Pediatric Annals

The Clinical Presentation of Tuberculous Disease in Children

David C Waagner, MD

Abstract

The myriad presentations of tuberculous disease are as variable as the systems the tubercle bacilli invade. Infection with Mycobacterium tubercubsis can develop in virtually any organ system. Because infection most commonly occurs through inhalation of bacilli-laden droplets, pulmonary disease predominates in both children and adults. In children with tuberculous disease, 25% of cases are extrapulmonary compared with 15% of cases in adults.1 The principal manifestations of extrapulmonary tuberculosis in children are shown in Figure 1. Tuberculous meningitis, the most common cause of death in children with tuberculosis, comprises 13% of childhood extrapulmonary tuberculosis in contrast to 4% of adult extrapulmonary disease.2 Thus, children are not only more prone to present with extrapulmonary disease, but also have a greater risk of developing more severe forms.

PULMONARY TUBERCULOSIS

Asymptomatic Primary Tuberculosis

Primary tuberculous infection in young children is typically an asymptomatic illness characterized by a positive tuberculin skin test, a normal chest roentgenogram, and no clinical manifestations. Following the initial exposure, the tuberculin skin test remains negative during the 2- to 8-week incubation period, after which delayed hypersensitivity to tuberculin protein develops, and the skin test converts to positive. Once tuberculin hypersensitivity develops, nonspecific symptoms such as fever, malaise, and erythema nodosum can occur; but most patients remain asymptomatic. The diagnosis of asymptomatic primary tuberculosis is often made during investigation of adult tuberculosis contacts and routine skin-test screening. Despite the asymptomatic appearance, contact investigations and chemotherapy should be initiated promptly to prevent progression and spread of disease.

Endothoracic Lympadenopathy and Endobronchial Disease

Tubercle bacilli spread from the primary parenchymal focus through the lymphatic drainage of the affected pulmonary segment into regional lymph nodes. The right paratracheal nodes are involved most often, but infection can spread via lymphatic connections to involve other lymphatic chains. With development of tuberculin hypersensitivity, the infected hilar nodes enlarge dramatically (Figure 2). The enlarged hilar nodes often elicit the earliest symptoms of tuberculous disease through compression or obstruction of blood vessels and airways.

The anatomical position of infected lymphatic chains directly influences potential early manifestations of tuberculous disease. Subcarinal lymphadenopathy can produce odynophagia with recurrent emesis as a result of esophageal compression. Impingement of nodes on the subclavian vein or superior vena cava can cause edema of an upper extremity. Nodal compression of the recurrent laryngeal nerve or phrenic nerve can result in vocal cord paralysis or hemidiaphragmatic paralysis, respectively. The spread of tubercle bacilli from adjacent hilar nodes to the pericardium can produce pericarditis.

Bronchial obstruction is the most common consequence of hilar adenopathy.3 Obstruction can occur not only from nodal compression, but also through severe tuberculous infection of the bronchial wall and by perforation of an infected node into a bronchus. Most often, bronchial obstruction results in atelectatic changes within the pulmonary segment containing the original parenchymal focus. Chest roentgenograms display a segmental fan-shaped opacification described as "collapse-consolidation* of the pulmonary segment or, rarely, an entire lobe (Figure 3). Collapse -consolidation lesions occur more commonly among younger children, most likely due to the narrower bronchial lumen, typically developing within 3 to 6 months after primary infection.4 Despite the marked roentgenographic abnormalities, most children with collapse-consolidation lesions have few pulmonary symptoms. Bronchial obstruction also can present with obstructive hyperinflation of a pulmonary segment resembling foreign-body aspiration. Hyperaeration occurs primarily in children younger than 2 years of age and can progress to spontaneous pneumothorax. The erosion of an infected node into a bronchus with the resultant release of caseous debris into the distal airways produces the clinical and radiographic appearance of an acute pneumonia.

CONCLUSION

With the nationwide resurgence in tuberculosis, health-care providers undoubtedly will be confronted with…

The myriad presentations of tuberculous disease are as variable as the systems the tubercle bacilli invade. Infection with Mycobacterium tubercubsis can develop in virtually any organ system. Because infection most commonly occurs through inhalation of bacilli-laden droplets, pulmonary disease predominates in both children and adults. In children with tuberculous disease, 25% of cases are extrapulmonary compared with 15% of cases in adults.1 The principal manifestations of extrapulmonary tuberculosis in children are shown in Figure 1. Tuberculous meningitis, the most common cause of death in children with tuberculosis, comprises 13% of childhood extrapulmonary tuberculosis in contrast to 4% of adult extrapulmonary disease.2 Thus, children are not only more prone to present with extrapulmonary disease, but also have a greater risk of developing more severe forms.

PULMONARY TUBERCULOSIS

Asymptomatic Primary Tuberculosis

Primary tuberculous infection in young children is typically an asymptomatic illness characterized by a positive tuberculin skin test, a normal chest roentgenogram, and no clinical manifestations. Following the initial exposure, the tuberculin skin test remains negative during the 2- to 8-week incubation period, after which delayed hypersensitivity to tuberculin protein develops, and the skin test converts to positive. Once tuberculin hypersensitivity develops, nonspecific symptoms such as fever, malaise, and erythema nodosum can occur; but most patients remain asymptomatic. The diagnosis of asymptomatic primary tuberculosis is often made during investigation of adult tuberculosis contacts and routine skin-test screening. Despite the asymptomatic appearance, contact investigations and chemotherapy should be initiated promptly to prevent progression and spread of disease.

Endothoracic Lympadenopathy and Endobronchial Disease

Tubercle bacilli spread from the primary parenchymal focus through the lymphatic drainage of the affected pulmonary segment into regional lymph nodes. The right paratracheal nodes are involved most often, but infection can spread via lymphatic connections to involve other lymphatic chains. With development of tuberculin hypersensitivity, the infected hilar nodes enlarge dramatically (Figure 2). The enlarged hilar nodes often elicit the earliest symptoms of tuberculous disease through compression or obstruction of blood vessels and airways.

The anatomical position of infected lymphatic chains directly influences potential early manifestations of tuberculous disease. Subcarinal lymphadenopathy can produce odynophagia with recurrent emesis as a result of esophageal compression. Impingement of nodes on the subclavian vein or superior vena cava can cause edema of an upper extremity. Nodal compression of the recurrent laryngeal nerve or phrenic nerve can result in vocal cord paralysis or hemidiaphragmatic paralysis, respectively. The spread of tubercle bacilli from adjacent hilar nodes to the pericardium can produce pericarditis.

Bronchial obstruction is the most common consequence of hilar adenopathy.3 Obstruction can occur not only from nodal compression, but also through severe tuberculous infection of the bronchial wall and by perforation of an infected node into a bronchus. Most often, bronchial obstruction results in atelectatic changes within the pulmonary segment containing the original parenchymal focus. Chest roentgenograms display a segmental fan-shaped opacification described as "collapse-consolidation* of the pulmonary segment or, rarely, an entire lobe (Figure 3). Collapse -consolidation lesions occur more commonly among younger children, most likely due to the narrower bronchial lumen, typically developing within 3 to 6 months after primary infection.4 Despite the marked roentgenographic abnormalities, most children with collapse-consolidation lesions have few pulmonary symptoms. Bronchial obstruction also can present with obstructive hyperinflation of a pulmonary segment resembling foreign-body aspiration. Hyperaeration occurs primarily in children younger than 2 years of age and can progress to spontaneous pneumothorax. The erosion of an infected node into a bronchus with the resultant release of caseous debris into the distal airways produces the clinical and radiographic appearance of an acute pneumonia.

Figure 2. Prominent hilar adenopathy with an enlarged mediastinum in a child with tuberculosis.

Figure 2. Prominent hilar adenopathy with an enlarged mediastinum in a child with tuberculosis.

Figure 3. A "collapse-consolidation" lesion of a pulmonary segment secondary to bronchial obstruction from hilar adenopathy.

Figure 3. A "collapse-consolidation" lesion of a pulmonary segment secondary to bronchial obstruction from hilar adenopathy.

Even with extensive endobronchial disease, older children most often are asymptomatic. Cough is often absent, although infants tend to have a persistent cough. When present, the cough is typically dry or hacking, but can become brassy and paroxysmal with progressive disease. Narrowing of the bronchial lumen by granulation tissue can produce localized wheezing. In children with collapse-consolidation lesions, a decrease in breath sounds may be discernible on chest auscultation. Rales are infrequent and usually localized. The discharge of the contents of an infected node into a bronchus can result in the immediate resolution of symptoms prior to the subsequent development of a pneumonia-like appearance.

Figure 4. A large tuberculous pleural effusion producing mediastinal shift.

Figure 4. A large tuberculous pleural effusion producing mediastinal shift.

Progressive Primary Pulmonary Tuberculosis

Progressive primary pulmonary tuberculosis develops when the primary pulmonary focus does not resolve or calcify, but progresses locally to form a large caseous mass. "The enlarging area of caseation softens and ultimately drains into adjacent bronchi, producing a cavitary lesion and disseminating infection to other areas of the lung.3 The cavitary lesion is usually visible on chest roentgenograms within the area of clouding produced by the primary focus resembling a superimposed, necrotizing bacterial pneumonia. Progressive primary pulmonary tuberculosis occurs most commonly in infants and immunosuppressed patients.

Unlike asymptomatic primary tuberculosis, children with progressive primary tuberculosis are quite ill-appearing with fevei; weight loss, malaise, cachexia, and a productive cough. Chest examination reveals dullness to percussion, diminished breath sounds, and egophony over the area of cavitation. Of significance is the frequent presence of constant moist rales over the affected area. Rales are seldom heard over a primary tuberculosis complex, and their presence should raise suspicion of a destructive lesion.

Chronic Pulmonary Tuberculosis

Chronic pulmonary tuberculosis, also known as adult tuberculosis or reactivation tuberculosis, develops through endogenous reinfection from a prior established foci of tuberculous infection in the body. The previously established foci is seldom the primary complex because it does not harbor tubercle bacilli for long periods. Lymphohematogenous spread of tubercle bacilli at the time of initial infection can lead to the establishment of minute caseous foci of tuberculosis in the apical or posterior pulmonary segments, which often calcify (Simon's foci). These small foci can form a gradually expanding infiltrate progressing to caseation, liquefaction, and rarely, cavity formation. The previous tissue sensitization to tuberculin tends to localize the tubercle bacilli, minimizing the development of lymphadenitis.

Chronic pulmonary tuberculosis is uncommon, accounting for only 6% to 7% of childhood pulmonary tuberculosis cases. Most cases of chronic pulmonary tuberculosis occur in children acquiring primary infection after 7 years of age, with the highest risk during adolescence. The clinical presentation consists of fever, cough, malaise, weight loss, and occasionally hemoptysis. Examination typically reveals a cachectic appearance, supraclavicular adenopathy, and moist rales auscultated over the pulmonary apical areas.

Pleural Effusion

Pleurisy with effusion develops as an early complication of primary pulmonary tuberculosis in approximately 8% of children with pulmonary disease. Tubercle bacilli spread into the pleural space from a subpleural pulmonary focus or from subpleural lymph nodes. Tuberculous pleural effusions are most often unilateral, predominantly on the side of the primary pulmonary focus, and can be localized or generalized (Figure 4). Bilateral effusion can occur rarely in association with miliary tuberculosis. Development of pleural effusion typically occurs within 3 to 6 months after primary infection and is seen most often in older children and adolescents.

The clinical presentation consists initially of fevei; cough, and weight loss, followed by the acute onset of chest pain and shortness of breath. The chest pain is exacerbated with deep inspiration. The fever with tuberculous pleural emisión follows a unique course, remaining elevated for 1 to 2 weeks with a gradual defervescence over the 3rd week. A large effusion can elicit mediastinal shift producing a worsening of the shortness of breath and tachycardia. Chest examination reveals a marked decrease in breath sounds with dullness to percussion. One side of the chest wall can appear to move less than the other. Chest roentgenograms must include lateral decubitus views to distinguish the effusion from a consolidated pneumonia.

Figure 5, The characteristic diffuse miliary pattern in miliary disease. Tubercles are distributed evenly throughout the lung and are of the same size.

Figure 5, The characteristic diffuse miliary pattern in miliary disease. Tubercles are distributed evenly throughout the lung and are of the same size.

EXTRAPULMONARY TUBERCULOSIS

Miliary Tuberculosis

Miliary tuberculosis is the most severe form of hematogenous tuberculosis, resulting from the erosion of a caseous focus into a blood vessel with widespread hematogenous dissemination of tubercle bacilli.5 The tubercle bacilli lodge in small capillaries throughout the body and form tubercles, which, if untreated, can progress to caseation and necrosis. Children are more prone to develop miliary disease, with infants having the highest risk, possibly due to the decreased number of elastic fibers in the blood vessel walls compared with adults. Miliary disease occurs as an early complication of primary tuberculous infection, developing within 3 to 6 months.

The clinical presentation of miliary tuberculosis is highly variable depending on the number of tubercle bacilli discharged into the blood. The onset occasionally can be subtle with low-grade fever, malaise, and weight loss. More often, the patient has an acute onset of high fever (102° to 105°), lethargy, anorexia, and generalized weakness. On examination, the patient appears acutely ill with hepatomegaly, splenomegaly, and generalized lymphadenopathy. Respiratory signs and symptoms are typically absent at presentation with subsequent development of tachypnea, dyspnea, cough, and cyanosis with diffuse rales on chest ausculatation. Several weeks after onset of illness, choroidal tubercles can be visualized on ophthalmic examination in 13% to 87% of patients. Approximately one third to one half of children with miliary disease have meningitis at the time of presentation. Cutaneous metastasis is seen rarely, primarily in the form of papulonecrotic tuberculides or purpuric lesions. Chest roentgenography reveals the characteristic diffuse bilateral miliary lesions with equal distribution of tubercles over the entire lung fields (Figure 5).

Tuberculous Meningitis

Meningitis is the most grave complication of childhood tuberculosis and the most common cause of death. Tuberculous meningitis is virtually always fatal if untreated and has a high morbidity even with therapy. Meningitis develops as an early complication of primary infection with an estimated occurrence of 1 in 300 primary infections. Children younger than 6 years of age are affected most frequently, usually within 3 to 6 months after primary infection.

Tubercle bacilli gain entrance into the subarachnoid space through discharge from small caseous foci within the brain or meninges seeded during prior lymphohematogenous spread.2 The intrathecal tuberculin reaction precipitates the development of a thick gelatinous exudate with a predilection for the basal meninges. This basilar involvement can compress cranial nerves resulting in paresis, most often involving the third, sixth, and seventh cranial nerves and the optic chiasm. The obliteration of cerebrospinal fluid outflow produces hydrocephalus. Infiltration of the exudate into meningeal and cerebral blood vessels can produce occlusion resulting in ischemia of brain tissue and infarcts.

The development of tuberculous meningitis usually is an insidious process occurring over a 3 -week period6; the prognosis of tuberculous meningitis strongly correlates with the stage of disease at which treatment is initiated. For clinical purposes, the course of tuberculous meningitis is divided into 3 stages. It is of critical importance to maintain a high index of suspicion to ensure prompt diagnosis and rapid initiation of therapy. The first stage consists of generalized nonspecific signs and symptoms of 1 to 2 weeks duration without focal neurologic findings or alteration in consciousness. The patient often has fever, anorexia, emesis, a change in personality, and mood swings. A marked apathy with loss of interest in play has been noted in 50% of cases. On occasion, headache and abdominal pain are present. The second stage is characterized by signs and symptoms of increased intracranial pressure, meningeal irritation, and cerebral dysfunction. Clinical manifestations include drowsiness, emesis, stiff neck, seizures, tremors, disorientation, and slurred speech. At examination, most patients have resistance to neck flexion with positive Kernig's and Brudzinskis signs. Young children can have a bulging anterior fontanelle. Additional findings include asymmetric pupils, increased deep tendon reflexes, loss of abdominal reflexes, hearing loss, loss of visual acuity, and cranial nerve palsies (primarily the third, sixth, and seventh nerves). By the third stage, patients have evidence of extensive cerebral injury with decerebrate or decorticate posturing, coma, opisthotonos, and irregular respirations.

Superficial Tuberculous Lymphadenitis

Tuberculous lymphadenitis of the superficial lymph nodes is the most common extrapulmonary tuberculous infection. Lymphadenitis is an early complication of primary tuberculous infection, typically developing within 6 months. The majority of tuberculous lymphadenitis arises from localized extension from the primary infection, particularly the paratracheal and supraclavicular nodes. Lymphadenitis also can develop following the lymphohematogenous dissemination of tubercle bacilli after primary infection. Rarely, adenitis will develop in an extremity as a result of an extrapulmonary primary focus. Most tuberculous lymphadenopathy occurs in the neck region (scrofula) secondary to the rich lymphatic supply of this area. The anterior cervical lymph nodes are involved most often, followed by the posterior cervical, supraclavicular, submandibular, and submental chains. Axillary and inguinal lymphadenitis occur infrequently.

The clinical presentation is that of a firm, painless, enlarged lymph node. Several nodes in the same chain can be involved, and bilateral presentations may occur. There is seldom any erythema, fluctuance, or overlying skin changes initially. In time, caseation and necrosis progress within the node to the extent that fluctuance and erythema may develop. A draining sinus tract forms occasionally. A low-grade fever, weight loss, and malaise are often present but frequently overlooked. If the infected nodes reach sufficient size to compress adjacent structures, additional symptoms may develop. The greatest difficulty in recognizing tuberculous lymphadenitis is the exclusion of other common causes of lymphadenopathy, particularly pyogenic lymphadenitis, cat-scratch disease, malignancy, and nontuberculous mycobacterial infection.7,8 Nontuberculous mycobacterial lymphadenitis is clinically and histologically indistinguishable from tuberculous lymphadenitis, often requiring culture for confirmation.9

Skeletal Tuberculosis

Bone and joint tuberculosis most often develops from the initial lymphohematogenous spread of tubercle bacilli during primary infection. Although skeletal disease is an early complication of the primary infection, skeletal tuberculosis may not manifest for 2 to 3 years depending on the site and the age of the child. Infants and young children are at greater risk due to the increased vascularity of bones during growth. The tubercle bacilli lodge in the metaphysis forming an endarteritis with progressive bone destruction and cold abscess formation, and can eventually rupture into a joint capsule or form draining sinus tracts. Bone infection predominantly occurs in the large weightbearing bones, with the most common sites being the vertebrae (30% to 40%), hip (7%), knee (7%), and elbow (5%).10 Young infants, however, have a high incidence of involvement oí the small bones of the hands and feet. Tuberculosis arthritis predominantly involves the weight-bearing joints of the lower extremity, primarily the hip, knee, and ankle joints.

The clinical presentation of skeletal tuberculosis is unique to the affected bone or joint. Children with vertebral osteomyelitis may complain of focal tenderness or referred pain to the neck, chest, abdomen, or extremities, depending on the vertebrae involved. Abnormal posturing is often the first sign of vertebral infection. The spine is typically kept rigid due to the muscular spasm in an attempt to minimize motion and pain. Relaxation of dorsal muscle spasms during sleep gives rise to "night cries." Involvement of the cervical vertebrae may produce torticollis or opisthotonos. With the gradual destruction of vertebrae, bony deformities can be visible on examination with increased angulation of the spine, ultimately progressing to kyphosis (Figure 6). Dactylitis in infants presents as a painless or mildly tender edema of the digits with roentgenographic evidence of cystic bone lesions. Tuberculous arthritis presents similarly to pyogenic arthritis with pain and limitation of motion, often accompanied by muscle spasm.11

ADDITIONAL TUBERCULOUS INFECTIONS

Presentation of tuberculous disease involving other OTgan systems can be seen occasionally. Tuberculous otitis often presents as a chronic painless otorrhea with perforation of the tympanic membrane, unresponsive to conventional therapy. Close examination of the bony ossicles frequently reveals minute erosions. Renal tuberculosis is quite rare in childhood and follows primary infection after 4 to 5 years. Dysuria, hematuria, and a sterile pyuria often are present. Tuberculous pericarditis is a rare but deadly complication of early pulmonary tuberculosis resulting from erosion of a hilar node into the pericardium. The presentation is similar to pericarditis caused by other etiologic agents with fever, chest pain, orthopnea, tachycardia, diminished heart sounds, and a friction rub. Ocular tuberculosis most frequently involves the cornea and conjunctiva. Phlyctenular conjunctivitis manifests with severe pain and photophobia with gray, gelatinous nodules on the limbus of the eye. Phlyctenular conjunctivitis also is characterized by severe hypersensitivity to tuberculin protein and should be screened for with one tuberculin unit of purified protein derivative given intradermally.

Figure 6. Marked kyphosis of the spine due to destruction of the vertebrae by tuberculosis (Pott's disease).

Figure 6. Marked kyphosis of the spine due to destruction of the vertebrae by tuberculosis (Pott's disease).

CONCLUSION

With the nationwide resurgence in tuberculosis, health-care providers undoubtedly will be confronted with children presenting with the often subtle signs and symptoms of tuberculous disease.1,12 Tuberculosis always must be considered in the differential diagnosis of children with pulmonary infection. Similarly, tuberculosis always should be considered in the evaluation of any child with persistent fever, weight loss, malaise, or failure to thrive. Diagnostic screening of child contacts of adult tuberculosis cases is mandatory to identify early infection and initiate therapy before disease develops. A high index of suspicion with prompt diagnostic procedures and initiation of chemotherapy are critical to decrease the devastating morbidity and mortality still associated with this centuries-old disease.

REFERENCES

1. Wier MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985;79:467-478.

2. Smith MHD, Starke JR, Marquis JR. Tuberculosis and opportunistic mycobacterial infections. In: Feigin RTA Cherry JDi eds. Textbook of Pediatric Infectious Diseases. Philadelphia, Pa: WB Saunders Co; 1992:13364337.

3. Lincoln EM, Sewell EM. Tuberculosis in Children. New York, NY: McGraw-Hill Book Co; 1963.

4. Morrison JB. Natural history of segmental lesions in primary pulmonary tuberculosis. Arch Dis Child. 1973;48;90-98.

5. Schuit KE. Miliary tuberculosis in children. Am/ Dis Child. 1979;133:583-585.

6. Waeker NJ, Connor JD. Central nervous system tuberculosis in children: a review of 30 cases. Pediatr Infect Dia). 1990;9:539-543.

7. Barton LL, Feigin RD. Childhood cervical lymphadenitis; a reappraisal. J Pediatr. 1974;84:846-852.

8. Dandapac MC, Mishra BM, Dash SP, et al. Peripheral lymph node tuberculosis: review of 80 cases. Br J Surg. 1990;77:911-912.

9. Wolinsky E. Nonruberculous mycobacteria and associated disease. Am Rev Respir Dis. 1979;119:107-154.

10. Tuli SM. Tuberculosis of the Spine. New Delhi: Amerind Publishing Co; 1975.

11. Bemey S, Goldstein M, Bisko E Clinical and diagnostic features of tuberculous arthritis. AmJ Med. 1972;53:36-42.

12. Starke JR, Taylor- Warts KT. Tuberculosis in the pediatric population of Houston, Texas. Pediatria. 1989;84:28-35.

10.3928/0090-4481-19931001-11

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