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The Case Files: An Infection that Vaccine Doesn't Prevent over Time

Cazeau, Natalie MSC; Hernandez, Erica Roman; Ijaz, Kinza; Scheuermann, Amy; Raziuddin, Ahmed MD

doi: 10.1097/01.EEM.0000525970.73514.1c
The Case Files

Ms. Cazeau, Ms. Roman Hernandez, Ms. Scheuermann, andMs. Ijazare third-year medical students at the University of Medicine and Health Sciences in St. Kitts. Dr. Raziuddinis an internist and emergency physician at Weiss Memorial Hospital, Gottlieb Memorial Hospital, and Westlake Hospital, all in Illinois. (Clockwise from top left.)

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A 43-year-old man presented to the ED with a rash in a C7 dermatomal pattern that was burning and painful. The patient said the rash began three weeks before the ED visit as a group of little blisters on his right upper back and extending down his right arm. The patient was worried and in mild distress as the rash continued to burn, and he reported numbness to the area. He mentioned he had received the shingles vaccine in the past.

The patient's rash was yellow, crusty, and tender upon palpation. The area was hyperkeratotic with noticeable scabbed lesions and cracked skin. The patient had normal range of motion without motor deficits in the right arm. Herpes zoster (HZ) is caused by the reactivation of varicella zoster virus (VZV), which occurs when immunity to VZV declines because of aging and or immunosuppression. This condition most commonly affects the elderly population; more than half of the cases of HZ occur in patients over 60. (Mayo Clin Proc 2009;84[3]:274.) The condition is diagnosed clinically by the distinctive dermatomal characteristics of the rash and the painful sensation. Herpes zoster lesions contain high concentrations of VZV, which can spread through physical contact or airborne transmission. Exposure to airborne VZV can result in primary varicella infection in susceptible people. HZ is only contagious, however, from the time after the rash appears until the lesions crust.

The condition, commonly referred to as shingles, comes from the Latin word cingulum meaning belt, which describes the rash's dermatomal pattern. The shingles infection is a well-known, dreaded potential consequence of a prior VZV infection. The rash is characterized as grouped vesicles on a red base that are located unilaterally (do not cross the midline) and undergo different stages: red macule to papule within the first seven to 10 days, which then progresses to vesicles and ultimately pustules and crusty lesions. These crusty lesions may take up to four weeks or more to completely resolve. Herpes zoster presents with pruritus, dysesthesia, and pain along the involved dermatome. This pain may occur days before the onset of the rash, leading to multiple workups and misdiagnoses.

Early detection and treatment of HZ reduces the acute symptoms and severity of postherpetic neuralgia (PHN). Differential diagnoses for HZ include the herpes simplex virus, candidiasis, contact dermatitis, impetigo, autoimmune blistering diseases, and dermatitis herpetiformis. The most sensitive and specific diagnostic test to confirm the diagnosis of HZ is viral DNA PCR, but PCR is not necessary if the clinical presentation is distinctive for HZ.

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Timing is Key

Common complications include postherpetic neuralgia, superinfection with Staphyloccocus aureus and Streptococcus pyogenes, scarring, and hyperpigmentation. Shingles can also lead to pneumonia, hearing problems, blindness (herpes zoster ophthalmicus), encephalitis, cranial and peripheral nerve palsies, and sometimes death. Approximately 13 percent of those 60 and older with HZ will get PHN, which mainly consists of pain persisting for more than three months after the initial shingles rash has healed. (Mayo Clin Proc 2009;84[3]:274.)

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The risk of PHN increases with age and low immunity. A large population study found the rate of PHN increased from five percent in HZ patients under 60 to 10 percent in those 60-69 and to 20 percent in those 80 and older. (Mayo Clin Proc 2007;82[11]:1341.)

The pain occurs due to viral damage to the sensory nerves. The condition is refractory to most analgesics, but effective therapy often requires multiple drugs started in a systematic pattern, initially administering a low dose and increasing the dose gradually until the pain is resolved and adverse effects are noted. The medications used for PHN include topical agents, antidepressants, anticonvulsants, and opioids. During an acute episode of HZ, symptom control and disease complication prevention is achieved with a combination of antiviral therapy, corticosteroids, and analgesics. The antivirals include acyclovir, famciclovir, and valacyclovir, which inhibit viral replication and thus decrease the duration of viral shedding. This decrease allows for faster rash healing, and reduces the duration of severe pain and the risk of PHN. Antiviral treatment is specifically recommended for patients over 50 who have moderate to severe pain and facial involvement. (Mayo Clin Proc 2009;84[3]:274.)

Clinical trials have demonstrated the effectiveness of treatment 72 hours after rash onset, though this timing is not always feasible in a clinical practice setting. Initiating antiviral treatment after 72 hours of rash onset and its benefits have not been studied, but patients with severe HZ symptoms should be started on antivirals regardless of timing, especially if there is new vesicle formation. Valacyclovir and famciclovir may be administered in an outpatient setting because they require less frequent dosing than acyclovir. Immunocompromised patients require a more aggressive IV treatment. Corticosteroids do not have any effect on PHN; their only benefit is assisting a faster resolution of the acute symptoms when combined with antiviral therapy. NSAIDs are ineffective in treating acute HZ pain; instead, acute pain can be relieved by antivirals, and associated HZ pain can be treated with opioids.

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Decreased Efficacy

The shingles vaccine is a protective measure recommended for those 60 and older. (http://bit.ly/2xVBWDS.) The shingles vaccine, Zostavax, is a live attenuated vaccine given as a one-time subcutaneous injection. It is composed of an antigen glycoprotein E (IgE) and an adjuvant system. Zostavax has been the only shingles vaccine approved in the United States since 2006. A 2016 study by Cunningham, et al., found that the herpes zoster subunit vaccine reduces the risks of herpes zoster by 89.8 percent and postherpetic neuralgia by 88.8 percent among adults 70 and older. (N Engl J Med 2016;375[11]:1019.) The 2015 Shingles Prevention Study gathered individuals 60 and older who received the shingles vaccine, and determined that the vaccine significantly reduced the incidence of shingles. The shingles vaccine decreases the risk of contracting shingles and PHN by 51 percent and 67 percent, respectively. (http://bit.ly/2xVBWDS.)

These results suggest a benefit associated with early vaccination, but a study by Morrisson, et al., showed there is still a risk of reactivation of VZV resulting in shingles. (Clin Infect Dis 2015;60[6]:900.) One of the causes for shingles infection in vaccinated adults is the issue of decreased vaccination efficacy over time. The Morrisson study highlights the decline of the vaccine's efficacy from years seven to 11 post-vaccination (46% decline in efficacy year seven to 14% decline in efficacy in year 10). The downward trend of the vaccine's efficacy throughout the years may be due to decreasing levels of vaccine-induced immunity and or a decline in the host's immunosenescence.

HZ vaccination is recommended for the elderly population as a preventive measure against shingles, though vaccination does not prevent all shingles infections. Current guidelines do not support revaccination with Zostavax, but future studies may allow researchers to assess the long-term protection of the HZ vaccine as well as the possible benefit of revaccination.

The patient in this case was discharged with tramadol, acyclovir ointment, clindamycin, and oral acyclovir. He was instructed to follow up with his primary care physician in one to two days.

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