Warts, Herpes Simplex, And Ot... Health Article

Between 20% and 72% develop ocular complications. Anterior uveitis and the various varieties of keratitis are most common, affecting 92% and 52% of patients with ocular involvement, respectively. Sight-threatening complications include neuropathic keratitis, perforation, secondary glaucoma, posterior scleritis/orbital apex syndrome, optic neuritis, and acute retinal necrosis (Table 12-3). Twenty-eight percent of initially involved eyes develop long-term ocular disease (6 months), with chronic uveitis, keratitis, and neuropathic ulceration being the most common.

Prompt treatment with oral antiviral drugs (see Table 12-4) reduces the severity of the skin eruption, the incidence and the severity of late ocular manifestations, and the intensity of PHN. At 6 months, late ocular inflammatory complications are seen in 29.1% of acyclovir-treated patients versus 50% to 71% of untreated patients. Ophthalmic 3% acyclovir ointment may be used for established ocular complications. ⁶⁹

The strict definition of the Ramsay Hunt syndrome (geniculate ganglion zoster) is peripheral facial nerve palsy accompanied by a vesicular rash on the ear (zoster oticus) or in the mouth. It is caused by zoster of the geniculate ganglion. Other frequent signs and symptoms include tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. These eighth nerve features are caused by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Bell's palsy (facial paralysis without rash) is significantly associated with herpes simplex virus infection.

There is involvement of the sensory portion and motor portion of the seventh cranial nerve. There may be unilateral loss of taste on the anterior two thirds of the tongue and vesicles on the tympanic membrane, external auditory meatus, concha, and pinna. Involvement of the motor division of the seventh cranial nerve causes unilateral facial paralysis. Auditory nerve involvement occurs in 37.2% of patients, resulting in hearing deficits and vertigo. ⁷⁰ Recovery from the motor paralysis is generally complete, but residual weakness is possible. Sweeney discusses and diagrams the complex neuroanatomy of this syndrome. ⁷¹

The syndrome also may result from zoster of ninth or tenth cranial nerves since the external ear has complex innervation by branches of several cranial nerves.

Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. About 14% developed vesicles after the onset of facial weakness. Thus Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy.

Some patients develop peripheral facial paralysis without ear or mouth rash, associated with a fourfold rise in antibody to VZV. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete (zoster without the rash). Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy. ⁷¹

A neurogenic bladder with urinary hesitancy or urinary retention has reportedly been associated with zoster of the sacral dermatome S2, S3, or S4 (Figures 12-61 and 12-62). Migration of virus to the adjacent autonomic nerves is responsible for these symptoms. ⁷²

Pain persisting after herpes zoster is called postherpetic neuralgia. It is the most common and most feared complication and the major cause of morbidity. The risk of PHN increases with age (especially in patients older than 50 years) and increases in patients who have severe pain or severe rash during the acute episode or who have a prodrome of dermatomal pain before the rash appears. The pain is often severe, intractable, and exhausting. The patient protects areas of hyperesthesia to avoid the slightest pressure, which activates another wave of pain. There is a yearning for a few hours of sleep, but sharp paroxysms of lancinating pain invade the mind and the patient is again awakened. "The pain is sometimes so severe as to make the patient weary of existence." These words were written more than 100 years ago. Despair and sometimes suicide occur if hope and encouragement are not provided.

Pain can persist in a dermatome for months or years after the lesions have disappeared. The probability of longstanding pain in patients not treated with antiviral drugs is low. One large study provided the following data. Regardless of age, the prevalence of pain was 19.2% at 1 month, 7.2% at 3 months, and 3.4% at 1 year. Among patients younger than 60 years, the risk of PHN 3 months after the start of the zoster rash was 2% and pain was mild in all cases. After the age of 60, both the frequency and severity of pain increased, although moderate pain was rare after 3 months and severe pain was uncommon at all times (Figure 12-63). The probability of having severe PHN after 3 months in this age group was less than 7%, and it was less than 3% at 12 months. ⁷³

Once present, neuralgia can persist for years, but spontaneous remission may occur after several years.

Postherpetic neuralgia is associated with scarring of the dorsal root ganglion and atrophy of the dorsal horn on the affected side. These changes are caused by the extensive inflammation that occurs during the active infection.

A few vesicles may be found remote from the affected dermatome in immunocompetent patients and is probably a result of hematogenous spread of the virus. Cutaneous dissemination is defined as more than 20 vesicles outside the primary and immediately adjacent dermatomes. Visceral dissemination (lungs, liver, brain) occurs in 10% of immunocompromised patients. In addition, patients with Hodgkin's disease are uniquely susceptible to herpes zoster. Furthermore, 15% to 50% of zoster patients with active Hodgkin's disease have disseminated disease involving the skin, lungs, and brain; 10% to 25% of those patients die. ⁷⁴ In patients with other types of cancer, death from zoster is unusual. HIV-infected patients with zoster have increased neurologic (e.g., aseptic meningitis, radiculitis, and myelitis) and ophthalmologic complications.

Muscle weakness in the muscle group associated with the infected dermatome may be observed before, during, or after an episode of herpes zoster. The paralysis usually occurs in the first 2 to 3 weeks after rash onset and can persist for several weeks. The weakness results from the spread of the virus from the dorsal root ganglia to the anterior root horn. Patients in the sixth to eighth decade of life are most commonly involved. Motor neuropathies are usually transient and approximately 75% of patients recover. They occur in approximately 5% of all cases of zoster but in up to 12% of patients with cephalic zoster. Ramsay Hunt syndrome accounts for more than half of the cephalic motor neuropathies.

Neurologic symptoms characteristically appear within the first 2 weeks of onset of the skin lesions. It is possible that encephalitis is immune mediated rather than a result of viral invasion. Patients at greatest risk are those with trigeminal and disseminated zoster, as well as the immunosuppressed. The mortality rate is 10% to 20%; most survivors recover completely. The diagnosis is hampered by the fact that the virus is rarely isolated from the spinal fluid. Cell counts and protein concentration of the spinal fluid are elevated in encephalitis and in approximately 40% of typical zoster patients.

Elderly, malnourished, debilitated, or immunosuppressed patients tend to have a more virulent and extensive course of disease. The entire skin area of a dermatome may be lost after diffuse vesiculation. Large adherent crusts promote infection and increase the depth of involvement (Figure 12-64). Scarring, sometimes hypertrophic or keloidal (see Figures 12-57 and 12-58), follows.

The diagnosis of herpes zoster is usually obvious. Herpes simplex can be extensive, particularly on the trunk. It may be confined to a dermatome and possess many of the same features as zoster (zosteriform herpes simplex). The vesicles of zoster vary in size, whereas those of simplex are uniform within a cluster. A later recurrence proves the diagnosis.

A group of vesicles on a red, inflamed base may be mistaken for poison ivy (Figure 12-65).

Neuralgia within a dermatome without the typical rash can be confusing. A concurrent rise in varicella zoster complement–fixation titers has been demonstrated in a number of such cases.

The eruption of zoster may never evolve to the vesicular stage. The red, inflamed, edematous, or urticarial-like plaques may appear infected, but they usually have a fine, cobblestone surface indicative of a cluster of minute vesicles. A skin biopsy shows characteristic changes.

Burrow's solution or cool tap water can be used in a wet compress. The compresses, applied for 20 minutes several times a day, macerate the vesicles, remove serum and crust, and suppress bacterial growth. A whirlpool with Betadine (povidone-iodine) solution is particularly helpful in removing the crust and serum that occur with extensive eruptions in the elderly.

Antiviral drugs reduce the severity, duration, and prevalence of PHN by as much as 50%, but 20% of patients over 50 years of age treated with famciclovir or valacyclovir report pain at 6 months (Table 12-4). ⁷⁷

Topical acyclovir ointment applied 4 times a day for 10 days to immunocompromised patients significantly shortened complete-healing time.

Valacyclovir is available only as an oral formulation. After ingestion, the drug is converted to acyclovir in the gastrointestinal tract and liver. Its oral bioavailability is 3 to 5 times that of acyclovir. Studies demonstrate a significant advantage of Valtrex compared with Zovirax on decreasing the duration and incidence of pain, including both acute pain and PHN. Valacyclovir reduced the median duration of pain from 60 days after healing (with acyclovir) to 40 days. Six months after healing, only 19% of patients taking valacyclovir had pain compared with 26% of patients taking acyclovir. Patients who may have trouble complying with 5-times-daily dosing of oral Zovirax, and patients at highest risk for PHN (e.g., older patients and those with prodromal pain) may benefit from valacyclovir.

Famciclovir is an analogue of penciclovir. It is well absorbed after oral administration and is rapidly metabolized to penciclovir in the gastrointestinal tract, blood, and liver. The intracellular half-life of the active drug, penciclovir triphosphate, is very long. Famciclovir is available for oral treatment of acute uncomplicated herpes zoster. The benefits appear to be similar to those of acyclovir. It was found to decrease the duration of PHN among elderly patients compared with placebo.

Acyclovir decreases acute pain, inflammation, vesicle formation, and viral shedding. The median duration of pain in acyclovir recipients is 20 days vs. 62 days for their placebo counterparts. Several studies show no effect on the subsequent development of PHN, even in patients who experience immediate pain relief. A study showed a possible reduction in the incidence of PHN if treatment began within 4 days of the onset of pain or within 48 hours of the onset of rash. ⁷⁸ Acyclovir appears to change the nature of PHN. Its use should be considered for immunosuppressed, debilitated patients who appear to be developing extensive cutaneous disease and for patients with ophthalmic zoster who are at increased risk of ocular complications. Treatment is most effective when started within the first 72 hours of infection. If lesions are not completely crusted and the patient is older than 50 years, immunocompromised, and/or has trigeminal zoster, treatment after 72 hours of the onset of vesicles should be considered. The recommended oral dosage is shown in Table 12-4. Proper hydration and urine flow must be maintained.

Persons with AIDS who have CD4 ⁺ counts of less than 100 cells/mm ³ and transplant recipients, especially bone marrow allograft recipients, may experience infections with acyclovir-resistant VZV. Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Treatment with foscarnet (40 mg/kg intravenously every 8 hours) should be initiated within 7 to 10 days in patients suspected to have acyclovir-resistant VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed. ⁷⁹

Acyclovir (30 mg/kg/day at 8-hour intervals) and vidarabine (continuous 12-hour infusion at 10 mg/kg/day) for 7 days (longer if resolution of cutaneous or visceral disease is incomplete) are equally effective for the treatment of disseminated herpes zoster. The resultant mortality rate is low. ⁸⁰

The use of systemic steroids during the early acute phases of herpes zoster to prevent PHN has been controversial. A double-blind, controlled trial showed that prednisolone therapy initiated at a dose of 40 mg/day and tapered over a 3-week period does not reduce the frequency of PHN. Pain reduction is, however, greater during the acute phase of disease and a quicker rash resolution. ⁸¹

There are no significant differences between steroid-treated and non–steroid-treated patients in the time to a first or a complete cessation of pain. Steroid recipients report more complications. ⁸¹

In another controlled study, patients were treated with acyclovir and prednisone (60 mg/day for the first 7 days, 30 mg/day for days 8 to 14, and 15 mg/day for days 15 to 21). Time to total crusting and healing was accelerated. There was accelerated time to cessation of acute neuritis, time to return to uninterrupted sleep, time to return to usual daily activity, and time to cessation of analgesic therapy. Resolution of pain during the 6 months after disease onset did not statistically differ from that of patients with no treatment. No important clinical or laboratory adverse events occurred in any group. The authors concluded that in relatively healthy persons older than 50 years who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life. ⁸²

Attenuation or elimination of pain in the eruptive stage and for PHN may be accomplished with the following technique. ⁸³ Lidocaine (Xylocaine) 0.5% to a total of 4 to 5 ml is injected into the subcutaneous tissue at the most painful sites. For patients with intolerable pain and/or necrotic herpes zoster, 2 ml of 1% lidocaine is injected deep into the proximal area, innervating the herpes zoster lesions. Injections are repeated every 4 to 5 days as needed. Others have claimed substantial relief with a similar schedule using subcutaneous injections through the affected skin with a combination of lidocaine and triamcinolone acetonide (Kenalog). ⁸⁴ The mixture is prepared by diluting triamcinolone acetonide (10 mg/5 ml) with equal parts 1% lidocaine. Tumescent infiltration of corticosteroids, lidocaine, and epinephrine into dermatomes of acute herpetic pain or PHN provided immediate and sustained relief in several patients in a pilot study. ⁸⁵

Sympathetic blocks (stellate ganglion or epidural) with 0.25% bupivacaine terminates the pain of acute herpes zoster ⁸⁶ and possibly prevents or relieves PHN in patients treated within 2 months of onset of the acute phase of the disease. Three injections are made on alternate days. When thoracic dermatomes are involved, an epidural catheter is left in place for the 5 days of therapy to avoid having to replace the needle each time. Epidural injections are made at or just above the highest dermatome of the rash. There is prompt relief of pain and all symptoms are usually gone after the second injection. ⁸⁷ Sympathetic blockade applied within the first 2 months after the onset of acute herpes zoster terminates ⁸⁸ the acute phase of the disease, probably by restoring intraneural blood flow and thus preventing the death of the large fibers and avoiding the development of PHN. After 2 months, the damage to the large fibers is irreversible.