Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

Abstract

BackgroundHerpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors.MethodsPatients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method.ResultsFour hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression).ConclusionsSmoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden.

Preventing and managing herpes zoster: key actions to foster healthy aging

“…In the chronic phase, 90 % of PHN patients report having difficulty with their usual daily tasks and sleep disturbances [31,32]. PHN is significantly associated with pain intensity at HZ presentation, age, smoking, symptoms of anxiety and depression, trauma, and missed antiviral prescription [33,34].…”

Zoster-Associated Pain and Post Herpetic Neuralgia

“…HZ incidence is known to increase in immunodepression, being more frequent and aggressive in transplant recipients, cancer patients, HIV-infected people, and in patients with autoimmune diseases (rheumatoid arthritis and lupus erythematosus sistemicus among others), diabetes, hypertension, renal failure and chronic obstructive pulmonary disease (Hata et al, 2011;Yi et al, 2010;Yang et al, 2011;Schmader et al, 2008). Notwithstanding this evidence, HZ can be considered a disease involving immunocompetent subjects in the vast majority of cases (Hegalsson et al, 2000;Oxman et al, 2005;Yawn et al, 2007;Parruti et al, 2010;. Contacts with patients with Varicella, more frequent for some professionals as pediatricians and teachers, turned out to be protective , in line with the biological assumption that exposure to VZV may boost and strengthen natural cell-mediated immunity (Vossen et al, 2004).…”

“…Detailed information about pain, clinical aspects and therapy are not usually present in such databases, even though these studies usually include larger number of patients in comparison with prospective collections. In at least two cases, however, prospective evaluation of the incidence of HZ has been attempted in recent years (Oxman et al, 2005;Parruti et al, 2010). The Shingles Prevention Study (Oxman et al, 2005) was a randomized double-blind placebo-controlled trial set up to demonstrate that vaccination against VZV can decrease the incidence and severity of HZ and post herpetic neuralgia (PHN), its more frequent complication.…”

“…In the large placebo arm (19,276 subjects) the incidence of HZ was 11.12 cases/1000 person-years (Oxman et al, 2005). An Italian cohort (Parruti et al, 2010) prospectively enrolled HZ patients of any age (mean age was 58 years, with 46% of patients aged <60 years) presenting to general practitioners, pediatricians or hospital specialists (dermatology, infectious diseases, pain management center) in a Local Health District. Incidence of HZ was prospectively calculated in a subset of that study, that is considering only cases consecutively enrolled by general practitioners, whose reference population is known.…”

The Current Treatment and Prevention of Post Herpetic Neuralgia

“…These agents reduce the duration of viral shedding, hasten rash healing, reduce the severity and duration of acute pain, and reduce the risk of progression to PHN [39]. For example, Dworkin et al [40] and Parruti et al [41] done a cohort study of 419 and 519 Hz patients respectively found that patients receiving antiviral therapy in the acute phase had a significantly lower prevalence of PHN.…”