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Tuberculosis of lymph nodes and the reticuloendothelial system in adults
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36
Tuberculosis of lymph nodes and the reticuloendothelial system in adults Helmuth Reuter and Robin Wood
INTRODUCTION Tuberculous lymphadenitis is the most common manifestation of extrapulmonary TB, which is defined as disease involving structures other than lung parenchyma, and is less common than pulmonary TB. It is the result of infection with the same organisms that cause pulmonary TB, namely Mycobacterium tuberculosis, Mycobacterium bovis or Mycobacterium africanum. In areas where TB is endemic and bovine TB is well controlled M. tuberculosis is the most common cause,1,2 whereas infection with M. bovis may be a frequent cause in areas where the control of bovine TB is poor and milk is not routinely pasteurized.3 In developed countries with low rates of TB transmission, environmental mycobacteria, also referred to as non-tuberculous mycobacteria (NTM), are mainly responsible for peripheral lymphadenitis, particularly Mycobacterium avium complex (MAC).4
PERIPHERAL LYMPH NODE TUBERCULOSIS Lymphadenitis is the most frequently occurring form of extrapulmonary TB with cervical nodes being most commonly involved in adults (Figs 36.1 and 36.2), although inguinal, mesenteric and mediastinal nodes may also be involved.5,6 NTM lymphadenitis is rare in adults, but relatively common in children and it may affect human immunodeficiency virus (HIV)-infected adults.7,8 The disease generally remains localized to the cervical region and is usually not accompanied by constitutional symptoms.6,9 It can be adequately managed with local excision, but, if left untreated, the nodes often progress to softening, rupture, sinus formation, healing with fibrosis and calcification.6–9 In contrast to children, M. tuberculosis is the major cause of mycobacterial lymphadenitis in adults and is usually a local manifestation of systemic disease. It seems to affect predominantly young women, although it can affect any age or race and those living in developing countries or immigrants from areas of high tuberculosis prevalence.10–14 Tuberculous lymphadenitis is characteristically indolent and usually presents as a unilateral painless mass sited along the upper border of the sternocleidomastoid muscle, although more than one site may be involved in up to 35% of cases.12 Constitutional symptoms are usually mild or absent9–11,13 and tuberculin skin tests (TSTs) are positive in 75–100% of HIV-uninfected individuals with lymph node TB.5,6,11–14 Fine needle aspiration (FNA) is the diagnostic procedure of choice with a reported diagnostic yield varying from 42% to 83%.4–6,14,15 In children the procedure is most effective when a 22-G needle (fine needle) is used,2 whereas in adults better yields were obtained
with larger needle sizes (18 or 19 G) and the procedure has been termed wide needle aspiration.15 In some cases an excision biopsy is required, and this may result in higher yields, especially if both histology and mycobacterial culture are obtained.6,14 Excision may also be a treatment option, particularly in NTM disease where the therapeutic response to chemotherapy is frequently suboptimal.4 Incisional biopsy should be avoided because it tends to result in sinus formation, a complication not seen with FNA.2 The prevalence of associated chest radiographic abnormalities varies considerably between reported series, probably reflecting differing age distributions, and has been as high as 38% in a predominantly middle-aged adult European cohort.14 HIV infection predisposes to M. tuberculosis dissemination with multifocal involvement, anergic responses to purified protein derivatives (PPDs), an increased presence of constitutional symptoms and higher mortality.9,11,16 HIV infection is associated with modified histological features including less mature tuberculous granulomata with numerous acid-fast bacilli and abundant caseation.17 The prevalence of HIV coinfection among individuals with TB lymphadenitis is considerably higher than that of the general population. In Rwanda, Tanzania and Zambia, HIV infection was confirmed in 80–92% of M. tuberculosis lymphadenitis cases,17–19 and in Sydney, Australia, 18.9% of cases were coinfected.20 HIV infection is a cause of generalized lymphadenopathy, and TB lymphadenitis may thus be an unexpected finding. It was identified in 52% of 727 lymph node biopsies performed in Lusaka, Zambia,19 and in 24% of individuals thought to have HIV-related lymphadenopathy in Rwanda,17 demonstrating the need for a high index of suspicion for TB lymphadenitis in regions with a high prevalence of HIV/TB dual infection.18,19 Needle biopsy has a higher positive acid-fast and mycobacterial culture yield in HIV-infected individuals than in HIV-seronegative individuals, probably reflecting the higher burden of organisms in this group, while cytological and histological findings may be less specific in HIV-infected individuals.21 However, macroscopic caseation, visible on naked-eye examination alone of wide needle aspiration (19 G), may be a useful diagnostic modality in low-resourced areas as it has been observed in up to 41% of 120 consecutive lymph node aspirates conducted in Zambia.15
MEDIASTINAL TUBERCULOUS LYMPHADENOPATHY Mediastinal lymphadenopathy is a feature of primary TB and is a common finding on chest radiographs of children with TB disease.22,23 In contrast, postprimary TB of HIV-seronegative adults
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associated with focally enlarged mediastinal lymph nodes is also a rare cause of fibrosing mediastinitis, which may cause dyspnoea due to compression of intrathoracic vascular structures including the pulmonary veins or arteries and less commonly the superior vena cava.31
MESENTERIC TUBERCULOUS LYMPHADENOPATHY
Fig. 36.1 A 19-year-old woman presented with weight loss and non-tender cervical lymphadenopathy involving anterior and posterior triangle of the neck (white arrows).
Fig. 36.2 Ziehl–Neelsen staining and microscopy yielded numerous acid-fast bacilli.
is characterized by cavitation and poorly defined consolidation of the apical and posterior segments of the upper lobe and/or superior segment of the lower lobe,22 and isolated intrathoracic tuberculous lymphadenopathy is a rare presentation, which must be differentiated from other more common infective and neoplastic causes.24 However, a primary pattern of TB is frequently observed in HIVinfected individuals coinfected with TB,25 and mediastinal lymphadenopathy has been reported in up to 80% of those with AIDS and pulmonary TB in Kigali, Rwanda.26 M. tuberculosis infection was also found to be a major cause of isolated mediastinal adenopathy in HIV-infected patients presenting to a New York City adult HIV outpatient clinic, where it was found in 63%, of whom 37% were coinfected with MAC. The computed tomography (CT) characterization of tuberculous mediastinal adenopathy includes extensive, frequently massive, heterogeneous soft-tissue lesions which appear as matted nodes of low density with peripheral enhancement.28 Magnetic resonance imaging (MRI) of mediastinal tuberculous lymphadenopathy with caseous necrosis shows inhomogeneous nodes with marked hyperintensity on T2-weighted images and peripheral enhancement after injection of contrast.29 Tuberculous mediastinal lymph nodes may rarely erode into neighbouring structures, leading to fistula formation.30 Tuberculosis
398
In HIV-seronegative individuals isolated tuberculous mesenteric lymphadenopathy in the absence of peritoneal or bowel involvement is rare. In a series of 49 cases of abdominal TB undergoing CT scans in Kuwait, lymphadenopathy was demonstrated in 47% of cases, of whom most had concomitant evidence of peritonitis, bowel wall thickening or solid organ involvement.32 In almost half of the cases lymph node involvement was diffuse and the remaining individuals had localized disease involving mesenteric, peripancreatic or portal, and para-aortic nodes. A similar distribution of lymph node involvement has been demonstrated in a series of abdominal TB investigated with ultrasound and MRI.33,34 Enlarged peripancreatic/portal nodes may be a rare cause of obstruction of nearby structures and consequently result in pyloric stenosis, portal hypertension and jaundice.35,36 Mesenteric adenopathy is common in HIV-infected individuals as a result of both MAC and M. tuberculosis infections. In industrialized countries MAC appears to be the more frequent cause of mesenteric lymphadenopathy,37,38 while mesenteric adenitis due to M. tuberculosis is the predominant cause in developing world settings.39 Whereas the distribution of intra-abdominal lymph node involvement in HIV-seronegative individuals may reflect the local lymphatic drainage of ingested organisms from the small bowel, in advanced HIV infection there is a wider dissemination of organisms, characterized by frequent involvement of other intraabdominal organs such as the pancreas and kidneys together with abscesses of the spleen, liver and retroperitoneal space.40 Increasing mesenteric lymphadenopathy is also one of the most frequent manifestations of immune restoration disease (IRD) in HIV/TB coinfected individuals starting antiretroviral therapy (ART).40
TREATMENT OF TUBERCULOUS LYMPHADENITIS There have been fewer treatment studies evaluating duration and response to treatment of lymph node TB than that of pulmonary TB. However, tuberculous infection of lymph nodes generally appears to respond to standard 6- to 9-month regimens including isoniazid (INH) and rifampicin, in a fashion similar to that of pulmonary tuberculous lesions and a 2-month regimen of INH, rifampicin, pyrazinamide and ethambutol followed by 4–7 months of INH and rifampicin.5,6,14,41,42 Paradoxical expansion of lymphadenopathy may be seen during the first 2 months of treatment in up to 20% of cases, but the occurrence thereof does not indicate failure of chemotherapy.12 The ideal duration of therapy for lymph node TB caused by drug-resistant organisms is not known. In HIV/TB coinfected patients paradoxical worsening of lymphadenopathy may be associated with initiation of antituberculous chemotherapy,12 but is more commonly seen as a manifestation of antiretroviral-mediated immune reconstitution syndrome, which frequently affects abdominal, axillary and mediastinal lymph nodes.43,44 IRD in the HIV-infected is an adverse consequence of
CHAPTER
Tuberculosis of lymph nodes and the reticuloendothelial system in adults
the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral therapy (HAART). Conditions previously subclinical may be ‘unmasked’ or previously recognized conditions may worsen as a result of increased immunopathological inflammatory responses. IRD is most frequently associated with mycobacterial infections and was first reported in 1998 soon after the advent of HAART.45–47
TUBERCULOSIS OF THE RETICULOENDOTHELIAL SYSTEM Tuberculosis of the reticuloendothelial system (RES) is usually a manifestation of extrapulmonary TB involving the bone marrow, liver or spleen and being demonstrable as tubercles on liver or bone marrow biopsy. The clinical presentation may include hepatosplenomegaly, hypersplenism, solitary splenic lesions or splenic abscesses.48–50 Diagnosis of tuberculous involvement of the RES is often delayed due to its non-specific presentation as fever, rigors, hepato-
REFERENCES 1. Krishnaswami H, Koshi G, Kulkarni KG, et al. Tuberculous lymphadenitis in South India—a histopathological and bacteriological study. Tubercle 1972; 53:215–220. 2. Marais BJ, Wright CA, Schaaf HS, et al. Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in children from a tuberculosisendemic area. Pediatr Infect Dis J 2006;25:142–146. 3. Grzybowski S, Allen EA. History and importance of scrofula. Lancet 1995;346:1472–1474. 4. Lindeboom JA, Kuijper EJ, Prins JM, et al. Tuberculin skin testing is useful in the screening for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis 2006; 43:1547–1551. 5. Dandapat MC, Mishra BM, Dash SP, et al. Peripheral lymph node tuberculosis: a review of 80 cases. Br J Surg 1990;77:911–912. 6. Memish ZA, Mah MW, Mahmood SA, et al. Clinico-diagnostic experience with tuberculous lymphadenitis in Saudi Arabia. Clin Microbiol Infect 2000;6:137–141. 7. Stanley BR, Fernandez AJ, Peppard BS. Cervicofacial mycobacterial infections presenting as major salivary gland disease. Laryngoscope 1983;93:1271–1275. 8. Pang SC. Mycobacterial lymphadenitis in Western Australia. Tuber Lung Dis 1992;73:362–367. 9. White MP, Bangash H, Goel KM, et al. Non-tuberculous mycobacterial lymphadenitis. Arch Dis Child 1986;61:368–371. 10. Chen YM, Lee PY, Su WJ, et al. Lymph node tuberculosis: 7-year experience in Veterans General Hospital, Taipei, Taiwan. Tuber Lung Dis 1992; 73:368–371. 11. Artenstein AW, Kim JH, Williams WJ, et al. Isolated peripheral tuberculous lymphadenitis in adults: current clinical and diagnostic issues. Clin Infect Dis 1995;20:876–882. 12. Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in Northern Germany: A clinical review. Chest 2002;121:1177–1182. 13. Ebdrup L, Storgaard M, Jensen-Fangel S, et al. Ten years of extrapulmonary tuberculosis in a Danish university hospital. Scand J Infect Dis 2003;35:244–246. 14. Polesky A, Grove W, Bhatia G. Peripheral tuberculous lymphadenitis: epidemiology, diagnosis, treatment and outcome. Medicine (Baltimore) 2005;84:350–362.
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splenomegaly or pyrexia of unknown origin. Needle aspiration and liver biopsy for smear and culture and for characteristic histological features are useful diagnostic procedures for larger granuloma or abscesses and are usually reserved for that purpose. Diagnosis and management can be facilitated by imaging such as ultrasound or CT imaging of the abdomen, demonstrating the granulomatous lesions often associated with abdominal lymphadenopathy. Tuberculous involvement of the bone marrow may result in a range of haematological abnormalities, including normochromic normocytic anaemia, leucopenia, neutropenia, thrombocytopenia and rarely pancytopenia or leucaemoid reaction occurring with disseminated TB.51,52 The treatment of TB of the RES is as for extrapulmonary TB in adults, but, in addition, surgical intervention may be required to drain or remove abscesses of the liver or spleen if there is a poor response to anti-TB chemotherapy. In HIV/TB coinfected patients paradoxical worsening of hepatic and splenic involvement may be associated with the initiation of ART due to IRD, resulting in rapidly worsening hepatosplenomegaly, splenic abscesses or splenic rupture.45
15. Bem C, Patil PS, Elliot AM, et al. The value of wideneedle aspiration in the diagnosis of tuberculous lymphadenitis in Africa. AIDS 1993;7:1221–1225. 16. Bem C. Human immunodeficiency virus-positive tuberculous lymphadenitis in Central Africa: a clinical presentation of 157 cases. Int J Tuberc Lung Dis 1997;1:215–219. 17. Ngilimana PJ, Metz T, Munyantore S, et al. Lymph node tuberculosis in HIV seropositive patients in Central Africa. A characteristic histopathologic picture. Ann Pathol 1995;15:38–44. 18. Parenboom RM, Richter, Swai AB, et al. Diagnosis of tuberculous lymphadenitis in an area of HIV infection and limited diagnostic facilities. Trop Georg Med 1994;46:228–232. 19. Bem C, Patil PS, Bharucha H, et al. Importance of human immunodeficiency virus-associated lymphadenopathy and tuberculous lymphadenitis in patients undergoing lymph node biopsy in Zambia. Br J Surg 1996;83:75–78. 20. Wark P, Gildberg H, Ferson M, et al. Mycobacterial lymphadenitis in eastern Sydney. Aust N Z J Med 1998;28:453–458. 21. Shriner KA, Mathisen GE, Goetz MB. Comparisons of mycobacterial lymphadenitis among persons infected with human immunodeficiency virus and seronegative controls. Clin Infect Dis 1992; 15:601–605. 22. Kim WS, Choi JI, Cheon JE, et al. Pulmonary tuberculosis in infants: radiographic and CT findings. AJR Am J Roentgenol 2006;187:1024–1033. 23. Mabiala Babela JR, Makosso E, Senga P. Radiological specificities of pulmonary tuberculosis in Congolese children: effect of HIV infection. Med Trop (Mars) 2006;66:255–259. 24. Van den Brande P, Vijgen J, Demedts M. Isolated intrathoracic tuberculous lymphadenopathy. Eur Respir J 1991;4:758–760. 25. Long R, Maycher B, Scalcini M, et al. The chest roentgenogram in pulmonary tuberculosis patients seropositive for human immunodeficiency virus type 1. Chest 1991;99:123–127. 26. Batungwanayo J, Taelman H, Dhote R, et al. Pulmonary tuberculosis in Kigali, Rwanda. Impact of human immunodeficiency virus infection on clinical and radiographic presentation. Am Rev Respir Dis 1992;146:53–56. 27. Haramati LB, Choi Y, Widrow CA, et al. Isolated lymphadenopathy on chest radiographs of HIVinfected patients. Clin Radiol 1996;51:345–349. 28. Pastores SM, Naidich DP, Aranda CP, et al. Intrathoracic adenopathy associated with pulmonary tuberculosis in patients with human
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immunodeficiency virus infection. Chest 1993;103:1433–1437. Moon WK, Im JG, Yu IK, et al. Mediastinal tuberculous lymphadenitis: MR imaging appearance with clinicopathologic correlation. AJR Am J Roentgenol 1996;166:21–25. Fatima SH, Javed MA, Ahmad U, et al. Tuberculous hilar lymph nodes leading to tracheopulmonary artery fistula and pseudoaneurysm of pulmonary artery. Ann Thorac Surg 2006;82:e35–36. Atasoy C, Fitoz S, Erguvan B, et al. Tuberculous fibrosing mediastinitis: CT and MRI findings. J Thorac Imaging 2001;16:191–193. Sinan T, Sheik M, Ramadan S, et al. CT features in abdominal tuberculosis: 20 years experience. BMC Med Imaging 2002;12:3–7. Kim SY, Kim MJ, Chung JJ, et al. Abdominal tuberculous lymphadenopathy: MR imaging findings. Abdom Imaging 2000;25:627–632. Malik A, Saxena NC. Ultrasound in abdominal tuberculosis. Abdom Imaging 2003;28:574–579. Fernandez OU, Canizares LL. Tuberculous mesenteric lymphadenitis presenting as pyloric stenosis. Dig Dis Sci 1995;40:1909–1912. Caroli-Bosc FX, Conio M, Maes B, et al. Abdominal tuberculosis involving hepatic hilar lymph nodes. A cause of portal vein thrombosis and portal hypertension. J Clin Gastroenterol 1997;25:541–543. Koh DM, Burn PR, Mathews G, et al. Abdominal computer tomographic findings of Mycobacterium tuberculosis and Mycobacterium avium intracellulare infection in HIV seropositive patients. Can Assoc Radiol J 2003;54:45–50. Radin DR. Intraabdominal Mycobacterium tuberculosis vs Mycobacterium avium intracellulare infections in patients with AIDS: distinction based on CT findings. AJR Am J Roentgenol 1991;156:487–491. O’Keefe EA, Wood R, Van Zyl A, et al. HIV-related abdominal pain in South Africa: Etiology, diagnosis and survival. Scand J Gastroenterol 1998;33:212–217. Monill-Serra JM, Martinez-Noguera A, Montserrat E, et al. Abdominal ultrasound findings of disseminated tuberculosis in AIDS. J Clin Ultrasound 1997; 25:1–6. Campbell IA, Ormerod LP, Friend PA, et al. Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final results. Respir Med 1993;87:621–623. Yuen APW, Wong SHW, Tam CM, et al. Prospective randomized study of the thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy. Otolaryngol Head Neck Surg 1997;116:189–192.
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43. Rajeswaran G, Becker JL, Michailidis C, et al. The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients with mycobacterial tuberculosis and HIV co-infection: appearances in 11 patients. Clin Radiol 2006;61: 833–843. 44. Lawn SD, Myer L, Bekker L-G, et al. Tuberculosis associated immune reconstitution disease: risk factors and impact in an antiretroviral treatment programme in sub-Saharan Africa. AIDS 2007;21:335–341. 45. Lawn SD, Bekker L-G, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis 2005;5:361–373.
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46. Narita M, Ashkin D, Hollender ES, et al. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Respir Crit Care Med 1998;158:157–161. 47. Crump JA, Tyrer MJ, Lloyd-Owen SJ, et al. Miliary tuberculosis with paradoxical expansion of intracranial tuberculomas complicating human immunodeficiency virus infection in a patient receiving highly active antiretroviral therapy. Clin Infect Dis 1998;26:1008–1009. 48. Sheen-Chen SM, Chou FF, Wan YL, et al. Tuberculosis presenting as a solitary splenic tumour. Tuber Lung Dis 1995;76:80–83.
49. Soriano V, Tor J, Gabarre E, et al. Multifocal splenic abscesses caused by Mycobacterium tuberculosis in HIV-infected drug users. AIDS 1991;5:901–902. 50. Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316–353. 51. Keeton GR, Naidoo G, Jacobs P. Leukaemoid reaction and disseminated tuberculosis. A case report. S Afr Med J 1975;49:1930–1932. 52. Singh KJ, Ahluwalia G, Sharma SK, et al. Significance of haematological manifestations in patients with tuberculosis. J Assoc Physicians India 2001;49:790–794.
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Tuberculosis of lymph nodes and the reticuloendothelial system in adults Helmuth Reuter and Robin Wood
INTRODUCTION Tuberculous lymphadenitis is the most common manifestation of extrapulmonary TB, which is defined as disease involving structures other than lung parenchyma, and is less common than pulmonary TB. It is the result of infection with the same organisms that cause pulmonary TB, namely Mycobacterium tuberculosis, Mycobacterium bovis or Mycobacterium africanum. In areas where TB is endemic and bovine TB is well controlled M. tuberculosis is the most common cause,1,2 whereas infection with M. bovis may be a frequent cause in areas where the control of bovine TB is poor and milk is not routinely pasteurized.3 In developed countries with low rates of TB transmission, environmental mycobacteria, also referred to as non-tuberculous mycobacteria (NTM), are mainly responsible for peripheral lymphadenitis, particularly Mycobacterium avium complex (MAC).4
PERIPHERAL LYMPH NODE TUBERCULOSIS Lymphadenitis is the most frequently occurring form of extrapulmonary TB with cervical nodes being most commonly involved in adults (Figs 36.1 and 36.2), although inguinal, mesenteric and mediastinal nodes may also be involved.5,6 NTM lymphadenitis is rare in adults, but relatively common in children and it may affect human immunodeficiency virus (HIV)-infected adults.7,8 The disease generally remains localized to the cervical region and is usually not accompanied by constitutional symptoms.6,9 It can be adequately managed with local excision, but, if left untreated, the nodes often progress to softening, rupture, sinus formation, healing with fibrosis and calcification.6–9 In contrast to children, M. tuberculosis is the major cause of mycobacterial lymphadenitis in adults and is usually a local manifestation of systemic disease. It seems to affect predominantly young women, although it can affect any age or race and those living in developing countries or immigrants from areas of high tuberculosis prevalence.10–14 Tuberculous lymphadenitis is characteristically indolent and usually presents as a unilateral painless mass sited along the upper border of the sternocleidomastoid muscle, although more than one site may be involved in up to 35% of cases.12 Constitutional symptoms are usually mild or absent9–11,13 and tuberculin skin tests (TSTs) are positive in 75–100% of HIV-uninfected individuals with lymph node TB.5,6,11–14 Fine needle aspiration (FNA) is the diagnostic procedure of choice with a reported diagnostic yield varying from 42% to 83%.4–6,14,15 In children the procedure is most effective when a 22-G needle (fine needle) is used,2 whereas in adults better yields were obtained
with larger needle sizes (18 or 19 G) and the procedure has been termed wide needle aspiration.15 In some cases an excision biopsy is required, and this may result in higher yields, especially if both histology and mycobacterial culture are obtained.6,14 Excision may also be a treatment option, particularly in NTM disease where the therapeutic response to chemotherapy is frequently suboptimal.4 Incisional biopsy should be avoided because it tends to result in sinus formation, a complication not seen with FNA.2 The prevalence of associated chest radiographic abnormalities varies considerably between reported series, probably reflecting differing age distributions, and has been as high as 38% in a predominantly middle-aged adult European cohort.14 HIV infection predisposes to M. tuberculosis dissemination with multifocal involvement, anergic responses to purified protein derivatives (PPDs), an increased presence of constitutional symptoms and higher mortality.9,11,16 HIV infection is associated with modified histological features including less mature tuberculous granulomata with numerous acid-fast bacilli and abundant caseation.17 The prevalence of HIV coinfection among individuals with TB lymphadenitis is considerably higher than that of the general population. In Rwanda, Tanzania and Zambia, HIV infection was confirmed in 80–92% of M. tuberculosis lymphadenitis cases,17–19 and in Sydney, Australia, 18.9% of cases were coinfected.20 HIV infection is a cause of generalized lymphadenopathy, and TB lymphadenitis may thus be an unexpected finding. It was identified in 52% of 727 lymph node biopsies performed in Lusaka, Zambia,19 and in 24% of individuals thought to have HIV-related lymphadenopathy in Rwanda,17 demonstrating the need for a high index of suspicion for TB lymphadenitis in regions with a high prevalence of HIV/TB dual infection.18,19 Needle biopsy has a higher positive acid-fast and mycobacterial culture yield in HIV-infected individuals than in HIV-seronegative individuals, probably reflecting the higher burden of organisms in this group, while cytological and histological findings may be less specific in HIV-infected individuals.21 However, macroscopic caseation, visible on naked-eye examination alone of wide needle aspiration (19 G), may be a useful diagnostic modality in low-resourced areas as it has been observed in up to 41% of 120 consecutive lymph node aspirates conducted in Zambia.15
MEDIASTINAL TUBERCULOUS LYMPHADENOPATHY Mediastinal lymphadenopathy is a feature of primary TB and is a common finding on chest radiographs of children with TB disease.22,23 In contrast, postprimary TB of HIV-seronegative adults
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associated with focally enlarged mediastinal lymph nodes is also a rare cause of fibrosing mediastinitis, which may cause dyspnoea due to compression of intrathoracic vascular structures including the pulmonary veins or arteries and less commonly the superior vena cava.31
MESENTERIC TUBERCULOUS LYMPHADENOPATHY
Fig. 36.1 A 19-year-old woman presented with weight loss and non-tender cervical lymphadenopathy involving anterior and posterior triangle of the neck (white arrows).
Fig. 36.2 Ziehl–Neelsen staining and microscopy yielded numerous acid-fast bacilli.
is characterized by cavitation and poorly defined consolidation of the apical and posterior segments of the upper lobe and/or superior segment of the lower lobe,22 and isolated intrathoracic tuberculous lymphadenopathy is a rare presentation, which must be differentiated from other more common infective and neoplastic causes.24 However, a primary pattern of TB is frequently observed in HIVinfected individuals coinfected with TB,25 and mediastinal lymphadenopathy has been reported in up to 80% of those with AIDS and pulmonary TB in Kigali, Rwanda.26 M. tuberculosis infection was also found to be a major cause of isolated mediastinal adenopathy in HIV-infected patients presenting to a New York City adult HIV outpatient clinic, where it was found in 63%, of whom 37% were coinfected with MAC. The computed tomography (CT) characterization of tuberculous mediastinal adenopathy includes extensive, frequently massive, heterogeneous soft-tissue lesions which appear as matted nodes of low density with peripheral enhancement.28 Magnetic resonance imaging (MRI) of mediastinal tuberculous lymphadenopathy with caseous necrosis shows inhomogeneous nodes with marked hyperintensity on T2-weighted images and peripheral enhancement after injection of contrast.29 Tuberculous mediastinal lymph nodes may rarely erode into neighbouring structures, leading to fistula formation.30 Tuberculosis
398
In HIV-seronegative individuals isolated tuberculous mesenteric lymphadenopathy in the absence of peritoneal or bowel involvement is rare. In a series of 49 cases of abdominal TB undergoing CT scans in Kuwait, lymphadenopathy was demonstrated in 47% of cases, of whom most had concomitant evidence of peritonitis, bowel wall thickening or solid organ involvement.32 In almost half of the cases lymph node involvement was diffuse and the remaining individuals had localized disease involving mesenteric, peripancreatic or portal, and para-aortic nodes. A similar distribution of lymph node involvement has been demonstrated in a series of abdominal TB investigated with ultrasound and MRI.33,34 Enlarged peripancreatic/portal nodes may be a rare cause of obstruction of nearby structures and consequently result in pyloric stenosis, portal hypertension and jaundice.35,36 Mesenteric adenopathy is common in HIV-infected individuals as a result of both MAC and M. tuberculosis infections. In industrialized countries MAC appears to be the more frequent cause of mesenteric lymphadenopathy,37,38 while mesenteric adenitis due to M. tuberculosis is the predominant cause in developing world settings.39 Whereas the distribution of intra-abdominal lymph node involvement in HIV-seronegative individuals may reflect the local lymphatic drainage of ingested organisms from the small bowel, in advanced HIV infection there is a wider dissemination of organisms, characterized by frequent involvement of other intraabdominal organs such as the pancreas and kidneys together with abscesses of the spleen, liver and retroperitoneal space.40 Increasing mesenteric lymphadenopathy is also one of the most frequent manifestations of immune restoration disease (IRD) in HIV/TB coinfected individuals starting antiretroviral therapy (ART).40
TREATMENT OF TUBERCULOUS LYMPHADENITIS There have been fewer treatment studies evaluating duration and response to treatment of lymph node TB than that of pulmonary TB. However, tuberculous infection of lymph nodes generally appears to respond to standard 6- to 9-month regimens including isoniazid (INH) and rifampicin, in a fashion similar to that of pulmonary tuberculous lesions and a 2-month regimen of INH, rifampicin, pyrazinamide and ethambutol followed by 4–7 months of INH and rifampicin.5,6,14,41,42 Paradoxical expansion of lymphadenopathy may be seen during the first 2 months of treatment in up to 20% of cases, but the occurrence thereof does not indicate failure of chemotherapy.12 The ideal duration of therapy for lymph node TB caused by drug-resistant organisms is not known. In HIV/TB coinfected patients paradoxical worsening of lymphadenopathy may be associated with initiation of antituberculous chemotherapy,12 but is more commonly seen as a manifestation of antiretroviral-mediated immune reconstitution syndrome, which frequently affects abdominal, axillary and mediastinal lymph nodes.43,44 IRD in the HIV-infected is an adverse consequence of
CHAPTER
Tuberculosis of lymph nodes and the reticuloendothelial system in adults
the restoration of pathogen-specific immune responses during the initial months of highly active antiretroviral therapy (HAART). Conditions previously subclinical may be ‘unmasked’ or previously recognized conditions may worsen as a result of increased immunopathological inflammatory responses. IRD is most frequently associated with mycobacterial infections and was first reported in 1998 soon after the advent of HAART.45–47
TUBERCULOSIS OF THE RETICULOENDOTHELIAL SYSTEM Tuberculosis of the reticuloendothelial system (RES) is usually a manifestation of extrapulmonary TB involving the bone marrow, liver or spleen and being demonstrable as tubercles on liver or bone marrow biopsy. The clinical presentation may include hepatosplenomegaly, hypersplenism, solitary splenic lesions or splenic abscesses.48–50 Diagnosis of tuberculous involvement of the RES is often delayed due to its non-specific presentation as fever, rigors, hepato-
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splenomegaly or pyrexia of unknown origin. Needle aspiration and liver biopsy for smear and culture and for characteristic histological features are useful diagnostic procedures for larger granuloma or abscesses and are usually reserved for that purpose. Diagnosis and management can be facilitated by imaging such as ultrasound or CT imaging of the abdomen, demonstrating the granulomatous lesions often associated with abdominal lymphadenopathy. Tuberculous involvement of the bone marrow may result in a range of haematological abnormalities, including normochromic normocytic anaemia, leucopenia, neutropenia, thrombocytopenia and rarely pancytopenia or leucaemoid reaction occurring with disseminated TB.51,52 The treatment of TB of the RES is as for extrapulmonary TB in adults, but, in addition, surgical intervention may be required to drain or remove abscesses of the liver or spleen if there is a poor response to anti-TB chemotherapy. In HIV/TB coinfected patients paradoxical worsening of hepatic and splenic involvement may be associated with the initiation of ART due to IRD, resulting in rapidly worsening hepatosplenomegaly, splenic abscesses or splenic rupture.45
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