Patient-reported quality of life in patients suffering from acute herpes zoster

Abstract

Objectives

Herpes Zoster (HZ) is a common painful, debilitating condition caused by reactivation of the varicella-zoster virus. It is characterized by a painful skin eruption which is very complex to treat. Studies have reported that HZ negatively affects Quality of Life (QoL), but no large systematic review on this topic has been published to date. This systematic review aims to summarize the current data on patient-reported QoL amongst patients diagnosed with HZ.

Methods

We searched Medline, Embase, Cochrane Library, CINAHL, and PsycINFO. The primary outcome was the change in percent impairment of QoL compared to normative data. Secondary outcomes were meta-analyses comparing reported QoL to a control group or normative data.

Results

We assessed a total of 536 studies for inclusion. Thirteen studies were included in the systematic review and five studies in the meta-analyses. The total number of patients was 5472.

Conclusions

This systematic review and meta-analysis found lower reported QoL amongst patients diagnosed with acute herpes zoster compared to normative values. Our data show that acute herpes zoster significantly reduces the quality of life of the patients affected.

Keywords

herpes zoster varicella-zoster virus shingles quality of life

Introduction

Herpes zoster (HZ), also known as shingles, is a common painful and debilitating disease.¹ HZ is caused by the reactivation of the varicella-zoster virus (VZV), which as a primary infection, causes chickenpox.² After initial infection, the virus lies latent in the sensory ganglia and can from there be reactivated.³ In developed countries, over 95% of the population are seropositive for VZV and are at risk of developing HZ.³ The lifetime risk of developing HZ is between 25% and 30%.⁴ The risk increases with older age to around 50% in those aged 80 years.^4,5

Herpes zoster usually begins with prodromal symptoms such as fever, malaise, headache, and paresthesia, which precede the rash by a few hours and up to several days.⁶ After the prodromal phase, HZ is characterized by a painful unilateral vesicular eruption of blisters in the skin, usually within a limited dermatomal distribution.⁷ The predominant symptom of HZ is pain.³ Due to its intense nature, many colorful descriptions exist. In Arabic, Hezam “innar” means belt of fire; in Hindi, Baoisayaa “daga” means big rash; in Norwegian, “Helvetesild” means Hell’s fire (also described as a bell of roses from Hell); and in Spanish, “Culebrilla” means small snake.⁴

Treatment consists of both disease-limiting drugs such as antiviral medication and symptom-relieving medication such as analgesics.⁸ Treatment is, however, complex, and many patients fail to find sufficient relief. HZ is in most cases self-limiting, but in a portion of patients, the pain becomes chronic is a syndrome called postherpetic neuralgia (PHN).^9,10 To prevent the outbreak of HZ, several effective vaccines have been produced, but the degree of utilization of these vary substantially across countries.^11,12

Over the last decades, studies have reported a negative impact on Quality of Life (QoL) from HZ.¹³ Despite the large number of patients and the vast amount of published literature, no systematic review has previously been performed. Producing high-quality data on the subject of QoL in HZ is essential for understanding the impact of the disease on these patients and could aid health care professionals in treating these patients and authorities in prioritizing preventive measures, such as vaccines.

This systematic review and meta-analysis aim to summarize the current data on patient-reported quality of life amongst patients diagnosed with acute HZ.

Material and methods

We reported this systematic review following the PRISMA statement for systematic reviews.¹⁴

Eligibility criteria

We included studies from peer-reviewed journals that examined the quality of life in patients suffering from HZ using patient-reported outcomes measures. Eligible criteria were as follows: Study design of cohorts or randomized controlled trials (RCT); use of QoL-PROMs reporting on QoL; studies had to report on baseline measurements of PROMs; have a control group, or use a validated PROM where normative data could be accessed. We excluded studies that reported solely on sleep quality as an indicator for QoL and studies on immuno-compromised patients or children.

Search strategy

On 19 April 2021, we conducted a systematic literature search in MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO, identifying studies reporting on the quality of life in patients suffering from herpes zoster and postherpetic neuralgia. The search strategy consisted of three blocks: the construct of interest, population, and type of instrument. The search strategy was based on the search filter Patient-Reported Outcomes Measures (PROMs), developed by Oxford University and available through the COSMIN website (cosmin.nl).¹⁵ A research librarian was involved in the search strategy. Supplemental Appendix 1 depicts the full search strategy. In addition to the formal search, we explored reference lists of included articles for possible additional studies, and one study was added.¹⁶

Study selection and data extraction

Author MS and assistant PJ screened articles for inclusion using the Covidence software,¹⁷ developed by the Cochrane Collaboration. Data extraction was done using a prespecified spreadsheet. We collected data on the details of the publication, authors, title, year of publication, type of study, aim, patient characteristics, PROM used, available control group or normative data, and HZ-definition used.

Methodological quality assessment and risk of bias

The quality and risk of bias in the included studies were evaluated using the Newcastle–Ottawa Quality Assessment Scale (NOS) for cohort studies and the Risk of Bias tool for Randomized Trials (ROB 2.0).^18,19 We evaluated the quality of evidence from the different QoL measures using the Grading of Recommendations, Assessment, Development, and Evaluations system (GRADE).²⁰ The GRADE system evaluates the studies and ranks them in one of four levels of evidence: very low, low, moderate, and high.

Effect measures and synthesis methods

All results collected from PROMs were registered as mean and standard deviation when possible. If only median and ranges were available, these were collected and recalculated to means and standard deviations according to the algorithm published by Hozo et al.²¹ For all results, we identified normative data or data from a representative control group. The QoL reported from the HZ group was compared to the control data/normative data and a percentage of impairment compared to normal QoL was calculated. If more than four studies reported on the same PROM, we performed a meta-analysis. We used the Review Manager Software (RevMan) for all meta-analyses.²²

Results

Study selection and characteristics

Our literature search retrieved a total of 532 studies, of which 13 studies met the eligibility criteria^13,23–33 (Figure 1). The additional reference list search added four additional studies. For three studies, we could not find any normative reference data, and these were therefore excluded.^29,34,35

Figure 1.

Prisma flowchart depicting the flow of studies in the article screening process.

Table 1 depicts all the characteristics of the included studies. Three studies originated from China. Two studies each from Germany, France, Italy, and Spain. The last three studies originated from Canada, Italy, and one was an international study. The publication date ranged from 1995 to 2021 and reported on 5472 patients suffering from HZ. Eight studies were designed as cohort studies, and four were RCTs. The aim of the included studies varied. Five studies were intervention studies aiming to test the efficacy of new treatments.^{23,25,26,30,31} Five studies aimed to investigate the burden of HZ on QoL or economy.^{13,16,24,27,32} The remaining two investigated the risk of developing late symptoms after an outbreak of HZ.^28,33 All studies had a population of patients >50 years of age. The QoL PROMS used were the Short Form 12 (SF-12), Short Form 36 (SF-36), EuroQol five-dimension scale (EQ-5D), EuroQol VAS (EQ-VAS), and the Nottingham Health Profile. The study by Beutner et al. references normative data in their study, which was used in the comparison.²³ For the remaining studies, we retrieved normative data from other published sources. Four studies using the SF-12 were matched with data from Gandek et al., while Lam et al. provided data for the last study using SF-12.^36,37 Normative data for EQ-VAS were provided by Yang et al.³⁸ Jannsen et al., Scalone et al., and Poder et al. supplied normative data for the EQ-5D.^39–41 Normative data for the SF-36 were provided by Ellert et al.⁴² The normative data were matched on age with the study population, when possible.

Table 1.

Characteristics of the studies included in the systematic review.

#	Author	Title	Country/Year of publication	Type of study	Aim	Population (n)	Control group/Normative data	Definition of HZ	QoL-instrument used
1	Beutner et al.	Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults	US, UK, DK/1995	RCT	To compare safety and efficacy of oral valaciclovir and standard oral acyclovir for the treatment of herpes zoster in immunocompetent adults.	Patients aged ≥ 50 (n = 1141)	Aged matched normative data referenced in study.	New unilateral herpes zoster rash, included within 72 h of symptom debut	Nottingham Health profile
2	Bouhassira et al.	Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice.	FR/2011	Prospective cohort	To evaluate, from a patients’ perspective, the real-life burden of HZ and its effect on HRQoL.	Patients aged ≥ 50 (n = 1354)	Published normative data	New unilateral herpes zoster rash, included within 72 h of symptom debut	Short-form 12 (SF-12)
3	Bulilete et al.	Efficacy of gabapentin for the prevention of postherpetic neuralgia in patients with acute herpes zoster: a double blind, randomized controlled trial	ES/2021	RCT	To assess the efficacy of gabapentin added to the usual treament (valacyclovis and analgesics as needed) on reducing acute pain and preventing PHN at 12 weeks.	Patients aged ≥ 50 (n = 97)	Published normative data	New herpes zoster rash presenting within the first 72 h of vesicle formation, and had an average pain score of at least 4 of 10 on a visual analogue scale (VAS) before therapy	Short-form 12 (SF-12)
4	Curran et al.	Impact of herpes zoster and postherpetic neuralgia on the quality of life of germans aged 50 or above.	DE/2018	Prospective cohort	To assess the impact of herpes zoster and postherpetic neuralgia on the quality of life of germans aged 50 or above.	Patients aged ≥ 50 (n = 513)	Published normative data	New unilateral pain (including allodynia and pruritus) accompanied by a unilateral rash and no alterative diagnosis	EuroQol five-dimension scale (EQ-5D)
5	Diez-domingo et al.	Economic burden and impact on quality of life of Herpes zoster in Spanish adults aged 50 Years or older: A prospective cohort study	ES/2021	Prospective cohort	To report the impact of HZ and PHN on patients’ HRQL, healthcare resource utilization, and associated economic costs.	Patients aged ≥ 50 (n = 299)	Published normative data	New unilateral pain (broadly defined to inlcude allodynia and pruritus) accompanied by unilateral rash and no alternative diagnosis.	EuroQol five-dimension scale (EQ-5D)
6	Dong et al.	Efficacy of short-term spinal cord stimulation in acute/subacute zoster-related pain: A retrospective study	CN/2016	Prospective cohort	To evaluate the efficacy of short-term spinal cord stimulation in patients with refractory acute/subacute zoster-related pain.	Patients aged ≥ 50 (n = 46)	Published normative data	New unilateral herpes zoster rash, included within 120 days of rash onset.	Short-form 12 (SF-12)
7	Drolet et al.	The impact of herpes zoster on postherpetic neuralgia on health-related quality of life: a prospective study	CA/2010	Prospective cohort	To describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life.	Patients aged ≥ 50 (n = 261)	Published normative data	Physicians’ diagnosis of herpes zoster with outbreak within last 14 days.	EuroQol five-dimension scale (EQ-5D)
8	Duracinski et al.	ARIZONA study: Is the risk of post-herpetic neuralgia and its burden increased in the most elderly patients?	FR/2014	Prospective cohort	To identify an age threshold for increased risk and burden of herpes zoster in 70+ patients.	Patients aged > 50 (n = 609)	Published normative data	New unilateral herpes zoster rash, included within 7 days of rash onset.	Short-form 12 (SF-12)
9	Kramer et al.	Somatosensory profiles in acute herpes zoster and predictors of postherpetic neuralgia	DE/2019	Prospective cohort	To characterize AHZ patients with regard to their somatosensory phenotype and psychosocial health in the acute stage in association with the occurrence of PHN after 6 months.	All patients (n = 70)	Published normative data	Acute herpes zoster accompanied by pain present for less than 120 days.	Short-form 36 (SF-36)
10	Matthews et al.	The economic burden and impact on quality of life of Herpes zoster and postherpetic Neuralgia in individuals aged 50 Years or older in Italy	IT/2019	Prospective cohort	To estimate the health care resource utilization, costs, and impact of quality of life of herpes zoster and postherpetic neuralgia in adults aged ≥ 50 years in Italy.	Patients aged ≥ 50 (n = 391)	Published normative data	New diagnosis of acute herpes zoster.	EuroQol five-dimension scale (EQ-5D)
11	Torcel-Pagnon et al.	Impact of Underlying conditions on zoster-related pain and on quality-of-life following zoster	IT/2016	Prospective cohort	To investigate zoster-associated chronic pain and its management in a cohort of immunocompetent patients aged 50 or older.	Patients aged ≥ 50 (n = 413)	Published normative data	Diagnosis of acute herpes zoster.	Short-form 12 (SF-12)
12	Xu et al.	Local Administration of methylcobalamin and lidocaine for acute ophthalmic Herpetic neuralgia: a single-center randomized controlled trial	CN/2015	RCT	To determine the therapeutic efficacy of combined methylcobalamin and lidocaine for acute opthalmin herpetic neuralgia.	Patients aged > 50 (n = 98)	Published normative data	New unilateral herpes zoster rash, included within 7 days of rash onset.	EuroQol VAS (EQ-VAS)
13	Xu et al.	Local injection of methylcobalamin combined with lidocain for acute Herpetic neuralgia	CN/2018	RCT	To determine the efficacy of methylcobalamin combined with lidocaine for acute herpetic neuralgia.	Patients aged ≥ 50 (n = 180)	Published normative data	New unilateral herpes zoster rash, included within 7 days of onset of rash	EuroQol VAS (EQ-VAS)

Results of included studies

Table 2 depicts the individual studies. Results of QoL-proms of each study are presented as mean, and the associated standard deviation, standard error, or confidence interval for each subgroup reported. We matched each study with the appropriate normative data, which served as the basis for calculating a percentage of impairment. The percent impairment indicates how large the reduction in QoL is amongst the HZ patients compared to healthy patients in the normative population. The SF-12 and SF-36 divide their QoL-items in a Physical Component Score (PCS) and Mental Component Score (MCS), while the other PROMs report a total score for all QoL-items. All five studies reporting results for PCS reports a lower QoL of between 5.5–32.2%. For the MCS, all studies report a reduction of 6.4–21.1%. All studies reported a reduced level of QoL, with a reduction in QoL of 5.5–83.6%.

Table 2.

Results of the studies included in the systematic review.

Author	QoL-instrument	Results			N	Normative reference	N	Percent impairment	Study population country/Age	Normative population country/Age	Source of reference
Beutner et al.	Nottingham Health profile (mean)	Group							US/UK/DK (≥ 50)	NS	Stated in article
		Intervention	1	36	384	11	N/A	34.7%
		Intervention	2	40	381	24	N/A	21.1%
		Intervention	3	38	376	22	N/A	20.6%
Bouhassira et al.	Short-form 12 (mean ± SD)	Physical component score							FR (< 70 and ≥ 70)	FR (46 – 64 and 65 – 74)	Gandek et al.
		Group
		Age <70 years	1	46.7 ± 8.9	745	49.4 ± 8.0	763	5.5%
		Age ≥70 years	2	40.2 ± 9.8	609	45.7 ± 9.0	472	12.1%
		Mental component score
		Group
		Age < 70 years	1	42.1 ± 11.5	745	48.6 ± 9.4	763	13.4%
		Age ≥70 years	2	40.1 ± 10.7	609	48.3 ± 9.2	472	17.0%
Bulilete et al.	Short-form 12 (mean ± SD)	Physical component score							ES (≥ 50)	ES (45–64)	Gandek et al.
		Group
		Intervention	1	44.3 ± 9.8	49	47.8 ± 9.8	1253	7.4%
		Placebo	2	45.1 ± 7.6	48	47.8 ± 9.8	1253	5.7%
		Mental component score
		Group
		Intervention	1	40.9 ± 8.7	49	51.5 ± 9.6	1253	20.6%
		Placebo	2	41.7 ± 9.8	48	51.5 ± 9.6	1253	19.1%
Curran et al.	EuroQol five-dimension scale (EQ-5D) + EuroQol VAS (EQ-VAS) mean (SE)	EQ-5d		0.740 (0.012)	513	0.937		21.1%	DE (≥ 50)	DE (45–54)	Janssen et al.
Curran et al.		EQ VAS		60.2 (1.1)	513	78.5		23.3%	DE (≥ 50)	DE (45–54)	Janssen et al.
Diez-domingo et al.	EuroQol five-dimension scale (EQ-5D) mean (SE)	EQ-5d		0.661 (0.018)	299	0.914		27.7%	ES (≥ 50)	ES (18+, total)	Janssen et al.
Dong et al.	Short-form 12 (mean ± SD)	Physical component score		34.0 ± 4.83	46	50.2 ± 9.1	2533	32.2%	CN (≥ 50)	CN (18+, total)	Lam et al.
Dong et al.	Short-form 12 (mean ± SD)	Mental component score		42.1 ± 4.13	46	50.1 ± 9.5	2533	15.8%	CN (≥ 50)	CN (18+, total)	Lam et al.
Drolet et al.	EuroQol five-dimension scale (EQ-5D) mean (95% CI)	EQ-5d		0.59 (0.55–0.64)	261	0.867 (0.784–0.905)	153	31.7%	CA (≥ 50)	CA (50–54, men)	Poder et al.
Duracinski et al.	Short-form 12 (mean ± SD)	Physical component score							FR (70–74, 75–79, 80–84, 85–89)	FR (45–64)	Gandek et al.
		Group
		Age 70–74 years	1	42.7 ± 8.9	220	45.7 ± 9.0	472	6.6%
		Age 75–79 years	2	41.8 ± 9.4	163	45.7 ± 9.0	472	8.6%
		Age 80–84 years	3	37.9 ± 10.0	137	45.7 ± 9.0	472	17.1%
		Age 85–89 years	4	34.2 ± 8.9	89	45.7 ± 9.0	472	25.2%
		Mental component score
		Group
		Age 70–74 years	1	41.1 ± 10.2	220	48.3 ± 9.2	472	15%
		Age 75–79 years	2	38.7 ± 11.5	163	48.3 ± 9.2	472	20%
		Age 80–84 years	3	39.6 ± 10.9	137	48.3 ± 9.2	472	18.1%
		Age 85–89 years	4	41.0 ± 9.8	89	48.3 ± 9.2	472	15.2%
Kramer et al.	Short-form 36 (median (IQR))	Physical component score							DE (< 18, mean 52)	DE (50–59)	Ellert et al.
				38.9 (31.8–50.0)
			a)	38.9 ± 3.0	70	50.4 (49.9–51.0)	7525	22.8%
		Mental component score
				38.7 (32.9–42.9)
			a)	38.7 ± 1.6	70	49.1 (48.4–49.8)	7525	21.1%
Matthews et al.	EuroQol five-dimension scale (EQ-5D) mean (SE)	EQ-5d	1	0.746 (0.011)	391	0.915 (0.107) mean (SD)	6000	18.5%	IT (≥ 50)	IT (all ages)	Scalone et al.
Torcel-Pagnon et al.	Short-form 12 (mean ± SD)	Physical component score							IT (≥ 50)	IT (46–64)	Gandek et al.
		Group
		Without underlying condition	1	43.0 ± 7.4	110	49.7 ± 7.9	479	13.5%
		With underlying condition	2	39.1 ± 8.9	303	49.7 ± 7.9	479	21.4%
		Mental component score
		Group
		Without underlying condition	1	44.4 ± 10.2	110	47.5 ± 10.3	479	6.4%
		With underlying condition	2	40.7 ± 10.6	303	47.5 ± 10.3	479	14.4%
Xu et al.	EuroQol VAS (mean ± SD)	Group							CN > 50	CN (50–59)	Yang et al.
		Intervention	1	15.5 ± 6.08	24	84.8 (82.6–87.1)	110	81.7%
		Intervention	2	15.4 ± 4.5	25	84.8 (82.6–87.1)	110	81.8%
		Intervention	3	16.8 ± 7.7	25	84.8 (82.6–87.1)	110	80.1%
		Intervention	4	17.4 ± 9.2	24	84.8 (82.6–87.1)	110	79.4%
Xu et al.	EuroQol VAS (mean ± SD)	Group							CN ≥ 50	CN (50–59)	Yang et al.
		Intervention	1	16.7 ± 7.4	45	84.8 (82.6–87.1)	110	80.3%
		Intervention	2	17.7 ± 6.7	46	84.8 (82.6–87.1)	110	79.1%
		Intervention	3	15.2 ± 7.3	44	84.8 (82.6–87.1)	110	82.0%
		Intervention	4	13.9 ± 7.1	45	84.8 (82.6–87.1)	110	83.6%

a) The mean (SD) has been calculated from the median (IQR) in order to make the data comparable to the normative data. Method by hozo et al. Stated in methods section. NS - not specified.

Synthesis of results/meta-analyses

We performed meta-analyses on data from the five studies reporting QoL using the SF-12. This PROM reports on two parameters, PCS and MCS, and separate meta-analyses were performed on these two. Four studies did not report SF-12 baseline data as a total, but rather in subgroups such as age or treatment group.^24,25,32,33 We added these subgroups separately to the meta-analysis, making it possible to tailor the normative data to these groups.

Physical component score

Regarding the PCS, the meta-analysis showed a statistically significant lower QoL-score in individuals diagnosed with HZ when compared to normative data (Figure 2). Patients with HZ had a QoL score that was 7.48 (−7.97, -7.00), points lower (mean 95% CI). p < .0001. When we assume a normative value of approximately 49, this translates into a reduction in QoL-score of around 15%.

Figure 2.

Results and forest plot of the physical component score reported by studies using QoL using the SF-12.

Mental component score

The meta-analysis showed a statistically significant lower MHC QoL-score in individuals diagnosed with HZ when compared to normative data (Figure 3). Patients with HZ had a QoL score that was 6.38 (−6.79, - 5.93), points lower (mean 95% CI). p < .0001. When we assume a normative value of approximately 48, this translates into a reduction in QoL-score of around 13%.

Figure 3.

Results and forest plot of the Mental Component Score reported by studies using QoL using the SF-12.

Risk of bias of the included studies

We evaluated the risk of bias of the included cohort studies using the NOS, and the included RCTs using the RoB 2.0. The quality of the included cohort studies was generally good, scoring a 7–8 on a scale from 0–9 (Table 3). Two studies did not describe factors they controlled for.^26,27 Two studies did not describe the loss of follow-up in their cohort.^24,28 The quality of the included RCTs was good (Table 3). Two studies raised some concerns of bias as they did not have a blinded intervention.^30,31

Table 3.

Table showing the results of the risk of bias evaluation of the included Cohort studies and RCTs. The RCTs were evaluated using the risk of bias tool 2.0, while the cohort studies were evaluated using the Newcastle-Ottawa scale.

		Risk of bias of the included cohort studies - (New Castle Ottawa Scale)
Study	Year	Selection				Comparability	Outcome			Quality Score
		Representativeness of the exposed cohort	Selection of the non-exposed cohort	Ascertainment of exposure	Demonstration that the current outcome of interest was not present at start of study	Comparability of cohorts on the basis of the design or analysis.	Assessment of outcome	Was follow-up long enough for outcomes to occur	Adequacy of follow-up of cohorts.	Quality Score
		(Maximum: *)	(Maximum: *)	(Maximum: *)	(Maximum: *)	(Maximum: **)	(Maximum: *)	(Maximum: *)	(Maximum: *)	Out of 9
Bouhassira et al.	2011	*	*	*	*	*	*	*		7
Curran et al.	2018	*	*	*	*	*	*	*	*	8
Diez-domingo et al.	2021	*	*	*	*	*	*	*	*	8
Dong et al.	2016	*	*	*	*		*	*	*	7
Drolet et al.	2010	*	*	*	*		*	*	*	7
Duracinski et al.	2014	*	*	*	*	*	*	*	*	8
Kramer et al.	2019	*	*	*	*	*	*	*		7
Matthews et al.	2019	*	*	*	*	*	*	*	*	8
Torcel-Pagnon et al.	2016	*	*	*	*	*	*	*	*	8

Risk of bias of the included RCTs (RoB 2.0)
Study	Year	Randomization process	Deviations from the intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported result	Overall
Beutner et al.	1995
Bulilete et al.	2019
Liang et al.	2015
Xu et al.	2015
Xu et al.	2016
			Low risk		Some concerns		High risk

Quality of evidence

When assessing the quality of the collected data, all outcomes were assessed to have no serious risk of bias or inconsistency (Table 4). The studies by Kramer et al., Xu et al., Curran et al., and Drolet et al. were evaluated as having some problems with indirectness as they did not have a control group or stated normative data as a comparator for their results.^{13,27,28,30,31} Imprecision was evaluated as serious in Kramer et al. as they had a low number of participants (n = 74).

Table 4.

GRADE summary of findings: table showing the study quality and summary of findings evaluation based on the grading of recommendations, assessment, development, and evaluations framework.

Number of studies	Certainty assessment						Effect		Certainty
Number of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Number of individuals	Mean reduction in QoL between HZ-population and normative data mean(range) or percent change	Certainty
Quality of life (mental component score) (assessed with: SF-12; scale from: 0 to 100)									⊕⊕⊕○
5	Randomized trials	not serious	not serious	serious	not serious	none	2519	7.55 (−8.52 to −6.57)	MODERATE
Quality of life (physical component score) (assessed with: SF-12; scale from: 0 to 100)									⊕⊕⊕○
5	Randomized trials	not serious	not serious	serious	not serious	none	2519	−6.71 (−8.95 to 4.46)	MODERATE
Quality of life (physical component score) (assessed with: SF 36; scale from: 0 to 100)									⊕⊕○○
1	observational study	not serious	not serious	serious	serious	none	74	−32.2%	LOW
Quality of life (mental component score) (assessed with: SF-36; scale from: 0 to 100)									⊕⊕○○
1	observational study	not serious	not serious	serious	serious	none	74	−15.8%	LOW
Quality of life (assessed with: Nottingham Health profile)									⊕⊕⊕⊕
1	Randomized trial	not serious	not serious	not serious	not serious	none	1141	−20.6% to −34.7%	HIGH
Quality of life (assessed with: EQ-5D)									⊕⊕⊕○
4	observational studies	not serious	not serious	serious	not serious	none	1165	−18.5% to −31.7%	MODERATE
Quality of life (assessed with: EQ-VAS)									⊕⊕⊕○
3	Randomized trials	not serious	not serious	serious	not serious	none	3023	−23.3% to −83.6%	MODERATE

Discussion

We have performed the first systematic review and meta-analysis investigating the degree of QoL in patients suffering from HZ.

The results of our systematic study showed that all studies reported a reduced level of QoL in patients suffering from HZ when we compared them to relevant normative data. The QoL level reported was 5.5–83.6% lower than the controls. Five studies were eligible for inclusion in a meta-analysis. Our two meta-analyses showed a statistically significant reduced level of both physical and mental QoL in patients with HZ compared to normative data or healthy controls.

Strengths and limitations

The major strength of our study is the number of papers and patients included. The studies were surprisingly homogeneous in populations, both when looking at age and their definition of HZ. There were some differences in the duration of symptoms at inclusion, but all studies included patients according to the typical definition of acute HZ versus PHN on the duration of pain with a cut-off of 3 months. One study by Xu et al. had a population of patients suffering from ophthalmic herpetic neuralgia. As most of the other studies had a population of patients with symptoms other than ophthalmic HZ, this is a source of heterogeneity. We chose to include this paper in our study as we wanted a broad representation of HZ patients. This should, however, be taken into consideration when looking at our results.

Only five of the twelve included studies were eligible for inclusion in the meta-analyses. This is a limitation of our study as not all data were included. However, the meta-analyses included about half our patients n = 2519), which is arguably a relatively large population.

Normative data

Using normative/control data not originating from the original studies is a major limitation of our study. Optimally, the studies would recruit a control group from a representative population comparable to the intervention group. Unfortunately, this was not the case in any of our studies, and only one study reported normative data for their group. The available normative data are generally of good quality, and we were able to find matching scores for the PROMS. Some of the normative data used are decades old, which is problematic as the normal data from the populations could change over time. Still, we feel that we were able to find matching normative data, resulting in robust results of our meta-analyses.

As an alternative to using normative data for the comparison, we could have used the patients as their own control. This was done by Matthews et al., where they assumed that the mean QoL scores at 90 days amongst the patients not developing PHN reflected a normal or baseline score. The main advantage is that the same population acts as their own controls, but there is a risk of not obtaining a true baseline value.⁴³ Still, this should be taken into consideration for future reviews on this subject.

Statistical heterogeneity

When examining heterogeneity between our studies, the I² value calculated when doing the meta-analysis ranged between 73 and 97%. The highest I² of 97% might indicate a substantial inconsistency between the groups included in our study. The Chic and Tau² for all meta-analyses also indicate heterogeneity. As there is evidence of possible heterogeneity across studies, extra care should be taken when concluding on our results.

Risk of bias and study quality

We evaluated the risk of bias of the included studies as low. The two studies that raised some concerns by Xu et al. did so based on their control group not being blinded. When assessing study quality, the certainty of their results was rated as low to high, as there were some problems with inconsistency and indirectness. We do not evaluate that this has influenced the certainty of our results as the data we collected from the individual studies were baseline data. The most important aspect of the study design and method of our included studies was not the design itself but rather that the population of herpes zoster patients was a representative one. In all studies, we assessed the representativeness of the population as good. Even though some studies were evaluated with low certainty, this represents their study as a whole and not necessarily our outcome of interest, baseline QoL.

Interpretation of results

When interpreting our results, caution has to be made. Does the lower score in QoL mean that Herpes Zoster causes lower QoL? From our results, no direct causality can be drawn, as we do not know whether or not this lower QoL-score was present before the outbreak. There are potentially many other sources of lower QoL scores, such as comorbidities, work-related issues, etc. However, we have a large dataset with clear indications that there is a lower QoL in those affected by HZ. Our included studies also report an improvement in QoL over time with or without interventions being made, suggesting that HZ is one of the main causes of the lower score. Without having extensive cohort data, with baseline values collected before the outbreak of HZ, this is the best data we will have on the subject, and when taking this into account, we feel that we can conclude that HZ does interfere with QoL.

The data from this systematic review and meta-analyses, together with the specific duration of disease state, could also be used to calculate quality-adjusted life-years (QALYs) amongst our patients. This would enable the data to be used in future health economic models.

Conclusion

This systematic review and meta-analysis found lower levels of reported Quality of Life amongst patients diagnosed with acute herpes zoster when compared to normative values. This shows that acute herpes zoster significantly reduces the quality of life of the patients affected. This emphasizes the importance of preventing this disease and increased focus on treatment to minimize Herpes Zosters’ effect on Quality of Life.

Supplemental Material

sj-pdf-1-bjp-10.1177_20494637211073050 – Supplemental Material for Patient-reported quality of life in patients suffering from acute herpes zoster—a systematic review with meta-analysis

Supplemental Material, sj-pdf-1-bjp-10.1177_20494637211073050 for Patient-reported quality of life in patients suffering from acute herpes zoster—a systematic review with meta-analysis by Martin Sollie, Pernille Jepsen and Jens A Sørensen in British Journal of Pain

Footnotes

Contributionship

M.S. contributed for planning, search and data collection, quality evaluation, writing of draft and final paper. P.J. contributed for Planning, search and data collection, quality evaluation, writing. J.A.S. contributed for planning and writing.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Registration of review

Before initiation, this review was registered (Reg. No.CRD42021242606) in the PROSPERO database ().

ORCID iD

Martin Sollie

Supplemental material

Supplemental material for this article is available online.

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