Lymph node TB is one of the most common forms of EPTB, and cervical lymph nodes are the most common site with or without associated disease of other lymphoid tissue. It usually occurs in the age group of 5-9 years. The presenting features are enlarging masses over weeks to months. Cervical lymph nodes, particularly jugular, posterior triangle and supraclavicular, are affected; axillary and inguinal are sometimes involved. Systemic symptoms may be seen in some patients. A clinical correlate of diagnosis includes progressive enlargement of lymph node for more than two weeks, firm, minimally tender or non-tender, with or without fluctuation. Affected nodes may get matted, turn into a cold abscess and may rupture and develop chronic sinus. Moreover, large lymph nodes may be present due to various infections or malignancy. Histopathology is the usual gold standard test for establishing the aetiology of enlarged nodes. Fine Needle Aspiration Cytology (FNAC) is an alternative test usually considered adequate for accurate diagnosis as it correlates well with biopsy in more than 90% of cases.  However, both these tests require a skilled pathologist to report on the specimen and therefore, these tests are may not always be feasible in the peripheries. Besides, needle aspirate from the node can be easily tested for the presence of AFB or NAAT to diagnose TB in such cases in a more decentralised fashion without needing the services of a skilled pathologist. However, since there are better alternatives available and the yield of smear for AFB / NAAT is moderate at best, all cases negative for these tests should be subjected to a detailed FNAC/ histopathology.  In the case of tuberculosis, histopathology typically shows epithelioid granuloma with or without central acellular necrosis (Annexure 4 for Needle aspiration of LN and similar swellings video available at: https://tbcindia.gov.in/index1.php?lang=1&level=3&sublinkid=5320&lid=3419 )

 

 

 

Figure. 3 Diagnostic Algorithm for Tubercular Lymphadenitis

 

Ultrasonography may be helpful to identify affected non-palpable or deep-seated nodes for needle aspiration and testing. Central hypoechogenicity in a node on USG is considered suggestive of TB and may improve testing yield by targeting such nodes for aspiration. 

Furthermore, on chest X-Ray, 5-40% of patients identified to have peripheral TB lymphadenitis may have pulmonary/ pleural abnormalities, hilar/ mediastinal lymph nodes, parenchymal lesions or pleural effusion. Skin test for TB test is positive in a significant proportion (>70%) of patients but does not contribute to establishing the diagnosis. Reactive adenitis in a child with positive TST does not mean TB adenitis.

In children, lymphadenopathy is expected due to recurrent tonsillitis and upper respiratory tract infections. Reactive lymphadenitis may clinically mimic tuberculosis but do not warrant anti-TB drugs. Hence, anti-TB drugs should not be given unless the diagnosis of TB is confirmed by microbiological tests (smear for AFB or NAAT / Mycobacteria Growth Indicator Tube (MGIT) for M.tb ) or by suggestive FNAC or histopathology. Figure 3, depicts the diagnostic algorithm for tubercular lymphadenitis. 

Children with tuberculous Pleural Effusion (PE) usually present with fever, chest pain, anorexia and weight loss. While more prolonged duration symptoms may make TB aetiology more likely, TB PE can often present acutely. TB effusion can present with high-grade fever. The clinical examination would reveal signs of effusion (decreased air entry with dull percussion).

The presence of effusion can be confirmed by chest imaging (USG or chest radiograph). Pleural diseases are best imaged with a USG, and its benefit relates to establishing the presence and extent of PE and not for establishing an etiological diagnosis. Nevertheless, CT Chest makes little contribution to suggest aetiology. Pleural fluid aspiration should always be performed, and the aspirate should be sent for biochemical, cytological and smear examination by Ziehl-Neelsen (ZN) stain to confirm the diagnosis. In the absence of a pleural fluid examination, it is usually not possible to infer any aetiology based on radiology alone. Typically, a tubercular effusion fluid is straw-coloured (pus, if aspirated, is very rarely due to TB aetiology) has large numbers of cells (in hundreds; predominantly mononuclear), with high proteins (>3g/dL). Moreover, the high protein content of the exudative effusion in tuberculosis causes it to form a cobweb on standing. However, the yield of NAAT in tubercular pleural effusion is low. Induced sputum/GA should always be tested for M.tb as about a quarter of the children with PE, GA or IS were positive on culture. On the other hand, the M.tb detection in Pleural fluid, by culture or NAAT, is about 5%. Similarly, positive skin test for TB is supportive and not diagnostic. Blood count within the normal range makes empyema or a complicated para-pneumonic effusion less likely. ESR has no role in establishing the aetiological diagnosis.

Although Adenosine Deaminase (ADA) has been used extensively to diagnose TB effusion in adults, its utility in children appears limited. Studies among adults have compared TB effusions with malignant effusions and have found it to be a good marker. However, very few studies compare TB effusion with parapneumonic effusions, which is the commonest other cause in children. Limited data suggest a significant overlap between the ADA values in TB effusion and pyogenic effusions, and therefore, it is not recommended to be used for children.

A pleural biopsy may be performed in unclear situations using Cope’s or Abraham’s pleural biopsy needle. The pleural tissue can be subjected to histopathology, ZN staining and MGIT cultures. The findings of granulomas with caseous necrotic tissue in the pleural biopsy makes the diagnosis of tuberculosis highly probable. The yield of pleural biopsy is more than 80%. In most circumstances, the diagnosis can be made by a combination of a long history, a non-sick child, an exudative (not pus) lymphocytic effusion. A skin test for TB may be another supportive clue.

Abdominal TB is a broad term as the disease can be present in intestinal, nodal, peritoneal, visceral and disseminated forms, with almost one-third of patients having the involvement of more than one of these sites. Symptoms and signs vary as per the site. However, common symptoms are abdominal pain, fever, distension, weight loss and anorexia. On examination, doughy abdomen, ascites, omental mass, organomegaly may be seen. Isolated recurrent or chronic pain without any other symptom is usually not due to TB.

Multimodality evaluation, including clinical, laboratory, radiology, endoscopy, microbiology, histopathology, is needed to reach a definitive diagnosis of abdominal TB. Tissue diagnosis remains most reliable though it is often not feasible.  Plain X-Rays are not helpful for the diagnosis of abdominal TB. It may sometimes show non-specific features like enteroliths, perforation and features of intestinal obstruction.

 

 

 

Box 1. Characteristic Image Findings of Abdominal TB

 

Ultrasonography is recommended as an initial modality of choice and may pick up lymphadenopathy, peritoneal thickening, omental thickening, bowel wall thickening, and ascites. Non-specific bowel wall thickening, a small amount of fluid in the mesentery or dependent areas of the abdomen, or the presence of non-matted intra-abdominal lymphadenopathy can be misleading. Contrast-enhanced CT and CT enterography provide adequate cross-sectional imaging in depicting various forms of abdominal TB. Barium studies are gold standards in diagnosing strictures, fistulae, erosions etc. Typical imaging findings are detailed in the box.

For peritoneal TB diagnosis, peritoneoscopy has a very high sensitivity (93%) and specificity (98%). There are usually one of these three types of findings on peritoneoscopy, viz. Hyperemic peritoneum with ascites and whitish miliary nodules, hyperemic peritoneum with ascites and adhesions and markedly thickened parietal peritoneum with yellowish nodules multiple thickened adhesions. 

Diagnosis of abdominal TB is a challenge because of non-specific variable symptoms, low microbiological yield, need for multimodality investigations, complications of the wrong diagnosis. Many times, there is insufficient evidence to start ATT. Children with fever or failure to gain weight or functional abdominal pain often get diagnosed with abdominal TB as lymph nodes (usually around a centimetre in size) are detected on the USG abdomen. Chronic diarrhoea without proper evaluation is also often wrongly treated as TB abdomen.

3.4.1. TB Meningitis (TBM)

TBM most commonly presents between six months to four years of age but can occur at any age. It is the most severe form of TB in children and uniformly leads to mortality if not treated timely and effectively. The clinical presentation is divided into three stages. The disease usually progresses over several weeks from stage one to three and may progress rapidly over days in infants and young children. The stage at which treatment begins predicts the prognosis. 

 

 

Table 1. Stages of TB Meningitis

 

Cerebrospinal fluid (CSF) tap is mostly clear, and CSF leukocyte count usually ranges from 10 to 500 cells /mm3 (occasionally higher), and the majority are usually lymphocytes. CSF glucose usually remains below 40mg/dl (CSF glucose / blood glucose below 0.5, protein is elevated (often more than 100 mg/dl). Rapid NAAT may be positive in about 30-40% of cases. Tuberculin Skin Test may not be reactive in 50% of cases. Chest X-ray may show abnormality in 20-50% of cases. Not uncommonly, the aetiological diagnosis may come from concomitant extra-neural disease.

The CECT head is the initial modality of diagnosis. It may have one or more of the following: basal meningeal enhancement, hydrocephalus, tuberculoma, infarcts in different areas, especially the basal ganglia and pre-contrast basal hyperdensity. It sometimes is even found normal. Contrast MRI has higher sensitivity than CECT for abnormalities such as meningeal enhancements, infarcts, and tuberculoma, especially of brain stem lesions.

Usually, Magnetic Resonance Imaging (MRI) is preferred when CT is inconclusive, and suspicion is high. Cryptococcal meningitis, Cytomegalovirus encephalitis, toxoplasmosis, sarcoidosis, meningeal metastases, and lymphoma can result in similar radiological findings.

 

 

Figure 4. Algorithm for diagnosis of TBM

 

3.4.2. CNS tuberculosis other than TBM - Tuberculoma

Tuberculoma in the brain presents an intracranial space-occupying lesion (ICSOL). Its location, size and peri-lesional oedema predisposes the manifestations like seizures, headache and focal neurological deficits. Neurocysticercosis (NCC) is an important differential diagnosis.

The table below describes the differentiating features of these two entities on neuroimaging.

 

 

 

Table 2.  Differences Between Tuberculoma and Neurocysticercosis
 

 

Bone and Joint TB roughly accounts for 5-15% of all EPTB and 2-5% of all TB in children and adults. It occurs due to the reactivation of bacilli which had seeded the bones during the initial mycobacteremia. The symptomatic disease usually develops within 1-3years of infection, but TB dactylitis can have an early manifestation (usually one month). Typical presentations of Bone and Joint TB are Potts spine (50% of osteoarticular TB), Dactylitis, Arthritis (as an extension from the metaphysitis), Osteomyelitis. A few uncommon ones are reactive arthritis (Poncet’s arthritis), tenosynovitis and bursitis. 

 

3.5.1. Dactylitis (Spina ventosa)

Tuberculous osteitis, the dactylitis form, often affects children. It may involve multiple or consecutive bones. In children, short tubular bones of the hands and feet are usually affected, typically involving the proximal phalanx of the index/middle fingers and middle/ring finger metacarpals. It often follows a benign course without pyrexia and acute inflammatory signs. On X-Ray, the involved bones show a diaphyseal expansile lesion, a periosteal reaction is uncommon, and healing is by sclerosis.

 

3.5.2. Spinal TB or Pott’s Spine

The most common site of Pott’s Spine is thoracic, followed by lumbar/ cervical areas. Pain may be localized over the involved vertebra or could be referred to due to root pains. There can be local tenderness or deformity. Fever and constitutional symptoms are present in one among three cases. Neurological complications include paraparesis (20-50% cases), and cauda equina syndrome. Moreover, about 15% of patients can have a paradoxical response with increased neurologic deficit following therapy. However, this entity is diagnosed only after ruling out other causes of non-response like DRTB, pus collection, etc. There is a risk of kyphosis later in life, especially in children below 7-10 years.

Plain X-Ray of the spine is less sensitive in early disease as it does not reveal any abnormality till about 30-50% of bone loss has occurred. The typical findings are one more of the following: endplate erosion decreased vertebra height, collapse and narrowing of discal space and paravertebral soft tissue shadow. MRI is the most sensitive for picking up abnormalities (nearly 100%). Features in MRI are marrow oedema, destruction of adjacent vertebral bodies and opposing endplates, destruction of the intervening disc, occurrence of prevertebral, paravertebral, and epidural abscesses. 

Microbiology should always be attempted for definitive diagnosis and to pick up MDR-TB. One should look for the coexistence of pulmonary TB. If surgery is not planned, a CT-guided biopsy of the paravertebral soft tissue/ vertebral body should be carried out and subjected to histopathological examination (HPE), culture, or NAAT. Diagnostic yield varies with various methods from 50-70%.

 

3.5.3. TB Arthritis

TB arthritis occurs from intra-articular spread from osteomyelitis. Usually, it involves the weight-bearing joints such as the hip and knee (90%). There is single joint involvement commonly. Pain is the first symptom (usually at night) later followed by local tenderness and restriction of joint movement. Fever and constitutional symptoms may be absent. Often, TB arthritis may be confused sometimes with oligoarticular Juvenile Rheumatoid Arthritis (JRA). Plain X-ray shows soft tissue swelling, osteopenia, periarticular bone destruction and periosteal reactions. Moreover, MRI is very sensitive. However, joint fluid aspiration or synovial biopsy should be carried out for a definitive diagnosis and subjected to HPE or culture or CBNAAT.