenat detected Mycobacterium tuberculosis in lymph node
Figure 5: Truenat detected rifampicin resistance in lymph node
Figure 6: Cartridge-Based Nucleic Acid Amplification Test detected Mycobacterium tuberculosis, and no rifampicin resistance in bronchoalveolar fluid
She was started on first-line antitubercular treatment (ATT) as BAL CBNAAT revealed no RIF resistance. She had significant clinical recovery after 1 month of ATT.
DISCUSSION
DTB is due to progressive primary infection or reactivation of latent infection following lymphohematogenous spread. The exact mechanism of pathogenesis is not clear. One suggested mechanism is that lung TB causes erosion of alveolar epithelium and spreads to the pulmonary vein. The bacilli enter the left side of the heart and reach the systemic circulation, where they multiply and affect extrapulmonary organs. The bacilli also affect the alveolar epithelium, reach the lymph nodes, and enter the systemic venous circulation, circulating back to the lungs through the right heart, resulting in miliary tuberculosis. These two forms of dissemination can occur together or separately.[4] Dissemination rarely occurs due to iatrogenic infection following renal system instrumentation, surgical intervention for tuberculous epididymitis, intravesical Bacillus Calmette–Guerin (BCG) immunotherapy for transitional bladder cancer, or organ transplantation involving an unnoticed infected kidney or homograft valve.[5] Risk factors for TB are immunocompromised states such as HIV, diabetes mellitus, drugs, alcohol abuse, smoking, overcrowding, malnutrition, pregnancy, chronic liver or kidney failure, organ transplant, elderly individuals, childhood infections, and symptoms lasting more than 12 weeks.[6-8] DTB is infrequent among immunocompetent individuals and the only risk factor in our patient was symptoms lasting more than 12 weeks. Recent studies reported that genetic abnormality in the macrophages can decrease the expression of interferon gamma, resulting in the dissemination of the infection.[9]
Many studies reported that lymph node TB is the most common type of extrapulmonary TB (EPTB).[10] This patient also had a generalized lymphadenopathy.
Radiological investigations such as X-ray, CT, ultrasound, and magnetic resonance imaging are crucial in diagnosing dTB.[3] The classic miliary pattern will be present in 85%–90% of cases, which is not specific for dTB, as this finding may present in other conditions such as histoplasmosis, sarcoidosis, pneumoconiosis, metastasis, bronchoalveolar carcinoma, and pulmonary siderosis. Patients may present with infrequent findings such as consolidation, cavities, calcification, granuloma, and pleural effusion on chest X-rays.[4,11]
Many a times, microscopic examination of the tissue specimens with special stains is negative; it is not feasible to discriminate MTB from nontuberculous mycobacteria (NTM).[12]
HPE continues to be a crucial method in the diagnosis usually revealing caseating granuloma, rarely noncaseating granuloma with or without AFB positivity.[13]
Tuberculin skin test has no diagnostic value in dTB as it mostly produces negative results.[4] Sensitivity of QuantiFERON-TB in tube in dTB is 67%–68%.[14]
Though culture is the gold standard test, it has a low yield, especially for non-respiratory samples, and takes 2 to 6 weeks.[10] The load of bacilli to attain a positive culture is 100 bacilli/ml of sputum. Blood culture for mycobacteria can be advised as a diagnostic test in dTB and requires multiple samples to improve the yield. Blood and urine lipoarabinomannan assay by lateral flow method or ELISA can also be done in dTB which are easily accessible specimens.[15]
The limit of detection (LoD) of CBNAAT for MTB is 130–150 cfu/ml of sputum.[16] CBNAAT has a sensitivity of 84.9% and a specificity of 99.8% for lymph nodes. Sensitivity for other samples varies considerably, resulting in false negative results. Most of the nonrespiratory samples are paucibacillary.[10] For RIF resistance detection, sensitivity and specificity were 94.5% and 97.7%, respectively.[16]
The LoD of Truenat for MTB is 100 cfu/ml. The load of bacilli required to obtain positive RIF resistance by Truenat is 104 bacilli.[2] In this case, RIF resistance was detected by Truenat, but not by CBNAAT. It needs further studies, especially for nonrespiratory samples.
As there is no single test used to diagnose TB, we need to combine imaging studies to identify the involved organs to collect appropriate specimens, microscopy, and molecular methods to make the diagnosis earlier. A high level of clinical intuition, an attempt toward early diagnosis, and initiation of ATT are required to prevent complications.
CONCLUSION
DTB can be cagey like EPTB owing to the vague symptoms, varied clinical presentation with a subacute or chronic course, and uncertainty in infective foci during the initial phase. The diagnosis may be hindered by a lack of access to the sampling site and is mostly based on imaging or histopathology.
Limitation of the study
- BAL fluid for RIF resistance detection by CBNAAT was not repeated
- Sputum sample for AFB stain/CBAAT/Truenat was not performed since the patient had dry cough.
Outcome of the study
A high level of clinical intuition, an attempt toward early diagnosis, and initiation of ATT are required to prevent complications.
Rationale of the study
Combined clinical examination, imaging, microscopy, and molecular methods should be done in suspected tuberculosis patients, especially in endemic areas.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for his images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Ethical Consideration
Ethics approval and consent to participate was obtained from TIREC (Tirunelveli Institutional Ethics Committee) - Ref No. 20232511/2023.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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