Tuberculous lymphadenitis

INTRODUCTION — Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis (TB). Tuberculous lymphadenitis in the cervical region is known as scrofula [1]. This syndrome can also be caused by nontuberculous mycobacteria.

TB is responsible for up to 43 percent of peripheral lymphadenopathy in resource-limited settings [2]. In rural India, the prevalence of tuberculous lymphadenitis in children up to 14 years of age is approximately 4.4 cases per 1000 [3]. In the United States, about 20 percent of patients with TB have extrapulmonary disease, and lymphadenitis is a presenting symptom in about 30 to 40 percent of cases [4-6]. In a Danish reported including more than 480 patients with TB between 2007 and 2016, lymphadenitis was observed in 13.5 percent of cases [7]. (See "Evaluation of peripheral lymphadenopathy in adults".)

The human immunodeficiency virus (HIV) epidemic has been associated with an increase in the total incidence of TB and an increased proportion of miliary, disseminated, and extrapulmonary TB cases including lymphadenitis [8]. (See "Epidemiology of tuberculosis" and "Epidemiology and pathology of miliary and extrapulmonary tuberculosis".)

Issues related to tuberculous lymphadenitis will be reviewed here. Other issues related to TB are discussed separately. (See related topics.)

PATHOGENESIS — Isolated peripheral tuberculous lymphadenopathy is usually due to reactivation of disease at a site seeded hematogenously during primary tuberculosis (TB) infection, perhaps years earlier [9].

It has been postulated that cervical tuberculous lymphadenitis occurs as a result of TB infection involving the tonsils, adenoids, and Waldeyer's ring, leading to cervical lymphadenopathy [2]. Abdominal tuberculous lymphadenopathy may occur via ingestion of sputum or milk infected with Mycobacterium tuberculosis or M. bovis [10]. (See "Tuberculosis: Natural history, microbiology, and pathogenesis" and "Mycobacterium bovis".)

Though most cases of tuberculous lymphadenitis occur in the setting of reactivation of latent infection, miliary dissemination with prominent lymph node involvement in the setting of primary infection can also occur [8,11,12].

EPIDEMIOLOGY — The epidemiology of tuberculous lymphadenitis varies between resource-limited and resource-rich countries.

In resource-rich countries, most cases of tuberculous lymphadenitis occur among adult immigrants from tuberculosis (TB)-endemic countries [13-15]. This was illustrated by case series of tuberculous lymphadenitis in France and Germany in which about 70 percent of cases occurred in immigrants; in the German study, two-thirds of patients had immigrated >3 years prior to diagnosis [13,14]. In a subsequent review of more than 480 cases reported from Denmark (a low TB incidence country with 4.8 cases per 100,000 population in 2017) between 2007 and 2016, more than 90 percent of patients with tuberculous lymphadenitis were immigrants. Furthermore, molecular analysis demonstrated a high proportion of unique genotypes, suggesting reactivation disease [7].

In the United States, the rate of tuberculous lymphadenitis is higher among individuals of Asian Pacific Island descent and in females [2,5,16]. Rarely, tuberculous lymphadenitis can also occur in travelers to endemic areas [17,18]. Tuberculous lymphadenitis occurs more frequently in women than in men [1].

Previously, tuberculous lymphadenitis was considered a disease of childhood; however, the peak age of onset in developed countries has shifted from childhood to ages 20 to 40 years [19]. In contemporary series, the median age has been approximately 40 years in developed countries (range 1 to 88 years) [13,15,20].

In resource-limited countries where TB is endemic, extrapulmonary TB occurs in up to 60 percent of patients with HIV infection with TB and is frequently accompanied by signs of pulmonary involvement [21-23]. Most extrapulmonary TB cases (including tuberculous lymphadenitis) occur among patients with HIV at CD4 counts <300 cells/microL (usually below 100 cells/microL) [8,24]. A Danish study described not only HIV infection but also other factors such alcohol abuse, homelessness, diabetes, and renal insufficiency as risk factors for tuberculous lymphadenitis [7].

CLINICAL MANIFESTATIONS — Clinical manifestations depend on the site of the lymphadenopathy and the immune status of the patient [9,11,16,17].

The most common presentation in young adults is isolated chronic nontender lymphadenopathy. Systemic symptoms are not common; fever has been reported in 20 to 50 percent of cases in patients without HIV infection and 60 to 80 percent in patients with HIV infection [1]. The mass may be present for up to 12 months before diagnosis [17,25]. Physical examination reveals a firm, discrete mass or matted nodes fixed to surrounding structures; the overlying skin may be indurated [9]. Uncommon findings include fluctuance, draining sinus, or erythema nodosum.

Cervical lymphadenopathy — Cervical lymphadenopathy is the most common manifestation of tuberculous lymphadenitis; in contemporary series, it represents 63 to 77 percent of cases [13,20].

Most frequently, a unilateral mass appears in the anterior or posterior cervical triangles; submandibular and supraclavicular lymph node involvement also occurs [17,21,25,26]. Bilateral disease is uncommon (up to 26 percent of cases) [17,27]. Although most patients have disease at only one site, multiple nodes may be involved at that site [16,25].

Other involved nodes — Local complications of tuberculous lymphadenitis are dependent on local anatomical structures:

●Tuberculous cervical lymphadenitis can be complicated by ulceration, fistula, or abscess formation.

●Mediastinal lymph node involvement usually occurs as a complication of primary tuberculosis (TB). Nodal enlargement can result in compression of the upper airways with bronchial or tracheal stenosis [28-30]. These complications may be more common in children, who have softer cartilage in their airways, and also more common in patients with HIV [28]. Tuberculous mediastinal lymphadenopathy can present with dysphagia, esophageal perforation, vocal cord paralysis due to recurrent laryngeal nerve involvement, or pulmonary artery occlusion mimicking pulmonary embolism [31-34].

●Subcarinal node enlargement can cause external compression of both the esophagus (producing dysphagia) [35] and bronchus [36]. Esophageal perforation and tracheoesophageal fistula have both been reported [37].

●Tuberculous peritoneal lymphadenopathy most commonly involves lymph nodes in the periportal region, followed by peripancreatic and mesenteric lymph nodes [11]. Hepatic lymph node involvement can lead to jaundice, portal vein thrombosis, and portal hypertension [38]. Extrinsic compression of renal arteries due to tuberculous abdominal lymphadenopathy can result in renovascular hypertension [39]. Enlargement of tuberculous intraabdominal lymph nodes has resulted in external compression of segments of the gastrointestinal tract, such as the duodenum [40,41].

Other sites of tuberculous lymphadenitis include the axillary, inguinal, and intramammary lymph nodes [9,11,42].

HIV coinfection — Among patients with tuberculous lymphadenitis in the setting of HIV infection, there may be a significant mycobacterial load with concomitant systemic findings including fever, sweats, and weight loss [21]. Abnormal chest radiography is frequently observed, and such patients are more likely to have disseminated TB with lymphadenitis at more than one site [11,21]. Patients with mediastinal and hilar node involvement are likely to have active pulmonary TB also and may have symptoms including dyspnea and tachypnea [43].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of isolated peripheral lymphadenopathy is extensive and includes malignancy (eg, Hodgkin lymphoma and non-Hodgkin lymphoma) and other infections (eg, nontuberculous mycobacteria [M. scrofulaceum, M. avium complex, M. kansasii ,M. fortuitum] [44], cat scratch disease, fungal infection, sarcoidosis, and bacterial adenitis).

Kikuchi disease (idiopathic histiocytic necrotizing lymphadenitis) can mimic tuberculous cervical lymphadenopathy; indistinct margins of necrotic foci demonstrated on computed tomography scan may be an independent predictor of Kikuchi disease [45,46]. The most likely alternative diagnoses depend on the clinical setting including the patient's age, ethnic background, immune status, and presenting clinical features. (See "Kikuchi disease".)

It is difficult to differentiate tuberculosis from other causes of lymphadenitis on clinical grounds. One study found no distinguishing clinical features between patients with lymphadenitis due to tuberculous or nontuberculous mycobacteria [47]. Another report noted the same results regardless of HIV status [21].

DIAGNOSIS

Clinical approach — The diagnosis of tuberculous lymphadenitis is established by histopathology examination along with acid-fast bacilli (AFB) smear and culture of lymph node material. Chest imaging should also be obtained.

In the United States, no specific bacteriologic confirmation is established in at least 13 percent of patients with a “clinical diagnosis” of tuberculosus (TB) [48]. In such cases, a presumptive clinical diagnosis may be based on epidemiologic factors together with physical findings, radiographic findings, histopathology, and/or positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA). In the setting of high clinical suspicion for TB, initiation of empiric therapy based on these findings is appropriate.

Patients with suspected or proven TB should undergo HIV testing [43]. (See "Screening and diagnostic testing for HIV infection".)

Diagnostic tools

Histopathology — Material for histopathology evaluation may be obtained by fine needle aspiration or excisional lymph node biopsy.

Specimens should be submitted for histology, acid-fast stain, culture, and nucleic acid amplification (NAA) testing. (See 'Nucleic acid amplification testing' below and 'Culture' below.)

●Fine-needle aspiration − Fine-needle aspiration (FNA) is appropriate for initial evaluation of cervical lymphadenopathy to evaluate for tuberculous lymphadenitis. The yield of FNA appears to be highest in the setting of HIV infection and in regions where the prevalence of TB is high [17,21,49-51]. In these circumstances, the burden of organisms is likely to be high. In a series of 1193 patients evaluated for tuberculous lymphadenitis in Hong Kong, for example, FNA had good sensitivity and specificity (77 and 93 percent, respectively) [52].

FNA is a relatively safe and inexpensive procedure, with few complications when a 21 to 23 gauge needle is used [17]. Specimens should be submitted for microscopy, culture, cytology, and polymerase chain reaction testing (where available).

●Excisional biopsy − Excisional lymph node biopsy for histopathologic and microbiological evaluations has the highest diagnostic yield and should be pursued in cases where fine needle aspiration is not diagnostic [26,52]. In a series of 47 patients evaluated for tuberculous lymphadenitis, for example, the diagnosis of TB was established by excisional biopsy in all cases; FNA was definitive in only 62 percent [26]. In studies from developed countries, M. tuberculosis is typically cultured from excisional biopsies in 70 to 90 percent of cases [1]. Excisional biopsy is preferred over incisional biopsy; the latter may be associated with sinus tract formation. For mediastinal lymph node biopsy, mediastinoscopy may be required.

The finding of caseating granulomas on histopathology is highly suggestive of TB although is not diagnostic since other diseases can also have similar histology [26].

Microbiologic testing

Culture — Culture for mycobacteria remains the gold standard for diagnosis of tuberculosis (TB). Culture permits drug susceptibility testing and must be performed to inform treatment decisions, even if NAA testing is positive.

Nucleic acid amplification testing — NAA testing can facilitate the diagnosis of TB in lymph node tissues (including aspirates) for which histology findings are not specific and acid-fast organisms are not seen [53-57]. In a systematic review and meta-analysis including 18 studies, the sensitivity and specificity for the Xpert MTB/RIF assay (compared with culture) in lymph nodes were 83 and 94 percent, respectively [55].

In a comparative study of FNA specimens from patients with presumptive TB lymphadenitis, the Xpert MTB/RIF Ultra had improved sensitivity (91 versus 72 percent) but reduced specificity (76 versus 93 percent) compared with the Xpert MTB/RIF assay [58]. In a small study, loop-mediated isothermal amplification assay compared favorably with GeneXpert MTB/Rif in diagnosis of tubercular lymphadenitis in patients with HIV [59].

No commercial NAA platform is approved by the US Food and Drug Administration for use with nonrespiratory specimens, and Xpert MTB/RIF Ultra is not available in the United States. However, individual laboratories may validate and perform NAA testing on nonrespiratory samples; reporting language should indicate that this is a non-approved ("off-label") use of the test.

Serial NAA testing cannot be used to monitor response to therapy, since it reflects presence of M. tuberculosis-complex nucleic acid but not viability.

Role of IGRA and TST — In the absence of a definitive diagnosis (based on histopathology along with AFB smear and culture), a presumptive clinical diagnosis may be based on other factors including positive TST or IGRA. (See 'Clinical approach' above.)

●TST – The TST is positive in the majority (74 to 100 percent) of patients with tuberculous lymphadenitis (in the absence of HIV infection); however, a positive TST is not sufficient to establish the diagnosis of active TB [9,13,15,17,18,21]. A negative TST is not helpful in excluding the diagnosis, especially in immunosuppressed individuals [21].

●IGRA – The sensitivity and specificity of IGRA in tuberculous lymphadenitis is similar to the TST; however, a positive IGRA result is not sufficient to establish a diagnosis [60,61].

Radiographic imaging

●Chest imaging − In nonendemic countries, most patients with tuberculous lymphadenitis have no evidence of active pulmonary TB on chest radiograph (90 to 100 percent) [7,13,18]. In TB-endemic countries, pulmonary involvement is observed in 20 to 40 percent of patients with tuberculous lymphadenitis. Pleural thickening and apical fibrosis suggestive of previous TB may be observed [9,21]. In addition, central lymphadenopathy may lead to extrinsic airway compression and atelectasis [62,63]. This may be seen on the original presentation or appear paradoxically during treatment, even as the patient is improving clinically. (See 'Paradoxical reaction' below.)

Chest radiograph abnormalities have been described more frequently among patients with HIV infection in some series. One report of 10 patients with HIV infection described abnormal radiography on presentation with tuberculous lymphadenitis in 90 percent of cases [21].

Chest imaging suggestive of active pulmonary TB should prompt further evaluation, as outlined separately. (See "Diagnosis of pulmonary tuberculosis in adults", section on 'Radiographic imaging'.)

●Neck imaging − Neck imaging modalities include ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI).

•Ultrasonography – In a study comparing lymph node metastases with tuberculous lymphadenitis, the latter was associated with a higher incidence of abnormal surrounding soft tissue, cystic necrosis, matting, posterior enhancement (when structures posterior to the node were more echogenic than neighboring structures), and a heterogeneous rather than a homogenous pattern [64]. A subsequent study using endobronchial ultrasound demonstrated that presence of necrosis and absence of the clustered formation were independent predictors of tuberculous lymph nodes [65].

•Computed tomography – CT and positron emission tomography (PET-CT) can be useful to identify involved lymph nodes for biopsy or to monitor responses to treatment (image 1). However, radiographic findings of lymphadenopathy are not specific for TB, especially when trying to distinguish tuberculous lymphadenitis from lymphoma or other malignancy [66-68]. In one Chinese series including 26 patients with tuberculous lymphadenitis and 43 patients with lymphoma, lower paraaortic node involvement was more common in lymphoma; TB more often involved upper paraaortic, lesser omental, mesenteric, and anterior pararenal lymph nodes [10]. Peripheral enhancement (often with a multilocular appearance) was also a feature of tuberculous lymphadenopathy; homogeneous attenuation was more common in the setting of lymphomatous adenopathy. In another study comparing CT findings in Kikuchi disease and tuberculous lymphadenitis, patients with Kikuchi disease had involvement of multiple nodal levels, minimal or no nodal necrosis, marked perinodal infiltration, and no evidence of upper lung pathology or mediastinal lymphadenopathy [69].

•Magnetic resonance imaging – In a report of MRI evaluation among nine Chinese patients with tuberculous lymphadenitis, three patterns of disease were noted: discrete nodes, matted nodes, and confluent masses [70]. Necrotic foci, when present, were more frequently peripheral rather than central.

Other tools — Diagnosis of tuberculous lymphadenitis is established by histopathology examination and AFB smear and culture of lymph node material as discussed above. Additional diagnostic tools that may be useful in the setting of suspected tuberculous lymphadenitis are outlined below. Further discussion of issues related to diagnosis of TB is presented separately. (See "Diagnosis of pulmonary tuberculosis in adults".)

●Sputum smear and culture – Positive sputum cultures are uncommon (0 to 14 percent) in the setting of tuberculous lymphadenitis [13,17,71]. Chest radiography findings consistent with active pulmonary TB should prompt sputum cultures; if positive, evaluation for miliary TB should be pursued. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

●Bronchoscopy – In the setting of isolated intrathoracic lymphadenopathy, bronchoscopy may be useful to establish a diagnosis of TB if sputum studies are negative [72,73].

●Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) – This modality may be useful in the setting of isolated intrathoracic lymphadenopathy [74-79]. In one report of 24 patients with isolated intrathoracic lymphadenopathy and a high clinical suspicion for TB, material obtained by EBUS-TBNA confirmed the diagnosis in 79 percent of cases (sensitivity and specificity 95 and 100 percent, respectively) [74].

●Ultrasound-guided core biopsy is an uncommonly used tool with reported utility in the tissue diagnosis of TB [80].

●Blood culture – Blood cultures for M. tuberculosis are rarely positive but may be positive in disseminated TB, especially in patients with HIV and other forms of immunosuppression [81].

TREATMENT — Treatment of tuberculous lymphadenitis consists of multidrug antimycobacterial therapy. In some circumstances, excisional biopsy in theory may be sufficient for treatment of immunocompetent patients with localized disease, though in general all patients should also receive antimycobacterial therapy.

Choice of therapy — The American Thoracic Society, United States Centers for Disease Control and Prevention (CDC), and the Infectious Diseases Society of America have published recommendations for the treatment of tuberculosis (TB) [82]. In general, treatment for adults with presumed drug-susceptible tuberculous lymphadenitis consists of two months of rifampicin, isoniazid, ethambutol, and pyrazinamide (given daily) followed by four months of rifampicin and isoniazid (given either daily or three times weekly) [83]. Ethambutol may be discontinued from the regimen once drug susceptibility of the isolate to the other drugs in the regimen is confirmed. Selection of medications, dosing, monitoring, and further details related to antimycobacterial regimens for TB are presented separately as are issues related to patients with HIV infection. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection" and "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy".)

The recommended duration of therapy for adults without HIV infection is six months [82,84,85]. In a randomized trial comparing a six-month regimen (four drugs for four months followed by two drugs for two months) with a nine-month regimen (four drugs for four months followed by two drugs for five months), there was no difference in treatment failure or remission at five years between the two regimens [84].

Alternative regimens for drug-susceptible M. tuberculosis have been evaluated among 277 patients with tuberculous lymphadenitis in India (90 percent of patients had fully susceptible M. tuberculosis), including two months of rifampicin, isoniazid, and pyrazinamide (two times weekly) followed by four months of rifampicin and isoniazid (two times weekly), and six-month regimen of daily rifampicin and isoniazid [83]. These regimens are not recommended [82]. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

The optimal duration of therapy in children is uncertain [86]. The relapse rate in children after six months of therapy is not well established; nine months of therapy may be appropriate pending further study.

Longer duration of therapy also may be appropriate for patients with HIV infection with evidence of suboptimal response, those who cannot tolerate first-line medications, or patients who have infection due to resistant organisms [82]. In such situations, selection and duration of therapy should be individualized in consultation with a clinician with expertise in TB. Further consultation for diagnosis and management may be obtained through the CDC's Regional Training and Medical Consultation Centers. Treatment of drug-resistant tuberculosis is discussed separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults".)

Response to therapy — Tuberculous lymphadenitis is characteristically slow to respond to effective treatment, and nodes may enlarge during treatment or after cessation of treatment.

Paradoxical reaction — Antimycobacterial therapy may prompt a paradoxical reaction or increase in lymph node size and/or enlargement of additional lymph nodes in up to 20 percent of patients during or after cessation of treatment [1,13,71]. Most paradoxical reactions occur between three weeks and four months after initiation of treatment [1]. Cultures are usually negative, and such reactions do not usually indicate treatment failure.

Paradoxical reactions have been attributed to an immune response to dying M. tuberculosis organisms [87,88]. Clinical manifestations may include lymph node enlargement (12 percent), fluctuance (11 percent), overlying erythema, and/or spontaneous discharge (7 percent) [71,89]. In the chest, paradoxically enlarged nodes can cause atelectasis during treatment (see above). Constitutional symptoms are uncommon [71]. (See "Immune reconstitution inflammatory syndrome".)

In patients without HIV infection, such paradoxical reactions occur in up to 23 percent of cases [13,71,87,90]. Predictors include male sex, presence of local erythema at the time of diagnosis [87], presence of a positive M. tuberculosis culture, and peripheral lymph node disease [91].

In patients with HIV infection, paradoxical reactions are more common in some but not all reports [92,93]. It may be more temporally associated with the initiation of antiretroviral therapy (ART) than anti-TB therapy [92]. There appears to be no association between baseline CD4 counts or CD4 response to ART [94].

The differential diagnosis includes treatment failure due to resistance or noncompliance, another infection, or an alternative diagnosis [94].

There are no consensus guidelines for management of paradoxical reaction, and the approach should be based on whether the patient is experiencing significant discomfort. Options include observation, aspiration, surgical excision, or a trial of nonsteroidal anti-inflammatory agents or corticosteroids. Infliximab has also been used in this setting [95].

Fine-needle aspiration for acid-fast bacillus microscopy and culture may be pursued to distinguish between a paradoxical reaction and treatment failure.

In one study of 235 patients without HIV infection, spontaneous resolution of paradoxical lymph node enlargement occurred in 56 percent of cases [87]. In a second study including both patients with and without HIV infection, spontaneous resolution occurred in all patients in mean period of 2.5 months; some patients underwent aspiration or excision [71].

Relapse rates — Relapse rates of up to 3.5 percent have been reported in patients treated for tuberculous lymphadenitis [85]. A minority of patients have palpable lymph nodes present at the end of the treatment course (7 to 11 percent) [85,89,96].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis".)

SUMMARY AND RECOMMENDATIONS

●Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis (TB). Tuberculous lymphadenitis in the cervical region is known as scrofula. (See 'Introduction' above.)

●Isolated peripheral tuberculous lymphadenopathy is usually due to reactivation of disease at a site seeded hematogenously during primary TB infection, perhaps years earlier. Miliary dissemination with prominent lymph node involvement in the setting of primary infection can also occur. (See 'Pathogenesis' above.)

●Previously, tuberculous lymphadenitis was considered a disease of childhood; however, in reports from developed countries, the peak age of onset has shifted from childhood to ages 20 to 40 years. In developed countries, most cases of tuberculous lymphadenitis occur among immigrants from TB-endemic countries. In regions where TB is endemic, extrapulmonary TB occurs in approximately 60 percent of patients with HIV infection with TB and is frequently accompanied by signs of pulmonary involvement. (See 'Epidemiology' above.)

●Clinical manifestations depend on the site of the lymphadenopathy and the immune status of the patient. The most common presentation is isolated chronic nontender lymphadenopathy in a young adult without systemic symptoms other than fever, most commonly in the cervical region. Physical examination reveals a firm, discrete mass or matted nodes fixed to surrounding structures; the overlying skin may be indurated. (See 'Clinical manifestations' above.)

●Among patients with tuberculous lymphadenitis in the setting of HIV infection, there may be a significant mycobacterial load with concomitant systemic findings including fever, sweats, and weight loss. Abnormal chest radiography is frequently observed, and such patients are more likely to have disseminated TB with lymphadenitis at more than one site. (See 'HIV coinfection' above.)

●Diagnosis of tuberculous lymphadenitis is established by histopathology examination along with acid-fast bacilli (AFB) smear and culture of lymph node material. Fine needle aspiration (FNA) is appropriate for initial evaluation of cervical lymphadenopathy to evaluate for tuberculous lymphadenitis. The yield of FNA 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 microscopy, culture, cytology, and nucleic acid testing (where available). Excisional lymph node biopsy for histopathologic and microbiological evaluation has the highest diagnostic yield and should be pursued in cases where fine needle aspiration is not diagnostic or for persistent disease despite appropriate therapy. (See 'Histopathology' above.)

●Chest imaging should be pursued in the setting of suspected tuberculous lymphadenitis. Most patients from nonendemic countries with suspected tuberculous lymphadenitis have no evidence of active pulmonary TB on chest radiograph, while patients from endemic countries have chest radiograph abnormalities in 20 to 40 percent of cases. Abnormalities have been described more frequently among patients with HIV infection in some series. (See 'Radiographic imaging' above.)

●For treatment for adults without HIV infection with tuberculous lymphadenitis, we suggest the following regimen: two months of rifampicin, isoniazid, ethambutol, and pyrazinamide (given daily) followed by four months of rifampicin and isoniazid (given either daily or three times weekly) (Grade 2B). The preferred duration of therapy for adults is six months. The optimal duration of therapy in children is uncertain, as the relapse rate after six months of therapy is not well established; nine months of therapy may be appropriate pending further study. (See 'Treatment' above.)

●Paradoxical upgrading reactions may occur in as many as 20 percent of patients, are usually culture negative, and do not usually represent treatment failure. (See 'Paradoxical reaction' above.)