Infections are usually self-limiting; however, consider antivirals in all patients, especially those who have severe disease and/or are >50 years of age. Because of a higher risk of HZ-related complications, including postherpetic neuralgia, treatment with antivirals is strongly recommended for immunocompromised patients, especially those living with HIV. Treatment aims are to reduce viral replication, manage pain, and reduce postherpetic neuralgia. The treatment of HZ during pregnancy is the same as for any other HZ patient. Among all antivirals, acyclovir has been most extensively studied among pregnant women and is the most commonly used.
Viral replication reduction
Antivirals are used to reduce viral replication in all patients, especially those who have severe disease, are >50 years of age, are immunocompromised, and/or have evidence of trigeminal nerve involvement. Administration shortens the duration of viral shedding, stops the formation of new lesions, prevents ocular complications, and reduces the severity of pain.[78]Pavan-Langston D. Herpes zoster antivirals and pain management. Opthalmology. 2008 Feb;115(2 Suppl):S13-20.
http://www.ncbi.nlm.nih.gov/pubmed/18243927?tool=bestpractice.com
[79]Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J Med. 1988 Aug 29;85(2A):84-9.
http://www.ncbi.nlm.nih.gov/pubmed/3044099?tool=bestpractice.com
[80]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Jul 15;123(2):89-96.
http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com
[81]Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000 Sep-Oct;9(9):863-9.
http://www.ncbi.nlm.nih.gov/pubmed/11031393?tool=bestpractice.com
[82]Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003 Mar;121(3):386-90.
https://jamanetwork.com/journals/jamaophthalmology/fullarticle/415180
http://www.ncbi.nlm.nih.gov/pubmed/12617710?tool=bestpractice.com
Treatment is usually with orally administered antiviral medicines such as aciclovir, famciclovir, and valaciclovir, and is most effective when started within 72 hours after rash onset. Use intravenous aciclovir in patients who cannot tolerate oral medicines. Topical antivirals are not recommended.
Studies comparing the effects on cutaneous and pain end points between famciclovir and valaciclovir found that there are no differences in the efficacy.[81]Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000 Sep-Oct;9(9):863-9.
http://www.ncbi.nlm.nih.gov/pubmed/11031393?tool=bestpractice.com
[83]Wassilew SW. Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study. J Eur Acad Dermatol Venereol. 2005 Jan;19(1):47-55.
http://www.ncbi.nlm.nih.gov/pubmed/15649191?tool=bestpractice.com
A systematic review of high-quality trials has found that famciclovir and valaciclovir are superior to aciclovir in reducing the likelihood of prolonged pain.[84]McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir Ther. 2012;17(2):255-64.
http://www.ncbi.nlm.nih.gov/pubmed/22300753?tool=bestpractice.com
Some meta-analyses of randomised controlled trials have found that treating HZ patients with antiviral therapy reduces the duration or incidence of prolonged pain.[80]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Jul 15;123(2):89-96.
http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com
[83]Wassilew SW. Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study. J Eur Acad Dermatol Venereol. 2005 Jan;19(1):47-55.
http://www.ncbi.nlm.nih.gov/pubmed/15649191?tool=bestpractice.com
[85]Degreef H; Famciclovir Herpes Zoster Clinical Study Group. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int J Antimicrob Agents. 1994;4(4):241-6.
http://www.ncbi.nlm.nih.gov/pubmed/18611615?tool=bestpractice.com
[86]Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995 Jul;39(7):1546-53.
http://www.ncbi.nlm.nih.gov/pubmed/7492102?tool=bestpractice.com
[87]Wassilew SW, Wutzler P. Oral brivudin in comparison with acyclovir for herpes zoster: a survey study on postherpetic neuralgia. Antiviral Res. 2003 Jun;59(1):57-60.
http://www.ncbi.nlm.nih.gov/pubmed/12834861?tool=bestpractice.com
[88]Huff JC, Drucker JL, Clemmer A, et al. Effect of oral acyclovir on pain resolution in herpes zoster: a reanalysis. J Med Virol. 1993 Jan 1;Suppl 1:93-6.
http://www.ncbi.nlm.nih.gov/pubmed/8245901?tool=bestpractice.com
[89]Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J. 1989 Mar 8;102(863):93-5.
http://www.ncbi.nlm.nih.gov/pubmed/2648213?tool=bestpractice.com
However, others have found contrary results.[90]McKendrick MW, McGill JI, White JE, et al. Oral acyclovir in acute herpes zoster. BMJ. 1986 Dec 13;293(6561):1529-32.
http://www.ncbi.nlm.nih.gov/pubmed/3099943?tool=bestpractice.com
[91]McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on postherpetic neuralgia. BMJ. 1989 Feb 18;298(6671):431.
http://www.ncbi.nlm.nih.gov/pubmed/2495051?tool=bestpractice.com
[92]Wood MJ, Ogan PH, McKendrick MW, et al. Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med. 1988 Aug 29;85(2A):79-83.
http://www.ncbi.nlm.nih.gov/pubmed/3044098?tool=bestpractice.com
Famciclovir, valaciclovir, and aciclovir have been shown to be superior to placebo in reducing the amount of time to complete cessation of pain.[80]Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Jul 15;123(2):89-96.
http://www.ncbi.nlm.nih.gov/pubmed/7778840?tool=bestpractice.com
[86]Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995 Jul;39(7):1546-53.
http://www.ncbi.nlm.nih.gov/pubmed/7492102?tool=bestpractice.com
[93]Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis. 1996 Feb;22(2):341-7.
http://www.ncbi.nlm.nih.gov/pubmed/8838194?tool=bestpractice.com
[94]Jackson JL, Gibbons R, Meyer G, et al. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis. Arch Intern Med. 1997 Apr 28;157(8):909-12.
http://www.ncbi.nlm.nih.gov/pubmed/9129551?tool=bestpractice.com
However, the effect of aciclovir on chronic pain has been less clear in other clinical trials.[91]McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on postherpetic neuralgia. BMJ. 1989 Feb 18;298(6671):431.
http://www.ncbi.nlm.nih.gov/pubmed/2495051?tool=bestpractice.com
[95]Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med. 1996 Sep 1;125(5):376-83.
http://www.ncbi.nlm.nih.gov/pubmed/8702088?tool=bestpractice.com
Immunocompromised patients
HZ infections are more common and often more complicated in immunocompromised patients. The main objective of treatment in these patients is to reduce the incidence of cutaneous and visceral dissemination that can lead to life-threatening complications. It is therefore recommended that immunocompromised patients should promptly receive antiviral therapy within 1 week of rash onset or any time before full crusting of lesions. Treat localised disease with oral valaciclovir, famciclovir, or aciclovir, with close outpatient follow-up. Reserve intravenous aciclovir therapy for patients with disseminated varicella zoster virus infection, ophthalmic involvement, very severe immunosuppression, or the inability to take oral medications.
Pain management
For all patients, analgesics work to reduce pain in the acute phase as well as postherpetic neuralgia, and the type administered will depend on the severity. For mild pain, analgesics such as paracetamol and ibuprofen are appropriate. For severe pain, opioid analgesics are an option. Topically administered lidocaine and nerve blocks have also been reported to be effective.[96]Opstelten W, Zaal MJ. Managing ophthalmic herpes zoster in primary care. BMJ. 2005 Jul 16;331(7509):147-51.
http://www.ncbi.nlm.nih.gov/pubmed/16020856?tool=bestpractice.com
[97]Kumar V, Krone K, Mathieu A. Neuraxial and sympathetic blocks in herpes zoster and postherpetic neuralgia: an appraisal of current evidence. Reg Anesth Pain Med. 2004 Sep-Oct;29(5):454-61.
http://www.ncbi.nlm.nih.gov/pubmed/15372391?tool=bestpractice.com
[98]Wolff RF, Bala MM, Westwood M, et al. 5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review. Acta Neurol Scand. 2011 May;123(5):295-309.
http://www.ncbi.nlm.nih.gov/pubmed/21039364?tool=bestpractice.com
Lotions containing calamine may also be used on open lesions to reduce pain and pruritus.
Postherpetic pain
The most common complication, suspected if pain persists >30 days after rash onset or cutaneous healing. The pain usually presents as a burning sensation or itching. The severity ranges from mild to debilitating.[2]Roxas M. Herpes zoster and postherpetic neuralgia: diagnosis and therapeutic considerations. Altern Med Rev. 2006 Jun;11(2):102-13.
http://www.ncbi.nlm.nih.gov/pubmed/16813460?tool=bestpractice.com
Patients at least 50 years old have an increased risk for complication and for severe pain.[99]Choo PW, Galil K, Donahue JG, et al. Risk factors for postherpetic neuralgia. Arch Intern Med. 1997 Jun 9;157(11):1217-24.
http://www.ncbi.nlm.nih.gov/pubmed/9183233?tool=bestpractice.com
Usually resolves within 6 months; however, patients older than 70 years are at greater risk for longer pain duration.
Treatment is primarily for pain control. Patients with mild-to-moderate pain may be treated with non-steroidal anti-inflammatory drugs or paracetamol, alone or in combination with a weak opioid analgesic.[100]Wu CL, Marsh A, Dworkin RH. The role of sympathetic nerve blocks in herpes zoster and postherpetic neuralgia. Pain. 2000 Aug;87(2):121-9.
http://www.ncbi.nlm.nih.gov/pubmed/10924805?tool=bestpractice.com
[101]Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998 Dec 2;280(21):1837-42.
https://jamanetwork.com/journals/jama/fullarticle/188226
http://www.ncbi.nlm.nih.gov/pubmed/9846778?tool=bestpractice.com
[102]Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology. 1998 Jun;50(6):1837-41.
http://www.ncbi.nlm.nih.gov/pubmed/9633737?tool=bestpractice.com
[103]Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol. 1989 Aug;21(2 Pt 1):265-70.
http://www.ncbi.nlm.nih.gov/pubmed/2768576?tool=bestpractice.com
[104]Galer BS, Rowbotham MC, Perander J, et al. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999 Apr;80(3):533-8.
http://www.ncbi.nlm.nih.gov/pubmed/10342414?tool=bestpractice.com
Topical capsaicin has also been shown to provide pain relief.[105]Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008 Dec;7(12):1106-12.
http://www.ncbi.nlm.nih.gov/pubmed/18977178?tool=bestpractice.com
[106]Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017 Jan 13;(1):CD007393.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007393.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/28085183?tool=bestpractice.com
[107]Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011 Jan;12(1):99-109.
http://www.ncbi.nlm.nih.gov/pubmed/21087403?tool=bestpractice.com
[108]Webster LR, Malan TP, Tuchman MM, et al. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. J Pain. 2010 Oct;11(10):972-82.
http://www.ncbi.nlm.nih.gov/pubmed/20655809?tool=bestpractice.com
For patients with moderate-to-severe pain, a strong opioid analgesic may be considered. Treatment with either a tricyclic antidepressant such as amitriptyline or an anticonvulsant such as gabapentin or pregabalin is also effective.[109]Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005454.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005454.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/17943857?tool=bestpractice.com
[110]Roth TV, van Seventer R, Murphy TK. The effect of pregabalin on pain-related sleep interference in diabetic peripheral neuropathy or postherpetic neuralgia: a review of nine clinical trials. Cur Med Res Op. 2010 Oct;26(10):2411-9.
http://www.ncbi.nlm.nih.gov/pubmed/20812792?tool=bestpractice.com
[111]Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017 Jun 9;(6):CD007938.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007938.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/28597471?tool=bestpractice.com
[112]Semel D, Murphy TK, Zlateva G, et al. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam Pract. 2010 Nov 5;11:85.
https://bmcfampract.biomedcentral.com/articles/10.1186/1471-2296-11-85
http://www.ncbi.nlm.nih.gov/pubmed/21054853?tool=bestpractice.com
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For adults with postherpetic neuralgia, how does pregabalin compare with placebo?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2480/fullShow me the answer
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What are the effects of gabapentin in adults with chronic neuropathic pain?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2525/fullShow me the answer One meta-analysis showed no difference in pain relief between gabapentin and tricyclic antidepressants.[113]Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials. J Gen Intern Med. 2009 Feb;24(2):178-88.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628998
http://www.ncbi.nlm.nih.gov/pubmed/19089502?tool=bestpractice.com
For those intolerant of opioids or at high risk for addiction, one or a combination of anticonvulsants, tricyclic antidepressants, or corticosteroids are appropriate.
There are no standard guidelines on which medication to initially use for treatment.[114]Edelsberg JS, Lord C, Oster G. Systematic review and meta-analysis of efficacy, safety, and tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. Ann Pharmacother. 2011 Dec;45(12):1483-90.
http://www.ncbi.nlm.nih.gov/pubmed/22085778?tool=bestpractice.com
These treatments are given as single agents or in combination depending on the severity of pain and the response to treatment.
Eye involvement
Treatment includes the use of antiviral drugs such as aciclovir, famciclovir, or valaciclovir for 7 to 10 days, preferably started within 72 hours of rash onset. Intravenous aciclovir is given as needed for retinitis. Oral antiviral drugs resolve acute disease and inhibit late inflammatory recurrences.[82]Severson EA, Baratz KH, Hodge DO, et al. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003 Mar;121(3):386-90.
https://jamanetwork.com/journals/jamaophthalmology/fullarticle/415180
http://www.ncbi.nlm.nih.gov/pubmed/12617710?tool=bestpractice.com
[115]Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol. 2001 May;85(5):576-81.
http://www.ncbi.nlm.nih.gov/pubmed/11316720?tool=bestpractice.com
Other treatment includes pain medicines, antibiotic ophthalmic ointment to protect the ocular surface, and topical corticosteroids. Prompt referral to an ophthalmologist is required for all patients who have eye manifestations. Begin antiviral treatment as soon as possible, and before referral.[3]Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007 Jan 1;44 Suppl 1:S1-26.
https://academic.oup.com/cid/article/44/Supplement_1/S1/334966
http://www.ncbi.nlm.nih.gov/pubmed/17143845?tool=bestpractice.com
Therapy for chronic problems includes the following:[3]Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007 Jan 1;44 Suppl 1:S1-26.
https://academic.oup.com/cid/article/44/Supplement_1/S1/334966
http://www.ncbi.nlm.nih.gov/pubmed/17143845?tool=bestpractice.com
Lubricating, preservative-free artificial tear gels or tears
Antibiotic ointment
Lateral tarsorrhaphy to protect the corneas (which are often hypoaesthetic/anaesthetic as a result of neuronal damage) from breakdown
Continuous-wear, therapeutic soft contact lenses and antibiotic drops
Topical corticosteroids and antibiotics for inflammatory disease (iritis, episcleritis, scleritis, and immune keratitis)
Dilation for iritis
Glaucoma therapy as needed
Surgical management as needed: for example, for amniotic membrane transplantation, tissue-adhesive seal ulcers, keratoprosthesis, and glaucoma trabeculectomy.
Chronic pain management is generally similar to that for postherpetic neuralgia.