New Findings on Risk Factors for Postherpetic Neuralgia From 2014 to 2024: A Systematic Review and Meta-Analysis

Bing Liang,1 Yiwen Wan,2 Xinglai Su,2 Xiang Pan,2 Zhe Zhang,3 Xiaojing Guo,1,* Mi Li2,* 1Department of Pain Therapeutics, School of Anesthesiology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2School of Anesthesiology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mi Li, School of Anesthesiology, Naval Medical University, Shanghai, 200433, People’s Republic of China, Email [email protected] Xiaojing Guo, Department of Pain Therapeutics,School of Anesthesiology, Naval Medical University, Shanghai, 200433, People’s Republic of China, Email [email protected]: Postherpetic neuralgia (PHN) is a significant public health issue that severely impacts patients’ quality of life. This systematic review is the first to conduct a meta-analysis of newly identified risk factors for PHN over the past decade, evaluating the temporal changes in these risk factors to assist clinicians in predicting the occurrence of PHN.Methods: Cohort and case-control studies on PHN risk factors were retrieved from PubMed, Web of Science, Embase and Cochrane Library (January 1, 2014–March 26, 2024). Study quality was assessed using the Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess risk factor effects.Results: Seventeen studies involving 124,078 participants were included, identifying 81 potential risk factors. Eleven factors were meta-analyzed, and significant risk factors among these included age (age 60– 69 (OR=2.05, 95% CI=[1.92,2.19], P< 0.00001, I2=0%, age over 70 (OR=3.08, 95% CI=[2.89,3.29], P< 0.00001, I2=0%)), severe rash (OR=2.69, 95% CI=[1.23,1.88], P=0.01, I2=0%), acute pain severity (OR=2.01, 95% CI=[1.28,3.15], P=0.002, I2=21%), anxiety/depression (OR=1.30, 95% CI=[1.21,1.41], P< 0.00001, I2=0%), diabetes mellitus (OR=1.46, 95% CI=[1.40,1.53], P< 0.00001, I2=28%), malignancy (OR=1.56, 95% CI=[1.23,1.99], P=0.0002, I2=25%), chronic obstructive pulmonary disease(COPD) (OR=1.88, 95% CI=[1.79,1.98], P< 0.00001, I2=0%), hypertension (OR=1.22, 95% CI=[1.12,1.32], P< 0.00001, I2=2%) and peptic ulcer (OR=3.71, 95% CI=[2.31,5.96], P< 0.00001, I2=0%). Female sex (OR=0.69, 95% CI=[0.47,1.01], P= 0.06, I2=15%) and inflammatory factors (OR=1.01, 95% CI=[0.98,1.04], P=0.45, I2=30%) were not statistically significant.Conclusion: COPD, hypertension, anxiety/depression, malignancy and peptic ulcers may represent newly identified PHN risk factors. Given the limitations of the research, the results should be interpreted with caution. Future research should focus on these factors to enhance clinical prediction and prevention strategies.Trial Registration: This study is registered in the PROSPERO database (No. CRD42024543589).Keywords: postherpetic neuralgia, risk factors, meta-analysis