Herpes labialis 唇皰疹

Herpes labialis (from BMJ Clin Evid. 2009; 2009: 1704.)

下面中文是用google翻譯. 稍作修飾

摘要

介紹

1 型單純皰疹病毒感染通常會導致口腔周圍出現輕度、自限性疼痛水泡，20% 至 40% 的成年人有時會受到影響。原發感染通常發生在兒童時期，此後病毒被認為潛伏在三叉神經節中。暴露於強光、壓力和疲勞等因素可能會引發復發。

方法和結果

我們進行了系統評價，旨在回答以下臨床問題：抗病毒治療對唇皰疹首次發作有何影響？旨在預防唇皰疹復發的干預措施有何效果？唇皰疹反復發作的治療效果如何？我們檢索了：截至 2009 年 2 月的 Medline、Embase、Cochrane 圖書館和其他重要數據庫（臨床證據評論會定期更新；請查看我們的網站以獲取該評論的最新版本）。我們納入了美國食品和藥物管理局 (FDA) 和英國藥品和保健品監管機構 (MHRA) 等相關組織的危害警報。

結果

我們找到了 27 項符合我們納入標準的系統評價、隨機對照試驗或觀察性研究。我們對乾預措施的證據質量進行了 GRADE 評估。

結論

在這篇系統評價中，我們提供了與以下乾預措施的有效性和安全性相關的信息：口服抗病毒藥物、防曬霜、局部麻醉劑、局部抗病毒藥物和氧化鋅乳膏。

關鍵點

1 型單純皰疹病毒感染通常會導致口腔周圍出現輕度、自限性疼痛水泡，20% 至 40% 的成年人有時會受到影響。

原發感染通常發生在兒童時期，此後病毒被認為潛伏在三叉神經節中。

暴露於強光、壓力和疲勞等因素可能會引發復發。

與安慰劑相比，阿昔洛韋等口服抗病毒藥物可以縮短唇皰疹首次發作時的疼痛持續時間和癒合時間；然而，證據有限。

我們不知道局部抗病毒藥物是否可以減輕首次發作時的疼痛或縮短癒合時間。

與安慰劑相比，預防性口服抗病毒藥物可能會降低發作的頻率和嚴重程度，但我們不知道治療的最佳時機和持續時間。

我們不知道局部抗病毒治療是否有助於預防復發性發作。

紫外線防曬霜可以減少復發；然而，證據有限。

口服抗病毒藥物可以縮短唇皰疹反復發作的症狀持續時間和治愈時間。

如果在反復發作的早期服用口服阿昔洛韋、泛昔洛韋和伐昔洛韋可能會略微縮短癒合時間，但伐昔洛韋可能會引起頭痛。

我們發現有限的證據表明局部抗病毒藥物可以減少反復發作的疼痛和癒合時間。然而，結果不一致且臨床重要性不高。

我們不知道局部麻醉劑或氧化鋅霜是否會縮短癒合時間。氧化鋅霜可能會增加皮膚刺激。

定義

唇皰疹是一種輕度、自限性的 1 型單純皰疹病毒 (HSV-1) 感染。它會導致嘴唇和口周區域疼痛和起泡（唇皰疹）；發燒和全身症狀很少見。大多數人沒有任何攻擊的警告，但有些人會經歷明顯的前驅症狀。在本次綜述中，我們納入了針對免疫力正常人群的研究，排除了針對免疫功能低下人群的研究（例如，針對艾滋病毒感染者或正在接受化療的癌症患者的研究）。

發病率/流行率

在英國，唇皰疹每年約佔初級保健諮詢的 1%；20% 到 40% 的人曾在某個時候經歷過唇皰疹。

病因/風險因素

唇皰疹是由 HSV-1 引起的。通常發生在兒童時期的原發性感染後，病毒被認為潛伏在三叉神經節中。多種因素，包括暴露在明亮的陽光下、疲勞或心理壓力，都可能導致復發。

預後

對於大多數人來說，唇皰疹是一種輕微的自限性疾病。復發通常比初次發作的時間更短且不那麼嚴重。通常 7 至 10 天內即可完全癒合，不會留下疤痕。重新激活的速率未知。唇皰疹可導致免疫功能低下的人患上嚴重疾病。

干預目的

減少反復發作的頻率和嚴重程度；加速病變的癒合；以減輕疼痛，將副作用降到最低。

結果

症狀改善（症狀嚴重程度和症狀持續時間；不包括病變癒合或結痂的時間）；癒合時間（癒合時間/病變結痂時間）；復發率；生活質量; 治療的不良反應。

方法

臨床證據搜索和評估 2009 年 2 月。以下數據庫用於確定該系統評價的研究：Medline 1966 年至 2009 年 2 月，Embase 1980 年至 2009 年 2 月，以及 Cochrane 系統評價數據庫，2009 年，第 1 期（1966 年至今問題）。在 Cochrane 圖書館內進行了額外的搜索，以查找效果評論摘要數據庫 (DARE) 和衛生技術評估 (HTA)。我們還搜索了審查中包含的研究的撤回。從初始搜索中檢索到的研究摘要由信息專家進行評估。然後將選定的研究發送給貢獻者進行額外評估，使用預先確定的標準來識別相關研究。本次評價的研究設計標準是：發表了任何語言的隨機對照試驗和隨機對照試驗的系統評價，至少是單盲的，並且包含 20 多個個體，其中 80% 以上得到了隨訪。納入研究所需的最短隨訪時間沒有限制。我們排除了所有被描述為“開放”、“開放標籤”或非盲法的研究，除非盲法是不可能的。我們納入了隨機對照試驗和隨機對照試驗的系統評價，其中研究了納入乾預措施的危害，採用與我們針對獲益所做的相同的納入研究設計標準。此外，我們使用常規監視協議來捕獲來自 FDA 和英國藥品和保健產品監管機構 (MHRA) 等組織的危害警報，並根據需要將其添加到評論中。為了幫助我們評論中的數字數據的可讀性，我們將許多百分比四捨五入到最接近的整數。讀者在將百分比與匯總統計數據（例如相對風險 (RR) 和比值比 (OR)）相關聯時應注意這一點。我們對本綜述中包含的干預措施的證據質量進行了 GRADE 評估（見表）。證據質量的分類（高、中、低或極低）反映了我們在定義的目標人群中選擇的結果可用的證據質量。這些分類不一定反映任何單個研究的整體方法學質量，因為臨床證據人群和選擇的結果可能僅代表任何單個試驗中報告的總結果和包括的人群的一小部分。
我們最初將 4 分分配給隨機對照試驗的證據，將 2 分分配給觀察性研究的證據。為了獲得給定比較的最終 GRADE 分數，根據與質量、直接性、一致性和影響大小類別相關的預設標準，從該初始分數中扣除或添加分數。質量：基於影響方法嚴謹性的問題（例如，結果報告不完整、半隨機化、數據稀疏 [<200 人參與分析]）。一致性：基於研究結果的相似性。直接性：基於人口或結果的普遍性。影響大小：基於通過相對風險、比值比或風險比等統計數據衡量的影響大小。

以下部分來自uptodate網站
復發性感染 — 當病毒從三叉神經感覺神經節重新激活並持續處於潛伏狀態時，口腔 HSV-1 復發就會發生。症狀重新激活會導致口腔皰疹（“唇皰疹”），發生在嘴唇的朱紅色邊緣。復發性粘膜 HSV-1 感染通常與原發性疾病相比，臨床症狀較輕，病程較短。一些患者認識到，由於前驅症狀（例如疼痛、刺痛、燒灼感）的出現，疾病即將重新激活，這些症狀先於水皰的形成。 

預防新的 HSV-1 感染 大多數 HSV-1 感染是在親密（但不一定是性）接觸過程中獲得的。家庭成員是最有可能的來源，但當發生唾液分享行為時，其他人也可能是來源。

儘管沒有獲得許可的疫苗可以預防 HSV-1 感染 [ 60 ]，但某些策略可能有助於降低將 HSV-1 傳播給未感染過的人的風險。例如，當患者口腔單純皰疹病毒活躍爆發時，患者應避免親吻或共用餐具、玻璃杯、水瓶、毛巾或潤唇膏。儘管這可能無法完全降低風險，但由於可能會發生無症狀的脫落，因此在活動性病變的情況下最有可能傳播。

Abstract

Introduction

Herpes simplex virus type 1 infection usually causes a mild, self-limiting painful blistering around the mouth, with 20% to 40% of adults affected at some time. Primary infection usually occurs in childhood, after which the virus is thought to remain latent in the trigeminal ganglion. Recurrence may be triggered by factors such as exposure to bright light, stress, and fatigue.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antiviral treatments for the first attack of herpes labialis? What are the effects of interventions aimed at preventing recurrent attacks of herpes labialis? What are the effects of treatments for recurrent attacks of herpes labialis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: oral antiviral agents, sunscreen, topical anaesthetic agents, topical antiviral agents, and zinc oxide cream.

Key Points

Herpes simplex virus type 1 infection usually causes a mild, self-limiting painful blistering around the mouth, with 20% to 40% of adults affected at some time.

Primary infection usually occurs in childhood, after which the virus is thought to remain latent in the trigeminal ganglion.

Recurrence may be triggered by factors such as exposure to bright light, stress, and fatigue.

Oral antiviral agents such as aciclovir may reduce the duration of pain and time to healing for a first attack of herpes labialis compared with placebo; however, evidence is limited.

We don't know whether topical antiviral agents can reduce pain or time to healing in a first attack.

Prophylactic oral antiviral agents may reduce the frequency and severity of attacks compared with placebo, but we don't know the best timing and duration of treatment.

We don't know whether topical antiviral treatments are beneficial as prophylaxis against recurrent attacks.

Ultraviolet sunscreen may reduce recurrent attacks; however, evidence is limited.

Oral antiviral agents may reduce the duration of symptoms and the time to heal in recurrent attacks of herpes labialis.

Oral aciclovir, famciclovir, and valaciclovir may marginally reduce healing time if taken early in a recurrent attack, but valaciclovir may cause headache.

We found limited evidence that topical antiviral agents may reduce pain and healing time in recurrent attacks. However, results are inconsistent and of marginal clinical importance.

We don't know whether topical anaesthetic agents or zinc oxide cream reduce healing time. Zinc oxide cream may increase skin irritation.

Definition

Herpes labialis is a mild, self-limiting infection with herpes simplex virus type 1 (HSV-1). It causes pain and blistering on the lips and perioral area (cold sores); fever and constitutional symptoms are rare. Most people have no warning of an attack, but some experience a recognisable prodrome. In this review, we have included studies in people with normal immunity and excluded studies in people who are immunocompromised (e.g., studies in people with HIV or with cancer undergoing chemotherapy).

Incidence/ Prevalence

Herpes labialis accounts for about 1% of primary care consultations in the UK each year; 20% to 40% of people have experienced cold sores at some time.

Aetiology/ Risk factors

Herpes labialis is caused by HSV-1. After the primary infection, which usually occurs in childhood, the virus is thought to remain latent in the trigeminal ganglion. A variety of factors, including exposure to bright sunlight, fatigue, or psychological stress, can precipitate a recurrence.

Prognosis

In most people, herpes labialis is a mild, self-limiting illness. Recurrences are usually shorter and less severe than the initial attack. Healing is usually complete in 7 to 10 days without scarring. Rates of reactivation are unknown. Herpes labialis can cause serious illness in immunocompromised people.

Aims of intervention

To reduce the frequency and severity of recurrent attacks; to speed healing of lesions; to reduce pain, with minimal adverse effects.

Outcomes

Symptom improvement (severity of symptoms and duration of symptoms; does not include time to healing or crusting of lesions); time to healing (time to healing/time to crusting of lesions); rate of recurrence; quality of life; adverse effects of treatment.

Methods

Clinical Evidence search and appraisal February 2009. The following databases were used to identify studies for this systematic review: Medline 1966 to February 2009, Embase 1980 to February 2009, and The Cochrane Database of Systematic Reviews, 2009, Issue 1 (1966 to date of issue). An additional search within the Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for evaluation in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

下面這部分來自 uptodate
Recurrent infections — Oral HSV-1 recurrences occur when the virus reactivates from the trigeminal sensory ganglion, where it persists in a latent state. Symptomatic reactivation leads to oral herpes ("cold sores"), which occur along the vermillion border of the lips. Recurrent mucosal HSV-1 infections are generally associated with less severe clinical symptoms and a shorter duration of illness than primary disease. Some patients recognize that reactivation of disease is about to occur due to the onset of prodromal symptoms (eg, pain, tingling, burning), which precede the development of vesicles. 

PREVENTING NEW HSV-1 INFECTIONSMost HSV-1 infections are acquired during intimate (but not necessarily sexual) contact. Family members are the most likely source, but others may be a source when saliva-sharing behavior occurs.

Although there are no licensed vaccines to prevent HSV-1 infection [60], certain strategies may help reduce the risk of transmitting HSV-1 to someone without prior infection. As an example, when a patient has an active outbreak of oral HSV, patients should avoid kissing or sharing utensils, glasses, water bottles, towels, or lip balm. Although this may not reduce the risk completely, since asymptomatic shedding can occur, transmission is most likely in the setting of active lesions.