In this study, cervical tuberculous lymphadenopathy remains in almost a quarter of the patients on CT scans after 6 months of treatment, and none experienced treatment failure.
Lymphadenopathy usually disappears in 30–40% of patients after 3 months of antituberculous chemotherapy and in 80% after 6 months of treatment. However, LN that is > 5 mm in diameter may last for a long period of time in 20% of patients . Although all residual LNs do not have an unfavorable outcome, defined as treatment failure or relapse , treatment might be prolonged or re-started in real world because unfavorable outcomes were not only on bacteriological or histological examination but also according to clinical findings. In contrast to smear-positive pulmonary TB, bacteriological treatment cannot be confirmed because it is challenging to obtain specimens from tuberculous lymphadenitis. In hospitals with poor healthcare facilities, decision-making in terms of treatment usually depends on clinical judgement when post-treatment lymphadenopathy occurs. In Korea where the prevalence of TB and the rate of drug-resistance is high, antituberculous treatment may be prolonged to 9–12 months when residual LNs remain .
In the absence of a consensus regarding the interpretation of the post-treatment residual LNs, this study revealed the characteristics of residual LNs based on pathologic findings. Biopsy or culture of residual nodes showed granuloma formation and negative culture results with or without positive AFB stains and/or TB PCR previously described as post-treatment paradoxical response [17, 18]. These features are consistent with hypersensitivity to the antigen of M. tuberculosis, which may be poorly cleared from the disease site even after prolonged therapy [1, 18]. Notably, not all residual LNs indicate treatment failure.
The risk factors of residual LNs must be identified because residual LNs, not treatment failure, can occur in some patients. However, the risk factors are not fully elucidated to date. Prior studies have indicated the following risk factors: younger age, male gender, size ≥3 cm, and local tenderness [11, 12, 17]. In our study, younger age was significantly correlated to residual LNs, which is consistent with previous studies. Thus, residual LNs may appear at the end of the six-month antituberculous therapy in younger patients, and treatment failure must be confirmed through bacteriological examination after short-term observation rather than prolonged treatment or drug changes.
Non-invasive methods, such as CT or fluorodeoxyglucose (FDG)-positron emission tomography (PET), and the identification of clinical risk factors may be helpful in evaluating the treatment response for tuberculous lymphadenitis [13, 16, 19]. Previous studies have shown that central necrosis, perinodal infiltration, and peripheral rim enhancement on CT scans were more frequently observed in patients with treatment failure . When a higher SUVmax value from FDG is added to this CT scan findings, distinguishing the treatment responder and non-responder was more helpful . Therefore, the size of the LN at the end of antituberculous treatment was not associated with treatment failure.
In the treatment period, the guidelines recommends six-month treatment for tuberculous lymphadenitis caused by drug-susceptible organisms [1, 20, 21]. The six-month recommendation is supported by studies showing that no difference was observed between 6 and 9 months of treatment in terms of cure rates (89–94%) [8, 22] or relapse rates (3%) . The Joint Tuberculosis Committee of the British Thoracic Society has stated that follow-up is not required after a successful treatment. However, patients should be re-referred if symptoms recur due to the limited number of relapse cases [9, 23]. In this study, the duration of antituberculous treatment with residual LNs was shorter in the group whose microbiological characteristics were identified through FNAB. Considering the microbiological characteristics of residual LNs, this study may be supporting the six-month therapy in the preexisting guideline.
During the follow-up period with a median of 658 days, no differences were observed in terms of recurrence between the groups with and without residual LNs. However, recurrences are diagnosed without microbiological findings in patients with recurrence, which may reflect post-treatment paradoxical response rather than recurrence . The gold standard for confirming recurrence is mycobacterial culture. However, culture alone cannot diagnose recurrence because of low sensitivity. Prior studies have already pointed out these problems [9, 17]. In one study, among patients with recurrence, three were diagnosed with recurrence according to mycobacterial culture results and based on histological findings, indicating that clinical judgement is still critical in identifying recurrence . The recurrence period is usually within 12 months after the end of treatment. However, recurrence may occur after 1 year. Therefore, further investigation must be conducted as it remains unclear how long the required follow-up period is for residual LNs after antituberculous treatment.
This study presents the clinical, radiologic, and pathologic findings at the end of six-month treatment for tuberculous lymphadenitis. The limitations of this study are as follows: FNAB was not performed in all patients with residual LNs, and some of the specimens were inappropriate. Most patients with residual LNs were treated with antituberculous drugs for more than 6 months, and CT scans were not obtained in further follow up course. The variables correlated to the recurrence of TB among the residual LN group must be identified next. Further follow-up studies with a higher number of patients must be conducted for statistical significance.