Treating Herpes Zoster and Postherpetic Neuralgia
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® VOVOLL XX I XXIII• NO 1• NO• JU 4N E• MAY2013 2015 Treating Herpes Zoster and Postherpetic Neuralgia Vol.ÊXXI,ÊIssueÊ1Ê JuneÊ2013 Editorialostherpetic Board neuralgia (PHN) but a minority of patients experience months and 15% had pain at 2 years in is the most frequent chronic pain (PHN) persisting for months, years, a Dutch study.6 In the landmark zoster Editor-in-Chief PsychosocialÊAspectsÊofÊChronicÊPelvicÊPain complication of herpes zoster or even a lifetime. vaccine study, which included almost JaneÊC.ÊBallantyne,ÊMD,ÊFRCA (shingles).1 Herpes zoster (HZ) Anesthesiology,ÊPainÊMedicine 40,000 people aged 60 years or older PUSA represents a reactivation of the vari- Epidemiology of HZ and PHN (of whom fewer than 1000 developed cella zoster virus (VZV), a ubiquitous, Pain is unwanted, is unfortunately common, and remains essential for survival (i.e., AdvisoryÊBoard HZ) and where PHN was defined as highly neurotropic, exclusively human Accordingevading toda ang recenter) and systematic facilitating medical diagnoses. This complex amalgamation of MichaelÊJ.ÊCousins,ÊMD,ÊDSC pain intensity of 3/10 or more, 30% of -herpesvirus. Primary infection causes review,sensati theon, incidence emotions, of a ndHZ t houghis 3–5 ts manifests itself as pain behavior. Pain is a moti- α PainÊMedicine,ÊPalliativeÊMedicine 1patients who developed HZ had PHN - Australia casesvati perng f1000actor person-years.for physician 3c Theonsu ltations and for emergency department visits and is varicella (chickenpox), after which VZV at 1 month, 12% at 3 months, and 5% age-specific incidence rates of HZ were becomes latent in sensory ganglia along at 6 months in the placebo group.7 Ac- similar across countries, with a steep the entire neuraxis. With the decline in cording to a meta-analysis, incidence rise after 50 years of age. The incidence VZV-specific cell-mediated immunity rates of PHN varied from 3.9 cases per was 6–8 cases/1000 person-years at in elderly and immunocompromised 100,000 person-years to 42.0 cases per individuals, VZV reactivates to cause 60 years of age and 8–12 cases/1000 100,000 person-years across all ages.8 HZ, characterized by a painful maculo- person-years at 80 years of papular or vesicular rash in all or part of age. The incidence of HZ has the skin territory innervated by a single increased in the past several dorsal root ganglion.2 The most common decades across seven coun- 3 site of HZ is thoracic, comprising about tries. A study in the United half of all cases, followed by trigemi- States could not explain the nal (usually the ophthalmic branch), increase by changes in age cervical, and lumbar distributions. HZ or by the prevalence of im- 4 generally resolves within a few weeks, munocompromised people. Two-thirds of HZ cases occur in those 50 years or older, and Maija Haanpää, MD, PhD the lifetime risk is 30%.2 Department of Neurosurgery, Helsinki University Hospital Estimates of the inci- Mutual Insurance Company Etera, dence of PHN vary widely Helsinki, Finland depending on the popula- Email: [email protected] tion and the definition of PHN used. PHN risk increases with age. In Andrew S.C. Rice, MB BS, MD, Definitions include the duration of a study from the United States, the FRCA, FFPMRCA persistent pain (30, 90, or 180 days) and incidence of PHN (defined as pain at 3 Pain Research, Department of Surgery months) in zoster patients was 18% in and Cancer, the severity of pain, either clinically Faculty of Medicine meaningful pain (i.e., pain intensity of persons older than 50 years and 33% Imperial College London at least 3/10) or any pain.3 In a popula- in those older than 80 years. Overall, Chelsea and Westminster Hospital Campus 80% of all PHN occurs among persons London, United Kingdom tion-based study using medical records 2 Email: [email protected] in the United States, 18% of patients aged 50 years and older. Analysis of reported pain for at least 30 days and data from the United Kingdom General Michael C. Rowbotham, MD 10% for at least 90 days.4 Similarly, Practice Research Database showed California Pacific Medical Center Research Institute 20% of patients had pain for at least 30 that the incidence of PHN (as defined Department of Anesthesia, days and 14% for at least 90 days in a by pain at 3 months) rose from 8% at UCSF School of Medicine study from the United Kingdom,5 and 50–54 years of age to 21% at 80–84 San Francisco, Calif., USA Email: [email protected] 20% of zoster patients had pain at 3 years of age.5 PAIN: CLINICAL UPDATES • MAY 2015 1 Advancing age and the severity component.13 Itching and dysesthesias HZ and PHN also cause a substan- of acute HZ pain are the strongest risk may accompany the pain, and in some tial economic burden to society in the factors for PHN. Other predictors of patients these symptoms can be even form of increased health care use and PHN are the severity of the rash, the more annoying than the pain itself. need for medication, lost working days presence of prodromal pain, and the A longitudinal study of zoster in those at working age, and the need occurrence of sensory abnormalities patients using quantitative sensory test- for assistance or even loss of indepen- such as hypoesthesia or allodynia.9,10 ing (QST) and skin biopsies showed that dence in frail, elderly, people with mul- Ophthalmic location of rash, psycho- those who developed PHN (defined as tiple comorbidities. In a study from the social distress in the acute phase, and pain at 6 months) had significantly more United Kingdom, the average total cost problems with usual activities before impaired sensory function and more of a PHN case was estimated to be £340 developing HZ (the last reflecting severe allodynia in the acute phase com- in 2006. The cost included outpatient poorer health) are also reported as risk pared to those who experienced pain visits and prescribed medication, but 14 factors.11 resolution. Sensory recovery pro- at that time pregabalin and lidocaine ceeded at the same rate in both groups patches were not available there, which during the first 6 months. Epidermal would increase the current cost.20 Course of the Disease nerve fiber density was decreased by HZ viral replication first manifests as about 40% in the affected skin but not Pharmacotherapy of Acute ganglionitis and then spreads along the in contralateral “mirror image” skin, Herpes Zoster corresponding peripheral nerve and with no improvement during the first The treatment of HZ aims to limit the the skin. Hemorrhage and inflam- 6 months.15 In a long-term follow-up of duration and severity of the attack, mation in the affected dorsal root 7 years, epidermal nerve fiber density relieve symptoms, and prevent com- ganglion and associated nerve may remained low in spite of good clinical plications. All patients should receive be seen, and in patients with PHN, recovery, which strongly supports the a medical and psychosocial history fibrosis and cell loss have been docu- concept that recovery of sensory func- evaluation and targeted physical mented post mortem in the dorsal root tion and anatomical reinnervation of examination to confirm the diagnosis, ganglion.12 Pain and unilateral rash the skin are not prerequisites for pain document comorbid illnesses, and are typical symptoms, often accompa- resolution.16 provide a basis for treatment. nied by paresthesias and itching. Most patients experience pain during HZ. Burden of the Disease Antiviral Agents Pain precedes rash in three-quarters of cases, lasting usually for some days Pain is the most important outcome of Although HZ is a self-limiting and before the eruption of the rash. As HZ. It interferes with general activity, benign disease in most patients, those described above, only a minority of sleep, and mood, and patients with who have a high risk of develop- patients continue to have pain long more severe pain are more likely to re- ing complications should be treated after the healing of the rash. port symptoms of anxiety and depres- actively. Systemic antiviral therapy HZ can also give rise to non-pain sion.17, 18 Health-related quality of life is strongly recommended as first-line complications, which can be ophthal- instruments measure four key health treatment for all immunocompetent mic (e.g., keratitis or uveitis), neuro- domains: physical, psychological, so- patients with HZ who fulfill any of the logical (e.g., cranial and peripheral cial, and functional. Both HZ and PHN following criteria (ideally within 72 nerve palsies), circulatory (vasculitis have effects on patients’ lives across hours of the onset of rash): (1) are at and stroke), dermatological (e.g., bacte- all four health domains. Reduced qual- least 50 years of age; (2) have moder- rial superinfection), or visceral (e.g., ity of life is a particular problem in ate or severe pain; (3) have a moderate pneumonia).13 patients whose pain persists as PHN, or severe rash; or (4) have non-truncal 21 Those who continue to suffer from and there is a correlation between in- involvement. prolonged pain after HZ may describe creasing pain severity and the extent Acyclovir, famciclovir, and valacy- one or more of three broad types of of PHN’s negative impact on quality of clovir have been approved by the U.S. pain: (1) a constant deep aching or life.13 A study comparing patients with Food and Drug Administration for the burning pain; (2) an intermittent parox- PHN to patients with chronic low back treatment of HZ. All of them inhibit ysmal pain with a lancinating quality; pain showed similar pain intensity, viral replication in the infected cells, and (3) an intermittent pain evoked by physical function, cognitive function, resulting in accelerated healing of rash normally innocuous sensory stimuli and mood in both groups, but pain and decreased severity and duration of (allodynia), typically mechanical but in severity depended on different things acute pain.