帶狀泡疹(皰疹)神經痛 2. Postherpetic Neuralgia from Uptodate

2023-09-16 中午12:12
另一篇參考資料(帶狀泡疹(皰疹)神經痛 1. Postherpetic Neuralgia-StatPerls)太龐大.
本來想把兩篇文章寫在同一篇筆記. 但實在不好閱讀. 還是切割開來

這裡只列出在 uptodate 上面關於治療的部分. 其他部分請自己看原文(沒有附)
下面中文是google翻譯. 第一段自動沒有翻譯, google翻譯的程式邏輯還有缺陷
治療這段的英文原文在筆記最下面

初始治療 —臨床試驗和薈萃分析發現，加巴噴丁類藥物（即加巴噴丁和普加巴林）和三環類抗抑鬱藥 (TCA) 對 PHN 有效且普遍耐受性良好[ 40-44 ]。與 TCA 相比，加巴噴丁類藥物因不良反應而停藥的風險可能較低，但尚未直接比較這些藥物對 PHN 的影響。我們使用患者變量（包括藥物副作用、合併症和症狀嚴重程度）來幫助選擇初始治療。例如，加巴噴丁或普瑞巴林可能是患者的首選，以幫助共同治療癲癇症或避免與 TCA 相關的認知障礙風險。阿米替林或其他 TCA 可能是患者首選，以幫助共同治療抑鬱症。

加巴噴丁類藥物用於大多數中度或重度疼痛患者 — 對於大多數中度至重度疼痛患者，我們建議加巴噴丁類藥物（加巴噴丁或普加巴林）作為初始治療[ 45 ]。加巴噴丁和普瑞巴林是γ-氨基丁酸（GABA）的結構類似物，已被美國食品和藥物管理局（FDA）批准用於治療PHN。兩者通常都具有良好的耐受性，並且不會改變其他藥物的藥代動力學，因為兩者都不與血漿蛋白結合[ 46,47 ]。我們通常從加巴噴丁開始，因為成本更低且耐受性更好[ 43]。然而，根據療效，普瑞巴林也是治療 PHN 的合理初始選擇，因為沒有與加巴噴丁的直接比較。

●加巴噴丁-加巴噴丁通常以低劑量開始，以盡量減少因不良反應而停藥的風險。每日劑量逐漸調整至有效，對於大多數患者來說，通常為 1800 至 3600 毫克。我們建議的加巴噴丁速釋製劑治療 PHN 的初始滴定劑量為：


• 第 1 天 300 mg
• 第 2 天 300 mg，每天兩次
• 第 3 天 300 mg，每天 3 次
• 此後，根據需要每三天增加300 mg每日 3 次，最多 600 毫克

對於在初始滴定過程中報告中等劑量緩解或不良反應的患者，可以使用較低劑量或減慢滴定速度。

對於每日總劑量 1800 mg 一個月後報告症狀緩解甚微或無緩解的患者，我們改用 TCA。


對於每日總劑量為 1800 mg 時疼痛部分緩解但不充分的患者，加巴噴丁可根據需要進一步增加，並可耐受，每週最多 600 mg，分三次給藥，最大劑量為 3600 mg。加巴噴丁



緩釋製劑根據相同的時間表使用每日總劑量進行滴定，以確定每日一次的劑量。速釋製劑和緩釋製劑都需要針對腎功能損害進行調整，並且不建議在嚴重腎功能損害（例如肌酐清除率<30 mL/分鐘）的患者中使用緩釋製劑。有中等質量的證據支持加巴噴丁的功效



對於 PHN，但一些試驗未能顯示加巴噴丁緩釋製劑的益處，並且超過 12 週的益處尚不確定 [ 43,48 ]。在一項薈萃分析中，對2200 多名PHN 引起的中度至重度疼痛患者進行了8 項試驗，每天服用1200 毫克或更高劑量加巴噴丁的患者更有可能報告獲益（疼痛強度至少降低50% ）或“明顯改善”疼痛）比接受安慰劑的患者（32% 對 17%）[ 49 ]。



加巴噴丁通常耐受性良好。在一項針對多種類型神經性疼痛的 37 項試驗的不良反應匯總分析中，由於不良反應，患者比安慰劑更有可能停用加巴噴丁（11% 對 8%）[49 ]。最常見的不良反應是嗜睡或嗜睡（14% vs 5%）、頭暈（19% vs 7%）、外周水腫（7% vs 2%）以及共濟失調或步態障礙（14% vs 3%） 。兩組的嚴重不良反應發生率均為 3%。●普瑞巴林-普瑞巴林


的速釋製劑每天服用兩到三次。我們基於效果和耐受性的滴定方案是：• 75 毫克，每天兩次，持續一周，然後• 150 毫克，每天兩次，持續一到三週，然後• 300 毫克，每天兩次





緩釋製劑也可供每日一次給藥。滴定方案與速釋製劑相同；然而，起始劑量為每天 165 毫克，最大劑量為每天 660 毫克。

停藥時，普瑞巴林應在一周內逐漸減量，以降低戒斷症狀的風險[ 50 ]。

速釋製劑和緩釋製劑都需要針對腎損傷進行調整；不建議患有嚴重腎功能不全（例如肌酐清除率<30 mL/分鐘）的患者使用緩釋製劑。普瑞巴林在美國被指定為第五類管制物質，因為據報導它會引起欣快感。

普瑞巴林治療神經性疼痛的系統評價確定了 8 項試驗，其中包括 2300 多名 PHN 患者[ 51 ]。在四項PHN 患者試驗中對732 名患者進行的薈萃分析中，接受普瑞巴林的患者比接受安慰劑的患者更有可能出現劑量反應和疼痛顯著減輕（至少50%）：150 mg（24 % vs 13%） 、300 毫克（32% 對 13%）和 600 毫克（41% 對 15%）。與普瑞巴林給藥相關的常見副作用包括嗜睡（300 mg，16%；600 mg，25%）和頭暈（300 mg，29%；600 mg，35%）。其他副作用包括口乾、外周水腫和體重增加。

如果加巴噴丁類藥物無效或不耐受，則使用三環類抗抑鬱藥物 — 對於不耐受加巴噴丁類藥物或對加巴噴丁類藥物沒有反應的患者，我們建議使用 TCA。它們經常用於治療抑鬱症或其他類型的神經性疼痛，對 PHN 也有效，但耐受性低於加巴噴丁類藥物 [ 52,53 ]。對於大多數使用 TCA 的患者，我們通常從阿米替林開始；然而，對於有抗膽鹼能症狀風險的患者和有阿米替林不良反應的患者，去甲替林或地昔帕明可能是首選。

●阿米替林開始劑量為每晚 10 毫克。劑量可根據需要和耐受性在 4 週內增加，直至每晚 50 毫克。對於服用 50 毫克一個月後報告症狀緩解甚微或無緩解的患者，我們改用另一種藥物（參見下文“替代療法”）。對於那些在 50 mg 劑量下報告部分但不充分緩解的患者，可以每 4 週進一步增加劑量，直至每日最大劑量 150 mg，並監測不良反應。

●去甲替林通常從每晚 10 mg 開始，每週增加 10 至 20 mg，以達到耐受的效果，每日最大劑量為 150 mg。

●地昔帕明通常從每晚 25 毫克開始，每週增加 25 毫克，以達到耐受的效果，每日最大劑量為 150 毫克。

TCA 抑制中樞神經系統去甲腎上腺素和血清素的再攝取。它們被認為可以增強對來自外周的傷害性信號的抑制[ 54,55 ]。

抗膽鹼能副作用（主要是鎮靜和口乾）限制了 TCA 的耐受性（表 1）[ 56]]。由於 TCA 具有抗膽鹼能作用，老年患者尤其是患有認知障礙或癡呆的患者應謹慎使用 TCA。我們還避免對患有心髒病、癲癇或青光眼的患者使用 TCA。通過緩慢滴定可以減少不良反應；然而，在 TCA 開始減輕疼痛之前延遲起效（最多三週）可能會導致過早停藥。可能需要以目標劑量進行至少一個月的治療試驗來評估 TCA 的療效。在一項研究中，症狀緩解與阿米替林和活性代謝物的血清水平相關[ 57 ]。儘管血清水平為 100 ng/mL 至少三週，但報告沒有獲益的患者被認為 TCA 治療失敗。

2015 年的一項系統評價發現中等質量的證據支持 TCA 對 PHN 的療效[ 43 ]。TCA 中阿米替林的療效最為明確，多項短期研究發現阿米替林可有效緩解至少中度疼痛，通常劑量為每日 65 至 75 毫克 [57,58 ]。在一項針對 33 名 PHN 患者的小型交叉試驗中，去甲替林比阿米替林具有更好的耐受性 [ 59 ]。大約三分之二的患者報告這兩種藥物的反應良好，但阿米替林比去甲替林更常見導致停藥的不良反應（48% vs 30%）。研究規模較小限制了這些結果的普遍性。地昔帕明似乎是第一代 TCA 中副作用最少的，並且在一項小型試驗中以平均每天 165 毫克劑量對 PHN 有效 [ 60,61 ]。近一半的人表示服用地昔帕明效果良好。然而，對該試驗的方法學批評限制了這些結論的確定性[ 62 ]。

對症狀較輕的患者進行局部治療 — 對於輕度至中度局部疼痛的患者以及喜歡局部用藥的患者，我們建議使用辣椒素。對於那些不耐受辣椒素的人，我們改用利多卡因貼劑。

●辣椒素——辣椒素被配製成乳膏、凝膠、乳液或高濃度貼劑。

我們用對於大多數 PHN 患者，可使用辣椒素乳膏（0.025 至 0.075%），並為對辣椒素乳膏有部分反應且更喜歡長效配方的特定患者保留高濃度辣椒素（8%）貼劑。

•辣椒素霜每天最多可塗抹在患處四次。

•高濃度辣椒素貼劑單次使用60 分鐘。三個月後可以重複申請。它必須由醫療保健專業人員進行，並且治療後對患者進行長達兩個小時的監測。為了控制施用辣椒素引起的局部疼痛，通常用局部麻醉劑（例如局部利多卡因）預處理皮膚，一些研究還使用治療後口服鎮痛藥，例如羥考酮，持續時間長達五天[ 63 ]。需要進一步的研究來確認高濃度辣椒素貼劑的長期有效性和耐受性。

有限的數據表明局部應用標準濃度辣椒素對 PHN 有效[ 41 ]。在一項小型試驗中，143 名 PHN 患者被分配每天四次辣椒素乳膏（0.075%），持續六週，與接受安慰劑的患者相比，疼痛明顯緩解（21% vs 6%）[64 ]。接受辣椒素和安慰劑的患者皮膚不良反應發生率相似。

2013 年的一項系統回顧確定了四項隨機對照試驗，這些試驗評估了 1272 名 PHN 受試者，使用一次高濃度辣椒素貼劑或標準濃度辣椒素進行治療。所有四項試驗報告的唯一共同終點是，與基線相比，八週時疼痛強度降低≥30%，高濃度辣椒素貼片的效果顯著更高（43% vs 34%；相對效益1.3，95 % CI 1.1-1.5） [ 65 ]。

高濃度辣椒素貼劑經 FDA 批准用於治療 PHN。然而，辣椒素會引起灼燒感、刺痛感和紅斑，因此在臨床研究中很難實現真正的致盲。實際上，多達三分之一的患者無法忍受辣椒素的應用。

●利多卡因 —利多卡因貼劑 (5%) 可以短期緩解 PHN。每天最多可在受影響區域塗抹 3 片貼劑，持續時間長達 12 小時。

小規模試驗和開放標籤研究的數據表明，局部利多卡因（5%）可能有助於緩解 PHN 患者的疼痛[ 66]。利多卡因貼劑已獲得 FDA 批准用於 PHN。然而，2014 年對局部利多卡因治療神經性疼痛的系統評價（包括280 名PHN 患者）發現，由於數量少、結果評估不完整以及療效結果測量不充分，局部利多卡因療效的證據質量非常低[67 ]。

替代療法 — 對於不能耐受初始治療或對初始治療無反應的患者，我們改用替代藥物（流程 1）。對於初始治療反應部分但未達最佳的患者，我們通過添加替代藥物進行聯合治療。我們利用患者偏好和醫療合併症來幫助選擇選項。

抗驚厥藥物 — 對於一些對初始藥物選擇沒有反應或不能耐受的患者，試用一種（非加巴噴丁類）抗驚厥藥物可能有用。治療決策應根據患者特徵、合併症、副作用和藥物相互作用進行個體化。抗驚厥藥的益處部分基於其對其他神經性疼痛病症（如三叉神經痛和糖尿病神經病變）的療效，以及 PHN 的低質量和軼事證據。PHN 的選項和典型每日目標劑量包括：

●丙戊酸，每日 500 至 1000 毫克
●卡馬西平，每日 200 至 1200 毫克
●奧卡西平，每日 600 至 1200 毫克
●拉莫三嗪每天 100 至 300 mg


這些藥物治療 PHN 的劑量、滴定和監測與三叉神經痛的治療方案相似，通常比達到抗驚厥作用的劑量要低。(參見“三叉神經痛”，關於‘藥物治療’一節)

在一項對48 名PHN 患者進行的為期八週的試驗中，接受雙丙戊酸鈉治療（每天1000 mg）的患者與接受雙丙戊酸鈉治療的患者相比，更有可能報告疼痛至少有中度改善。分配給安慰劑（58% 對 15%）[ 68 ]。丙戊酸治療其他神經性疼痛的小型試驗結果好壞參半[ 69 ]。在三叉神經痛患者的短期試驗中，卡馬西平奧卡西平比安慰劑更能減輕疼痛，但這兩種藥物都沒有在 PHN 患者中進行測試 [ 70,71 ]。拉莫三嗪可能比卡馬西平具有更好的耐受性，但尚未針對神經性疼痛進行廣泛研究。

5-羥色胺-去甲腎上腺素再攝取抑製劑 — 根據疼痛性多發性神經病的療效數據，5-羥色胺-去甲腎上腺素再攝取抑製劑 (SNRI) 可能對某些 PHN 患者有用 [43 ]。這些藥物可能對患有抑鬱症的患者有用。對於 PHN 患者，我們使用度洛西汀或文拉法辛。

●度洛西汀通常從每天 30 毫克開始。典型的每日劑量為 60 至 120 毫克。可以每週增加劑量以達到效果並在耐受範圍內。高劑量時更常見的不良反應包括噁心、口乾、頭暈和失眠。

●文拉法辛可以每天 75 mg 開始，每兩週增加一次，直至達到耐受的效果。典型的每日劑量為 150 至 225 毫克。青光眼患者和服用抗凝劑的患者應謹慎使用文拉法辛。常見的不良反應包括噁心、頭暈和嗜睡。

SNRIs 的初始滴定和給藥詳見其他專題。(參見“5-羥色胺-去甲腎上腺素再攝取抑製劑：藥理學、給藥方法和副作用” )

度洛西汀和文拉法辛等 SNRI 藥物對 PHN 患者的有效性基於其他類型神經性疼痛患者的數據。對 8 項試驗（包括 4084 名患者）的系統評價發現，度洛西汀對患有疼痛性糖尿病神經病變的患者有益 [ 72 ]。一項針對 244 名患有疼痛性糖尿病多發性神經病患者的短期試驗發現文拉法辛有效 [ 73 ]。接受 150 至 225 mg 文拉法辛治療的患者比接受安慰劑治療的患者更有可能報告至少 50% 的疼痛減輕（50% 對 27%）。然而，2015 年對 6 項試驗（包括 460 名神經性疼痛患者）進行的系統回顧發現，文拉法辛僅具有中等療效的低質量數據。74 ]。SNRIs 對糖尿病神經病變的療效詳見其他專題。(參見“糖尿病神經病變的治療”，關於‘給藥方法和療效’一節)

輔助選擇— 對於先前治療難治性症狀的患者，可以嘗試或添加輔助選擇和其他介入治療，如肉毒毒素注射(流程1 ) 。這些包括口服或透皮阿片類鎮痛藥和鞘內糖皮質激素注射劑。這些藥物的選擇取決於患者個體的偏好和合併症。

阿片類藥物 — 阿片類藥物可能對某些在初始或替代療法滴定期間患有頑固性疼痛的患者有益。它們可以與非阿片類藥物同時給藥以實現短期緩解。如果使用的話，應以低劑量開始，並在等待非阿片類藥物治療獲益的同時逐步調整以提供緩解，此時應逐漸減少阿片類藥物的用量。

阿片類藥物有短效或長效製劑（表 2和表 3）。我們首先為未使用過阿片類藥物的患者提供短效選擇，並使用最低有效劑量。PHN 患者開始和長期使用阿片類藥物的策略與其他非癌性疼痛患者相似，將單獨更詳細地討論。（看“使用阿片類藥物治療慢性非癌症疼痛”。）

小型試驗支持阿片類鎮痛藥對 PHN 的療效[ 75-79 ]。在一項涉及 76 名 PHN 患者的交叉試驗中，嗎啡（平均每日劑量 91 mg）或美沙酮（平均每日劑量 15 mg）或 TCA 治療八週比安慰劑更有效[ 77 ]。阿片類藥物有更好地緩解疼痛的趨勢，但這些結果的確定性受到樣本量較小的限制。

應避免使用阿片類藥物治療慢性 PHN。由於存在身體依賴性、耐受性、成癮性和過量服用的風險，阿片類藥物治療慢性非癌性疼痛仍然存在爭議。由於這些風險，阿片類藥物被視為三線治療選擇，通常僅供 PHN 的短期輔助使用[ 38,43,80 ]。阿片類藥物治療包括 PHN 在內的神經性疼痛的現有試驗並未解決濫用和成癮問題 [ 81 ]。藥物警戒對於在任何人群中使用阿片類藥物至關重要（表 4）。(參見“阿片類藥物使用障礙：流行病學、臨床特徵、健康後果、篩查和評估” )

椎管內輸注糖皮質激素 — 鞘內註射糖皮質激素可能對經過初始治療或替代治療後仍存在頑固性疼痛的患者有益。這些注射對於三叉神經分佈區的疼痛沒有作用。

用於治療 PHN 的鞘內糖皮質激素通常是每週注射一次，持續 4 週 [ 82 ]。鞘內註射糖皮質激素的技術將單獨更詳細地討論。(參見“脊髓麻醉：技術” )

鞘內註射糖皮質激素與不確定但可能較低風險的嚴重不良事件相關，包括無菌性腦膜炎、橫貫性脊髓炎、馬尾綜合徵、腰神經根炎、頭痛、尿瀦留和蛛網膜炎[ 83,84 ]。

一些 [ 40,82,85 ] 但並非所有 [ 86 ] 研究發現鞘內注射甲潑尼龍對 PHN 患者有益。最大的試驗評估了 277 名頑固性 PHN 患者，他們被分配到三個治療組之一：鞘內註射甲基強的松龍加利多卡因，每週一次，持續四個星期，鞘內註射利多卡因，每週一次，持續四個星期，或不治療[ 82]。甲基強的松龍組中超過 90% 的患者在 4 週後報告疼痛緩解效果良好或良好，而利多卡因組和無治療組中這一比例分別為 6% 和 4%。這些結果在兩年的隨訪中得以維持。沒有與註射相關的嚴重不良事件。在一項對 25 名 PHN 患者進行的小型試驗中，發現鞘內註射

甲基潑尼松龍比硬膜外注射更有效[ 85 ]。

難治性症狀的治療 — 對於對其他治療無反應的難治性症狀患者，我們保留其他介入和手術方法，例如肉毒毒素注射、冷凍療法和神經調節（流程圖 1 ））。此類療法的益處已在小型試驗和觀察性研究中得到證實；需要更大規模的研究來更好地確定它們對 PHN 患者的作用。

肉毒桿菌毒素 — 肉毒桿菌毒素注射治療 PHN 尚未得到廣泛研究，但觀察性研究和小型試驗的證據表明它是有效的[ 87-90 ]。一項試驗評估了 30 名患有 PHN 的成年人，他們持續疼痛至少三個月[ 87 ]。分配至 A 型肉毒毒素 ( onabotulinumtoxinA)的患者與接受安慰劑注射的患者相比，注射安慰劑更有可能在兩週內實現 ≥50% 的疼痛減輕（15 名患者中有 13 名患者 [87%]，而 15 名患者中沒有一人）。獲益持續時間中位數為 16 週。在一項對 60 名 PHN 患者進行的比較研究中，與接受利多卡因注射的患者相比，接受肉毒桿菌毒素A 注射的患者在7 天時報告疼痛減輕幅度更大（4.5 分與2.6 分） [ 88 ]。這些發現持續了三個月。據報導，肉毒桿菌毒素組的睡眠有所改善，阿片類藥物的使用也有所減少。

肉毒毒素注射應由具有這種治療經驗的臨床醫生進行[ 91-93]。小型研究未發現安全問題[ 87,88 ]。然而，肉毒桿菌毒素可能會引起局部或全身不良反應，包括瘀傷、虛弱、疼痛或頭痛，並且可能對某些患者是禁忌的。更大規模、更長期的研究將有助於進一步闡明這種治療 PHN 的安全性和有效性。

神經調節和神經刺激 — 脊髓刺激和周圍神經刺激等侵入性神經調節策略被認為是實驗性的。這些技術針對周圍神經，被認為可以調節神經元信號傳導或炎症過程[ 94 ]。對 PHN 患者顯示出一些益處的技術包括：

●經皮神經電刺激 (TENS) [95 ]
●脈衝射頻[ 96-100 ]
●脊髓刺激[ 101,102 ]

據報導，在病例報告和病例係列中，這些技術對大約一半的患者有效[ 103 ]。它們應該由經驗豐富的臨床醫生在具有專業知識的中心進行。

認知和行為治療 — 一些 PHN 患者即使採用聯合藥物治療也只能部分緩解。對於其他患者來說，藥物治療的功效受到不良反應的限制。非藥物方法，包括認知行為療法（CBT），可能對一些患有難治性 PHN 疼痛或情緒、睡眠或其他生活質量領域相關損害的患者有用。104，105 ]。在一項對 40 名接受普瑞巴林治療的 PHN 患者進行的小型試驗中，被分配接受 CBT 的患者報告疼痛強度和情緒症狀比單獨接受普瑞巴林的患者有更大的改善 [ 106 ]。治療慢性疼痛的認知和行為療法將單獨詳細討論。(參見“成人慢性非癌性疼痛的治療方法”，關於‘心理治療’一節)

療效不確定或有限的治療

●NMDA 受體拮抗劑——動物數據表明興奮性氨基酸神經遞質在維持疼痛中發揮作用。神經損傷引起的慢性疼痛 [ 107,108]。N-甲基-D-天冬氨酸（NMDA）受體拮抗劑已被證明可以緩解人類的神經性疼痛[ 109 ]。

最廣泛使用的 NMDA 受體拮抗劑是氯胺酮和右美沙芬。靜脈注射氯胺酮可適度緩解 PHN 患者的疼痛，但劑量會導致鎮靜、煩躁和解離發作 [ 110 ]。在一項交叉試驗中，服用右美沙芬或安慰劑的患者六週後的疼痛緩解情況相似[ 111 ]。

●靜脈注射利多卡因 – 小型試驗未能發現靜脈注射利多卡因與安慰劑相比對 PHN 患者有持續的益處 [ 40,112]。輸注後立即測量的任何暫時的疼痛變化似乎不會持續四個星期[ 40,112-116 ]。局部利多卡因

治療 PHN的作用將單獨討論。(參見上文‘症狀較輕患者的局部治療’ ) ●手術消融和其他介入手術–冷凍療法是一種涉及冷凍周圍神經的消融技術。一項針對面部疼痛的冷凍療法的小型非盲研究未能顯示出對 PHN 患者有顯著益處 [ 117

]。作者沒有提供納入標準、伴隨療法或如何評估反應的信息。相比之下，第二項試驗報告稱，14 名接受冷凍治療的 PHN 患者中，有 11 名患者的肋間神經得到“顯著”緩解 [ 118 ]。然而，在大多數情況下，根據調查問卷評估，緩解持續時間不到兩週。

包括丘腦中樞電刺激、前外側皮質切除術消融和背根電凝術在內的手術干預措施存在造成永久性神經功能缺損的巨大風險。對難治性 PHN 患者的外科手術進行的系統評價報告稱，手術消融手術可減輕疼痛，但常常伴有嚴重的並發症，包括神經肌肉無力。119 ]。

●簡單的鎮痛藥——阿司匹林或其他非甾體類抗炎藥等鎮痛藥對於急性帶狀皰疹神經痛或PHN患者的價值有限[ 38,120 ]。
Postherpetic neuralgia from uptodate TREATMENT
Multiple medications have shown benefit in reducing PHN symptoms. However, PHN can be difficult to treat, and some patients require multimodal therapy to manage symptoms. The choice among treatments for PHN should be individualized according to the severity and location of pain, comorbid conditions, medication side effect profile, treatment cost and availability, and patient values and preferences (algorithm 1). Because the pain of PHN may be chronic, long-term therapy is often required [38]. However, the long-term benefits of most therapies are uncertain, and side effects are common [39].

Initial therapies — Both gabapentinoids (ie, gabapentin and pregabalin) and tricyclic antidepressants (TCAs) have been found to be effective and generally well tolerated for PHN in clinical trials and meta-analyses [40-44]. Gabapentinoids may have a lower risk of discontinuation due to adverse effects than TCAs, but these agents have not been compared directly for PHN. We use patient variables including medication side effect profile, comorbid conditions, and symptom severity to help select initial therapy. As examples, gabapentin or pregabalin may be preferred for patients to help co-treat a seizure disorder or to avoid the risk of cognitive impairment associated with TCAs. Amitriptyline or other TCAs may be preferred for patients to help co-treat depression.

Gabapentinoids for most patients with moderate or severe pain — For most patients with moderate to severe pain, we suggest a gabapentinoid (gabapentin or pregabalin) as initial therapy [45]. Gabapentin and pregabalin are structural analogs of gamma-aminobutyric acid (GABA) and have been approved by the US Food and Drug Administration (FDA) for PHN. Both are generally well tolerated and neither alters the pharmacokinetics of other medications because neither binds to plasma proteins [46,47]. We typically start with gabapentin because of lower cost and more favorable tolerability [43]. However, pregabalin is also a reasonable initial choice for PHN based on efficacy because there are no direct comparisons with gabapentin.

●Gabapentin − Gabapentin is typically started at a low dose to minimize the risk of discontinuation from adverse effects. The daily dose is titrated to effect, for most patients typically from 1800 up to 3600 mg. Our suggested initial titration of the immediate release formulation of gabapentin for PHN is:


•300 mg on day 1
•300 mg twice daily on day 2
•300 mg three times daily on day 3
•Thereafter, increase as needed by 300 mg every three days up to 600 mg three times daily

Lower doses may be used or the titration may be slowed for patients who report relief or adverse effects at intermediate doses during the initial titration.

For patients who report minimal or no relief after one month at a total daily dose of 1800 mg, we switch to a TCA.


For patients who report partial but inadequate pain relief at a total daily dose of 1800 mg, gabapentin may be further increased as needed and tolerated by up to 600 mg each week to a maximum of 3600 mg given in three divided doses.



The extended-release formulation of gabapentin is titrated according to the same schedule using the total daily dosage to determine the once-daily dosing. Adjustment for kidney impairment is required for both immediate- and extended-release formulations, and use of the extended-release formulation is not recommended in patients with severe kidney impairment (eg, creatinine clearance <30 mL/minute).



There is moderate-quality evidence supporting the efficacy of gabapentin for PHN, but some trials have failed to show a benefit with the extended-release formulation of gabapentin, and benefits beyond 12 weeks are uncertain [43,48]. In a meta-analysis including eight trials of more than 2200 patients with moderate to severe pain due to PHN, patients receiving gabapentin at a daily dose of 1200 mg or higher daily were more likely to report benefit (at least 50 percent reduction in pain intensity or "very much improved" pain) than those receiving placebo (32 versus 17 percent) [49].



Gabapentin is generally well tolerated. In a pooled analysis of adverse effects including 37 trials for multiple types of neuropathic pain, patients were more likely to discontinue gabapentin than placebo due to adverse effects (11 versus 8 percent) [49]. The most common adverse effects reported were somnolence or drowsiness (14 versus 5 percent), dizziness (19 versus 7 percent), peripheral edema (7 versus 2 percent), and ataxia or gait disturbance (14 versus 3 percent). The rate of serious adverse effects was 3 percent for both groups.


●Pregabalin − The immediate-release formulation of pregabalin is given two or three times daily. Our titration regimen based on effect and tolerability is:

•75 mg twice daily for one week, then
•150 mg twice daily for one to three weeks, then
•300 mg twice daily

An extended-release preparation is also available for once-daily dosing. The titration schedule is the same used for the immediate-release formulation; however, the starting dose is 165 mg daily and the maximum dose is 660 mg daily.

When stopping the drug, pregabalin should be tapered over a week to reduce the risk of withdrawal symptoms [50].

Adjustment for kidney impairment is required for both the immediate- and extended-release formulations; the extended-release formulation is not recommended for patients with severe kidney impairment (eg, creatinine clearance <30 mL/minute). Pregabalin is designated as a schedule V controlled substance in the United States because it has been reported to cause euphoria.

A systematic review of pregabalin for neuropathic pain identified eight trials including more than 2300 patients with PHN [51]. In the meta-analysis of 732 patients in four trials of patients with PHN, a dose response and significant reduction in pain (at least 50 percent) was more likely for patients receiving pregabalin than those receiving placebo: 150 mg (24 versus 13 percent), 300 mg (32 versus 13 percent), and 600 mg (41 versus 15 percent). Common side effects associated with pregabalin dosing included somnolence (300 mg, 16 percent; 600 mg, 25 percent) and dizziness (300 mg, 29 percent; 600 mg, 35 percent). Other side effects are dry mouth, peripheral edema, and weight gain.

Tricyclic antidepressants if gabapentinoids ineffective or not tolerated — For patients who do not tolerate or respond to a gabapentinoid, we suggest a TCA. They are frequently used for depression or other types of neuropathic pain and are also effective for PHN but have a lower tolerability than gabapentinoids [52,53]. For most patients using a TCA, we typically start with amitriptyline; however, nortriptyline or desipramine may be preferred for patients at risk for anticholinergic symptoms and those with adverse effects from amitriptyline.

●Amitriptyline is started at 10 mg each night. The dose may be uptitrated as needed and tolerated over four weeks up to a dose of 50 mg each night. For patients who report minimal or no relief after one month at 50 mg, we switch to an alternative agent (see 'Alternative therapies' below). For those who report partial but inadequate relief at a dose of 50 mg, the dose may be further uptitrated every four weeks up to a maximum daily dose of 150 mg, monitoring for adverse effects.

●Nortriptyline is typically started at 10 mg each night and increased by 10 to 20 mg each week to effect as tolerated, with a maximum daily dose of 150 mg.

●Desipramine is typically started at 25 mg each night and increased by 25 mg each week to effect as tolerated, with a maximum daily dose of 150 mg.

TCAs inhibit the reuptake of norepinephrine and serotonin in the central nervous system. They are thought to increase the inhibition of nociceptive signals from the periphery [54,55].

Anticholinergic side effects (principally sedation and dry mouth) limit the tolerability of TCAs (table 1) [56]. Because of their anticholinergic effects, TCAs should be used cautiously in older patients, particularly those with cognitive impairment or dementia. We also avoid TCAs in patients with heart disease, epilepsy, or glaucoma. Adverse effects may be reduced by using a slow titration; however, delayed onset of efficacy (up to three weeks) before TCAs begin to reduce pain may lead to premature discontinuation. A treatment trial of at least one month at a target dose may be needed to assess the efficacy of TCAs. In one study, symptom relief correlated with serum levels of amitriptyline and active metabolites [57]. Patients who reported no benefit despite serum levels of 100 ng/mL for at least three weeks were considered to have failed TCA therapy.

A 2015 systematic review found moderate-quality evidence supporting the efficacy of TCAs for PHN [43]. Efficacy among TCAs is best established for amitriptyline, which was found effective in producing at least moderate pain relief in multiple short-term studies, typically at doses of 65 to 75 mg daily [57,58]. Nortriptyline was better tolerated than amitriptyline in a small crossover trial of 33 patients with PHN [59]. Approximately two-thirds of patients reported a good response with either medication, but adverse effects leading to discontinuation were more common with amitriptyline than nortriptyline (48 versus 30 percent). The small study size limits generalizability of these results. Desipramine appears to have the fewest side effects of the first-generation TCAs and was effective for PHN in a small trial at mean dose 165 mg per day [60,61]. Almost half reported good response with desipramine. However, methodologic criticisms of this trial limit the certainty of these conclusions [62].

Topical therapy for patients with milder symptoms — For patients with mild to moderate and localized pain and for those who prefer a topical agent, we suggest capsaicin. We switch to lidocaine patches for those who do not tolerate capsaicin.

●Capsaicin – Capsaicin is formulated as a cream, gel, lotion, or a high-concentration patch.

We use capsaicin cream (0.025 to 0.075%) for most patients with PHN and reserve the high-concentration capsaicin (8%) patch for selected patients with partial response to capsaicin cream who prefer a longer acting formulation.

•Capsaicin cream may be applied to the affected area up to four times each day.

•High-concentration capsaicin patches are administered as a single 60-minute application. The application may be repeated after three months. It must be administered by a health care professional, and patients are monitored for up to two hours after treatment. To manage local pain from capsaicin application, the skin is usually pretreated with a local anesthetic such as topical lidocaine, and some studies also used post-treatment oral analgesics such as oxycodone for up to five days [63]. Further study is needed to confirm long-term effectiveness and tolerance of the high-concentration capsaicin patch.

Limited data suggest that topical application of standard-concentration capsaicin is effective for PHN [41]. In one small trial, 143 patients with PHN assigned to capsaicin cream (0.075%) four times per day for six weeks were likelier to report significant pain relief than those assigned to placebo (21 versus 6 percent) [64]. The rate of adverse skin reactions was similar in patients receiving capsaicin and placebo.

A 2013 systematic review identified four randomized controlled trials that evaluated 1272 subjects with PHN treated with one application of either high-concentration capsaicin patch or standard-concentration capsaicin. The only common endpoint reported by all four trials, a ≥30 percent pain intensity reduction at eight weeks compared with baseline, was significantly greater for high-concentration capsaicin patch (43 versus 34 percent; relative benefit 1.3, 95% CI 1.1-1.5) [65].

High-concentration capsaicin patches are approved by the FDA for the treatment of PHN. However, capsaicin can cause burning, stinging, and erythema, making it difficult to achieve true blinding in clinical studies. In practice, application of capsaicin is intolerable in up to one-third of patients.

●Lidocaine — Lidocaine patches (5%) may provide short term relief for PHN. Up to 3 patches may be applied over the affected area for up to 12 hours daily.

Data from small trials and open-label studies suggest that topical lidocaine (5 percent) may be beneficial for pain relief in patients with PHN [66]. Lidocaine patches have been approved by the FDA for PHN. However, a 2014 systematic review of topical lidocaine for neuropathic pain (including 280 patients with PHN) found only very low quality evidence of efficacy of topical lidocaine due to small numbers, incomplete outcome assessments, and modest outcome measures of efficacy [67].

Alternative therapies — For patients who do not tolerate or are unresponsive to initial therapy, we switch to an alternative agent (algorithm 1). For patients with a partial but suboptimal response with initial therapy, we use combination therapy by adding an alternative agent. We use patient preferences and medical comorbidities to help select among options.

Antiseizure medications — A trial of one of a (non-gabapentinoid) anticonvulsant agent may be useful for some patients who do not respond to or cannot tolerate initial medication options. Treatment decisions should be individualized based on patient characteristics, medical comorbidities, side effects, and drug interactions. The benefit of anticonvulsants is based in part on their efficacy in other neuropathic pain conditions such as trigeminal neuralgia and diabetic neuropathy and also on low-quality and anecdotal evidence for PHN. Options and typical target daily doses for PHN include:

●Valproic acid 500 to 1000 mg daily
●Carbamazepine 200 to 1200 mg daily
●Oxcarbazepine 600 to 1200 mg daily
●Lamotrigine 100 to 300 mg daily


The dosing, titration, and monitoring of these agents for PHN is similar to regimens used in trigeminal neuralgia and typically lower doses than those to achieve anticonvulsant effects. (See "Trigeminal neuralgia", section on 'Medical treatment'.)

In an eight-week trial of 48 patients with PHN, patients assigned to divalproex sodium (1000 mg per day) were likelier to report at least moderate improvement in pain than those assigned to placebo (58 versus 15 percent) [68]. Results of small trials of valproic acid in other neuropathic pain conditions were mixed [69]. In short-term trials in patients with trigeminal neuralgia, both carbamazepine and oxcarbazepine reduced pain more than placebo, but neither drug was tested in patients with PHN [70,71]. Lamotrigine may be better tolerated than carbamazepine but has not been studied extensively for neuropathic pain.

Serotonin-norepinephrine reuptake inhibitors — Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be useful for some patients with PHN based on efficacy data for painful polyneuropathy [43]. These medications may be useful for patients with comorbid depression. We use duloxetine or venlafaxine for patients with PHN.

●Duloxetine is typically started at 30 mg daily. Typical daily doses are 60 to 120 mg. The dose may be increased weekly to effect and as tolerated. Adverse effects including nausea, dry mouth, dizziness, and insomnia are more common at higher doses.

●Venlafaxine may be started at 75 mg daily and increased every two weeks to effect as tolerated. Typical daily doses are 150 to 225 mg. Venlafaxine should be used with caution in patients with glaucoma and in those taking anticoagulants. Common adverse effects include nausea, dizziness, and somnolence.

The initial titration and administration of SNRIs are presented in greater detail separately. (See "Serotonin-norepinephrine reuptake inhibitors: Pharmacology, administration, and side effects".)

The effectiveness of SNRIs such as duloxetine and venlafaxine for patients with PHN is based on data for those with other types of neuropathic pain. A systematic review of eight trials and including 4084 patients found that duloxetine was beneficial for patients with painful diabetic neuropathy [72]. Venlafaxine was found to be effective in a short-term trial of 244 patients with painful diabetic polyneuropathy [73]. Patients assigned venlafaxine at 150 to 225 mg were likelier to report at least 50 percent pain reduction than those assigned placebo (50 versus 27 percent). However, a 2015 systematic review of six trials including 460 patients with neuropathic pain found only low-quality data of modest efficacy for venlafaxine [74]. The efficacy of SNRIs for diabetic neuropathy is presented in greater detail separately. (See "Management of diabetic neuropathy", section on 'Administration and efficacy'.)

Adjunctive options — For patients with symptoms refractory to prior therapies, adjunctive options and other interventional therapies such as botulinum toxin injections may be tried or added (algorithm 1). These include oral or transdermal opioid analgesics and intrathecal glucocorticoid injections. The selection of these agents depends on individual patient preferences and comorbidities.

Opioids — Opioids may be beneficial for selected patients with intractable pain during the titration of initial or alternative therapies. They can be administered simultaneously for short-term relief along with the nonopioid agents. They should be initiated at low doses if used and titrated to provide relief while awaiting benefit from nonopioid treatments, at which point opioids should be tapered off.

Opioids are available in short- or long-acting formulations (table 2 and table 3). We start with short-acting options for opioid-naïve patients and use the lowest effective dose. The strategies for initiation and chronic use of opioids for patients with PHN is similar to that of other patients with noncancer pain and is discussed in greater detail separately. (See "Use of opioids in the management of chronic non-cancer pain".)

Small trials support the efficacy of opioid analgesics for PHN [75-79]. In one crossover trial involving 76 patients with PHN, treatment with morphine (mean daily dose 91 mg) or methadone (mean daily dose 15 mg) or a TCA for eight weeks was more effective than placebo [77]. There was a trend toward greater pain relief with opioids, but certainty with these results is limited by small sample size.

The use of opioids for chronic PHN should be avoided. Opioids for chronic noncancer pain remains controversial due to the risk of physical dependence, tolerance, addiction, and overdose. Because of these risks, opioids are regarded as third-line treatment options and typically reserved for short-term, adjunctive use for PHN [38,43,80]. Available trials of opioids for neuropathic pain including PHN do not address the issues of abuse and addiction [81]. Pharmacovigilance is essential to using opioids in any population (table 4). (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment".)

Neuraxial glucocorticoid infusion — Intrathecal glucocorticoid injections may be beneficial for patients who continue to have intractable pain despite initial or alternative therapies. These injections are not useful for pain in the distribution of the trigeminal nerve.

Intrathecal glucocorticoids for PHN are typically given as a single course of weekly injections over four weeks [82]. Techniques for intrathecal glucocorticoid infusion are discussed in greater detail separately. (See "Spinal anesthesia: Technique".)

Intrathecal glucocorticoid injections are associated with an uncertain but probably low risk of serious adverse events, including aseptic meningitis, transverse myelitis, cauda equina syndrome, lumbar radiculitis, headache, urinary retention, and arachnoiditis [83,84].

Some [40,82,85] but not all [86] studies have found a benefit with intrathecal methylprednisolone infusions for patients with PHN. The largest trial evaluated 277 patients with intractable PHN who were assigned to one of three treatment groups: intrathecal methylprednisolone plus lidocaine once per week for four weeks, intrathecal lidocaine alone once per week for four weeks, or no treatment [82]. More than 90 percent of patients in the methylprednisolone group reported excellent or good pain relief both at four weeks compared with 6 and 4 percent in the lidocaine and no treatment groups, respectively. These results were sustained at two-year follow-up. There were no serious adverse events associated with the injection.

Intrathecal administration of methylprednisolone was found more effective than administration in the epidural space in a small trial of 25 patients with PHN [85].

Therapies for refractory symptoms — We reserve other interventional and surgical approaches such as botulinum toxin injections, cryotherapy, and neuromodulation for patients with refractory symptoms who do not respond to other therapies (algorithm 1). The benefit of such therapies has been shown in small trials and observational studies; larger studies are needed to better define their role for patients with PHN.

Botulinum toxin — Botulinum toxin injection for PHN is not extensively studied, but evidence from observational studies and small trials suggests it is effective [87-90]. One trial evaluated 30 adults with PHN who had persistent pain for at least three months [87]. Patients assigned to botulinum toxin type A (onabotulinumtoxinA) injections were likelier to achieve ≥50 percent pain reduction at two weeks compared with those who received placebo injections (13 of 15 patients [87 percent] versus none of 15). The benefit persisted for a median of 16 weeks. In a comparative study of 60 patients with PHN, patients who received onabotulinumtoxinA injection reported a greater pain reduction at seven days when rated on the visual analog scale compared with those who received lidocaine injections (4.5 versus 2.6 points) [88]. These findings were sustained at three months. Improvement in sleep and reduction in opiate use were also reported in the botulinum toxin group.

Botulinum toxin injections should be performed by a clinician experienced with this treatment [91-93]. No safety concerns were identified in small studies [87,88]. However, botulinum toxin may cause localized or systemic adverse effects including bruising, weakness, pain, or headache and may be contraindicated for some patients. Larger and longer-term studies would be helpful to further clarify the safety and efficacy on this treatment in PHN.

Neuromodulation and nerve stimulation — Invasive neuromodulatory strategies such as spinal cord stimulation and peripheral nerve stimulation are considered experimental. These techniques target peripheral nerves and are thought to modulate neuronal signaling or inflammatory processes [94]. Techniques that have shown some benefit for patients with PHN include:

●Transcutaneous electrical nerve stimulation (TENS) [95]
●Pulsed radiofrequency [96-100]
●Spinal cord stimulation [101,102]

These techniques been reported to be effective in approximately half of patients in case reports and case series [103]. They should be performed by experienced clinicians and in centers with expertise.

Cognitive and behavioral therapies — Some patients with PHN achieve only partial relief even with combination pharmacotherapy. For other patients, the efficacy of pharmacotherapy is limited by adverse effects. Nonpharmacologic approaches, including cognitive-behavioral therapy (CBT), may be useful for some patients with refractory PHN pain or associated impairment in mood, sleep, or other quality-of-life domains [104,105]. In a small trial of 40 patients with PHN treated with pregabalin, patients who were assigned to also receive CBT reported a greater improvement in pain intensity and mood symptoms than those assigned to pregabalin alone [106]. Cognitive and behavioral therapies for the treatment of chronic pain are discussed in detail separately. (See "Approach to the management of chronic non-cancer pain in adults", section on 'Psychological therapy'.)

Therapies of uncertain or limited benefit

●NMDA receptor antagonists – Animal data suggest a role for excitatory amino acid neurotransmitters in the maintenance of chronic pain due to nerve injury [107,108]. Antagonists of the N-methyl-D-aspartate (NMDA) receptor have been shown to relieve neuropathic pain in humans [109].

The most widely available NMDA receptor antagonists are ketamine and dextromethorphan. Intravenous ketamine induces modest pain relief in patients with PHN but at doses that cause sedation, dysphoria, and dissociative episodes [110]. In a crossover trial, pain relief after six weeks was similar in those taking dextromethorphan or placebo [111].

●Intravenous lidocaine – Small trials have failed to find sustained benefit of intravenous lidocaine compared with placebo in patients with PHN [40,112]. Any temporary changes in pain measured immediately after infusion do not appear to be sustained by four weeks [40,112-116].

The role of topical lidocaine for PHN is discussed separately. (See 'Topical therapy for patients with milder symptoms' above.)

●Surgical ablation and other interventional procedures – Cryotherapy is an ablation technique that involves freezing peripheral nerves. A small, unblinded study of cryotherapy for facial pain failed to show a significant benefit in patients with PHN [117]. The authors did not provide inclusion criteria, concomitant therapies, or information on how the response was assessed. By contrast, a second trial reported "considerable" relief in 11 of 14 patients with cryotherapy to the intercostal nerves for PHN [118]. In most cases, however, the duration of relief was less than two weeks as assessed by questionnaire.

Surgical interventions including central electrical stimulation of the thalamus, ablation by anterolateral cordotomy, and electrocoagulation of the dorsal root carry substantial risks of permanent neurologic deficits. A systematic review of surgical procedures for patients with refractory PHN reported the pain reduction with surgical ablation procedures was frequently accompanied by serious complications including neuromuscular weakness [119].

●Simple analgesics – Analgesic medications such as aspirin or other nonsteroidal anti-inflammatory drugs are of limited value in patients with either acute herpetic neuralgia or PHN [38,120].

帶狀泡疹(皰疹)神經痛 1. Postherpetic Neuralgia-StatPerls

2023-09-16 中午 12:01
資料來源 Postherpetic Neuralgia-StatPearls [Internet].
(在uptodate上面關於 PHN的治療內容太龐大,另外寫一篇筆記(帶狀泡疹(皰疹)神經痛 2. Postherpetic Neuralgia from Uptodate)

下面中文是google翻譯

簡介
帶狀皰疹後神經痛 (PHN) 是水痘帶狀皰疹病毒 (VZV) 重新激活（也稱為人類皰疹病毒 3 (HHV-3)）最常見的長期並發症。[1] [2]這種休眠 VZV 的重新激活稱為帶狀皰疹或帶狀皰疹。VZV 是兒童水痘（俗稱水痘）的病原體。在 20 世紀 90 年代末和 2000 年代初疫苗接種出現之前，超過 90% 的美國成年人的水痘帶狀皰疹病毒血清檢測呈陽性。[3]雖然在下一代中繼續患帶狀皰疹和 PHN 的成年人數量和百分比可能會減少，但 PHN 目前是一個具有臨床重要性的話題。

PHN 的標誌是單側皮節模式的刀割樣/燒灼樣疼痛，這種疼痛在帶狀皰疹 (HZ) 爆發後持續三個月或更長時間。[4] HZ 的兩個普遍接受的危險因素是年齡增長和免疫抑制，並且由於 HZ 是 PHN 發生的先決條件，因此老年人和體弱者通常受到影響。[2]最成功的治療是多模式的，一些研究人員/臨床醫生專注於高危人群的預防而不是治療，因為 PHN 在本已脆弱的患者群體中具有使人衰弱且往往難治的性質。[5]



病原學
VZV 是一種雙鏈 DNA 病毒。水痘發作消退後（通常在青年時期），它會在某些外周和中樞神經的神經節中休眠，宿主的免疫系統會消滅體內大部分部位的病毒。[2]年齡增長加上免疫能力下降，通常伴隨著心理或身體壓力，可能會導致休眠/潛伏的 VZV 重新激活為帶狀皰疹。[2]病毒複製並沿著軸突傳播，直到到達皮膚，出現水皰、紅斑和局部炎症。[1]



流行病學
帶狀皰疹後神經痛發生在患有急性帶狀皰疹發作的人群中。急性帶狀皰疹發作進展為 PHN 的明確危險因素包括年齡、嚴重的免疫抑制、前驅期的存在、帶狀皰疹爆發期間的劇烈疼痛、異常性疼痛、眼部受累和糖尿病。[3]

2016 年發表的一項針對 PHN 發生危險因素的薈萃分析指出，年齡大於或等於 50 歲的帶狀皰疹患者中約有 13% 會發生 PHN。[3]發病率隨著年齡的增長而增加，這強調了免疫能力的重要性，因為帶狀皰疹患者可能已經存在細胞介導的免疫力下降。年齡增長與 PHN 之間存在顯著關聯。[6]根據一些研究，60歲時，約60%的帶狀皰疹患者會出現帶狀皰疹後神經痛，70歲時，這一比例上升至75%。

帶狀皰疹發病後1個月，9%至14.3%的患者出現帶狀皰疹後神經痛，三個月後，這一比例變為5%。一年後，3% 的患者仍然感到劇烈疼痛。

家族史也被認為是帶狀皰疹的危險因素。Hicks 等人在一項由 504 名患者和 523 名對照者組成的病例對照研究中發現，患者的血親比對照組更容易患帶狀皰疹（39% vs. 11%，p < . 001）。此外，在多個血親患有帶狀皰疹的患者中，這種風險比單個血親患有帶狀皰疹的患者更顯著。[7]

冰島的一項研究報告了不同年齡組的帶狀皰疹後神經痛風險的差異。50歲以下的患者在任何時候都沒有發現劇烈疼痛。在 60 歲以上的患者中觀察到嚴重疼痛：發病後 1 個月內有 6% 的患者出現劇烈疼痛，3 個月內有 4% 的患者出現嚴重疼痛。[8]

帶狀皰疹後神經痛沒有性別差異。



病理生理學
將自限性帶狀皰疹爆發與帶狀皰疹後神經痛區分開來的確切生理學尚不完全清楚。對 PHN 患者相關外周和中樞神經組織的組織學檢查顯示，在某些情況下，髓磷脂和軸突缺乏以及背角萎縮。[9]一項研究比較了患有 PHN 的患者和患有自限性帶狀皰疹的患者之間表皮軸突密度的差異。[10]在大多數情況下，患有 PHN 的人相關皮區的軸突比非患者少得多。[10]因此，解剖結構紊亂可能至少是 PHN 發生的部分原因。一些人認為，神經元水平上不受控制的炎症反應是 PHN 最終發展的主要原因，特別是通過減少中樞介導的傷害性輸入抑制以及通過受損的傷害性感受器促進外周敏化。[11]


病史和體格 與
其他神經病不同，帶狀皰疹後神經痛的診斷相對簡單，而不是排除性的。[11]如前所述，帶狀皰疹發作是 PHN 的先決條件。因此，可以建立皮節型水皰皮疹病史。很少會發現特徵性皮疹。[12]皮疹區域或附近的持續（超過或等於 3 個月）刺痛/燒灼痛、異常性疼痛、感覺異常、瘙癢、感覺遲鈍和/或痛覺過敏是 PHN 的特徵。[11]

帶狀皰疹可以在亞臨床狀態下重新激活，但不會出現皮疹。[13]這種情況稱為帶狀皰疹，比較複雜。它在多個層面影響中樞神經系統，並引起顱神經病、脊髓炎、多發性神經炎或無菌性腦膜炎。[14]

帶狀皰疹後神經痛患者的體格檢查可能會揭示以下信息： 先前帶狀皰疹區域的皮膚疤痕證據 受
影響區域的感覺改變，要么過敏，要么感覺減退
疼痛是由非傷害性刺激產生的，例如輕觸，稱為異常性疼痛
自主功能障礙，例如相關區域出汗過多

評估
帶狀皰疹後神經痛幾乎都是根據病史和體格診斷的。然而，實驗室測試和一些有針對性的成像可能會提供一定程度的實用性。它們對於 PHN 的非典型表現（如帶狀皰疹或喉部帶狀皰疹）具有更大的價值。儘管敏感性和特異性不太理想，但可以進行 VZV IgG 和 IgM 滴度的血清學檢測。四倍的上升已用於診斷亞臨床帶狀皰疹（帶狀皰疹）。然而，這種滴度的上升可能是也可能不是繼發於病毒暴露或重新激活。相比之下，囊泡刮片的免疫熒光以高度特異性和靈敏的方式檢測 VZV 抗原。同樣，PCR 對於 VZV DNA 的檢測也非常敏感。[15]

61% 的患者腦脊液 (CSF) 分析結果異常。通常可以看到細胞增多、蛋白質升高和水痘帶狀皰疹病毒 (VZV) DNA。病毒培養或免疫熒光染色有助於區分單純皰疹和帶狀皰疹。

小規模研究表明，磁共振成像 (MRI) 可能有望用於診斷具有挑戰性的 PHN 病例並區分 PHN 和 HZ。Haanpaa 等人的一項研究。報導稱，MRI 顯示 9 名患者 (56%) 的頸髓和腦幹有 HZ 病變。帶狀皰疹發病後三個月，5 名 MRI 異常的患者 (56%) 出現 PHN。在 MRI 上，七名沒有帶狀皰疹病變的患者沒有出現殘餘疼痛。[16]



治療/管理
帶狀皰疹後神經痛可考慮三種基本治療方法。第一個是預防，重點是識別有感染帶狀皰疹風險的人群並接種疫苗。第二是早期識別和治療急性帶狀皰疹感染，因為延遲可能會增加發生帶狀皰疹病毒性神經炎的機會。第三種方法是通過多模式藥物治療和介入治療進行 PHN 症狀管理。關於這些方法有效性的證據多種多樣，但正在迅速發展，並且某些方法似乎比其他方法更成功。許多人主張預防，因為 PHN 一旦建立，可能難以治療，儘管採用多模式治療，仍有大量患者只能暫時和/或適度減輕症狀嚴重程度。[17]

由於多種原因，PHN 很難治療。症狀完全緩解的情況很少見。2014 年的一項研究得出結論，不到一半的 PHN 患者症狀得到顯著減輕。[5]患者群體通常年老體弱，患有多種合併症。因此，干預措施的副作用特徵變得更加重要。[4]比較治療方法及其結果的相關研究通常設計得不夠理想。沒有一種更好的治療方案；然而，專家共識表明多模式治療可能是最好的方法。最後，許多提倡的方法通常治療慢性神經性疼痛，而不是針對 PHN。

傳統的非侵入性治療包括口服藥物和局部藥物。美國神經病學學會(AAN)、神經性疼痛特別興趣小組(NeuPSIG) 和歐洲神經學會聯合會(EFNS) 均推薦口服三環類抗抑鬱藥(TCA)、普瑞巴林和5% 利多卡因貼劑作為一線藥物療法。[18]必須考慮 TCA 的抗膽鹼能、抗組胺能和 α 受體阻斷副作用，因為老年人更容易受到影響。[19]因此，最初開具加巴噴丁類藥物並滴定是很常見的，請記住，腎功能下降的患者應以較低劑量開始，並更緩慢地增加滴定。儘管缺乏令人信服的證據支持這種策略，但一些臨床醫生將加巴噴丁和普瑞巴林結合使用。使用阿片類藥物來對抗 PHN 是有爭議的，因為關於什麼構成適當使用的情況正在發生變化，而且考慮到濫用、成癮和死亡率的流行，政府對其管理重新產生了興趣。[20]上述三個醫學會推薦阿片類藥物作為一線或二線治療，這強調了此類藥物的減輕疼痛的能力。[21]

還有其他幾種藥理學方式需要考慮。多項研究已證實 5% 利多卡因貼劑的短期和長期療效。[22]該貼劑還有一個額外的好處，即副作用小，主要限於應用部位反應。貼劑和乳膏配方中的辣椒素製劑也可用，但不像利多卡因貼劑那樣得到充分研究。[19] [23]停止使用辣椒素治療的主要原因是施用部位的疼痛和刺激，幾乎所有使用者都會遭受這種疼痛，其程度與辣椒素濃度成比例。該霜的辣椒素濃度較低，需要全天多次塗抹才能達到治療效果。相反，辣椒素貼劑的配方為 8%，只需一次塗抹即可提供治療劑量。[24]然而，通常需要在應用部位使用口服鎮痛藥和局部麻醉劑進行預處理，以避免疼痛刺激。總體疼痛減輕程度一般低於利多卡因5%貼劑。然而，令人鼓舞的病例報告和其他文獻表明，干預措施值得考慮和進一步研究。

其他藥物類別包括非 TCA 抗抑鬱藥和 NMDA 拮抗劑，但支持其有用性的證據有限。例如，涉及SNRI（5-羥色胺-去甲腎上腺素再攝取抑製劑）和SSRI（選擇性5-羥色胺再攝取抑製劑）的大型研究並未顯示出比TCA 更好的結果，並且這兩類藥物都具有相關副作用，儘管通常不如TCA 嚴重。[19]最近氯胺酮輸注診所的激增以及用於治療從神經性疼痛到抑鬱症等多種疾病的相關研究也引起了人們對 NMDA 拮抗劑在治療 PHN 中的作用的新興趣。[25]

有傳聞稱氯胺酮可能有益，一些小型研究也支持這一發現，但長期數據和大規模研究尚不存在。利多卡因輸注也已被考慮。1999 年的一項雙盲研究表明，靜脈注射利多卡因可為 PHN 患者提供具有臨床意義的短期疼痛緩解。[26]一般來說，小型研究和病例報告已經證實，新療法與其他輔助療法相結合可能對某些 PHN 患者有用。PHN 的病理生理學很複雜，有時個體化的非傳統方法可能對特定患者有益。

侵入性療法包括肉毒桿菌毒素注射、局部麻醉劑交感神經阻滯、硬膜外/鞘內註射和脊髓刺激。肉毒桿菌注射操作簡單且副作用有限。[27]然而，需要進行更多的研究來評估其功效。提到的其他侵入性療法可能會帶來顯著的圍手術期風險和/或副作用。根據病例報告，硬膜外類固醇注射和神經調節（脊髓和周圍神經刺激）產生的結果好壞參半，但很有趣，前者充其量只能帶來有限的短期改善，而後者有時會導致長期症狀完全緩解。 。最近開發的用於治療局灶性皮節神經病理性疼痛的背根神經節刺激器理論上對於 PHN 來說是有希望的。2008 年來自中國的一項研究表明，CT 引導下的背根神經節射頻消融術可能會顯著減輕 PHN 的症狀，有時甚至完全消融。但樣本量較小，該技術可能導致氣胸，且缺乏重複研究。鞘內給藥也顯示出前景。2000 年的一項 270 人參與的研究調查了鞘內註射甲基潑尼松龍和利多卡因治療 PHN，通過兩年的隨訪，對 90% 的患者產生了顯著的鎮痛效果。



鑑別診斷
神經性疼痛是一個總稱，描述了許多疾病和病症常見的疼痛類型。然而，先前帶狀皰疹皮疹區域或附近的皮節模式中的單側神經性疼痛對於帶狀皰疹後神經痛具有高度特異性。然而，在極少數情況下應考慮其他神經性疾病。例如，至少有一例 CRPS 影響三個月前受帶狀皰疹感染的皮節的病例報告。神經性疼痛的位置將有助於做出鑑別診斷；如果出現在面部，則可能考慮三叉神經痛和貝爾麻痺。胸部皮區看似 PHN 的情況很少見，可能是闌尾炎、膽石症或結腸炎。[28]在 PHN 診斷不清楚的特殊情況下，VZV 血清學研究可能會有所幫助。



預後
帶狀皰疹後神經痛的治療具有挑戰性。症狀可能持續數年，有時甚至一生。隨著成人疫苗接種和新開發的非活疫苗配方的出現，預防成為大多數易感美國人群的現實目標。[3]當無法預防帶狀皰疹時，建議及時治療，因為疼痛的持續時間和嚴重程度被認為是 PHN 的危險因素。不幸的是，一旦出現 PHN，保守的一線治療很少能解決症狀，並且不能提供持久的緩解。因此，應考慮專家共識推薦的多模式治療方法。有限但發人深省的證據表明，某些非常規技術，無論是侵入性還是非侵入性，都是有希望的，值得進一步研究。

並發症
根據帶狀皰疹後神經痛的持續時間和疼痛程度，患者可能會出現以下並發症：抑鬱、疲勞、睡眠
不安
、
食慾不振、
注意力不集中、


威懾和患者教育，
預防的主要措施是接種帶狀皰疹病毒疫苗。[3] 2005年《NEJM》發表的一項大型（n = 38,000）雙盲研究表明，老年人接種疫苗可將帶狀皰疹的發病率降低51%，PHN的發病率降低66%。此外，即使在患有 PHN 的人中，疾病負擔也減少了約 61%。必須注意的是，疫苗接種的增強免疫效果並不持久，需要間隔重新接種以維持其功效。[3]此外，目前的疫苗配方是減毒活病毒，理論上能夠在免疫功能低下的個體中引起感染，因此限制了其在該人群中的使用。[3]然而，2017 年底，FDA 諮詢委員會批准了一種亞單位非活疫苗在美國用於50 歲以上的個體。它可用於免疫功能低下的個體，並針對帶狀皰疹和帶狀皰疹病毒提供更好的保護在所有患者群體中，其感染率均高於原始減毒活病毒。對高危人群進行預防性疫苗接種可能最終被證明是解決與 PHN 相關的重大發病率的最安全、最有效的方法。

另一種方法是嘗試阻止帶狀皰疹進展為帶狀皰疹後遺症（PHN），但要認識到帶狀皰疹發作的嚴重程度是帶狀皰疹後遺症（PHN）的危險因素。不幸的是，支持該技術的現有證據絕不是可靠的，並且現有的調查研究針對所討論的終點進行了次優設計。因此，雖然抗病毒藥物、糖皮質激素給藥和/或侵入性操作在某些情況下可能會降低帶狀皰疹發作的嚴重程度，但沒有明確的證據表明這些方法單獨或聯合使用可以降低PHN 的發生率。需要更高質量的研究來確定明確的立場。

提高醫療團隊的成果
考慮到帶狀皰疹後神經痛治療難度大且結果多變，預防至關重要。因此，初級保健醫生和老年病學家的任務是為高危人群接種疫苗。當預防措施失敗或從未採取時，應諮詢具有該病症經驗和多模式治療技術的疼痛管理領域專家。採用跨專業方法來治療帶狀皰疹後神經痛患者是最好的方法
Introduction
Postherpetic neuralgia (PHN) is the most common long-term complication of varicella-zoster virus (VZV) reactivation, also known as human herpesvirus-3 (HHV-3).[1][2] This reactivation of the dormant VZV is known as herpes zoster or shingles. VZV is the causative agent for the childhood condition varicella, colloquially known as chickenpox. Before the advent of vaccination in the late 1990s and early 2000s, upward of 90% of American adults would test seropositive for VZV.[3] Although this number and the percentage of adults who go on to develop herpes zoster and PHN may decrease in the coming generations, PHN is currently a topic of clinical importance.

The hallmark of PHN is a lancinating/burning pain in a unilateral dermatomal pattern that persists for three or more months after the onset of a herpes zoster (HZ) outbreak.[4] Two universally accepted risk factors for HZ are increasing age and immunosuppression, and because HZ is a prerequisite for the development of PHN, the elderly and infirm are commonly afflicted.[2] The most successful treatments are multi-modal, with some researchers/clinicians focusing on prevention in high-risk populations rather than cure because of the debilitating and often refractory nature of PHN in already fragile patient populations.[5]



Etiology
The VZV is a double-stranded DNA virus. It lays dormant in the ganglia of certain peripheral and central nerves after an episode of varicella resolves, generally in youth, with the immune system of the host eradicating the virus in most locations within the body.[2] Advancing age combined with a decrease in immunocompetence, usually accompanied by a psychological or physical stressor, may result in reactivation of the dormant/latent VZV as HZ.[2] The virus replicates and travels down axons until it reaches the skin, where blistering, erythema, and local inflammation occur.[1]



Epidemiology
Postherpetic neuralgia occurs in a subset of the population suffering from an episode of acute HZ. Well-established risk factors for an acute HZ episode progressing to PHN include age, severe immunosuppression, the presence of a prodromal phase, severe pain during zoster outbreak, allodynia, ophthalmic involvement, and diabetes mellitus.[3]

A meta-analysis of the risk factors for the development of PHN published in 2016 noted that approximately 13% of patients older than or equal to 50 years of age with HZ would develop PHN.[3] The incidence increases with advancing age, which underscores the importance of immunocompetence, as a decrease in cell-mediated immunity is likely already present in those with HZ. The association between increasing age and PHN is significant.[6]According to some studies, at age 60, around 60% of patients with shingles develop postherpetic neuralgia, and at age 70, this percentage rises to 75%.

One month after the onset of shingles, 9 to 14.3% of patients develop postherpetic neuralgia, and at three months, this percentage becomes 5%. At one year, 3% of patients continue to have severe pain.

Family history has also been considered a risk factor for herpes zoster. In a case-control study by Hicks et al., comprising 504 patients and 523 controls, it was observed that the blood relatives of patients were more likely to have herpes zoster than the control group (39% vs. 11%, p< .001). Moreover, this risk was more significant in patients with multiple blood relatives having herpes zoster than those with a single blood relative having herpes zoster.[7]

A study from Iceland reported variations in the risk of postherpetic neuralgia associated with various age groups. Patients younger than 50 years were not found to have severe pain at any time. Severe pain was observed in patients older than 60 years: 6% at one month and 4% at three months from the onset.[8]

There is no sex predilection for postherpetic neuralgia.



Pathophysiology
The exact physiology that separates a self-limited zoster outbreak from postherpetic neuralgia is not fully understood. Histological examinations of relevant peripheral and central nervous tissue from sufferers of PHN reveal myelin and axon deficiency and atrophy of the dorsal horn in certain instances.[9] One study compared the difference in epidermal axon densities between patients who suffered from PHN and those who had a self-limited occurrence of HZ.[10] Those afflicted with PHN had, in most instances, far fewer axons in the relevant dermatomes than non-sufferers.[10] Therefore, an anatomical derangement is likely at least partially responsible for the development of PHN. Some suggest that an unchecked inflammatory response at the neuronal level is the main culprit of the eventual development of PHN, specifically via the reduction of centrally-mediated inhibition of nociceptive input and the promotion of peripheral sensitization via damaged nociceptors.[11]


History and Physical
Unlike other neuropathic conditions, the diagnosis of postherpetic neuralgia is relatively straightforward and not one of exclusion.[11] As mentioned, an episode of herpes zoster is a prerequisite for PHN. Therefore, a history of rash with blisters in a dermatomal pattern could be established. Rarely the characteristic rash will not be found.[12] Persistent (more than or equal to 3 months) lancinating/burning pain, allodynia, paresthesias, pruritus, dysesthesias, and/or hyperalgesia at or near the area of the rash is characteristic of PHN.[11]

Herpes zoster can reactivate subclinically with no rash.[13] This condition is called zoster sine herpete and is more complicated. It affects the central nervous system at multiple levels and causes cranial neuropathies, myelitis, polyneuritis, or aseptic meningitis.[14]

Physical examination of a patient with postherpetic neuralgia may reveal the following:Evidence of cutaneous scarring on an area of previous herpes zoster
Altered sensation in the affected areas, either hypersensitivity or hypoesthesia
Pain is produced by non-noxious stimuli, such as a light touch, known as allodynia
Autonomic dysfunction, such as excessive sweating over the involved area

Evaluation
Postherpetic neuralgia is almost universally diagnosed based on history and physical. However, laboratory tests and some targeted imaging may provide a degree of utility. They are of greater value in atypical presentations of PHN, such as zoster sine herpete or herpes zoster of the larynx. Serological testing for VZV IgG and IgM titers is available, although the sensitivity and specificity are less than ideal. A four-fold rise has been used to diagnose subclinical HZ (zoster sine herpete). However, this rising titer may or may not be secondary to viral exposure or reactivation. Comparatively, immunofluorescence of vesicle scrapings detects VZV antigens in a highly specific and sensitive manner. Similarly, PCR is exquisitely sensitive for the detection of VZV DNA.[15]

Results of cerebrospinal fluid (CSF) analysis are abnormal in 61% of patients. Pleocytosis, elevated protein, and varicella-zoster virus (VZV) DNA are usually seen. Viral culture or immunofluorescent staining helps distinguish herpes simplex from herpes zoster.

Small-scale studies suggest that magnetic resonance imaging (MRI) may hold promise for diagnosing challenging PHN cases and differentiating between PHN and HZ. A study by Haanpaa et al. reported that MRI revealed lesions attributable to HZ in the cervical cord and the brain stem in 9 patients (56%). At three months after the onset of HZ, PHN developed in 5 patients (56%) who had an abnormal MRI. On MRI, seven patients with no HZ lesions did not develop residual pain.[16]



Treatment / Management
Three fundamental treatment approaches may be considered for postherpetic neuralgia. The first is prevention, which focuses on identifying populations at risk for contracting HZ and administering a vaccine. The second is early recognition and treatment of an acute HZ infection, as delay may increase the chance of developing PHN. The third approach is symptom management of PHN via multimodal medication regimens and interventional procedures. The evidence regarding the efficacy of these methods is mixed but rapidly evolving, and certain approaches appear to be more successful than others. Prevention is advocated by many because, once established, PHN can be refractory to treatment, with a substantial number of sufferers achieving only a temporary and/or modest reduction in symptom severity despite multimodal therapy.[17]

PHN is notoriously difficult to treat for many reasons. Complete resolution of symptoms is rare. A 2014 study concluded that less than half of patients with PHN achieve significant symptom reduction.[5] The patient population is usually old and frail with multiple comorbidities. Therefore side effect profiles of interventions take on greater importance.[4] Relevant studies comparing treatments and their outcomes are often suboptimally designed. There is no one superior treatment regimen; however, expert consensus suggests that multimodal therapy is likely the best approach. Lastly, many of the advocated approaches treat chronic neuropathic pain in general and are not specific to PHN.

Traditional non-invasive treatments include oral and topical medications. The American Academy of Neurology (AAN), Special Interest Group on Neuropathic Pain (NeuPSIG), and European Federation of Neurological Societies (EFNS) all recommend an oral tricyclic antidepressant (TCA), pregabalin, and the lidocaine 5% patch as first-line therapies.[18] The anticholinergic, antihistaminergic, and alpha receptor-blocking side effects of TCAs must be considered, as the elderly are more susceptible.[19] As a result, it is commonplace to initially prescribe and titrate a gabapentinoid, keeping in mind that patients with reduced renal function should be started at a lower dose and up-titrated more slowly. Some clinicians combine gabapentin and pregabalin despite a lack of compelling evidence that supports this tactic. The use of opioids to combat PHN is controversial because of the changing landscape regarding what constitutes appropriate use and also renewed governmental interest in their administration given the epidemic of abuse, addiction, and mortality.[20] The above three medical societies recommend opioids as either first or second-line treatments, which underscores the pain-reducing capability of this medication class.[21]

There are several other pharmacologic modalities to consider. Multiple studies have confirmed the short and long-term efficacy of the lidocaine 5% patch.[22] This patch also has the additional benefit of a small side effect profile that is mostly limited to application site reactions. Capsaicin preparations in the patch and cream formulations are also available but not as well-studied as the lidocaine patch.[19][23] The leading cause of discontinuing capsaicin treatment is pain and irritation at the application site, suffered by almost all users in proportion to the capsaicin concentration. The cream has a low concentration of capsaicin, requiring multiple applications to achieve a therapeutic effect throughout the day. Conversely, the capsaicin patch is available in an 8% formulation, delivering a therapeutic dose in just one application.[24] However, pre-treatment with oral analgesics and local anesthetic at the application site is often necessary to avoid painful irritation. The degree of overall pain reduction is generally less than the lidocaine 5% patch. Nevertheless, encouraging case reports and other literature suggest the intervention warrants consideration and further study.

Other medication classes include non-TCA antidepressants and NMDA antagonists, but limited evidence supports their usefulness. For example, larger studies involving SNRIs (serotonin-norepinephrine reuptake inhibitors) and SSRIs (selective serotonin reuptake inhibitors) have not shown better outcomes than TCAs, and both classes possess concerning side effect profile, though typically less severe than TCAs.[19] The recent explosion of ketamine infusion clinics and related studies for treating a wide range of ailments, from neuropathic pain to depression, has also resulted in renewed interest in the role of NMDA antagonism in treating PHN.[25]

There are anecdotal reports that ketamine may prove beneficial, and a few small studies support this finding, but long-term data and large-scale studies are non-existent. Lidocaine infusions have also been considered. One double-blind study in 1999 showed that an intravenous lidocaine infusion provided clinically significant short-term pain reduction in patients with PHN.[26] In general, small studies and case reports have established that novel therapies may be useful in certain PHN sufferers when combined with other adjuncts. The pathophysiology of PHN is complex, and sometimes an individualized non-traditional approach may prove beneficial for a particular patient.

Invasive therapies include botulinum toxin injections, sympathetic blockade with local anesthetics, epidural/intrathecal injections, and spinal cord stimulation. Botox injections are simple to perform and have a limited side effect profile.[27] However, more studies need to be conducted to evaluate their efficacy. The other invasive therapies mentioned carry the potential for significant peri-procedural risk and/or side effects. Epidural steroid injections and neuromodulation (both spinal cord and peripheral nerve stimulation) produce mixed results but are intriguing, with the former resulting in limited short-term improvement at best and the latter sometimes resulting in complete long-term symptom resolution, according to case reports. The recent development of the dorsal root ganglion stimulator to treat focal dermatomal neuropathic pain conditions is theoretically promising for PHN. One study originating from China in 2008 suggests that CT-guided radiofrequency ablation of the dorsal root ganglion may result in a significant reduction in symptomatology and sometimes complete resolution of PHN. However, the sample size was small, the technique may cause a pneumothorax, and repeat studies are lacking. Intrathecal medication administration also demonstrates promise. One 270-person study in 2000 investigated the use of intrathecal methylprednisolone with lidocaine for the treatment of PHN, resulting in a significant analgesic effect in ninety percent of patients through two years of follow-up.



Differential Diagnosis
Neuropathic pain is an umbrella term that describes a type of pain common to many diseases and conditions. Nevertheless, unilateral neuropathic pain in a dermatomal pattern at or near the area of a previous HZ rash is highly specific for postherpetic neuralgia. However, there are rare instances where other neuropathic conditions should be considered. For example, there is at least one case report of CRPS affecting dermatomes afflicted by HZ just three months prior. The location of neuropathic pain will assist in the development of a differential diagnosis; if present in the face, trigeminal neuralgia and Bell’s palsy may be considered. What appears to be PHN in the thoracic dermatomes may infrequently be appendicitis, cholelithiasis, or colitis.[28] In the exceptional case where PHN diagnosis is unclear, serological studies for the VZV may be beneficial.



Prognosis
Postherpetic neuralgia is challenging to treat. Symptoms may continue for years, sometimes whole life. With the advent of adult vaccination and the newly developed non-live vaccine formulation, prevention looms as a realistic goal for most of the susceptible American population.[3] When prevention of HZ is not possible, timely treatment is advisable, as duration and severity of pain are considered risk factors for PHN. Unfortunately, once PHN is established, conservative first-line treatment rarely results in symptom resolution and does not offer long-lasting relief. Therefore, multimodal therapeutic approaches recommended by expert consensus should be considered. Limited but thought-provoking evidence suggests that certain unconventional techniques, both invasive and non-invasive, are promising and merit further investigation.

Complications
Depending on the duration of postherpetic neuralgia and how painful it is, the following complications can arise in patients:Depression
Fatigue
Disturbed sleep
Lack of appetite
Impaired concentration


Deterrence and Patient Education
The mainstay of prevention is the vaccination against HZV.[3] A large (n = 38,000) double-blind study published in the NEJM in 2005 showed that vaccination in the elderly reduced the incidence of HZ by 51% and PHN by 66%. Moreover, even among those who developed PHN, the burden of illness was reduced by approximately 61%. It must be noted that the immune-boosting effect of the vaccination is not long-lasting, and interval re-vaccination is necessary to maintain its efficacy.[3] Additionally, the current formulation of the vaccine is a live-attenuated virus, theoretically capable of causing infection in immunocompromised individuals, therefore limiting its use in this population.[3] However, in late 2017, the FDA Advisory Committee approved a subunit, non-live vaccine for use in the United States for individuals over the age of 50. It may be used in immunocompromised individuals and confer greater protection against HZ and PHN than the original live-attenuated virus in all patient populations. Preventative vaccination of at-risk populations may ultimately prove to be the safest and most efficacious approach to addressing the significant morbidity associated with PHN.

The other approach is to attempt to prevent the progression of HZ to PHN, with the understanding that the severity of an HZ episode is a risk factor for PHN. Unfortunately, the available evidence supporting this technique is by no means robust, and existing investigatory studies are suboptimally designed for the endpoint in question. Therefore, while antiviral drugs, glucocorticoid administration, and/or invasive procedures may reduce the severity of an HZ episode in certain instances, there is no clear evidence that these methods, alone or in combination, result in a reduced incidence of PHN. Higher-quality studies are needed for a definitive stance.

Enhancing Healthcare Team Outcomes
Considering that postherpetic neuralgia is difficult to treat and outcomes are variable, prevention is of paramount importance. Therefore, primary care physicians and geriatricians are tasked with administering vaccinations to at-risk populations. When preventative measures fail or are never instituted, experts in the field of pain management who have experience with the condition and multimodal treatment techniques should be consulted. An interprofessional approach to managing patients with postherpetic neuralgia is the best way forward.