
==== Front
Pain Ther
Pain Ther
Pain and Therapy
2193-8237
2193-651X
Springer Healthcare Cheshire

37129752
510
10.1007/s40122-023-00510-4
Review
Early Diagnosis of Herpes Zoster Neuralgia: A Narrative Review
Fan Han-Rui 1
Zhang En-Ming 1
http://orcid.org/0000-0002-1776-4993
Fei Yong jxfy6666662022@sina.com

2
Huang Bing 2
Yao Ming 2
1 https://ror.org/04epb4p87 grid.268505.c 0000 0000 8744 8924 Zhejiang Chinese Medicine University, Hangzhou, People’s Republic of China
2 https://ror.org/00j2a7k55 grid.411870.b 0000 0001 0063 8301 Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, 1882 Zhong-Huan-South Road, Jiaxing, 314000 People’s Republic of China
2 5 2023
2 5 2023
8 2023
12 4 893901
17 12 2022
30 3 2023
© The Author(s) 2023
https://creativecommons.org/licenses/by-nc/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Background

Early intervention reduces the incidence of postherpetic neuralgia (PHN). Typical shingles are easy to diagnose; however, there is no clear diagnostic method for neuralgia symptoms manifested before the onset of the rash, which can easily cause misdiagnosis. This not only increases the patient’s pain, medical expenses, and mental burden, but more importantly, delays the valuable time for early treatment of shingles, and increases the probability of complications and PHN.

Objective

In this paper, the diagnostic methods of preherpetic neuralgia were summarized and analyzed, and the current challenges were put forward to provide directions for the early diagnosis of herpes zoster (HZ) in the future.

Methods

PubMed, and China National Knowledge Infrastructure (CNKI) libraries were searched using the terms “herpes zoster,” “before the blistering,” “diagnosis,” and “neuralgia.” Clinical trials, reviews, and case reports were collected and reviewed. The period of literature search is from 1 January 1980 to 1 October 2022.

Results

The early diagnosis of herpes zoster neuralgia can reduce misdiagnosis and mistreatment, and timely and effective intervention can significantly reduce the incidence of PHN. The body may possess a mechanism that limits the local breakthrough of the virus in the skin, causing blistering later than the onset of pain. Changes in the plasma proteins of patients with varicella-zoster virus shingles neuralgia may be used as an early diagnostic indicator in patients with HZ neuralgia before eruption.

Conclusion

Early diagnosis of HZ neuralgia before eruption can facilitate timely targeted treatment, thereby reducing the incidence of PHN. Proteomic quantitative analysis and validation results can serve as a simple, micro, rapid, and accurate diagnostic method.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40122-023-00510-4.

Keywords

Herpes zoster
Early diagnosis
Varicella‐zoster virus
Polymerase chain reaction
Antibody titer
Biomarker
Thermography
High-frequency ultrasonography
Medical and Health Science and Technology Research Program of Zhejiang Province2021KY352 Fei Yong Key Discipline Established by Zhejiang Province and Jiaxing City Jointly-Pain Medicine2019-ss-ttyx Fei Yong Traditional Chinese Medicine Science and Technology Program of Zhejiang Province2022ZB355 Fei Yong Jiaxing Key Laboratory of Neurology and Pain MedicineJiaxing Key Laboratory of Neurology and Pain Medicine; Science and Technology Project of Jiaxing City2022AD30077 Fei Yong issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2023
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pmcIntroduction

Herpes zoster (HZ) neuralgia is among the most common neuropathic pains in the clinic and severely affects quality of life [1–3]. Varicella-zoster virus (VZV) infection in early childhood remains latent in the cranial ganglia, dorsal root ganglion, and other sensory ganglion neurons. When the immunity of the body is reduced, the latent virus is reactivated through peripheral nerve fibers to sensory nerve fibers to induce shingles [4, 5]. Patients with HZ require prompt diagnoses and treatment to avoid severe progression to postherpetic neuralgia (PHN) [6–9]. Currently, most patients with HZ rely on clinical presentations and rashes to obtain a diagnosis [5, 10]. However, most patients initially present with symptoms of neuralgia, such as paroxysmal or persistent pinpricks, knife cuts, burning pain, itching, banding, and ant walking. The rash generally appears 2–5 days after neuralgia onset, and a small number of patients do not develop herpes until 2 weeks after the onset of neuralgia symptoms. These patients are often misdiagnosed with migraine, myocardial infarction, pleurisy, intercostal neuralgia, cholelithiasis, appendicitis, and gastric ulcer, depending on the nerve involved [1, 11–13]. Misdiagnosis not only increases the patient’s pain, medical expenses, and mental burden, but more importantly, delays the valuable time for early treatment of shingles and increases the risk of complications and PHN.

Clinicians and researchers have attempted to solve the problems of the early diagnosis of herpetic neuralgia using laboratory diagnostic methods, infrared thermography, and high-frequency ultrasound diagnosis [14–16]. However, most of the previous reviews on the diagnosis of herpes zoster only describe PCR and antibody detection methods, which is not comprehensive enough [5, 17]. Based on some clinical studies published in recent years and related research results of our team, this review summarizes the possible methods for the early diagnosis of herpes zoster, and points out the direction for the research of early diagnosis of herpes zoster. The proteomic quantitative analysis and validation results described in this paper provide a simple, microscopic, rapid, and accurate diagnostic method that allows researchers to conduct further studies and identify proteins that can recognize shingles before the rash appears. This will help clinicians improve diagnosis and reduce misdiagnosis, help patients fight for early treatment time, reduce the pain of patients, and reduce the burden of life caused by frequent medical treatment.

Methods

Study Design

We conducted a narrative review. To comprehensively summarize the methods used for early diagnosis of herpes zoster, we searched PubMed and CNKI databases using the terms “herpes zoster,” “before the blistering,” “diagnosis,” and “neuralgia.” Literature was retrieved from 1 January 1980 to 1 October 2022. We analyzed and summarized the retrieved reviews, clinical studies, and case reports, and combined our team’s relevant research results and clinical experience to write this paper. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Setting

The settings mentioned in the literature collected were hospitals, neurology departments, pain departments, dermatology departments, and thoracic surgery departments.

Results

Laboratory Test Methods

Polymerase chain reaction (PCR)

PCR is a highly sensitive method for detecting VZV [17–19]. PCR is useful to detect VZV DNA in the blood [including whole blood, serum, plasma, peripheral blood mononuclear cells (PBMC)], saliva, and cerebrospinal fluid (CSF) of patients for the early diagnosis of atypical HZ in patients without a rash [20–23]. VZV is detectable in the blood from 5 days before eruption to 4 days after eruption, while VZV in T lymphocytes is detectable as early as 8–10 days before eruption and persists beyond six months [24]. In whole blood, approximately 60% of VZV is present in PBMC and 40% in serum or plasma, and the DNA positivity rate of VZV in PBMC samples detected using PCR is higher than that in plasma and serum samples in patients with HZ. Whole blood is more sensitive for the detection of VZV DNA than PBMC, possibly because it contains VZV DNA from lysed cells [25, 26]. The viral load gradually decreases with treatment of the disease, and real-time PCR can help monitor the effectiveness of treatment in patients with HZ.

Collecting saliva from patients and detecting VZA DNA is more convenient and readily available than collecting plasma. Mehta et al. detected VZV DNA in the saliva of 54 shingles patients (100%) on the day of rash onset [27]. In a study including 70 patients with first-time HZ detected using PCR testing, saliva VZV was detected in 85.7% of patients, and the positive rates on days 1, 8, 15, and 29 were 85.7%, 47.6%, 19.2%, and 23.1%, respectively [28]. Another study reported that in patients with suspected shingles, the sensitivity of salivary DNA PCR for VZV detection (88%) was significantly higher than that of plasma DNA PCR (28%), with no difference in specificity [29]. Nagel et al. detected VZV DNA using PCR in the saliva of a patient with a 12-year history of HZ, indicating that VZV DNA can persist in saliva samples for a long time [30].

CSF samples from patients infected with VZV in the central nervous system were detected using PCR, and the DNA positivity rate of VZV was higher than that of plasma samples and serological detection methods. Grahn et al. retrospectively analyzed 72 patients diagnosed with central nervous system (CNS) VZV infection and neurological symptoms using cerebrospinal fluid VZV DNA testing. Real-time PCR has been used to detect higher levels of VZV DNA in CSF samples than in serum samples [31]. In a study including 34 patients with VZV-infected central nervous system, VZV DNA (67.6%) and VZV-IgG antibodies (32.4%) in the CSF were detected using PCR and enzyme-linked immunosorbent assay (ELISA), respectively [32].

It is meaningful for PCR detection to collect blood and saliva from patients with suspected herpes zoster without eruption. These studies show that VZV DNA is more detectable in saliva than in blood. CSF testing is an invasive procedure that is not suitable for ordinary patients with shingles.

Antibody and Complement Detection

When VZV is reactivated, serum VZV antibody titers remain high and significantly different from those of healthy controls. Serum antibody levels are strongly associated with shingles development, and measurement of serum VZV antibody titers is helpful in the diagnosis of shingles [33, 34]. Kangr et al. used IgM antibody-capture radioimmunoassay (MACRIA) to detect IgM antibodies in the serum of 220 patients, of whom 216 (98%) were diagnosed with shingles, of which 94.4% of serum samples were acquired 2–6 weeks after the rash onset [35]. Serum samples of typical patients with HZ were collected, and 37% of patients with HZ were identified as positive for VZV-IgM antibody with VZV-IgM titer using ELISA. Subsequently, VZV-IgM titers of positive patients were analyzed, and the results revealed that VZV-IgM titers started increasing after the appearance of skin lesions, reached the highest level 6–10 days after the rash onset, and was negative in all patients after 10 weeks. Therefore, VZV-IgM titers are meaningful to detect within 3.5 weeks after the onset of symptoms [36].

In 141 patients with HZ, the positive rates of VZV-IgG antibody, VZV-IgM antibody, and complement fixation (CF) test were 93.9%, 12.0%, and 64.2%, respectively, among which VZV-IgG antibody had a strong correlation with CF titers, and the CF titer largely represented the IgG titer. CF titers tend to increase slowly over time and are weakly correlated with time of onset [37]. In a study including 865 shingles patients who presented with the incidence of VZV-specific CF at their initial presentation to a dermatological clinic, 66% of patients with HZ showed negative CF. Subsequently, paired complement binding tests performed over a short period of time showed a significantly elevated titer, peaking approximately 2 weeks after the onset, and gradually decreasing after 1 year [38].

IgM appears first but does not last long and is a marker of recent infection; therefore, VZV⁃IgM antibodies testing is only beneficial in confirming the diagnosis of acute-phase shingles. The relationship between complement titer and time of VZV onset remains controversial and requires further elucidation. IgG appears and persists at the initial infection with the VZV virus and is of little significance in the early diagnosis of shingles.

Inflammatory Cytokines

VZV is caused by the dorsal root ganglia, which causes nerve root inflammation and changes in cytokine levels in the body. Galectin-3 is a member of the β-galactose-bound lectin family, secreted by monocytes, phagocytes, and epithelial cells, and is involved in biological processes, such as cell interactions, cell cycle, regulation of cell growth, splicing of mRNA precursors, and angiogenesis. After VZV infection, the mRNA and protein expression of galectin-3 in the dorsal horn of the spinal cord of mice was significantly increased. Galectin-3 gene deletion in mice, or intrathecal injection of galectin-3 antibody, significantly reduced tactile pain, suggesting that galectin-3 is involved in PHN production [39]. Wang et al. reported that plasma galectin-3 and IL-6 levels in patients with HZ neuralgia were significantly higher than those in healthy physical examiners, and galectin-3 levels could be used as a new biochemical marker for patients with pre-HZ and PHN [40, 41].

Reduced immunity is a predisposing factor for shingle development. The immune response to shingles is thought to be dysfunctional and mainly manifested by specific cellular immunosuppression [42, 43]. In a case analysis including 83 patients with multiple myeloma, patients with multiple myeloma infected with HZ had elevated serum CD3+ and CD4+ levels and significantly lower CD8+ levels after treatment [44]. Jung et al. found that VZV induces a broad immune response by affecting the release of immunoactive substances such as cytokines, neurotrophic factors, and chemokines in vivo, leading to T-lymphocyte immunosuppression [45]. Zhu et al. reported that shingles patients had elevated levels of IL-6 in the acute phase; CD3+ , CD4+, and CD8+ levels were lower than normal and were closely associated with the occurrence of PHN [46]. Many markers of inflammation are used clinically to detect herpetic neuralgia but is rarely diagnosed before eruption. Gal-3, IL-6, and T lymphocytes detected in the above study were all conducted in patients with post-diagnosis herpes zoster. Studies on differences in blood levels of inflammatory factors between pre-eruption and healthy patients are lacking. The specificity of these inflammatory factors for the diagnosis of shingles also needs further study.

Proteomic Analysis and Non-coding RNA

Wang et al. reported 44 differentially expressed proteins found in the plasma of patients with HZ, and the main pathways in which these molecules were involved included the MAPK signaling pathway, neuroactive ligand-receptor interactions, acute myeloid leukemia, and transcriptional regulation disorders in tumors. Six key molecules were selected as candidate molecules for further study, and plasma from 40 patients with HZ and 40 healthy participants was validated using ELISA, immunoblot assay, and receiver operating characteristic curve analysis. Finally, three proteins, PLG, F2, and VTN, were found and can be used as biomarkers for the detection of early patients with HZ [47].

Non-coding RNA refers to RNA that does not code for proteins, including rRNA, tRNA, snRNA, snoRNA, and microRNA with a variety of known functions, as well as RNA with unknown functions. MicroRNAs are a class of endogenous non-coding RNAs found in eukaryotes with regulatory functions; they are involved in maintaining normal cell function, host-virus interactions, and restricting the replication of certain virus types. In a study including 41 patients with HZ for the detection of microRNAs, serum miRNA levels were analyzed using TaqMan low-density array and confirmed using quantitative reverse transcription PCR (RT-qPCR) analysis. The expression levels of six miRNAs, including miR-190b, miR-571, miR-1276, miR-1303, miR-943, and miR-661, were significantly increased in patients with HZ; therefore, it may be used as a biomarker to detect potential HZ infection [48]. Markus et al. reported VZV-encoded small non-coding RNAs (sncRNAs), with at least one VZV sncRNA expressed in productive infections in neurons and fibroblasts, which may reduce viral replication. Since sncRNAs are considered potential targets for antiviral therapy, identifying these molecules in VZV may provide a new direction for the development of HZ pain treatments [49].

Whether it is proteomic analysis or non-coding RNA research, large samples, multicenter research, and repeated validation are required. In addition, the acquisition of blood samples from patients before eruption is the focus and difficulty of this study. Based on previous studies, our research team will continue to investigate changes in blood protein expression in patients with preeruption.

Non-invasive Examination

Infrared Thermal Imaging

Infrared imaging technology uses thermal infrared with a wavelength of 2–1000 μm to image objects through thermal infrared-sensitive signal transduction materials and has been widely used in clinical research [50–52]. Infrared imaging technology collects infrared radiation from the human body and converts it into a digital signal to form a pseudo-color heat map that can accurately quantify temperature changes in different areas. It has the advantages of being non-traumatic, radiation-free, convenient, fast, and inexpensive [53, 54]. Infrared thermography can detect degenerative necrosis and vasoconstriction of local tissues of the body, which can be manifested as different degrees of local hypothermia; however, metabolically active stages such as granulation tissue proliferation, aseptic inflammation, edema, vasodilation, or tumor invasion can be manifested as varying degrees of local high temperature.

The affected skin area of patients with HZ produces inflammation. Yao et al. reported that infrared thermography is more valuable than visual analog scale scoring for early diagnosis of patients with HZ neuralgia before eruption, and has the advantages of being simple in operation, non-invasive, and without radiation [55]. In a case of 112 patients diagnosed with acute-phase HZ, infrared imaging techniques predicted the progression to PHN in acute patients with HZ, but could not be used as an objective assessment tool for subjective pain [56]. Park et al. reported that infrared thermography can be an effective predictor of PHN [57]. However, some patients may have an impact on infrared thermography because of scratching, patting, or acupuncture treatment in the painful area [55, 58]. In addition, the range of temperature differences between the unaffected and affected sides, and whether this specific value represents the early diagnosis of shingle neuralgia, has not been reported.

High-Frequency Ultrasound Diagnosis

High-frequency ultrasound diagnosis is also a non-invasive technique that can observe the epidermis, dermis, subcutaneous tissue, and cutaneous nerve structure of the skin. It has a good correlation with histopathology and has been widely used in the diagnosis of benign skin tumors, malignant tumors, localized scleroderma, and other diseases [59–61]. The main pathological changes in patients with shingles are inflammatory changes in the affected skin, subcutaneous tissues, nerve roots, and nerve endings.

Zheng et al. reported that in patients with HZ, the skin and subcutaneous tissue on the affected side were more thickened than on the healthy side, and the cutaneous nerve was also significantly thickened, which was associated with demyelinating lesions and edema of the nerve roots. Patients mainly present with symptoms of neuralgia before the eruption, and the affected nerve roots also begin to show pathological changes such as demyelination or edema; therefore, high-frequency ultrasound images of patients with preeruption neuralgia should be observed clinically. Unfortunately, studies on this topic are rare. However, with the development of neuroultrasound, the diagnosis of preherpanic HZ neuralgia using high-frequency ultrasound is bound to develop profoundly [62].

Discussion

Patients with HZ neuralgia cannot be accurately diagnosed in time before the onset of the rash, which causes misdiagnosis and delay in treatment. PCR detection of VZV has high sensitivity; however, due to equipment requirements and high detection costs, its wide clinical application is limited. Although infrared thermography uses temperature differences to distinguish between the unaffected and affected sides, it is difficult to determine whether patients with neuralgia have HZ. High-frequency ultrasound diagnosis can detect pathological changes, such as demyelination or edema of the affected nerve roots, and combined with clinical symptoms, it can improve the accuracy of diagnosis. However, pathological changes such as demyelination or edema of the nerve roots in preeruptive neuralgia patients are not obvious, which undoubtedly complicates the diagnosis. At present, most of the clinical proteomic analysis and non-coding RNA research are focused on patients diagnosed with shingles. However, future studies should focus on patients who develop shingles and PHN before the onset of rash.

Conclusions

Early diagnosis of HZ neuralgia before eruption can facilitate timely targeted treatment, thereby reducing the incidence of PHN. Proteomic analysis and non-coding RNA have great research prospects for the early diagnosis of herpes zoster.It is a simple, micro, rapid, and accurate diagnostic method. Our research team will continue to investigate changes in blood protein expression in patients with preeruption. More basic and clinical trials are needed to verify plasma protein expression in patients with herpes zoster neuralgia before eruption.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file 1 (DOC 25 KB)

Acknowledgements

Funding

Key discipline established by Zhejiang Province and Jiaxing City Jointly-Pain Medicine (2019-ss-ttyx), Medical and Health Science and Technology Research Program of Zhejiang Province (2021KY352), Traditional Chinese Medicine Science and Technology Program of Zhejiang Province (2022ZB355), Jiaxing Key Laboratory of Neurology and Pain Medicine, and Science and Technology Project of Jiaxing City (2022AD30077). The grant recipient of the above funding sources is Yong Fei. Yong Fei is funding the journal’s rapid service fee.

Authorship

Han-Rui Fan MD1, En-Ming Zhang, MD1, Yong Fei, MD2, Bing HuangMD2, Ming Yao, phD2. 1Graduate School of Zhejiang Chinese Medicine University Hangzhou, P. R. China, 2Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, Jiaxing, P.R. China. Corresponding author: Yong Fei, MD, Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University 1882 Zhong-Huan-South Road Jiaxing 314,000, P.R. China. Email: jxfy6666662022@sina.com.

Author Contributions

Han-Rui Fan conducted the literature search and drafted sections of the manuscript, and approved the final manuscript. En-Ming Zhang conducted the literature search and drafted sections of the manuscript, and approved the final manuscript. En-Ming Zhang, MD and Han-Rui Fan, MD contributed equally to this work. Yong Fei contributed to outlining the first draft, editorial review, and suggested references. He approved the final manuscript, and is also the corresponding author. Bing Huang contributed to editorial review, and approved the final manuscript. Ming Yao contributed to editorial review, and approved the final manuscript.

Disclosures

The authors have no relevant disclosures. Han-Rui Fan has nothing to disclose. En-Ming Zhang has nothing to disclose. Yong Fei has nothing to disclose. Bing Huang has nothing to disclose. Ming Yao has nothing to disclose.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

En-Ming Zhang and Han-Rui Fan have contributed equally to this work.
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References

1. Díez-Domingo J Curran D Del Rosario M Cambronero J-A-M Matthews S Economic burden and impact on quality of life of herpes zoster in spanish adults aged 50 years or older: a prospective cohort study Adv Ther 2021 38 6 3325 3341 10.1007/s12325-021-01717-7 34013498
2. Curran D Schmidt-Ott R Schutter U Simon J Anastassopoulou A Matthews S Impact of herpes zoster and postherpetic neuralgia on the quality of life of Germans aged 50 or above BMC Infect Dis 2018 18 1 496 10.1186/s12879-018-3395-z 30285731
3. Matthews S De Maria A Passamonti M Ristori G Loiacono I Puggina A Curran D The economic burden and impact on quality of life of herpes zoster and postherpetic neuralgia in individuals aged 50 years or older in Italy Open Forum Infect Dis 2019 6 2 ofz007 10.1093/ofid/ofz007 30793003
4. Levin MJ, Weinberg A, Schmid DS. Herpes simplex virus and varicella-zoster virus. Microbiol Spectr. 2016, 4(3).
5. Schmader K Herpes zoster Ann Intern Med 2018 169 3 ITC 19 ITC 31
6. John AR Canaday DH Herpes zoster in the older adult Infect Dis Clin North Am 2017 31 4 811 826 10.1016/j.idc.2017.07.016 29079160
7. Ma L Yao M Safety and efficacy of CT-guided pulsed radiofrequency combined with steroid and ozone injection-treated cervical 3–8 herpes zoster neuralgia using a posterior and upper quarter of the cervical foramina puncture approach J Pain Res 2022 15 23 32 10.2147/JPR.S333481 35023968
8. Gan EY Tian EAL Tey HL Management of herpes zoster and post-herpetic neuralgia Am J Clin Dermatol 2013 14 2 77 85 10.1007/s40257-013-0011-2 23456596
9. Sampathkumar P Drage LA Martin DP Herpes zoster (shingles) and postherpetic neuralgia Mayo Clin Proc 2009 84 3 274 80 10.4065/84.3.274 19252116
10. Bader Mazen S Herpes zoster: diagnostic, therapeutic, and preventive approaches Postgrad Med 2013 125 5 78 91 10.3810/pgm.2013.09.2703 24113666
11. Zhou J Li J Ma L Cao S Zoster sine herpete: a review Korean J Pain 2020 33 3 208 215 10.3344/kjp.2020.33.3.208 32606265
12. Drago F Herzum A Ciccarese G Broccolo F Rebora A Parodi A Acute pain and postherpetic neuralgia related to Varicella zoster virus reactivation: comparison between typical herpes zoster and zoster sine herpete J Med Virol 2019 91 2 287 295 10.1002/jmv.25304 30179265
13. Dayan Roy Rafael Peleg Roni Herpes zoster—typical and atypical presentations Postgrad Med 2017 129 6 567 571 10.1080/00325481.2017.1335574 28540752
14. Pinninti SG Kimberlin DW Neonatal herpes simplex virus infections Semin Perinatol. 2018 42 3 168 175 10.1053/j.semperi.2018.02.004 29544668
15. Ammer K Schartelmueller T Melnizky P Thermal imaging in acute herpes zoster or post-zoster neuralgia Skin Res Technol 2001 7 4 219 222 10.1034/j.1600-0846.2001.70403.x 11737816
16. Zheng Y Kang C Wang J Chang W Sun Y High frequency sonographic appearance of skin and skin nerves in patients of herpes zoster Chin J Ultrasound Imaging 2004 13 8 606 608
17. Gross Gerd E Lisa E Wilhelm DH S2k guidelines for the diagnosis and treatment of herpes zoster and postherpetic neuralgia J Dtsch Dermatol Ges 2020 18 55 78 10.1111/ddg.14013 31985151
18. Wilson DA Yen-Lieberman B Schindler S Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review J Clin Microbiol 2012 50 4120 2 10.1128/JCM.06753-11 23035203
19. Sauerbrei A Eichhorn U Schacke M Wutzler P Laboratory diagnosis of herpes zoster J Clin Virol 1999 14 1 31 36 10.1016/s1386-6532(99)00042-6 10548128
20. de Jong MD Weel JF Schuurman T Wertheim-van Dillen PM Boom R Quantitation of varicella-zoster virus DNA in whole blood, plasma, and serum by PCR and electrochemiluminescence J Clin Microbiol 2000 38 7 2568 2573 10.1128/JCM.38.7.2568-2573.2000.PMID:10878045;PMCID:PMC86970 10878045
21. Ito M Nishihara H Mizutani K Kitamura K Ihara T Kamiya H Sakurai M Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral blood mononuclear cells of immunocompromised patients with herpes zoster by polymerase chain reaction Clin Diagn Virol 1995 4 2 105 112 10.1016/0928-0197(94)00061-X 15566832
22. Mo X Lin F Yang L Detection of varicella-zoster virus in peripheral blood and blister fluid of patients with herpes zoster by polymerase chain reaction J Clin Dermatol 2019 3 133 136
23. Devlin ME Gilden DH Mahalingam R Peripheral blood mononuclear cells of the elderly contain varicella-zoster virus DNA J Infect Dis. 1992 165 619 22 10.1093/infdis/165.4.619 1313066
24. Levin MJ Varicella-zoster virus and virus DNA in the blood and oropharynx of people with latent or active varicella-zoster virus infections J Clin Virol 2014 61 4 487 95 10.1016/j.jcv.2014.09.012 25453570
25. Quinlivan ML Ayres KL Kelly PJ Parker SP Scott FT Johnson RW Maple C Breuer J Persistence of varicella-zoster virus viraemia in patients with herpes zoster J Clin Virol 2011 50 2 130 135 10.1016/j.jcv.2010.10.014 21093356
26. Satyaprakash AK Tremaine AM Stelter AA Viremia in acute herpes zoster J Infect Dis. 2009 200 1 26 32 10.1086/599381 19469706
27. Mehta Satish K Tyring Stephen K Gilden Donald H Varicella-zoster virus in the saliva of patients with herpes zoster. J Infect Dis 2008 197 654 7 10.1086/527420 18260763
28. Park SY Kim JY Kwon J-S Relationships of varicella zoster virus (VZV)-specific cell-mediated immunity and persistence of VZV DNA in saliva and the development of postherpetic neuralgia in patients with herpes zoster J Med Virol 2019 91 11 1995 2000 10.1002/jmv.25543 31286531
29. Park SY Kim JY Kim J-A Diagnostic usefulness of varicella-zoster virus real-time polymerase chain reaction analysis of dna in saliva and plasma specimens from patients with herpes zoster J Infect Dis 2017 217 1 51 57 10.1093/infdis/jix508 29029120
30. Nagel MA Choe A Cohrs RJ Persistence of varicella zoster virus DNA in saliva after herpes zoster J Infect Dis. 2011 204 6 820 4 10.1093/infdis/jir425 21849278
31. Grahn A Bergström T Runesson J Studahl M Varicella-zoster virus (VZV) DNA in serum of patients with VZV central nervous system infections J Infect 2016 73 3 254 260 10.1016/j.jinf.2016.04.035 27317379
32. Skripuletz T Pars K Schulte A Varicella zoster virus infections in neurological patients: a clinical study BMC Infect Dis. 2018 18 1 238 10.1186/s12879-018-3137-2 29801466
33. Warren-Gash C Forbes H Maple P Quinlivan M Breuer J Viral load and antibody boosting following herpes zoster diagnosis J Clin Virol 2018 103 12 15 10.1016/j.jcv.2018.03.010 29602095
34. Zajkowska A Garkowski A Świerzbińska R Evaluation of chosen cytokine levels among patients with herpes zoster as ability to provide immune response PLoS One 2016 11 3 e0150301 10.1371/journal.pone.0150301 26934574
35. Kangro HO Ward A Argent S Detection of specific IgM in varicella and herpes zoster by antibody-capture redioimmunoassay Epidemiol Infect 1988 101 1 187 195 10.1017/S0950268800029344 3402547
36. Min S-W Kim YS Nahm FS The positive duration of varicella zoster immunoglobulin M antibody test in herpes zoster Med (Baltim). 2016 95 33 e4616 10.1097/MD.0000000000004616
37. Ihara H Miyachi M Imafuku S Relationship between serum anti-varicella zoster virus antibody titer and time from onset of herpes zoster J Dermatol 2018 45 2 189 193 10.1111/1346-8138.14168 29239011
38. Miyachi M Ihara H Imafuku S Incidence of serum antibody titers against varicella zoster virus in Japanese patients with herpes zoster J Dermatol 2017 44 6 656 659 10.1111/1346-8138.13733 28012212
39. Takasaki I Taniguchi K Komatsu F Contribution of spinal galectin-3 to acute herpetic allodynia in mice Pain 2012 153 3 585 592 10.1016/j.pain.2011.11.022 22197693
40. Wang T Fei Y Yao M Tao J Deng J Huang B Correlation between Galectin-3 and early herpes zoster neuralgia and postherpetic neuralgia: a retrospective clinical observation Pain Res Manag 2020 2020 8730918 10.1155/2020/8730918 32351643
41. Fei Y Huang B Deng J Longsheng Xu Yao M Efficacy of dorsal root ganglion pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α2b in herpetic neuralgia J Pain Res 2021 14 711 719 10.2147/JPR.S290852 33732017
42. Weinberg A Canniff J Rouphael N Varicella-zoster virus-specific cellular immune responses to the live attenuated zoster vaccine in young and older adults J Immunol 2017 199 2 604 612 10.4049/jimmunol.1700290 28607114
43. Schwarz TF Aggarwal N Moeckesch B Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older J Infect Dis 2017 216 11 1352 1361 10.1093/infdis/jix481 29029224
44. Liu K Yin Y Zhou X Zhu K Luo Z Expression and correlation of IL-2, IL-10 and TNF-α in patients with multiple myeloma-infected herpes zoster treated by bortezomib-containing regimen Am J Transl Res 2021 13 12 13732 13740 35035711
45. Jung Y Hwan Lee J Kim W Hyub Yoon S Kwang Kim S Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression BMC Complement Altern Med 2017 17 1 48 10.1186/s12906-017-1556-z 28088201
46. Zhu SM Liu YM An ED Influence of systemic immune and cytokine responses during the acute phase of zoster on the development of postherpetic neuralgia J Zhejiang Univ Sci B. 2009 10 8 625 30 10.1631/jzus.B0920049 19650202
47. Wang T Shen H Deng H Quantitative proteomic analysis of human plasma using tandem mass tags to identify novel biomarkers for herpes zoster J Proteom 2020 225 103879 10.1016/j.jprot.2020.103879
48. Li X Huang Y Zhang Y He Na Evaluation of microRNA expression in patients with herpes zoster Viruses 2016 8 12 326 10.3390/v8120326 27918431
49. Markus A Golani L Ojha NK Varicella-zoster virus expresses multiple small noncoding RNAs J Virol 2017 91 24 e01710-17 10.1128/JVI.01710-17 29021397
50. Kazarian SG Perspectives on infrared spectroscopic imaging from cancer diagnostics to process analysis Spectrochim Acta A Mol Biomol Spectrosc 2021 251 119413 10.1016/j.saa.2020.119413 33461133
51. Liu Y Gao B Fang C Application of near-infrared fluorescence imaging technology in liver cancer surgery Surg Innov. 2021 10.1177/1553350621997777 34961370
52. Spreinat A Selvaggio G Erpenbeck L Kruss S Multispectral near infrared absorption imaging for histology of skin cancer J Biophotonics 2020 13 1 e201960080 10.1002/jbio.201960080 31602799
53. Yang M Wenbin Xu Sun Z Mid-wave infrared polarization imaging system for detecting moving scene Opt Lett 2020 45 20 5884 5887 10.1364/OL.400872 33057310
54. Yang Q Theoretical analysis of compact ultrahigh-spectral-resolution infrared imaging spectrometer Opt Express 2020 28 11 16616 16632 10.1364/OE.395475 32549480
55. Yao Y Xie K Huang B Infrared thermal imaging for the early diagnosis of herpes zoster Chin J Gen Pract 2018 16 1 7 9
56. Ko EJ No YA Park KY The clinical significance of infrared thermography for the prediction of postherpetic neuralgia in acute herpes zoster patients Skin Res Technol 2016 22 1 108 114 10.1111/srt.12237 26081167
57. Park J Jang WS Park KY Thermography as a predictor of postherpetic neuralgia in acute herpes zoster patients: a preliminary study Skin Res Technol 2012 18 1 88 93 10.1111/j.1600-0846.2011.00535.x 21605168
58. Pan L Wang X Zhou Z Application of infrared thermal imaging technology in acupuncture and moxibustion Heilongjiang Trad Chin Med 2014 43 04 44 47
59. Gong W Wang J Huang L Diagnosis of cervical plexus tumours by high-frequency ultrasonography BMC Med Imaging 2021 21 1 148 10.1186/s12880-021-00682-5 34649505
60. Vergilio MM Silva SAME Jales RM High-frequency ultrasound as a scientific tool for skin imaging analysis Exp Dermatol 2021 30 7 897 910 10.1111/exd.14363 33905589
61. Ranosz-Janicka I Lis-Święty A Skrzypek-Salamon A An extended high-frequency ultrasound protocol for assessing and quantifying of inflammation and fibrosis in localized scleroderma Skin Res Technol 2019 25 3 359 366 10.1111/srt.12660 30638285
62. Zheng Y Kang C Wang J High frequency sonographic appearance of skin and skin nerves in patients of herpes zoster Chin J Ultrasonogr 2004 13 8 606 608
