Headache, malaise, and a rash


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A 42-year-old man presents with a four-day history of experiencing headache, malaise, and stabbing right-sided headache. Two days after his initial symptoms appeared, he developed a rash over the area of pain. He reports that he went hiking through the Texas hill country prior to becoming ill. The patient is otherwise in good health and has an unremarkable medical history. Physical examination reveals unilateral erythematous, thin, raised plaques over the right forehead. In addition, he has no relevant social or family history.

Herpes zoster is one of the two clinical syndromes caused by the Varicella-zoster virus (VZV). Initial infection with VZV will result in varicella (chickenpox), a common pediatric infection that causes a widespread and extremely pruritic rash. After resolution, the VZV...

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Herpes zoster is one of the two clinical syndromes caused by the Varicella-zoster virus (VZV). Initial infection with VZV will result in varicella (chickenpox), a common pediatric infection that causes a widespread and extremely pruritic rash. After resolution, the VZV lays dormant in neural tissue.1-3 Shingles occurs when the virus reactivates in a sensory dorsal root ganglion and travels down the axon toward the skin.3 Patients with shingles can sometimes have a mild prodromal phase with fever, headache, and sensory changes in the dermatome corresponding to the affected ganglion.4,5 Before the appearance of the rash, this neuropathic pain can frequently lead the clinician toward incorrect diagnoses of angina, appendicitis, or early glaucoma.3

The condition usually progresses to the eruptive phase, in which groups of herpetiform vesicles gradually evolve from papules that appear over an erythematous base.3 These lesions can be immensely painful and are characteristically confined to a single dermatome, although it is not uncommon to have adjacent dermatome involvement or scattered lesions in other areas of the body. The vesicles can become necrotic, bullous, or hemorrhagic, and eventually become pustular and heal. The most frequently affected nerves are the thoracic (55%), cranial (20%), and lumbar nerves (15%). Involvement of the ophthalmic division of the trigeminal nerve (lesions on the tip of the nose) can lead to herpes zoster ophthalmicus, which can result in blindness; thus, an emergent ophthalmology referral is indicated.3-7 Although the presentation is classically that of dermatomal herpetiform vesicles, it is important to realize that varying presentations can occur (as in this patient presentation), such as unilateral erythematous plaques (without vesicles). In these nonclassic cases the presence of a prodrome preceding the rash, along with a dermatomal distribution, are instrumental in making the diagnosis.

Approximately 95% of adults in the United States are seropositive for VZV infection, and therefore at risk for developing herpes zoster.4 The annual incidence is between 1.5 and 3 cases per 1000 persons, approximating 1 million cases per year in the United States.5 The primary risk factor is age; 66% of all new cases occur in adults older than 50 years. By age 75 years, the annual incidence increases to 10 cases per 1000 persons.7 This increase is partly explained by waning cellular immunity, which keeps varicella in a latent state.8

Accordingly, immunosuppression has been associated with a higher risk of developing herpes zoster. Both corticosteroids and immune-modulating biologic drugs have been shown to increase the risk of developing shingles; HIV-positive patients have an annual incidence of 29.4 cases per 1000.9,10 A herpes zoster diagnosis has also been shown to slightly increase the risk of being diagnosed with cancer within the following year, and herpes zoster is up to 4 times more common in patients with hematologic malignancies.11,12

With the advent of the varicella vaccination, primary infections have been reduced by approximately 90%, and the live attenuated vaccine has reduced the incidence of herpes zoster in immunized individuals.13 Herpes zoster vaccination is recommended by the Centers for Disease Control and Prevention (Atlanta, GA) for all immunocompetent nonpregnant adults over the age of 60 years, as it has been shown to reduce herpes zoster rates by up to 70%.13

Diagnosis of herpes zoster is relatively straightforward given the characteristic dermatomal rash and associated pain. A thorough differential in this case includes ruling out cellulitis, zosteriform herpes simplex, contact dermatitis (in particular exposure to urushiol from poison ivy), scabies, atopic dermatitis, and pediculosis or other insect bites. If necessary, a Tzanck smear can be useful in helping to rapidly confirm the diagnosis.3 Newer laboratory tests, such as polymerase chain reaction and direct fluorescent antibody testing, offer greater sensitivity and specificity, but are more expensive and take longer to obtain results.14 Biopsy can be performed for atypical lesions, and reveal large “balloon cells” lining the intraepidermal vesicles and cellular inclusions in the cells of the vesicular epithelium.3 Atypical lymphocytes, as well as multinucleated keratinocytes, can also be present.3

Treatment of herpes zoster consists of oral or intravenous antiviral therapy. Treatment within the first 3 days of symptom onset has been shown to lessen the pain and severity of the rash. Acyclovir or its prodrugs are typically used to treat herpes zoster infections.3 Herpes zoster is commonly complicated by postherpetic neuralgia, which can cause the patient significant pain for weeks to months after the resolution of the rash. Persistent herpes zoster pain is typically the same in nature as the pain present during the eruptive phase.3 The quality of the pain is heterogeneous, but can be roughly divided into burning-aching pain, shooting-lancing pain, and allodynic or hyperalgesic pain produced by normal stimuli.3 Older individuals have a significantly higher risk for residual pain.13 Approximately 2% of patients under 40 years of age have residual pain 1 month after diagnosis, whereas in individuals aged over 60 and 70 years, these figures are 50% and 75%, respectively.3 The pain tends to recede gradually, but can last several years—although this is uncommon in any age group. Although there are many modalities used to treat the pain, the most widely prescribed medications are topical lidocaine 5% patch, tricyclic antidepressants (eg, nortriptyline), and gabapentin.

Aside from postherpetic neuralgia, herpes zoster includes a wide spectrum of complications, ranging from persistent herpes zoster to potentially fatal pneumonitis and chronic encephalitis.2 Fortunately, most of these complications are rare and occur more commonly in immunocompromised individuals.

After discussing treatment options with our patient, he was treated with a 7-day course of valacyclovir (oral 1000 mg every 8 h). His pain was treated with gabapentin, 100 mg three times daily. His rash gradually resolved over the subsequent 2 weeks and he reported no residual pain after 1 month.

Zachary Solomon, BS, is a medical student at the Baylor College of Medicine, David Rizk, BA, is a medical student at the University of South Alabama, and Connie Wang, MD, is a dermatology resident at the Baylor College of Medicine.


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