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Both intra- and extrathoracic manifestations of TB will be discussed below. Intrathoracic manifestations include mediastinal lymph node disease, pleural and pericardial effusion, disseminated or miliary disease, and adult-type intrathoracic disease. Extrathoracic manifestations include cervical lymphadenitis, tuberculous meningitis, other organ involvement, and, in patients with HIV, immune reconstitution.
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Intrathoracic Disease
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The TB bacillus usually enters its human host via the lungs; inhalation of an infectious droplet with the right size to penetrate into the periphery of the lung results in a localized area of pneumonic consolidation at the site of organism deposition. This is referred to as the primary (Ghon) focus, from where TB bacilli drain via local lymphatics to the regional lymph nodes. The combination of the Ghon focus and enlarged regional lymph nodes, usually involving the perihilar area, is referred to as the primary complex.11 Active disease may present with a diverse spectrum of pathology. Figure 36–2 provides a schematic illustration of potential disease progression following primary infection with M. tuberculosis and how the various disease manifestations develop.11 The different disease manifestations show clear patterns related to (1) the time since infection occurred (Figure 36–3)9 and (2) the age at the time of primary infection (Figure 36–4).12 The disease manifestations observed in immune-compromised children seem to correlate with those seen in very young (<3 years of age) children.12,13
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Involvement of the intrathoracic lymph nodes (perihilar and/or paratracheal) is considered the radiological hallmark of primary infection.14 Both anteroposterior and lateral views are required for optimal lymph node visualization (Figures 36–5 and 36–6). However, transient hilar adenopathy is not uncommon following recent primary infection, and particular care should be exercised when interpreting results of very sensitive tests such as high-resolution computed tomography of the lung, in the absence of clinical data.13
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Lymph node disease may be complicated by airway involvement and/or penetration into adjacent anatomical structures.11 Complicated lymph node disease occurs most commonly in children <5 years of age, probably because of exuberant lymph node responses and the small caliber of their airways. Airway compression results when an airway is surrounded and fixated by diseased lymph nodes and associated inflammation, and this may be best visualized on a high-kilovolt chest radiograph (CXR). Various disease presentations include partial airway obstruction with a check-valve effect and alveolar hyperinflation, or total airway obstruction with alveolar collapse. When a diseased lymph node erupts into an airway, caseous material may be aspirated and the resulting pathology may range from pure hypersensitivity-induced inflammation (dead bacilli and/or “toxins”) to destructive caseating pneumonia (virulent bacilli), depending on the bacterial load and viability of the bacilli aspirated. Caseating pneumonia often causes an expansile (bulging against their anatomical boundaries) pneumonic process with visible parenchymal breakdown (Figure 36–7).15 Penetration into adjacent anatomical structures may involve the phrenic nerve with unilateral diaphragmatic palsy, the esophagus with the formation of a broncho- or tracheoesophageal fistula, and/or the thoracic duct with the formation of a unilateral chylothorax.11
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Pleural and Pericardial Effusion
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The accumulation of the typical lymphocyte-rich, straw-colored fluid represents a hypersensitivity response. The pleural fluid typically obliterates 30–60% of the affected hemithorax (Figure 36–8), although massive fluid collections may cause mediastinal shift and cardiovascular compromise.11 In general, isolated pleural effusions are unusual in children <3 years of age and tend to develop soon (within the first 3–9 months) after primary infection.9
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A loculated fluid collection may indicate TB empyema that results when bacilli actively multiply within the pleural space. This is not common, but immune-compromised individuals seem to be at increased risk.
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Pericardial effusion usually develops when a subcarinal lymph node erupts into the pericardial space.9 On CXR the heart shadow may be enlarged with a suggestive globular appearance, but cardiac ultrasound is the most sensitive test to confirm or exclude the presence of a pericardial effusion. Long-term sequelae include constrictive pericarditis, and this is an indication for the use of corticosteroids together with anti-TB treatment.11
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Disseminated (Miliary) Disease
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Dissemination represents a condition of infinite gradation. Occult dissemination is common following primary infection; however, it rarely progresses to disseminated disease except in very young (<2–3 years of age) and immune-compromised children.9,13 Typical radiologic signs include the presence of even-sized miliary lesions (<2 mm), which are distributed bilaterally into the very periphery of the lung (Figure 36–9).11 Diagnostic confusion often exists in HIV-infected children in whom lymphocytic interstitial pneumonitis, malignancies, and opportunistic infections such as Pneumocystis jeroveci may present with a similar radiological picture.16 In these instances, response to treatment and/or bacteriologic confirmation may be the only way to establish a definitive diagnosis.
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Adult-type disease first appears around puberty (from 8 to 10 years of age) and becomes the dominant disease manifestation during adolescence.9 As with pulmonary TB in adults, the apical and posterior segments of the upper lobe and the apical segment of the lower lobe are most commonly affected (Figure 36–10). Complications include progressive cavity formation and bronchial spread.11
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Extrathoracic Disease
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Cervical Lymphadenitis
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The most common extrathoracic manifestation of TB in children is cervical lymphadenitis (Table 36–2). Disease pathology within the lymph node is similar to that seen in other organs, with initial tubercle formation and lymphoid hyperplasia that may progress to caseation and necrosis. Isolated involvement of a single node is rare, and nodes are usually matted because of considerable periadenitis. A cold abscess results when the caseous material liquefies, and this is signified by a soft fluctuant node with violaceous discoloration of the overlying skin; spontaneous drainage and sinus formation may follow. Untreated, the natural course of TB lymphadenitis in an immune-competent host follows a prolonged and relapsing course, often interrupted by transient lymph node enlargement, fluctuation, and/or sinus formation.
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Table 36–3 reflects the clinical characteristics of children diagnosed with TB lymphadenitis.17 A simple clinical algorithm that identifies children with persistent (>4 weeks) cervical adenopathy, without a visible local cause or response to first-line antibiotics, and a cervical mass ≥2 × 2 cm showed excellent diagnostic accuracy in this highly endemic area. However, a clinical diagnostic approach would be far less accurate in nonendemic areas and in areas where alternative diagnoses, such as Burkitt's lymphoma, are more common. In these settings, a positive TST result may have additional value to indicate mycobacterial disease,17 although it may not differentiate TB lymph adenitis from disease caused by non-TB mycobacteria.18 Establishing a definitive tissue and/or culture diagnosis remains preferable, and this can be done in a minimally invasive fashion using fine needle aspiration biopsy.17
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The mycobacteria that cause cervical lymphadenitis are highly variable in different settings. In areas where the control of bovine TB is poor and milk is not routinely pasteurized, Mycobacterium bovis may be a frequent cause, but in areas where TB is endemic and bovine TB is well controlled, M. tuberculosis would be the most common causative organism. In developed countries with low rates of TB transmission, non-TB (environmental) mycobacteria and, in particular, M. avium-intracellulare are most frequently responsible.18
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Tuberculous Meningitis
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Tuberculous meningitis is the most severe manifestation of childhood TB. Bacille Calmette Geurin (BCG) vaccination provides some degree of protection against the severe forms of TB (miliary disease and tuberculous meningitis), but despite universal BCG vaccination severe disease manifestations still occur, mainly affecting very young (immune immature) and/or immuno-compromised children in endemic areas.
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Other TB Manifestations
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TB can affect nearly every organ system (Table 36–2), and this is mostly the result of disease progression, which occurs at sites where the TB bacillus was deposited during the initial phase of occult dissemination. In addition, newborn babies may acquire congenital TB via the placenta, in which case the primary (Ghon) focus is usually located in the liver, if the mother develops active TB or M. tuberculosis infection with hematogenous dissemination during pregnancy. The experience is that cases of congenital TB are on the rise in countries where TB/HIV coinfection rates among expectant mothers are high.
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Immune Reconstitution
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The clinical syndrome was first documented in the prechemotherapy era, following nutritional rehabilitation and/or the termination of high-dose steroid treatment.9 Recently, immune reconstitution inflammatory syndrome (IRIS) has emerged as an important complication to consider after the introduction of highly active antiretroviral therapy in HIV-infected, immune-compromised patients.19 Radiologic signs may include airway compression as a result of increased inflammation surrounding diseased lymph nodes, or dense alveolar consolidation caused by excessive inflammation in areas of previous “subclinical” TB infiltration. This temporary exacerbation of TB symptoms and signs is mainly ascribed to the effects of improved immune function, although a “hypersensitivity” reaction to antigens released by killed TB bacilli may also contribute. It does not indicate treatment failure and should subside spontaneously, although severe cases may require treatment with corticosteroids. In a recent prospective survey of 152 Thai children with low CD4 percentages (<15%), IRIS was documented in 14 (19%), usually within 4 weeks of highly active antiretroviral therapy initiation.20 The majority of IRIS cases (nine) were caused by atypical mycobacteria, three because of M. tuberculosis, and two because of M. bovis BCG.