2.1 Case Definition of PHN

The pain persisting beyond 4 months from the onset of HZ prodrome [4].

2.2 Ethical Clearance

Ethics approval was obtained from the institutional research committee with reference number (IRC/1225/018). This study is part of original research entitled “Efficacy of pregabalin for the treatment of acute herpetic neuralgia and the prevention of postherpetic neuralgia-a randomized controlled trial.”

2.3 Statistical Analysis

Data were entered in Microsoft Excel 2010 and converted into Statistical Package for Social Science (SPSS) version 11.5. For descriptive statistics, percentage, frequency, proportion, mean, median, mode, standard deviation, and IQR were used. Similarly, for inferential statistics, we applied the chi-square test. Logistic regression analysis was conducted to find the predictors of PHN at 95% CI, where a p value < 0.05 was considered significant.

3.1 Clinico-Epidemiological Profiles of HZ

A total of 82 patients were enrolled in this study. The mean age of the participants was 47 ± 18.77 years. The majority (32.9%) of the participants belonged to the age group of 61–70 years. However, we also have a significant number of participants (9.8%) at age ≤ 20 years (Figure 1). Male and female were almost equal with a 1:1 ratio. Most of the participants, 25 (30.5%) were housewives, followed by farmers 19 (23.2%), government service holders 14 (17.1%), students 13 (15.9%), and business persons 11 (13.4%). Twenty (24.4%) participants were illiterate.

Mean duration of prodromal symptoms was 3.79 ± 2.29 days. Malaise was present in half of the participants (Table 1). Intermittent type of pain, 45 (54.9%) was slightly more than the persistent, 37 (45.1%). Fifty-nine (72.0%) participants pointed to some possible causes of reactivation of the disease; the most common being physical stress in 26 (40.2%) patients (Table 1).

The onset of pain was together with skin eruption in 49 (59.75%) and before skin eruption in 33 (40.25%) participants. Thoracic dermatome was the most frequently (56.1%) involved site, followed by lumbar, 14 (17.1%), and trigeminal, 12 (14.6%) (Figure 2). Out of these, 12 patients had trigeminal dermatome involvement, 10 had ophthalmic nerve involvement, and two had maxillary nerve involvement. However, mandibular nerve involvement was not found among our participants.

3.2 Postherpetic Neuralgia and Its Predictors

Out of 82 patients, only 77 completed the follow-up visit at 16 weeks. Out of 77 patients, 14 had persistent pain. Hence, the incidence of PHN was 14/77 (18.18%). The significant risk factors for PHN on the bivariate analysis (Table 2) were advancing age (> 50 years), associated headache, pain before skin eruption, diabetes, and trigeminal dermatome involvement. On logistic regression analysis, age > 50 years, prodromal pain, and diabetes were found to be significant risk factors for the PHN (Table 3).

4.1 Postherpetic Neuralgia

The incidence of PHN was (18.18%) in our study. There is a huge difference in the incidence of PHN in different countries. It can vary from 5% to 30% [17]. One recent report from China reported that 29.8% of patients with HZ developed PHN, which is significantly higher than our case [6]. The actual incidence of PHN in our population could also be more than what we have reported, as we had excluded patients with age > 75 years and serious systemic comorbidities to avoid follow-up difficulties, as we had a longer follow-up period of 4 months. Another possible reason for the lower incidence of PHN in our study is that we have considered PHN for persistent pain 4 months after the appearance of a rash [4]. However, in this study, they have defined PHN as persisting pain for > 1 month following the healing of the HZ rash. Also, we have tried to match the subjects by enrolling patients with pain scores ≥ 40 mm on VAS. Moreover, we recruited only those patients who presented within 72 h of the rash eruption, as a delay in the administration of treatment might have a direct impact on both acute and chronic pain [18].

4.2 Predictors of Postherpetic Neuralgia

We found that advanced age (> 50 years), prolonging prodromal pain before skin eruption, trigeminal dermatome involvement, associated diabetes, and associated prodromal symptoms like headache and malaise were significant risk factors for the PHN on bivariate analysis. Age > 50 years (adjusted odds ratio [OR] 2.95, 95% confidence interval [CI] 1.33–6.53), prodromal pain (adjusted OR 12.01, 95% CI 1.40–102.77) and diabetes (adjusted OR 13.09, 95% CI 1.40–122.24) were significant risk factors on logistic regression analysis as well (Table 3).

The significant predictors of PHN like advancing age, longer duration of prodromal pain were comparable to past reports. Recent meta-analysis reported that each 10-year increment in age, periocular lesions, larger areas of skin lesions, delay in initial treatment, prodromal pain, and pain severity in acute phase are the most important risk factors for PHN [14]. However, unlike these studies, we did not find the severity of baseline pain as a significant risk factor for PHN in our study [5, 8, 9, 12, 19]. This could be because we included only those patients with significant baseline pain score i.e. ≥ 40 mm on 100 mm VAS. Hence, all our participants had moderate to severe pain at the time of presentation.

We also found that trigeminal dermatome involvement (OR 4.39, 95% CI: 1.22–15.80, p = 0.002) is an important predictor for PHN. This finding is comparable to the previous study [19]. Opstelten et al. (2007) and Ding et al. (2024) reported similar findings. They reported that ophthalmic localization is one of the important predictors of PHN, with an odds ratio of 2.3 (95% CI 1.0–4.6) and 1.96 (95% CI 1.75–2.20), respectively [9, 14]. This could be explained as the trigeminal nerve has a complex neuronal course with a relatively superficial location. We also found that associated constitutional symptoms like headache (OR 4.64, 95% CI: 1.57–13.74, p = 0.004) and malaise (OR 11.73, 95% CI: 1.89–47.68, p = 0.002) are significant predictors of PHN. This is an unexpected new finding in our study, which has not been reported yet in other published studies. In a viral infection, the headache and malaise could be because of the release of inflammatory markers, and those inflammatory markers might cause more nerve injury and ganglionitis leading to PHN. As headache and malaise are commonly expected problems in any viral infection, both patients and treating doctors may not give much attention to inquire details about these symptoms. So, it is likely that we might have missed these factors as PHN predictors in past studies.

As reported previously by many studies, we also found that associated comorbidities like diabetes are significant risk factors (adjusted OR 13.09, 95% CI: 1.40–122.24, p < 0.024) for PHN. However, as we had excluded individuals with malignancy, HIV, severe systemic diseases, and very elderly patients (> 75 years) because of follow-up difficulties, these factors could not be assessed for the risk of PHN [5, 14, 20].

To conclude, although HZ is common among the elderly, it is becoming increasingly common in younger age groups as well. Further studies are necessary to identify this change in epidemiology. Physical and mental stress are common provoking factors for HZ. The incidence of PHN is 18.18% in our study. However, if we consider elderly and debilitated patients, it would be even higher in our part of the world. Out of the evaluated factors, advancing age (> 50 years), prolonged prodromal pain, associated diabetes, and history of prodromal symptoms like headache and malaise are important predictors of PHN in our study. Therefore, we must consider these risk factors to outrace individuals at higher risk of PHN, and early intervention must be planned to prevent PHN in these individuals with frequent follow-up, optimized treatment, and counseling.

4.3 Limitations of the Study

Single centered study with less number of sample size is one of the major limitations of the study. The confidence intervals were wide for many variables of PHN. A larger sample size and multicenter would overcome this limitation. As we could not include very old patients and those with severe comorbidities, we might have missed some of the important risk factors.