– Christian Hoffmann –
Herpes zoster is the reactivation of an earlier infection with varicella virus, which subsequently maintains a lifelong residence in the spinal ganglia. Herpes zoster episodes can occur even in HIV patients with relatively good immune status, and are also seen during immune reconstitution (Martinez 1998). With more advanced immunodeficiency, herpes zoster tends to become generalized. In addition to involvement of one or more dermatomes, dangerous involvement of the eye (affecting the ophthalmic branch of the trigeminal nerve, “herpes zoster ophthalmicus”, with corneal involvement) and ear (herpes zoster oticus) may occur. Most feared is involvement of the retina with necrotizing retinitis. The neurological complications include meningoencephalitis, myelitis and also involvement of other cranial nerves (Brown 2001).
Signs and symptoms
There are often prodromal signs with headache, malaise, and photophobia, accompanied only rarely by fever. The affected areas are initially hypersensitive, and then become pruritic and/or painful within hours or days. Pain can precede lesions by several days. Lesions often show segmental, yet always unilateral, erythema with herpetiform blisters within one or more dermatomes. Lesions ulcerate, are often hemorrhagic, and gradually dry up. They should be kept dry and clean to avoid bacterial superinfection. Involvement of several dermatomes often leaves treatment-resistant pain syndromes with zoster neuralgia. Post-herpetic neuralgia can be assumed if pain persists after more than a month (Gnann 2002).
Cutaneous involvement usually allows clinical diagnosis of herpes zoster. However, diagnosis may be difficult especially on the extremities and in complicated zoster cases. Typical cases do not require further diagnostic tests. If there is uncertainty, a swab may be taken from a blister and sent to the laboratory in viral culture media. An immunofluorescence assay is presumably more reliable. VZV encephalitis is only detectable through analysis of CSF by PCR. Herpes zoster oticus should be considered in cases of unilateral, peracute hearing loss, which is not always visible from the outside. Either examine the ear yourself or consult an ENT specialist! For visual impairment the same rules apply as for CMV retinitis – refer the patient to the ophthalmologist as quickly as possible.
Monosegmental zoster can be treated on an outpatient basis with oral acyclovir. Rapid initiation of treatment is important. Systemic therapy is always necessary, and doses are higher than for HSV. Lesions dry up more rapidly if calamine lotion is used, which also relieves pain. Gloves should be worn, given that the lesions are highly infectious initially. Likewise, unvaccinated individuals without a history of chickenpox should not come into close contact with a case of herpes zoster.
Analgesics (novaminsulfone, or better still tramadole) should be given generously. Any complicated, multi-segmental or facial herpes zoster should always be treated with intravenous therapy. This can also be done in ambulatory care with a competent nursing service.
As with HSV, several alternatives for treatment include valacyclovir, famcyclovir and brivudine (see HSV). The unpleasant post-herpetic neuralgia allegedly occurs less frequently under these drugs than under acyclovir in HIV-negative patients (Gnann 2002). However, according to the recent Cochrane analysis these results are not clear (Li 2009). Valacyclovir, famcyclovir and brivudine have not been tested widely in HIV patients, and are not licensed for treatment of immunocompromised patients. They are also substantially more expensive than the numerous acyclovir formulations. Acyclovir resistance may occur in the thymidine kinase gene, but is rare (Gershon 2001, Saint-Leger 2001). In these cases, foscarnet can be given.
Pain management of post-herpetic neuralgia is problematic. Carbamazepine or gabapentine only partially help. Steroids are generally not advised (Gnann 2002). Since November 2007 lidocaine medicated plasters (Versatis®) are licensed for Europe which are stuck on painful areas. Side effects are local skin irritation. Herpetic lesions should be healed before use (Garnock-Jones 2009). In 2009, the FDA approved Qutenza® 8% patch for the management of neuropathic pain due to postherpetic neuralgia (PHN). Qutenza® delivers a synthetic form of capsaicin, the substance in chili peppers that gives them their heat sensation, through a dermal delivery system. The patch is applied by a physician or a healthcare professional.
Varicella vaccination, previously contraindicated in HIV patients, seems to be fairly safe and effective for patients with more than 400 CD4 T cells/µl (Gershon 2001, Weinberg 2010). It should be considered if VZV serology is negative. In individuals with negative serology and exposure to highly infectious VZV, administration of hyperimmunoglobulin (2 mg/kg i.v.) may be attempted in individual cases. Long-term primary prophylaxis is not advised. Some dermatologists, however, prefer long-term therapy with low doses if there are persistently recurring episodes.
Treatment/prophylaxis of VZV infection (daily doses)
|Acute therapy||Duration: at least 7 days|
|Treatment of choice||Acyclovir||Acyclovir 1 tbl. at 800 mg 5x/day|
|Severe cases||Acyclovir 1-2 amp. at 500 mg tid (10 mg/kg tid) i.v.|
|Alternatives||Valacyclovir||Valacyclovir 2 tbl. at 500 mg tid|
|Alternatives||Famciclovir||Famciclovir 2 tbl. at 250 mg tid|
|Alternatives||Brivudin||Brivudin 1 tbl. at 125 mg qd|
Brown M, Scarborough M, Brink N, Manji H, Miller R. Varicella zoster virus-associated neurological disease in HIV-infected patients. Int J STD AIDS 2001, 12:79-83.
Garnock-Jones KP, Keating GM. Lidocaine 5% medicated plaster: a review of its use in postherpetic neuralgia. Drugs 2009, 69:2149-65.
Gershon AA. Prevention and treatment of VZV infections in patients with HIV. Herpes 2001, 8:32-6.
Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med 2002, 347:340-6.
Li Q, Chen N, Yang J, et al. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2009, 2: CD006866.
Martinez E, Gatell J, Moran Y, et al. High incidence of herpes zoster in patients with AIDS soon after therapy with protease inhibitors. Clin Infect Dis 1998, 27:1510-3.
Saint-Leger E, Caumes E, Breton G, et al. Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with AIDS. Clin Infect Dis 2001, 33:2061-7.
Weinberg A, Levin MJ, Macgregor RR. Safety and immunogenicity of a live attenuated varicella vaccine in VZV-seropositive HIV-infected adults. Hum Vaccin 2010, 6:318-21.