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Determining the Definitive Time Criterion for Postherpetic Neuralgia Using Infrared Thermographic Imaging

使用红外热成像确定带状疱疹后神经痛的确切时间标准

Introduction：

The time criteria used in many studies of postherpetic neuralgia （PHN） are arbitrary and do not have supporting evidence． Therefore， this study sought to determine the definite time criterion for PHN by analyzing the skin temperature to estimate the time point when zoster－induced skin inflammatory reaction ends．

许多带状疱疹后神经痛 （PHN） 研究中使用的时间标准是任意的，没有支持证据。因此，本研究试图通过分析皮肤温度来估计带状疱疹引起的皮肤炎症反应结束的时间点，从而确定 PHN 的确定时间标准。

Methods： Infrared thermography was used to measure the difference in skin temperature between the affected and unaffected areas （DTemp） in the craniocervical and thoracic regions of patients with herpes zoster （HZ）． Because the DTemp changes from a positive value to zero when the skin is no longer inflamed， a DTemp B 0 was defined as the end of skin inflammation， and this time point was considered the starting point for PHN． This cutoff time point was estimated using receiver operating characteristic （ROC） curve analysis．

Hot spots on the IRT image， which represent elevated skin temperature， appear when inflammatory mediators are released due to local inflammatory reactions， and cold spots appear due to sympathetic activation． In the early phase of HZ， the skin temperature rises due to inflammatory reactions in the affected area． However， in the chronic stage of PHN， skin temperature asymmetry is accompanied by low－temperature lesions due to sympathetic activation， appearing as cold spots in IRT images ， which implies the involvement of a neuropathic complication ． Therefore， it can be inferred that the time point at which the hot spots change to cold spots indicates the transition from HZ to PHN， and this can be observed using IRT．

方法：采用红外热像仪测量带状疱疹（HZ）患者颅颈和胸部受累区域和未受累区域（DTemp）的皮肤温度差异。因为当皮肤不再发炎时DTemp从正值变为0，所以将DTemp B 0 定义为皮肤发炎的结束，并且这个时间点被认为是PHN的起点。使用ROC曲线分析估计该截止时间点。

   IRT 图像上的热点代表皮肤温度升高，当炎症介质由于局部炎症反应而释放时出现，而冷点则由于交感神经激活而出现。在 HZ 的早期，由于患处的炎症反应，皮肤温度升高。然而，在 PHN 的慢性期，由于交感神经激活，皮肤温度不对称伴有低温病变，在 IRT 图像中表现为冷点 ，这意味着涉及神经性并发症。因此，可以推断出热点变为冷点的时间点表明了从 HZ 到 PHN 的转变，这可以通过 IRT 观察到。

Results： A total of 503 patients were included in this study． The ROC curve analysis showed that the time point when the DTemp was B 0 occurred at 12 weeks after HZ onset （95％ confidence interval 11–15 weeks， area under the ROC curve 0．901）． Using this time point as the time criterion of PHN， the sensitivity， specificity， and classification accuracy were 0．807， 0．905， and 0．871， respectively．

结果：本研究共纳入 503 名患者。ROC曲线分析显示，DTemp为B 0 的时间点发生在HZ发病后12周（95％置信区间11－15周，ROC曲线下面积0．901）。以此时间点作为PHN的时间标准，敏感性、特异性和分类准确率分别为0．807、0．905和0．871。

Conclusions： The transition of skin temperature from warm to cold occurs 12 weeks after HZ onset， which implies the end of local inflammation． Therefore， PHN associated with pathophysiologic change may be defined as 12 weeks after the skin rash． Thisfinding provides a theoretical basis for the timing definition of PHN．

结论：皮肤温度从温暖到寒冷的转变发生在HZ发病后12周，这意味着局部炎症的结束。因此，与病理生理变化相关的 PHN 可定义为皮疹后 12 周。这一发现为PHN的时序定义提供了理论依据。

主要统计结果：
1．

A表示带状疱疹引起的患侧和未患侧皮肤温差 （DTemp） 随时间的分布。DTemp 趋于随着时间逐渐降低。表示 DTemp 随时间（周）变化的散点图。红线显示数据的拟合曲线。b表示每个时间段 DTemp 的平均值 ± 标准差的线图。

2．

ROC曲线分析确定带状疱疹皮肤炎症停止的时间标准。ROC 曲线上的红点表示带状疱疹发病后皮肤温度从温暖转变为寒冷的最佳截止点（12 周：敏感性 0．807 和特异性 0．905）。此时Youden的J指数（0．712）和分类准确率（0．871）最高。曲线下面积为0．901（95％ CI 0．866－0．927），具有统计学意义（P＜0．001）。

3． 使用ROC曲线估计该时间点以最大化分类准确度和约登 J 指数：确定 C 组和 T 组 PHN 的最佳截止点分别为 11 周和 12 周。

limitations．First， the skin temperature was not measured sequentially in each patient． Although this would be best， it is impossible to observe the natural course of skin temperature change over time without any interventional or medical treatment after shingles due to ethical and practical reasons． Second， this study did not consider patients symptoms， which would have been better． However， a previous study has already evaluated patient symptoms and defined PHN through statistical modeling． The present study aimed to estimate the time point of skin inflammation change using an objective measurement． Third， this study focused on the changes in the skin temperature and did not consider changes in the central nervous system． The pathologic changes of PHN that occur in peripheral nerves and dorsal root ganglia may result in central sensitization． Many neuroimaging studies on HZ and PHN have demonstrated abnormalities in the function and structure of the brain ．Although the association of skin temperature and central sensitization in patients with PHN has not been reported， excessive vasoconstriction has been observed due to enhanced sympathetic outflow after spinal cord injury．

首先，没有按顺序测量每位患者的皮肤温度。尽管这是最好的，但由于伦理和实际原因，在带状疱疹后没有任何干预或医学治疗的情况下，不可能观察皮肤温度随时间变化的自然过程。

其次，本研究没有考虑患者的症状，可能会更好。然而，之前的一项研究已经通过统计模型评估了患者症状并定义了 PHN 。本研究旨在使用客观测量来估计皮肤炎症变化的时间点。

第三，本研究侧重于皮肤温度的变化，没有考虑中枢神经系统的变化。PHN发生在周围神经和背根神经节的病理变化可能导致中枢敏化。许多关于 HZ 和 PHN 的神经影像学研究表明，大脑的功能和结构存在异常 。尽管尚未报道 PHN 患者的皮肤温度和中枢敏化之间的关联，但由于脊髓损伤后交感神经外流增强，已观察到过度血管收缩。

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笔记／差劲先森。

排版／叮当丸子麻