Chickenpox: The Varicella Zoster Virus 2.0 Contact Hours Presented by: CEU Professor

Transcription

1 Chickenpox: The Varicella Zoster Virus 2.0 Contact Hours Presented by: CEU Professor 7 Copyright The Magellan Group, LLC All Rights Reserved. Reproduction and distribution of these materials is prohibited without the written consent of The Magellan Group, LLC

2 Chickenpox : The Varicella Zoster Virus By Joe Knight, PA-C Objectives 1. Explain what primary infection in childhood sets the stage for a herpes zoster attacks in later life. 2. List the three rare, but potentially serious, complications of childhood chickenpox. 3. Explain the primary complication of a herpes zoster (shingles) attack. 4. List and describe the three pain syndromes of post-herpetic neuralgia (PHN). 5. List, describe and be able to explain the dosage regimen for the three antiviral medications approved by the Food and Drug Administration (FDA) for the treatment of herpes zoster. Introduction The primary infection with the Varicella Zoster Virus (VZV) is typically a case of childhood chickenpox. Recurrence of the infection is localized and is known as herpes zoster, more commonly called shingles. With 500,000 to one million new cases occurring in the United States annually, herpes zoster (HZ) is a serious public health problem, particularly among the elderly. 1 The Varicella Zoster Virus (Chickenpox) Chickenpox is highly contagious, rapidly spreading in areas of crowding, such as schools and daycare centers. Chickenpox occurs worldwide and affects both sexes and all races equally. 2 By adulthood, more than 90% of the population has had chickenpox; in 20% of these patients, reactivation in the form of herpes zoster occurs. The medical importance of chickenpox continues to be significant. In 1995, before a vaccine was developed, there were an estimated 4 million cases in the United States, with about 11,000 to 13,500 hospitalizations and as many as 140 deaths. 3 Neurological complications are uncommon but potentially serious. In about 1 case in 1000, encephalitis, which can be lethal, develops a few days after the appearance of the rash. More rare neurological developments include Guillain- Barré Syndrome and Reye s Syndrome. Varicella has an incubation period of 13-to-17 days. After entry into the host, usually by the airborne route from a person with chickenpox or active herpes zoster, the virus presumably invades the respiratory tissue of the susceptible person. The virus then replicates in the

3 nasopharynx and regional lymph nodes about days four to five. The virus then replicates in the liver, spleen and other organs. 4 On days 10 to 12, blood-borne spread of the virus to the sensory ganglia occurs, and then the virus reaches the skin via the white blood cells. On or about day 14, the skin becomes infected and further replication of the virus in the skin results in the characteristic vesicles with a red base. 4, 5 Chickenpox usually presents as a pruritic, vesicular rash, usually preceded by systemic symptoms such as fever, chills and malaise. New vesicles generally stop forming in four-to-five days, and most have crusted within six-to-seven days. Patients are noncontagious and allowed to return to school once all the lesions have crusted. In 1995, the varicella vaccine was introduced in an effort to prevent cases of severe disease and death. It is a live attenuated virus vaccine, and is about 95% effective against severe forms of the disease. The vaccine has been extremely effective. For example, from 1995 to 2000, in the Antelope Valley, California, Travis County, Texas, and West Philadelphia, Pennsylvania, chickenpox cases declined 71, 84 and 79 percent respectively, while hospitalizations were 50 to 80 percent lower. Cases declined in all age groups, including infants and adults. The declines were greatest among preschool children aged one-to-four years old. 6 The advent of the varicella immunization, as well as many school districts requiring the immunization for school admission, should decrease the number of cases, as well as the severity of complications. Pathophysiology After chickenpox resolves, the virus is thought to remain latent in the dorsal root or cranial ganglion. Immune suppression caused by drug therapy, disease or physical or emotional stress may reactivate the virus. Aging also decreases the cell-mediated immunity to the virus, although the antibody to the virus remains. 7 The virus then reactivates as herpes zoster (shingles). The pain of shingles can be severe. The principal complication of shingles is postherpetic neuralgia (PHN) which is generally defined as pain that persists for more than three months following an outbreak; 8 the pain continues and can increase as time passes, even after the lesions have healed. Up to 70% of untreated elderly herpes zoster patients may experience PHN. Up to 15% of untreated patients have persistent pain after one month after healing of the acute rash, and 25% of these patients still have pain after one year. 9 Hope-Simpson noted that the prevalence of pain beyond one month of the onset of the rash was about 3% to 4% in those ages 30 to 49 years old, but reached 21% in those 60 to 69 years old, and 34% in those 80 and older. 10 The chronic pain may result in sleep loss, chronic fatigue and depression, which can disrupt the most basic of living skills such as dressing, bathing and walking. In one study, 59% of patients afflicted with PHN were prevented from pursing their usual activities for as long as 16 years, with an average duration being 1.4 years. 11 In another study, 31% of patients with PHN experienced low levels of satisfaction with pain medication, and 40% experienced moderated anxiety and depression. 12 The pain of PHN can be classified into three syndromes: dysesthesia, allodynia and hyperesthesia. Dysesthesia is defined as an unpleasant, abnormal sensation that is spontaneously

4 evoked. Allodynia is pain that is evoked by normal innocuous stimuli, such as the touch of a shirt. Hyperalegesia is pain of exaggerated severity in response to normal painful stimuli. 13 Epidemiology The aging of the population of the United States brings with it an increasing number of herpes zoster cases. Lifetime incidence of herpes zoster is 10% to 20%, and up to 50% in people that survive to 85 years old. 14 The incidence and severity of herpes zoster is also higher among immunocompromised individuals. 15 Patients with HIV or AIDS have a 12- to 17-fold greater risk of developing herpes zoster, while in patients with hematological malignancies have a 5% to 10% of being afflicted with herpes zoster. 16 Signs and Symptoms In 90% of herpes zoster cases, reactivation is presaged by pain and cutaneous sensitivity along a dermatome. Three-or-four days later, the lesions erupt. Over the course of several days, groups of vesicles on a red base develop along one or more of these dermatomes. The vesicles then become pustular as white blood cells infiltrate to kill the virus. Shingles usually present along a thoracic dermatome, but if the lesions occur in the lumbar region, management can be complex because patients may experience motor as well as sensory problems. 17 Cutaneous complications can occur, which includes scarring and disfigurement from the zoster rash and bacterial superinfection. 16 Ophthalmic complications affect 10% to 25% of individuals with herpes zoster. When the nasociliary nerve is involved, indicated by a herpetic lesion on the tip of the nose, the cornea generally becomes involved. Glaucoma is a common outcome often developing much later. Immunocompromised patients are at the highest risk for herpetic infections of the optic nerve or the retina. If left untreated, vision loss or blindness can result. 8 Any ophthalmic involvement, or herpetic lesions involving the tip of the nose, warrants immediate ophthalmologic referral. Patients with active, open herpes zoster lesions should be advised that the infection may be contagious if the fluid from the blisters comes in contact with another person, so the patient should be advised to sleep with a heavy shirt to prevent accidental contact with their bed partner. Treatment of Herpes Zoster As with most any medical condition, the earlier treatment starts, the better the outcome. Antiviral therapy should begin within 72 hours of the initial outbreak of the rash. Studies show that antiviral therapy shortens the duration of the initial outbreak by one to three days compared 18, 19 with placebo, and acute pain resolves more rapidly with these medications. Three oral antiviral agents are approved for the treatment of herpes zoster: acyclovir, famciclovir 12, 20 and valacyclovir. The following regimen for each medication is as follows:

5 Acyclovir, 800 mg five times-a-day for ten days. Famcyclovir, 500 mg three times-a-day for seven days, Valacyclovir, 1000 mg three times-a-day for ten days are also options. Pain management for herpes zoster varies on the severity of the pain. Minor pain or itching may respond nicely to NSAIDs and/or antihistamines; however, most patients will need more potent medication to alleviate the pain of herpes zoster. The main concern is PHN, which is notoriously difficult to treat. Local anesthetics, such as topical lidocaine (5%), may be of benefit. According to the International Herpes Forum, 96 pain management for PHN starts with analgesics, followed by tricyclic antidepressants such as nortriptyline or amitriptyline; nortriptyline is the preferred tricyclic antidepressant because of its more favorable side-effect profile. Narcotic medication can be employed for second-line therapy, but may be considered for first-line therapy if the pain is severe. Topical capsaicin (0.025% or 0.075%) may be effective in some patients. A combination of oral morphine and gabapentin has shown that the combination gives better pain relief than if either drug is used alone. 21 If tricyclics do not provide sufficient pain relief, the addition of anticonvulsants such as gabapentin may help. Dosage should start at 300 mg daily and slowly increased to 1,800 mg daily, though some patients may require dosages as high as 3,600 daily. Side effects include sedation and mental fogginess. 22 Tramadol is also another option for the treatment of PHN. If anticonvulsants do not provide adequate pain relief, then one should consider the use of the strong opioid analgesics, such as oxycodone or morphine. Since substance abuse among the elderly population is less of a risk than in the younger population, strong opioid medications may be safely considered. 23 On the Horizon A new vaccine for the prevention of HZ and subsequent PHN has become available. Forty years ago, Hope-Simpson reported that the incidence of HZ increased with advancing age, and hypothesized that this was due to an age-associated decline in immunity to VZV. Immunocompromisation, whether due to age, disease such as HIV/AIDS or to immunosuppressant therapies such as systemic corticosteroids or chemotherapy, is associated with a marked increase in the incidence and severity of herpes zoster. 24, 25 The vaccine helps prevent the age-related decline in cell-mediated immunity to the VZV in the elderly. Previous studies showed that VZV vaccination can boost cell-mediated immunity to VZV in immunocompetent adults, and reduce the incidence and severity of herpes zoster in bone marrow allograft recipients; 26 however, it requires a vaccine with higher potency than that of the vaccine currently licensed to prevent varicella in children to achieve a significant boost in VZV-specific immunity in older adults. This led to the hypothesis that immunization of older persons with a high-potency VZV vaccine would boost their immunity to VZV and would therefore provide protection against herpes zoster subsequent PHN. The Shingles Prevention Study (SPS) was conducted to test this hypothesis using a high-potency live attenuated VZV vaccine in adults

6 older than 59 years of age. 14 The study showed that the incidence of both herpes zoster and PHN were significantly lower in the vaccine group than in the placebo group. As a result of the SPS, vaccination of adults older than 59 years of age against herpes zoster may be recommended in the near future. Further studies need to be conducted to answer important questions that remain about herpes zoster vaccination. Conclusion The herpes viruses continue to affect patients worldwide. As the population of the United States ages, herpes zoster and postherpetic neuralgia will become more significant problems. The further development and refinement of the herpes zoster vaccine therefore holds significant promise in managing these problems as the population ages. The use of immunosuppressant medications, the AIDS epidemic and crowded living conditions will continue to present a challenge to our healthcare system. References 1. Insinga RP, Itzler RF, Pellissier JM, et al. The incidence of herpes zoster in a United States database. J Gen Intern Med. 2005;20: Straus SE, Oxman MN. In: Freedberg IM, Eisen AZ, Wolff K. et al, eds. Fitzpatrick s Dermatology in General Medicine. 5 th ed. New York: McGraw-Hill Professional;1999: Gilden DH, Mascola L, Shahady E. Herpes Zoster: Shingles, Postherpetic Neuralgia and Other Complications. Consultant. 2005(Supplement);45(12):59 4. Chartrand SA. Varicella vaccine. Ped Clin North Am. 2000;472: Rosen T, Ablon G. Cutaneous herpes virus infection update: part 2: varicella zoster virus. Consultant 1997;3(9): VZV Foundation. Accessed January 23, Arvin A. Aging, immunity and the vaicella-zoster virus. N Engl J Med. 2005;352: Jung BF, Johnson RW, Griffin DR, et al. Risk factors for post-herpetic neuralgia in patients with herpes zoster. Neurology. 2004;62: Lancaster T, Silagy C, Gray S. Primary care management of acute herpes zoster: systematic review of the evidence from ramdomized controlled trials. Br J Gen Prac. 1995;45: Hope-Simpson RE. Postherpetic neuralgia. J R Coll Gen Prac. 1975;25:

7 11. Davies L, Cossins L, Bowsher, D, et al. The cost of treatment for post-herpetic neuralgia in the UK. Pharmacoeconomics 1994;6: Prevention and Treatment of Herpes Zoster in the Primary Care Setting. Clinician Reviews CME Supplement, October, Petersen KL, Fields HL, Brennum J, et al. Capsiacin evoked pain and allodynia in postherpetic neuralgia. Pain. 2000;88: Oxman, MN, Levin MJ, Johnson, GR, et al. for the Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Eng J Med. 2005;352: Bernal I, Domenech E, Garcia-Planella E, et al. Opportunistic infections in patients with inflammatory bowel disease undergoing immunosuppressive therapy. Gastroenterol Hepatol. 2003;26: Gnann JW, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347: Ragozzino MW, Melton LJ, Kurland LT, et al. Population-based study of herpes zoster and its sequelae. Medicine (Baltimore). 1982;61: Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir [sic] compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39: Tyring S, Barbarash RA, Nahlik JE, et. Al. Famciclovir for the treatment of acute herpes zoster: effects on acute isease and postherpetic neuralgia: a randomized, double-blind, placebocontrolled trial. Ann Intern Med. 1995;123: Corey L. Clinical tools for preventing transmission of genital herpes. Medscape Infectious Diseases. 6(1) Combating Varicella Zoster Virus-related diseases. Herpes volume 13, supplement 1. June, Johnson, RW. Pain following herpes zoster: implications for management. Herpes 2004;11: Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998;50: Dolin R, Reichman RC, Mazur MH, et al. NIH conference. Herpes zoster-varicella infections in immunosuppressed patients. Ann Intern Med 1978;89:

8 25. Buchbinder SP, Katz MH,Hessol NA, Liu JY, O MalleyPM, Underwood R et al. Herpes zoster and human immunodeficiency virus infection. J Infect Dis 1992;166: Levin MJ, Smith JG, Kaufhold RM, et al. Decline in varicella-zoster virus (VZV)-specific cell mediated immunity with increasing age and boosting with a high-hose VZV vaccine. J Infect Dis 2003;188: