Other markers of increased risk for CNS involvement include HZ in a cranial nerve dermatome or the presence of cutaneous dissemination. Patients must understand that TCAs have an analgesic effect that is independent of their antidepressant effect. Because of the risk of ocular involvement, intravenous acyclovir and evaluation by an ophthalmologist is recommended for highly immunocompromised patients who present with HZ ophthalmicus [201]. Ocular findings. However, the recently completed trial of a vaccine to prevent HZ found that 20% of suspected cases could not be confirmed by PCR [28]. Nevertheless, multiple studies from clinical diagnostic laboratories indicate that as many as 10% of specimens submitted from patients with presumed HZ instead contain HSV [69, 70]. Acute retinal necrosis caused by VZV has been described in immunocompetent patients. Often affecting individuals with compromised immunity, it occurs when the virus spreads throughout the body. Neural blockade. For this reason, the delay in instituting antiviral therapy should be as short as possible, to limit additional neural damage beyond what may have occurred before rash onset. If antiviral treatment is delayed there is an increased risk of development of disseminated VZV [ 9 ]. Pharmacotherapeutic and nonpharmacologic approaches require particular attention in individuals with dementia. Prescription pain medicine may be … It is likely that the incidence of HZ will change further over the coming decades, as a result of the increasing age of the population, changes in therapy for malignant and autoimmune diseases, and the increasing use of organ transplantation, and, possibly, as a consequence of childhood varicella vaccination. Brivudin (125 mg once daily for 7 days) has been approved for the treatment of HZ in several countries. We report a case of VDVZV contracted during immunosuppressive therapy for membranous nephropathy. Nevertheless, a substantial percentage of patients are often refractory to these treatments used alone or in combination [111] and require treatment in settings specializing in pain management. Less commonly, the rash can be more widespread and affect three or more dermatomes. For stromal keratitis and uveitis, topical corticoste­roids are used judiciously with close monitoring. Patients should be monitored for four to six weeks after vaccine administration for viral reactivation, although this occur­rence is rare. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. However, in preliminary data analyses from a randomized trial [169], gabapentin titrated to a maximum dosage of 1800 mg daily did not differ from placebo in reducing acute pain in HZ within the first 2–3 weeks after rash onset. Two well-designed clinical trials demonstrated that the addition of a 3-week tapering dosage of a corticosteroid did not contribute significantly, beyond the benefits achieved by acyclovir alone, in reducing prolonged pain [148, 153]. Immunocompromised patients are clearly at increased risk for the development of encephalitis [73, 74]. Although rare, the development of HZ does occur during pregnancy. Mortality rate from disseminated herpes zoster is between 5% and 15%. Regarding prophylaxis, the varicella and the zoster vaccines are not recommended for pregnant women, and it is important to advise non-immune pregnant women to avoid an exposure to VZV. Antiviral treatment should be started at any time during the disease course (not only within the first 48 hours, as with zoster not associated with HIV). Specimens must be properly obtained for optimal laboratory diagnosis. Data sources and study selection. Atypical manifestations of HZ can also occur in immunocompromised patients. If I have disseminated zoster/shingles (more than one area of blisters), what can I expect for my hospital stay? Important elements in establishing the diagnosis by observation include (1) painful or abnormal sensory prodrome (not always present); (2) dermatomal distribution; (3) grouped vesicles (however, in some cases, only papules will be observed); (4) multiple sites filling the dermatome, especially where divisions of the sensory nerve are represented; (5) lack of history of a similar rash in the same distribution (to rule out recurrent zosteriform herpes simplex; see figure 7); and (6) pain and allodynia in the area of the rash. Even after you've gotten chickenpox as a … However, there is no difference in pain outcomes when antiviral therapy is initiated before 48 h versus 48–72 h after rash onset [150], and the results of 2 uncontrolled studies revealed no significant differences in the persistence of pain between patients who initiated treatment within 72 h and those who initiated treatment at a later time [151, 152]. The dosage is commonly 20 mg of prednisone administered (together with an oral antiviral agent) orally 3 times daily for 4 days, twice daily for 6 days, and then once daily every morning for 4 days. They may also decrease your risk of developing nerve pain. However, the well-replicated finding that more-severe acute pain is a risk factor for PHN, as well as research on the pathophysiologic mechanisms of PHN, provide the basis for hypothesizing that the combination of antiviral therapy with effective relief of acute pain may further lessen the risk of PHN beyond that achieved with antiviral therapy alone [155]. J Pediatr. Nonetheless, HZ will become a more common source of varicella as immunization programs eliminate varicella; this is already evident in cases of nosocomial varicella in the United Kingdom, where many cases arise from contact with HZ rather than varicella [30]. It is, therefore, recommended that antiviral therapy be considered even for patients whose risk of developing PHN and other complications of HZ is likely to be low. Disseminated herpes zoster (photograph provided by S.K.T.). A 36-year-old woman was diagnosed with membranous nephropathy and was being … The rash is usually accompanied by the same pain experienced during the prodrome, but this acute pain can worsen, improve, or appear for the first time during the cutaneous phase of HZ. However, it should be noted that subclinical MRI and CSF abnormalities have also been reported [60]. Potential conflicts of interest. We present a case of coinfection with disseminated HSV and VZV infection in a patient taking thalidomide for relapsed multiple myeloma. ORF 61 protein is absent from cell-free virions, which are able to establish latency in the gut ganglia. Herpes zoster (HZ), or shingles, results from reactivation of latent infection with varicella- zoster virus, which also causes chicken­pox. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. This literature and the authors' clinical and research experience were reviewed during the consensus meeting, which was chaired by the first 2 authors. Clinicians should familiarize themselves with medication acquisition costs and the reimbursements provided by their patients' insurance plans, to protect their patients' finances and encourage treatment compliance. Information on additional randomized trials that were not identified before the meeting was provided on request after the meeting. has received honoraria from Pfizer and Sanofi Pasteur MSD; S.W.W. Frail elderly individuals, a subset of vulnerable elderly individuals, are at the highest risk for death and functional decline and are characterized clinically by weakness, easy exhaustion, low levels of physical activity, slow walking speed, undernutrition/weight loss, and functional decline [237]. It is, therefore, recommended that the initiation of antiviral therapy be considered for patients presenting >72 h after rash onset with continued new vesicle formation or when there are cutaneous, motor, neurologic, or ocular complications. For such conditions as delayed contralateral hemiparesis, in which the role of active viral replication is less clear, the value of antiviral therapy is uncertain, but the potential benefits of antiviral therapy outweigh any potential risks [243]. Acyclovir (800 mg 5 times daily for 7–10 days), famciclovir (500 mg 3 times daily for 7 days, the approved dosage in United States; 250 mg 3 times daily is approved in some other countries), and valacyclovir (1000 mg 3 times daily for 7 days) have been approved by the US Food and Drug Administration for the treatment of HZ. The onset of encephalitis may occur months after an episode of HZ; 30%–40% of these patients have no recognized history of cutaneous VZV infection, which makes the diagnosis more difficult. R.H.D. Infection with VZV resistant to acyclovir (mediated by absent or altered expression of thymidine kinase) has been reported in immunocompromised but not in immunocompetent patients. Patients with chronic pruritis report substantial disability, not only because of the unpleasant sensations but also because of the disruptive need to scratch that is virtually impossible to ignore. Gabapentin and pregabalin can both cause sedation, and tolerability may be improved with initial doses given only at bedtime and subsequent dosage increases administered 3 times daily for gabapentin and twice daily for pregabalin. Populations at special risk include patients with lymphoproliferative malignancies, organ transplant recipients, patients receiving systemic corticosteroids, and patients with AIDS. Although the results of each of the antiviral clinical trials taken singly can be challenged, the preponderance of the findings provides strong support for the use of antiviral therapy not only to hasten resolution of the acute phase but also to attenuate the development of chronic pain in patients with HZ. Furthermore, these individuals are at high risk for adverse drug effects because of multiple comorbidities, age-related changes in pharmacokinetics and dynamics, use of multiple medications, and frequent inappropriate prescribing [239]. The incidence of herpes zoster in chronic kidney disease patients is 12.4/1000 people, several times higher than in healthy individuals [].Visceral disseminated VZV (VDVZV) infection is a rare disease with a high mortality rate that occurs in immunocompromised patients … Subsequent studies of bone marrow transplant recipients proved that acyclovir, in addition to promoting faster disease resolution, is highly effective at preventing VZV dissemination [195, 196]. Two to four days before the rash occurs there may be tingling or local pain in the area. Disseminated Zoster List of authors. The estimated rate of HZO is approximately 10% of all HZ cases.1,2 In recent years, the incidence of both HZ and HZO has almost tripled, possibly related to the larger aging population.2,3 HZO is a serious and vision-threatening disease. Herpes zoster ophthalmicus (HZO), also known as ophthalmic zoster, is shingles involving the eye. The differential diagnosis of HZO can be divided into the following categories, depending on presentation. The course of the disease is benign, with complete recovery expected in 1–2 weeks [61]. Oral antiviral medications for herpes zoster. HZ myelitis is thought to result from direct invasion of the spinal cord by VZV, with virus spreading along central axons of infected primary sensory neurons. Vaccination. MRI demonstrates plaque-like lesions in deep white matter, changes consistent with demyelination, and late development of ischemic or hemorrhagic infarcts of cortical and subcortical gray and white matter [77]. Rachelle M. Beste, M.D., and M. Fernanda Bellolio, M.D. HZ ophthalmicus with delayed contralateral hemiparesis. Relevant publications were identified by Medline searches, examination of reference lists of published articles and book chapters, and the personal knowledge of the authors. In general, HZ in children is less severe than that in older patients and is much less likely to result in severe acute and prolonged pain [67, 68]. There is great interest in the concept of VZV reactivation causing dermatomal pain in the absence of skin lesions, termed “zoster sine herpete.” This concept has been supported by serologic and PCR evidence of concurrent VZV reactivation during acute pain syndromes [62,63,64–65]. Analgesic treatments. In general, these agents decrease the severity and duration of acute pain, and it is therefore also likely that antiviral therapy reduces the adverse impact of the acute phase of HZ on quality of life. Before the meeting, all participants were provided copies of systematic literature reviews and meta-analyses [118,119,120–121], existing guidelines relevant to the management of HZ [122,123,124–125], and published randomized clinical trials, discussed below. Because the safety of antiviral therapy during pregnancy has not been firmly established, pregnant women with HZ should be treated only in cases in which the potential benefits of antiviral therapy to the mother outweigh the potential risks to the fetus. This persisting pain is termed PHN, and it is the most common complication of HZ. Illustration reproduced with permission from [8]. Pathologic findings associated with PHN include degeneration of affected primary afferent neuronal cell bodies and axons, atrophy of the spinal cord dorsal horn, scarring of the dorsal root ganglion, and loss of epidermal innervation, all of which are more prominent on the affected side [44, 108,109–110]. Participants were selected on the basis of research and clinical expertise relevant to HZ and its management and represent the fields of anesthesiology, geriatrics, infectious diseases, internal medicine, neurology, ophthalmology, outcomes research, pain management, and virology. Al­though rare, additional neurologic sequelae have been documented, including cerebellar ataxia and meningo­encephalitis.6, Multiple studies have evaluated the risk factors associated with the likeli­hood of acute, chronic, and recurrent HZO (Table 1). VZV and HSV account for the majority of cases of Bell palsy (idiopathic facial paralysis). Learn more about shingles symptoms, causes, contagiousness, vaccine, diagnosis, and treatment. Therapy for chronic problems includes the following: (1) lubricating, preservative-free artificial tear gels or tears administered 4 times daily, antibiotic ointment administered once daily, and, possibly, lateral tarsorrhaphy to protect the corneas (which are often hypesthetic/anesthetic as a result of neuronal damage) from breakdown; (2) continuous-wear, therapeutic soft contact lenses and antibiotic drops (e.g., polymyxin-trimethoprim given 4 times daily as needed for corneal ulceration); (3) topical steroids and antibiotics for inflammatory disease (iritis, episcleritis, scleritis, and immune keratitis); (4) dilation for iritis; (5) glaucoma therapy as needed; and (6) surgical management as needed—for example, for amniotic membrane transplantation, tissue-adhesive seal ulcers, keratoprosthesis, and glaucoma trabeculectomy. A guinea pig model of latency and reactivation in vitro has been developed. Pruritis associated with HZ is neuropathic and does not respond to antihistamines or treatments for inflammatory pruritis. The addition of cell-associated virus, the product of the ORF61 gene, or its herpes simplex virus (HSV) homologue ICP0 to the guinea pig gut model results in VZV reactivation and lytic infection [7]. Published data from clinical trials of famciclovir and valacyclovir for the treatment of HZ in immunocompromised patients remain limited, but a growing body of clinical experience suggests that these medications are safe and effective in this setting [198, 199]. A recent proof-of-concept study has demonstrated analgesic effects of a single 900-mg dose of gabapentin versus placebo in patients during the acute phase of HZ [177], and it has also been reported that open-label treatment of a sample of 64 patients with HZ, by use of the combination of gabapentin and the antiviral agent valacyclovir, appeared to reduce the incidence of PHN at 3 and 6 months after rash onset, compared with the results of published studies of antiviral monotherapy [178]. HZ in HIV-seropositive patients. has received consulting fees or royalties in the past 12 months from Alnylam, Biogen, Eli Lilly, Hind Health Care, Metaphore, and NeuroMolecular; K.E.S. However, HZ does increase … The treatment of choice is IV acyclovir [12,13]; minimal data has assessed oral therapy. Reducing the occurrence of HZ will be crucial to eliminating transmission of VZV. Many HIV-infected patients with varicella or zoster do not require hospitalization, however, and outpatient therapy for these individuals may be appropriate. These individuals experience significant age- and disease-related declines in glomerular filtration rate, so the dosages of renally excreted medications (e.g., antiviral agents, gabapentin, and pregabalin) must be adjusted, as is discussed further below [238]. has received research support, consulting fees, or honoraria in the past year from Allergan, Astellas Pharma, Cephalon, Eli Lilly, Eisai, Johnson & Johnson, Merck, NeurogesX, Pfizer, Schwarz Pharma, and Xenoport; A.A.G. One-third of immunocompetent patients without clinical symptoms of infection of the CNS had either PCR results positive for VZV or anti-VZV IgG present when a CSF sample was obtained within the first weeks after the rash onset. Analgesics or steroids are given to reduce pain. Zosteriform herpes simplex in an elderly woman who presented with what she called “her recurrent shingles.” Vesicles in a lumbosacral distribution had recurred many times over the past several years, and this outbreak began 1 week before the photo was taken. The appearance of new vesicles for >1 week should raise concern about an underlying immunodeficiency syndrome. The existence of barriers to the entry of antiviral agents from the bloodstream into tissues that are sites of HZ complications and the lower sensitivity of VZV compared with HSV make higher blood levels of antiviral medications important. By use of electromyography, it is possible to show that muscles are involved in 50% of cases [47]. In typical HZ, widespread involvement of multiple dermatomes, especially those that are widely separated, does not occur. Thus, it is expected that the incidence of HZ would decrease as the number of adults infected with latent wild-type virus decreases. Rachelle M. Beste, M.D., and M. Fernanda Bellolio, M.D. This condition is called disseminated zoster. In severe cases, the myelopathy can progress to a partial Brown-Séquard syndrome or total cord transection. VZV is a common cause of aseptic meningitis, which can present with or without rash that may precede or follow the meningeal symptoms. Therefore, when treating herpes zoster, it is imperative to initiate antiviral therapy within 72 h of onset of rash. Intravenous acyclovir remains the therapy of choice for VZV disease in severely immunocompromised patients, including (1) allogeneic hematopoietic stem cell transplant recipients within 4 months of transplantation, (2) hematopoietic stem cell transplant recipients with moderate to severe acute or chronic graft-versus-host disease, or (3) any transplant recipient receiving aggressive antirejection therapy. Herpes zoster (shingles) is diagnosed clinically by recognition of the distinctive, painful vesicular rash appearing in a unilateral, dermatomal distribution. These interventions usually require a multidisciplinary approach that involves nursing, social work, physical therapy, occupational therapy, and the family. Red eye, excessive tearing, eye pain, blurred vision, photophobia, and decreased visual acuity are common complaints. has received consulting fees from Endo Pharmaceuticals and honoraria from Pfizer in the past year; R.J.W. Other complications include zoster ophthalmicus, disseminated HZ and secondary bacterial infections. Immunocompromised patients are at increased risk for post-HZ myelitis, and the syndrome is well described in patients with AIDS [88]. Crusts usually are gone by the end of 3 or 4 weeks, but scarring and hypo- or hyperpigmentation may persist long after the HZ resolves. For pain that is moderate to severe in intensity, which is often accompanied by disturbed sleep, treatment with a strong opioid analgesic (e.g., oxycodone or morphine) is recommended on the basis of the consistent efficacy of this class of medications in patients with inflammatory and neuropathic pain (table 2). Although the reduction in chronic pain demonstrated by most antiviral trials is both statistically and clinically significant, antiviral therapy does not prevent PHN in all patients. Patients with active lymphoproliferative malignancies are at particular risk. Although multiple definitions of PHN have been used, the results of recent studies suggest that pain persisting for at least 120 days after rash onset may be considered to be a validated definition of PHN for research purposes [96,97–98]. Those patients with the greatest degree of immunosuppression are at highest risk for VZV dissemination and visceral organ involvement. HZ in the setting of malignancy or organ transplantation. has received consulting fees from GlaxoSmithKline and Merck and shares a patent with Merck for the herpes zoster vaccine; M.B. The reactivation of VZV in ganglia may be a frequent event. Cornea. The treatment for retinitis is similar, with the addition of several months of oral antiviral therapy.9, There is not yet an evidence-based treatment regimen for chronic HZO. The list of complications is protean: scarred lid malfunction or loss; paralytic ptosis; conjunctivitis; episcleritis; scleritis; infectious or neurotrophic keratitis; iridocyclitis; hemorrhagic retinitis; acute retinal necrosis; choroiditis; papillitis; retrobulbar neuritis; optic atrophy; Argyll Robertson pupil; partial or complete third, fourth, or sixth nerve palsy (always self-resolving); isolated pupillary paralysis; internuclear ophthalmoplegia; acute and chronic glaucoma; orbital apex syndrome; PHN; and sympathetic ophthalmia [210, 214,215,216,217–218]. 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disseminated zoster treatment 2020