Introduction Pyrexia of unknown origin (PUO) has been reported due to various etiologies, including infections, malignancies, autoimmune diseases, and drug reactions. Traditional diagnostic methods often include blood cultures, imaging studies, and serological tests. However, advances in molecular diagnostics and imaging techniques have transformed the diagnostic landscape. This narrative review aimed to evaluate the laboratory diagnostic approaches used in assessing PUO, emphasizing the importance of targeted investigations and advancements in diagnostic technologies. Materials and Methods A comprehensive literature search was conducted across multiple databases (PubMed, Cochrane Library, and Scopus) using keywords related to PUO and laboratory diagnostics. Inclusion criteria encompassed studies published since 2014 that focused on laboratory methods for diagnosing PUO. Data extraction included study design, sample size, diagnostic techniques, and outcomes. Results The heterogeneous nature of PUO necessitated a tailored diagnostic approach, and integrating advanced technologies such as molecular diagnostics has enhanced disease detection and expedited diagnosis. The gold standard blood culture tests yielded approximately 20%-30% positivity in PUO cases, and serological cases elevated utility in identifying specific infections but were often limited by cross-reactivity. Polymerase chain reaction (PCR) and next-generation sequencing have emerged as promising tools for the rapid identification of pathogens, particularly in cases with atypical presentations. Conclusion Laboratory diagnosis of PUO requires a systematic and methodical approach, and continuous advancements in diagnostic techniques hold promise for improving outcomes in patients with PUO. However, large-scale studies should focus on developing standardized protocols for the evaluation of PUO to enhance diagnostic accuracy and efficiency.
Sivasangeetha et al. (Fri,) studied this question.