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Tuberculous Lymphadenitis 감염내과 R3 김동현 INTRODUCTION Tuberculous lymphadenitis In Korea, 11~17% of patients with TB have extrapulmonary disease, TB pleursy, TB lymphadenitis, abdominal TBc, bone and joint TB was the order. Korea tuberculosis information management system June 2010 Epidemiology Male < Female ( about 2 folds ) Common in the 20 to 40 age group INTRODUCTION In developed countries Most cases occur adult immigrants from TB endemic countries Peak age of onset in developed countries has shifted from childhood to ages 20 to 40 years Curr Infect Dis Rep. 2001;3(3):233. In developing countries Extrapulmonary TB occurs in up to 60 % of HIV-infected patients with TB and is frequently accompanied by signs of pulmonary involvement (CD4 counts <300 / uL, usually < 100 / uL) Clin Infect Dis. 1992;15(4):601. Pathogenesis Usually, reactivation of disease at a site seeded hematogenously during primary TB, perhaps years earlier Medicine (Baltimore). 1984;63(1):25 Cervical TB lymphadenitis Due to TB infection involving the tonsils, adenoids and Waldeyer 's ring Abdominal TB lymphadenopathy Ingestion of sputum or milk infected with M. tuberculosis / M. bovis Miliary dissemination of primary infection can also occur Am Rev Respir Dis. 1991;144(5):1164 Clinical manifestations Depend on 1) the site of the lymphadenopathy and 2) the immune status of the patient Cervical lymphadenopathy The most common manifestation (63~77%) Most frequently a unilateral mass appears in the ant, or posterior cervical triangles, Bilateral disease is uncommon (up to 26 %) Schlossberg D. Tuberculosis & nontuberculous mycobacterial infections. 5th ed. . Cervical Lymphadenopathy Clinical manifestations Other involved nodes Axillary, inguinal, mesenteric, mediastinal, and intramammary LNs Mediastinal LAP Dysphagia, esophageal perforation, vocal cord paralysis, pulmonary artery occlusion Intra-abdominal LAP Peritoneal LAP • most commonly LNs in the periportal region, followed by peripancreatic and mesenteric LNs. Hepatic lymph node involvement can lead to jaundice, portal vein thrombosis, and portal hypertension. Axillary lymphadenopathy Mediastinal lymphadenopathy Mediastinal lymphadenopathy Intra-abdominal LAP Clinical manifestations HIV (+) patients Significant mycobacterial load with concomitant systemic findings (eg. fever, sweats, & weight loss) More likely to have disseminated TB with lymphadenitis at more than one site Differential Diagnosis Isolated peripheral lymphadenopathy Malignancy (eg, HL & NHL) Other infections (eg, NTM, cat scratch disease, fungal infection, sarcoidosis, and bacterial adenitis). Kikuchi's disease . Difficult to differentiate TB from other causes of lymphadenitis on clinical grounds. Diagnosis Established by Histopathology examination Along with AFB smear and culture of lymph node material. Chest imaging should be obtained Diagnosis - Histopathology Fine needle aspirate (FNA) Initial evaluation of cervical lymphadenopathy The yield appears to be highest in the setting of HIV infection and in regions where the prevalence of TB is high. Specimens should be submitted for 1) Microscopy, 2) Culture, 3) Cytology, and 4) PCR testing Diagnosis - Histopathology Infection and Chemotherapy: Vol.40, No.2, 2008 Diagnosis - Histopathology Lymph node biopsy In cases when FNA is not diagnostic 47 patients evaluated for TB lymphadenitis in San Francisco, the diagnosis of TB was established by excisional biopsy in all cases; FNA was definitive in only 62 percent Laryngoscope. 1992;102(1):60. Caseating granulomas on histopathology is highly suggestive of TB Diagnosis Diagnosis - Imaging Chest imaging Many patients (90~100 %) with TB lymphadenitis have no evidence of active pulmonary TB on chest x-ray Chest imaging suggestive of active pulmonary TB should prompt further evaluation Neck imaging Ultrasonography Computed tomography Useful tool to distinguish between TB lymphadenitis and lymphoma. Ularasonography Diagnosis - Others Sputum smear and culture Positive sputum cultures are uncommon (0 ~ 14 %) Blood culture Rarely positive, but may be positive in disseminated TB especially in patients with HIV and other forms of immunosuppression Diagnosis - Others Tuberculin skin test (PPD test) Sensitivity and specificity of 65 & 81%, Interferon-Gamma Release Assays (IGRA) Sensitivity and specificity of 86-94% & 81-87% Diagn Microbiol Infect Dis. 2009;63(2):182. HIV testing Patients with suspected or proven TB should undergo HIV testing Interferon-Gamma Release Assays Diagnostic tools for latent tuberculosis infection Measure T cell release of IFN-r following stimulation by antigens specific to M. tuberculosis (Specificity >95 % for diagnosis of LTBI) Type of assay Quantiferon-TB Gold In-Tube® (Cellestis) T-SPOT.TB® (oxford immunotec) Superial to TST Not affected by BCG vaccination status Limitation IGRAs cannot distinguish between latent infection and active TB disease Interferon-Gamma Release Assays Treatment In general all patients should receive antimycobacterial therapy. Choice of therapy Recommended duration for HIV (-) adults is 6 mo. 2 mo. Rifampicin, isoniazid, ethambutol, & pyrazinamide Followed by 4 mo. Rifampicin, isoniazid, ethambutol Infect and Chemother 36 (Suppl2):S124-31, 2004. Treatment Longer duration of therapy also may be appropriate HIV infection with evidence of suboptimal response Intolerable first line medications Infection due to resistant organisms Am J Respir Crit Care Med. 2003;167(4):603. Treatment Response to therapy TB lymphadenitis tends to respond slowly to effective treatment. Paradoxical reaction Increase in LN size and/or enlargement of additional LNs during or after cessation of treatment Due to an immune response to dying M. tuberculosis organisms Treatment Paradoxical reaction - continued Clinical manifestation LN enlargement (12 %), fluctuance (11 %), erythema and/or spontaneous discharge (7 %). Constitutional symptoms are rare The differential diagnosis Treatment failure • Resistance • Non-comliance Another infection Treatment Paradoxical reaction - continued FNA for AFB and culture may be pursued to distinguish between a paradoxical reaction and treatment failure. Management - no consensus guidelines Aspiration, surgical excision, or a trial of NSAIDs, corticosteroids, Infliximab Course In one study of 235 HIV (-) patients. spontaneous resolution of paradoxical lymph node enlargement occurred in 56 % of cases J Infect 2009;59:56-61. Treatment Relapse rates Relapse rates of up to 3.5 percent 7 to 11 % of patients have residual lymph nodes present at the end of the treatment course Leukocytoclastic vasculitis Infections (including TBc, HIV) Medications Connective tissue diseases Malignancy