대상포진 - 포진후 동통의 orthomolecular medicine 치료

[문형철]

beyond reason

미국에 100만명

일생에 한번 걸릴 확률 30%...

Postherpetic neuralgia is the most common complication, occurring in about one in five patients. It is defined as pain in a dermatomal distribution sustained for at least 90 days after acute herpes zoster.

급성 대상포진 발생후 90일이 지나서도 통증이 지속될때 포진후 동통(postherpetic neuralgia)라고 진단함. 

수두대상포진바이러스(varicella-zoster virus; VZV), 혹은 사람 알파헤르페스바이러스 3(Human alphaherpesvirus 3; HHV-3)은 수두를 일으키는 바이러스다. 청소년들에게 수두를, 성인에게 대상포진을 일으킨다. 수두바이러스, 대상포진바이러스 등의 이름으로도 불린다. 사람간 전염을 통해 전염되나, 외부 환경에서도 수시간부터 많게는 이틀까지 생존하기도 한다.^[3] 우선 허파에서 증식하며 다양한 증상을 일으킨다. 초기 감염증상인 수두가 지나고 나면 두개골 신경절, 배근 신경절, 자율신경절 등의 신경조직 잠복한다. 잠복한 바이러스들은 이후 조건이 갖춰지면 재활성화할 수 있다. 

초기 감염증은 수두로, 뇌염이나 폐렴(일차적인 바이러스성 폐렴이나 이차적인 세균성 폐렴), 기관지염 등의 호흡기 질환이 합병증으로 발생하기도 한다. 수두로부터 회복된 후에도 바이러스는 삼차신경절, 배근 신경절 등의 신경계통에 잠복한다.^[5]  호흡기를 통해 신체로 침투하며, 10~21일간의 증식 후에 피부와 말초신경계통을 감염시켜 3~4일간 증상을 일으킨다. 발진이 나타나기 하루이틀전에 가장 전염성이 높다. 고름으로 가득찬 수포가 증상으로 나타날 수 있다. 발진은 얼굴이나 목, 등 하부에까지 미치며 흉부나 어깨에 도달하기도 한다. 대상포진은 주로 허리에서 나타난다.^[6]

10~20%는 살아가면서 바이러스 재활성화를 겪는데 이것이 바로 대상포진이다. 또한 2013년의 조사에 의하면 스위스에서 10만명 중 1.02명, 스웨덴에서 매년 10만명 중 1.8명에서 중추신경계를 감염시킨 사례가 발견되었다.^[7]

대상포진후 신경통, 양성 재발성 수막염, 다발성 대상포진(zoster multiplex), 척수염, 안구헤르페스, 무발진대상포진 등의 심각한 합병증이 나타날 수 있으며, 뇌 동맥에 염증이 생긴 경우 뇌졸중으로 이어질 수 있다.^[8] 람세이헌트증후군 2형의 경우 슬상신경절에 영향을 줘 휘하의 안면 신경들에 병변을 일으킬 수 있다. 이 경우 혀나 귀에 대상포진이 생기거나, 얼굴의 한 쪽에 마비증상이나 청력 상실이 올 수 있다. 임신 초기에 감염되면 태아가 심각한 손상을 입어 라이 증후군 등을 일으킬 수 있다. 아스피린을 통해 일부 경감할 수 있다

포진후 동통에 대한 탐구(클릭클릭) 

2017년 논문 ..(클릭클릭)

Herpes zoster, or shingles, is caused by reactivation of varicella zoster virus, which causes chickenpox. There are an estimated 1 million cases in the Unites States annually, with an individual lifetime risk of 30%. Patients with conditions that decrease cell-mediated immunity are 20 to 100 times more likely to develop herpes zoster. 

Patients may present with malaise, headache, low-grade fever, and abnormal skin sensations for two to three days before the classic maculopapular rash appears. The rash is usually unilateral, confined to a single dermatome, and typically progresses to clear vesicles that become cloudy and crust over in seven to 10 days. 

Herpes zoster can be treated with acyclovir, valacyclovir, or famciclovir, ideally within 72 hours of the development of the rash. Postherpetic neuralgia is the most common complication, occurring in about one in five patients. It is defined as pain in a dermatomal distribution sustained for at least 90 days after acute herpes zoster. Treatment is focused on symptom control and includes topical lidocaine or capsaicin and oral gabapentin, pregabalin, or tricyclic antidepressants. The varicella zoster virus vaccine decreases the incidence of herpes zoster and is approved for adults 50 years and older. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends this vaccine for adults 60 years and older, except for certain immunosuppressed patients. 

(Am Fam Physician. 2017;96(10):656-663. Copyright © 2017 American Academy of Family Physicians.)

1) 비타민 B 12의 포진후 동통치료

   비타민 B12부족 증후군에서 삼차신경통(포진후 동통)이 흔히 발생함.

MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.

클릭클릭

Meta-Analysis

 

Complement Ther Med

. 2018 Dec;41:277-282.

 doi: 10.1016/j.ctim.2018.10.014. Epub 2018 Oct 21.

Vitamin B12 for Herpetic Neuralgia

: A Meta-Analysis of Randomised Controlled Trials

J Y Wang 1, Y H Wu 2, S J Liu 3, Y S Lin 4, P H Lu 5

Affiliations expand

• PMID: 30477853
 
• DOI: 10.1016/j.ctim.2018.10.014

Abstract

Background: Postherpetic neuralgia (PHN) is the most distressful complication of herpes zoster. PHN results in an impaired quality of life and higher healthcare utilization. Vitamin B12 has been proven to be effective in pain relief for various conditions.

Objective: We conducted a systematic review and a meta-analysis to eval‎uate the efficacy of vitamin B12 supplementation in PHN patients.

Methods: PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov registry were searched. Randomised control trials eval‎uating the efficacy and safety of vitamin B12 in PHN patients were selected. Eligible trials were abstracted and assessed for the risk of bias by two reviewers, and the results of pain indicators in the selected trials were analysed.

Results: Four trials including 383 participants were published between 2013 and 2016. Compared with the placebo group, the Vitamin B12 group exhibited a significant decrease in the Numeric Rating Scale score, with a mean difference of -4.01 (95% confidence interval = -4.70 to -3.33). Vitamin B12 administration improved the quality of life of PHN patients with moderate quality evidence and significantly decreased the number of patients using analgesics.

Conclusion: Vitamin B12 appears to be an attractive complementary therapy for PHN patients. Further investigation is needed before conclusive recommendations can be made.

Keywords: Herpetic neuralgia; Vitamin B12.

클릭클릭

Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer’s disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.

2) 비타민 C의 포진후 동통 치료효과

Ann Dermatol. 2016 Dec; 28(6): 677–683.

Published online 2016 Nov 23. doi: 10.5021/ad.2016.28.6.677

PMCID: PMC5125947

PMID: 27904265

A Study of Intravenous Administration of Vitamin C in the Treatment of Acute Herpetic Pain and Postherpetic Neuralgia

Min Sung Kim, Dong Jin Kim, Chan Ho Na, and Bong Seok Shin

Author information Article notes Copyright and License information Disclaimer

Abstract

Background

Although there are several available management strategies for treatment of both acute pain of herpes zoster (HZ) and postherpetic neuralgia (PHN), it is difficult to treat them adequately.

Objective

The aim of this study was to eval‎uate the efficacy of intravenously administrated vitamin C on acute pain and its preventive effects on PHN in patients with HZ.

Methods

Between September 2011 and May 2013 eighty-seven patients who were admitted for HZ were assessed according to age, sex, underlying diseases, duration of pain and skin lesion, dermatomal distribution, and PHN. It was a randomized controlled study, in which 87 patients were randomly allocated into the ascorbic acid group and control group. Each patient received normal saline infusion with or without 5 g of ascorbic acid on days 1, 3, and 5 then answered questionnaires that included side effects and pain severity using visual analogue scale on days 1, 2, 3, 4, and 5. After discharge, the severity of pain was obtained at out-patient clinic or by telephone on weeks 2, 4, 8, and 16.

Results

There was no differences in severity of pain on patients' age, sex, underlying diseases, duration of pain and skin lesion and dermatomal distribution between two groups (p>0.05). Since 8th week, pain score in ascorbic acid treatment group was significantly lower than control group (p <0.05). The incidence of PHN was significantly lower in the treatment group compared to control group (p=0.014). The changes of overall pain score was significantly different between the two groups (p<0.05).

Conclusion

Intravenously administered ascorbic acid did not relieve acute HZ pain; but is effective for reducing the incidence of PHN.

Keywords: Ascorbic acid, Herpes zoster, Postherpetic neuralgia

Treatment of Postherpetic Neuralgia with Intravenous Administration of Vitamin C

Chen, Jen-Yin, MD, MS; Chu, Chin-Chen, MD; So, Edmund C., MD; Hsing, Chung-Hsi, MD; Hu, Miao-Lin, PhD

Section Editor(s): Shafer, Steven L.

 Author Information

Anesthesia & Analgesia: December 2006 - Volume 103 - Issue 6 - p 1616-1617

doi: 10.1213/01.ane.0000246396.64010.ee

To the Editor:

A 78-yr-old male suffered from intractable T3-6 postherpetic neuralgia. He reported 8 mo of constant, aching pain and intermittent, spontaneous, shooting pain over his right anterior chest and upper back. His pain did not respond to multiple trials of antidepressants and anticonvulsants. Pain intensity ranged from 4 to 8 on an 11-point numerical pain rating scale. The pain he rated 8 occurred in 5-min episodes for about 8–10 times per day. His appetite was poor, he bruised easily, and his gums were swollen. Laboratory data were normal except for a low concentration of plasma vitamin C (4.9 mg/L), consistent with poor nutrition.

We treated this patient with IV 2.5 g ascorbate daily on days 1, 3, and 5. His intermittent, spontaneous, shooting pain completely resolved within 1 wk, and his baseline pain decreased to a level of 3 (his plasma vitamin C level reached 14.9 mg/L). We advised him to increase his intake of fruits and vegetables. On follow-up examination 3 mo later he has had no recurrence of the extreme intermittent pain, and his plasma vitamin C level was 11.6 mg/L.

Hanck and Weiser (¹) reported a dose-dependent pain reduction by oral vitamin C in rats. Ascorbate is an antioxidant that scavenges reactive oxygen species (ROS). ROS play a crucial role in neuropathic pain (²). By enhancing adenylyl cyclase-cAMP, ascorbic acid can also augment the production and the release of β-endorphin from rat hypothalamic neurons (³). β-Endorphin appears to be effective in alleviating neuropathic pain (⁴).

Formal studies are required to determine whether treatment with vitamin C may prove useful in patients with low plasma vitamin C and neuropathic pain.

• Review
• Published: 14 April 2017

The role of vitamin C in the treatment of pain

: new insights

• Anitra C. Carr & 
• Cate McCall 

Journal of Translational Medicine volume 15, Article number: 77 (2017) Cite this article

• details

Abstract

The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The preval‎ence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high dose vitamin C administration. Furthermore, cancer-related pain is decreased with high dose vitamin C, contributing to enhanced patient quality of life. A number of mechanisms have been proposed for vitamin C’s analgesic properties. Herein we propose a novel analgesic mechanism for vitamin C; as a cofactor for the biosynthesis of amidated opioid peptides. It is well established that vitamin C participates in the amidation of peptides, through acting as a cofactor for peptidyl-glycine α-amidating monooxygenase, the only enzyme known to amidate the carboxy terminal residue of neuropeptides and peptide hormones. Support for our proposed mechanism comes from studies which show a decreased requirement for opioid analgesics in surgical and cancer patients administered high dose vitamin C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.

J Headache Pain. 2012 Oct; 13(7): 591.

Published online 2012 Aug 30. doi: 10.1007/s10194-012-0476-z

PMCID: PMC3444542

PMID: 22932737

Vitamin C for attenuating postherpetic neuralgia pain: an emerging treatment alternative

Shailendra Kapoor

To the editor,

I read with great interest the recent article by Sayanlar et al. [1] in a recent issue of your esteemed journal. Interestingly, the past few years has seen the identification of a number of alternative treatments for postherpetic neuralgia.

One such emerging alternative is vitamin C. Vitamin C attenuates spontaneous pain in patients with postherpetic neuralgia [2]. This has been confirmed in recent studies. For instance, Schencking et al. [3] in a recent multicenter cohort study have demonstrated the effectiveness of vitamin C in herpes zoster treatment. Vitamin C acts by modulating serum levels of cytokine IL-6 and IL-8.

Vitamin C is especially useful in patient with recalcitrant postherpetic neuralgia resistant to standard therapy. Resolution of dermatologic Zoster lesions is seen in as less as 10 days following intravenous administration of ascorbic acid [4]. Interestingly, the patients afflicted with postherpetic neuralgia demonstrate lower levels of ascorbic acid [5].

Clearly, vitamin C has significant potential in mitigating postherpetic neuralgia, especially when administered intravenously. Hopefully, the coming few years will see the increased use of vitamin C in the treatment of herpes zoster, especially in treatment resistant patients.

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Conflict of interest

None.

Open Access

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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References

1. Sayanlar J, Guleyupoglu N, Portenoy R, Ashina S (2012) Trigeminal postherpetic neuralgia responsive to treatment with capsaicin 8 % topical patch: a case report. J Headache Pain. doi:10.1007/s10194-012-0467-0 [PMC free article] [PubMed]

2. Chen JY, Chu CC, So EC, Hsing CH, Hu ML. Treatment of postherpetic neuralgia with intravenous administration of vitamin C. Anesth Analg. 2006;103:1616–1617. doi: 10.1213/01.ane.0000246396.64010.ee. [PubMed] [CrossRef] [Google Scholar]

3. Schencking M, Vollbracht C, Weiss G, et al. Intravenous Vitamin C in the treatment of shingles: results of a multicenter prospective cohort study. Med Sci Monit. 2012;18:215–224. [PMC free article] [PubMed] [Google Scholar]

4. Schencking M, Sandholzer H, Frese T. Intravenous administration of vitamin C in the treatment of herpetic neuralgia: two case reports. Med Sci Monit. 2010;16:58–61. [PubMed] [Google Scholar]

5. Chen JY, Chang CY, Feng PH, Chu CC, So EC, Hu ML. Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin J Pain. 2009;25:562–569. doi: 10.1097/AJP.0b013e318193cf32. [PubMed] [CrossRef] [Google Scholar]

마그네슘의 포진후 동통 치료효과

Randomized Controlled Trial

 

J Clin Anesth

. 2015 Jun;27(4):296-300.

 doi: 10.1016/j.jclinane.2015.02.006. Epub 2015 Mar 17.

Is Magnesium Sulfate Effective for Pain in Chronic Postherpetic Neuralgia Patients Comparing With Ketamine Infusion Therapy?

Yang Hyun Kim 1, Pyung Bok Lee 2, Tak Kyu Oh 1

Affiliations expand

• PMID: 25792176
 
• DOI: 10.1016/j.jclinane.2015.02.006

Abstract

Background: Postherpetic neuralgia (PHN) is a frequent debilitating complication and one of the most intractable pain disorders, particularly in elderly patients. Although tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone are effective for alleviating PHN, many patients remain refractory to current therapies. Here, the analgesic effects of ketamine or magnesium for PHN were assessed in an open prospective study.

Method: Thirty patients with severe, intractable PHN who were unresponsive to conservative therapy participated. The effects of ketamine hydrochloride (Ketara, Parke Davis) 1 mg/kg and magnesium sulfate (Magnesin) 30 mg/kg were investigated. The patients were randomly divided into 2 groups of 15 patients each, and ketamine 1 mg/kg or magnesium 30 mg/kg was administered intravenously for 1 hour after midazolam sedation. Pain was rated on a visual analog scale (VAS) during a 2-week follow-up. All patients also completed the Doleur Neuropathique 4 questionnaire at baseline and final visits.

Results: Response to treatment, defined as a 50% reduction in VAS score 2 weeks after, was recorded in 10 of 15 patients in the ketamine group and 7 of 15 patients in the magnesium group. The difference in VAS reduction was not significant between the 2 groups.

Conclusions: Ketamine and magnesium showed significant analgesic effects in patients with PHN.

Keywords: Ketamine; Magnesium; Postherpetic neuralgia.

Case Reports

 

Pain Med

. 2012 Jul;13(7):915-8.

 doi: 10.1111/j.1526-4637.2012.01404.x. Epub 2012 Jun 8.

Successful Treatment of Refractory Postherpetic Neuralgia With Topical Gallium Maltolate: Case Report

Lawrence R Bernstein 1

Affiliations expand

• PMID: 22680305
 
• DOI: 10.1111/j.1526-4637.2012.01404.x

Abstract

Introduction: Postherpetic neuralgia is a common sequela of herpes zoster (shingles), in which chronic pain may last for weeks to years. Currently, available treatments include systemic opioid analgesics, tricyclic antidepressants, corticosteroids, and anticonvulsants, as well as topical capsaicin and lidocaine. These treatments are commonly unsatisfactory, with fewer than half of treated patients experiencing more than a 50% reduction in pain.

Case: A 99-year-old woman had a 4-year history of severe postherpetic (trigeminal) neuralgia on the left side of her face. During those 4 years, numerous treatments were tried, including systemic opioid analgesics and anticonvulsants, and topical lidocaine and capsaicin, all with unsatisfactory results. The topical application of gallium maltolate, at a concentration of 0.5% in an emulsion of water and hydrophilic petrolatum, was found to relieve the severe pain within about 10 minutes, with the relief lasting for about 6-8 hours. The patient has been using this treatment for more than 5 years, with no adverse effects and a highly significant improvement in her quality of life.

Discussion: Gallium has significant anti-inflammatory activity, inhibiting the activation and proliferation of pro-inflammatory T cells. Because gallium is chemically similar to zinc, it can interfere with the activity of matrix metalloproteinases (zinc-bearing proteases), which have been implicated in the etiology of neuropathic pain, and it may suppress the secretion of substance P. Gallium may also inhibit viral replication and the inflammatory activity of viral proteins. This case provides rationale to study topical gallium maltolate in patients with refractory peripheral neuropathic pain.

위궤양 - 헬리코박터에 의한 포진후 동통의 발생

Is peptic ulcer disease a risk factor of postherpetic neuralgia in patients with herpes zoster

Abstract

Postherpetic neuralgia is the most common complication of herpes zoster which is caused by a reactivation of latent varicella zoster virus. The pathogenesis of postherpetic neuralgia may involve peripheral and central mechanisms. Reported risk factors for postherpetic neuralgia include female gender, old age, diminished cell-mediated immunity and nutritional deficiencies. 

Based on our clinical observation which revealed that peptic ulcer disease (PUD) is one of the common comorbidities in patients with postherpetic neuralgia, we hypothesize that herpes zoster patients with PUD may be at a greater risk for the development of postherpetic neuralgia due to their impaired cellular immunity and depressed nutritional status. 

Major causes of PUD include Helicobacter pylori infection and usage of ulcerogenic medications. Patients with H. pylori infection may develop T cell dysfunctions and nutritional deficiencies including vitamin C, iron, cobalamin, carotenes and alpha-tocopherol. Ulcerogenic medications such as nonsteroidal anti-inflammatory drugs and steroids have been found not only to be ulcerogenic but also immunosuppressive to T cells. In addition, usage of steroids and nonsteroidal anti-inflammatory drugs may cause deficiencies of alpha-tocopherol, carotenes, cobalamin, iron, zinc and vitamin C. 

Vitamin C, carotenes and alpha-tocopherol are anti-inflammatory and the major oxidant scavengers in the aqua phase and biomembranes. Deficiencies of these nutrients may induce dysregulated inflammation and oxidative damage leading to neuropathic pain in patients with herpes zoster. 

Furthermore, nutrient deficiencies including zinc, iron, cobalamin and vitamin C are associated with dysregulation of Ca(v)3.2 T-channels and N-methyl-D-aspartate receptors, upregulation of nitric oxide synthase, the increase of nitric oxide formation and dysfunction of central norepinephrine inhibitory pain pathway. Prospective cohort studies are suggested to test the hypothesis. We further propose that a follow-up study that contains two groups of herpes zoster patients, i.e., with or without gastroendoscopy-proven PUD, be conducted to determine their incidence of postherpetic neuralgia. In addition, despite of the high proportion of zoster patients having been treated with antiviral therapies, prevention and treatment of postherpetic neuralgia remain challenging in clinical practice. The potential risk of postherpetic neuralgia in zoster patients with PUD could mean that physicians need to pay more attention to the comorbidity--PUD in patients with herpes zoster and treat PUD earlier in order to prevent the development of postherpetic neuralgia.