Clinical and metagenomic characteristics of lymphadenopathy related to fever of unknown origin in children.

BACKGROUND: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy.

METHODS: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed.

RESULTS: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results.

CONCLUSIONS: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases.

IMPACT STATEMENT: 1. The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features. 2. mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods. 3. mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated.