Woman With Vesicles and Crusts on Her Forehead

For 3 days, a 60-year-old woman has had a tender rash on her forehead. The lesions erupted 2 days after she sustained minor trauma to the left side of the forehead (Figure 1); no scratches or bleeding were associated with the injury. She noted a burning sensation and mild tenderness at the site shortly before the lesions arose. The patient has no significant medical history; she takes no medications and did not receive the varicella vaccine. She does not recall any similar eruptions in the past anywhere on her body. Vesicles and crusts on an erythematous base in a linear distribution are present on the left aspect of the forehead (Figure 2). The lesions do not cross the midline. The eyes and the nasal apex are not affected; lymph nodes are not palpable. Herpes zoster ophthalmicus (HZO) following trauma to the forehead is strongly suspected. The diagnosis is confirmed by polymerase chain reaction (PCR) for varicella zoster virus (VZV) DNA. Oral valacyclovir, 1000 mg tid, is prescribed. Seven days later, the pain has subsided and a crust has formed on the forehead at the site of the vesicles (Figure 3). Post-herpetic neuralgia has not developed. CLINICAL FEATURES
HZO—cutaneous lesions in the dermatome associated with the ophthalmic division of the trigeminal nerve (cranial nerve V1)—results from reactivated VZV that travels down the ophthalmic nerve from the trigeminal ganglion; the virus reaches the nerve endings within 3 to 4 days.^1,2 Cranial nerve V1 comprises the frontal nerve; the lacrimal nerve; and the nasociliary nerve, which provides sensory innervation to the cornea, ciliary body, iris, and conjunctiva. The terminal branch is the anterior ethmoidal nerve, which innervates the sides and tip of the nose. HZO most often involves the supraorbital and supratrochlear branches of the frontal nerve, which innervate the upper eyelid and forehead. Paresthesias or pain along the involved dermatome may precede the development of the vesicles. Vesicular eruption on the forehead, lymph node enlargement in the drainage areas, fever, malaise, headache, occasional neck stiffness, and a reactive conjunctivitis with or without corneal involvement follow. Prodromal lymphadenopathy can be confused with later reactive adenopathy that is caused by secondary infection of vesicles. The presence of VZV vesicles on the side or the tip of the nose in the distribution of the nasociliary nerve (Hutchinson sign) may herald ocular involvement. However, severe ocular complications can occur with a vesicular rash anywhere on the forehead. Herpes zoster develops in about 20% of persons who were exposed to VZV during childhood.³ Risk factors for reactivation of the latent VZV are diabetes, advancing age, cancer, surgery, radiation, chemotherapy, immunosuppressing drugs, systemic corticosteroid therapy, stress, and AIDS.^1,4 Persons with HIV infection are at increased risk for herpes zoster and are more likely to have severe disease. Thus, suspect HIV infection in patients younger than 45 years who present with herpes zoster.⁵ Trauma to the skin from injury or sunburn can also cause the VZV to reactivate, as in this patient. Older age, prolonged prodromal pain, and severe acute pain are risk factors for severe post-herpetic neuralgia.^6,7 CONFIRMING THE DIAGNOSIS
Several methods are available to confirm the diagnosis of a herpesvirus infection. Tzanck smear. A cytologic smear of scrapings from the base of a vesicle is prepared with Wright or Giemsa stain. Multinucleated giant cells are characteristic of herpes zoster, varicella, and herpes simplex. Punch biopsy. This technique provides more dependable material for histologic examination, particularly when a bacterial or fungal infection is present. Usually, results show multinucleated giant cells and Cowdry type A intranuclear inclusion bodies. Results of the biopsy can confirm the presence of Herpesviridae but—like a Tzanck smear—cannot identify the specific herpesvirus. Viral culture. A viral culture can distinguish among herpes simplex 1, herpes simplex 2, and VZV. VZV infection is best confirmed by isolation of virus in tissue culture. Often, a positive result is available within 48 hours of specimen inoculation; however, cytopathic effects may take up to 5 days. Direct immunofluorescence assay (DFA). This test uses fluorescein(Drug information on fluorescein)- tagged antibody directed against viral antigen. DFA has a higher sensitivity and specificity than Tzanck smear in vesicular lesions. This method yields rapid results and can differentiate herpes simplex virus from VZV. PCR. This method is growing in use and availability. It is a rapid, sensitive, and simple technique for diagnosis of VZV infection. COMPLICATIONS
Post-herpetic complications are more common in HZO than in other manifestations of zoster. Without prompt detection and treatment, eye involvement threatens the patient’s vision. Iritis, iridocyclitis, glaucoma secondary to uveitis, keratitis, corneal neovascularization, corneal tissue ulcerations, scarring, and secondary bacterial or fungal infection are possible sequelae. Immediate intervention can prevent or ameliorate complications; however, glaucoma may result from corticosteroid treatment. Palsy of the third cranial nerve, and occasionally of the fourth and sixth cranial nerves, may occur.^2,3 Post-herpetic neuralgia, which affects more than half of patients with HZO, may be severe and long-lasting; it requires intensive management.¹ TREATMENT
Herpes zoster ophthalmicus. This disease warrants aggressive treatment and assiduous follow-up. Obtain ophthalmologic consultation early for patients with significant ocular symptoms. Local therapies include warm, moist compresses. Prescribe ocular lubricants to hydrate the cornea and conjunctivae. Antiviral agents—initiated within 72 hours of disease onset—are the cornerstone of systemic treatment. Acyclovir, 800 mg 5 times daily for 7 days, can reduce pain and hasten resolution of lesions. This agent can abort recurrences if initiated immediately at onset of symptoms. Valacyclovir is a prodrug that rapidly converts to acyclovir. Given in the standard oral regimen of 1000 mg tid for 7 days, valacyclovir is as effective as acyclovir for the prevention of ocular complications of HZO. Patients tolerate both drugs equally; however, the valacyclovir regimen may be easier to follow.⁸ Famciclovir(Drug information on famciclovir) is also a prodrug; it is biotransformed into the active metabolite penciclovir. The recommended oral dose for adults is 500 mg q8h for 7 days. Famciclovir and valacyclovir are equally effective in hastening the resolution of zoster-associated pain and post-herpetic neuralgia⁹; some physicians believe acyclovir may be comparable to the other agents in this setting. Systemic corticosteroids are used to ameliorate pain. Oral prednisone(Drug information on prednisone), 1 to 2 mg/kg qd (not to exceed 60 mg/d) tapered over 2 weeks, may be prescribed as symptoms resolve. The use of these agents is controversial; they can increase the risk of visceral and cutaneous dissemination, especially in immunocompromised patients.¹⁰ Post-herpetic neuralgia. For patients with post-herpetic neuralgia, applications of capsaicin cream, 4 times daily, may help deplete pain fibers of substance P and reduce pain impulses. Tricyclic antidepressants, such as amitriptyline(Drug information on amitriptyline), are often helpful, particularly when the agents are initiated early in the course of HZO. Analgesics— including narcotics, acetaminophen, aspirin(Drug information on aspirin), and NSAIDs— may also be used. When secondary bacterial infection of the vesicles occurs, give an antibiotic that covers gram-positive skin flora. Studies of patients with acute herpes zoster who were older than 50 years showed that antiviral therapy (ie, famciclovir or valacyclovir for 7 days) started within 72 hours of rash onset and/or low-dose amitriptyline given for 90 days may reduce the incidence and duration of post-herpetic neuralgia. Corticosteroids and analgesics do not prevent post-herpetic neuralgia.¹¹ PREVENTION OF TRANSMISSION AND RECURRENCE
Persons who have not had chickenpox are at risk for contracting herpes zoster; advise such patients to avoid close contact with persons who have active zoster lesions. In addition, varicella can be contracted from exposure to herpes zoster. Patients infected with VZV need to avoid known precipitating factors— such as sun exposure, stress, and immunosuppressive medications— that can lead to recurrence of the infection.