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Fig. 2. PCR investigation by real-time technique.

combined with further immunological techniques [1-3] which are normally not used in routine diagnosis (fig. 1).

Direct Immunofluorescence Assay

Direct immunofluorescent antibody staining with monoclonal antibodies allows a rapid and specific diagnosis of VZV suspected lesions. Even cells from

Fig. 3. VZV-specific cytopathologic effect in retinal pigment epithelial cells.

crusted lesions contain enough viral antigen for detection. Some investigators recommend this assay as 'method of choice' for the diagnosis of VZV-infection, because it is easy to achieve and more sensitive than virus isolation and serology [4-8]. To reach optimal sensitivity cells have to be scraped off from the base of a lesion after unroofing the fresh vesicle. The sensitivity and recovery of this method depends on the quality of the scrap of tissue. Before immunohis-tostaining was available, cytologic methods (Tyzzer or Tzank smears) for detection of multinucleate giant cells with intranuclear inclusions were used. Like EM these methods are depending on the investigator's experience and allow no differentiation between HSV and VZV [9].

Detection of Viral DNA

The most sensitive and specific methods for detection of VZV in clinical specimens (like vitreous fluid or cerebrospinal fluid) are molecular amplification methods, especially the PCR [10-13]. PCR has proven to be a valuable tool for the diagnosis of VZV disease of the central nerve system, the ophthalmic division and VZV associated vasculopathy [14-16]. Further, it is also useful for the detection of VZV genome in vesicle fluid and crusts, especially when antiviral therapy has been started before [17]. Detection of VZV genome does not prove that infectious virus is present, and therefore detection of VZV with this highly sensitive method has to be correlated with the clinical condition before an aetiologic role is assumed [18]. Using quantitative PCR (fig. 2) it is possibly to find low numbers of genome copies in latently infected ganglionic cells without showing infectious virus forms or subsequent disease [14, 19, 20]. For special cases a molecular characterisation of VZV isolates can be ruled out by DNA sequencing, which allows to ascertain relatedness of different clinical isolates and detection of some acyclovir resistant mutations [21, 22].

Virus Isolation

Virus isolation in cell culture remains, in cases of positive testing, the most reliable method for the proof of infectious virus. It is less sensitive than direct immunofluorescent antibody staining, since viable virus persists shorter in vesicles and is more labile than viral antigen [23]. Usually results of viral cultures cannot be obtained fast enough to influence clinical decisions, but they can confirm diagnosis of VZV infection made by other methods, e.g. the antigen assay [24]. In addition, drug resistance of virus can be ruled out by testing cultured virus [25]. Thereby, it should be noted that isolation of VZV strains, especially acyclovir resistant strains and their characterisation are difficult by tissue culture procedures. This is mainly because VZV is not stable, highly cell associated and replicating slowly in cell culture of low titres [23, 26].

Infectious VZV is usually recoverable from vesicle fluid or the base of a fresh zoster lesions for up to 7 days [24, 27]. A spectrum of cultured cells, either of primary or of established cell lines can be used for the isolation and growth of VZV (fig. 3). The most recommended cell cultures are either primary or low passage cultures of human fibroblasts derived from embryonic skin, lung tissue, or preputial tissues. Even under improved conditions, a significant percentage of viral cultures remains negative, despite positive VZV-antigen or -DNA detection [4, 10, 17]. Methods like 'shell vial' cultures with centrifugation and VZV protein staining improve the sensitivity and allow a more rapid identification of positive specimens [28, 29]. Positive results may be available within 1-3 days after inoculation of cell culture [30, 31], while in conventional cultures up to 21 days are required [27].

Determination of the Immunity Status

Serological Diagnosis

Serological assays are frequently used for the diagnosis of chickenpox and herpes zoster. The preferred methods are enzyme immunoassays (ELISA) which show both a high specificity and sensitivity [32]. However, the detection of VZV-specific antibodies for the diagnosis of atypical zoster is only of limited value when a rapid confirmation of VZV-infection is needed. Nevertheless, some problems remain in the serological diagnosis of VZV infections. VZV

reactivation induces often a significant rise of IgG and IgA [33, 34] antibodies, which are found in 50-60% [10, 35] of the patients. However IgM antibodies are also sometimes detectable. Thus differentiation of primary and recurrent infection can be difficult [36]. Furthermore, sharing of antigens between VZV and HSV can result in high anti HSV and anti VZV levels and it will be difficult to differentiate between both diseases without further information or additional tests [23, 37]. The main value of serologic assays is the determination of the immune status of individuals, whose history of chickenpox is unknown [24]. In patients with pain syndromes or facial paresis due to zoster sine herpete a rise of VZV-IgG values in consecutive serum samples may be helpful to identify the aetiology [38]. Other serological test systems like the neutralisation assay and the fluorescent-antibody membrane antigen assay are too complex to carry out in routine diagnostic testing [23].

Determination of Cell-Mediated Immunity

The main role of cell-mediated immunity (CMI) is to prevent reactivation and to limit an established infection. Detection of CMI can be carried out by measuring the proliferative response [39] or by detection of cytokine production [40-42]. Examples for such methods are the determination of intracellular cytokines by flow cytometry [43] or of secreted extracellular cytokines by ELISA [44] or ELISPOT [45]. Generally all procedures for measurement of CMI are technically complex, time consuming, labour intensive and therefore used only in special cases on small scales. Nevertheless, in the future the demand for clinical studies concerning VZV-specific CMI on a large scale will rise considerably and so the development of well reproducible and easily practicable diagnosis methods will be necessary.


1 Folkers E, Vreeswijk J, Oranje AP, Duivenvoorden JN: Rapid diagnosis in varicella and herpes zoster: re-evaluation of direct smear (Tzanck test) and electron microscopy including colloidal gold immuno-electron microscopy in comparison with virus isolation. Br J Dermatol 1989;121:287-296.

2 Folkers E, Vreeswijk J, Oranje AP, Wagenaar F, Duivenvoorden JJN: Improved detection of HSV by electron microscopy in clinical specimens using ultracentrifugation and colloidal gold immuno-electron microscopy: comparison with viral culture and cytodiagnosis. J Virol Methods 1991;34: 273-289.

3 Vreeswijk J, Folkers E, Wagenaar F, Kapsenberg JG: The use of colloidal gold immunoelectron microscopy to diagnose varicella-zoster virus (VZV) infections by rapid discrimination between VZV HSV-1 and HSV-2. J Virol Methods 1988;22:255-271.

4 Dahl H, Marcoccia J, Linde A: Antigen detection: the method of choice in comparison with virus isolation and serology for laboratory diagnosis of herpes zoster in human immunodeficiency virus-infected patients. J Clin Microbiol 1997;35:347-349.

5 Drew WL, Mintz L: Rapid diagnosis of varicella-zoster virus infection by direct immunofluores-cence. Am J Clin Pathol 1980;73:699-701.

6 Gleaves CA, Lee CF, Bustamante CI, Meyers JD: Use of murine monoclonal antibodies for laboratory diagnosis of varicella-zoster virus infection. J Clin Microbiol 1988;26:1623-1625.

7 Perez JL, Garcia A, Niubo J, Salva J, Podzamczer D, Martin R: Comparison of techniques and evaluation of three commercial monoclonal antibodies for laboratory diagnosis of varicella-zoster virus in mucocutaneous specimens. J Clin Microbiol 1994;32:1610-1613.

8 Coffin SE, Hodinka RL: Utility of direct immunofluorescence and virus culture for detection of varicella-zoster virus in skin lesions. J Clin Microbiol 1995;33:2792-2795.

9 Waner JL, Weller TH, Schmidt NJ, Emmons RW (eds): Diagnostic Procedures for Viral, Rickettsial And Chlamydial Infections, ed 6. Varicella-Zoster Virus. Washington, DC, American Public Health Association, 1998, vol 13, pp 379-406.

10 Sauerbrei A, Eichhorn U, Schacke M, Wutzler P: Laboratory diagnosis of herpes zoster. J Clin Virol 1999;14:31-36.

11 Weidmann M, Meyer-Konig U, Hufert FT: Rapid detection of herpes simplex virus and varicella-zoster virus infections by real-time PCR. J Clin Microbiol 2003;41:1565-1568.

12 van Doornum GJ, Guldemeester J, Osterhaus AD, Niesters HG: Diagnosing herpesvirus infections by real-time amplification and rapid culture. J Clin Microbiol 2003;41:576-580.

13 Nahass GT, Goldstein BA, Zhu WY, Serfling U, Penneys NS, Leonardi CL: Comparison of Tzanck smear, viral culture, and DNA diagnostic methods in detection of herpes simplex and varicella-zoster infection. JAMA 1992;268:2541-2544.

14 Kleinschmidt-DeMasters BK, Gilden DH: Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates. Arch Pathol Lab Med 2001;125:770-780.

15 Madhavan HN, Priya K: The diagnostic significance of enzyme linked immuno-sorbent assay for herpes simplex, varicella zoster and cytomegalovirus retinitis. Indian J Ophthalmol 2003;51: 71-75.

16 Gargiulo F, De Francesco MA, Nascimbeni G, et al: Polymerase chain reaction as a rapid diagnostic tool for therapy of acute retinal necrosis syndrome. J Med Virol 2003;69:397-400.

17 Beards G, Graham C, Pillay D: Investigation of vesicular rashes for HSV and VZV by PCR. J Med Virol 1998;54:155-157.

18 Schunemann S, Mainka C, Wolff MH: Subclinical reactivation of varicella-zoster virus in immunocompromised and immunocompetent individuals. Intervirology 1998;41:98-102.

19 Liedtke W, Opalka B, Zimmermann CW, Lignitz E: Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J Neurol Sci 1993;116:6-11.

20 Mahalingam R, Wellish M, Lederer D, Forghani B, Cohrs R, Gilden D: Quantitation of latent varicella-zoster virus DNA in human trigeminal ganglia by polymerase chain reaction. J Virol 1993;67:2381-2384.

21 Morfin F, Thouvenot D, Turenne-Tessier M, Lina B, Aymard M, Ooka T: Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acy-clovir. Antimicrob Agents Chemother 1999;43:2412-2416.

22 Boivin G, Edelman CK, Pedneault L, Talarico CL, Biron KK, Balfour HH Jr: Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS. J Infect Dis 1994;170:68-75.

23 Gershon AA, Forghani B, Lennette EH, Lennette DA, Lennette ET (eds): Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, ed 7. Varicella-Zoster Virus. Washington, DC, American Public Health Association, 1995, Vol 42, pp 601-613.

24 Arvin AM, Knipe DM, Howley PM (eds): Fields Virology, ed 4. Varicella-Zoster Virus. Philadelphia, Lippincott Willians and Wilkins, 2001, Vol 79, pp 2731-2767.

25 Pillay D, Emery VC, Mutimer D, et al: Guidelines for laboratory monitoring of treatment of persistent virus infections. J Clin Virol 2002;25:73-92.

26 Sahli R, Andrei G, Estrade C, Snoeck R, Meylan PR: A rapid phenotypic assay for detection of acyclovir-resistant varicella-zoster virus with mutations in the thymidine kinase open reading frame. Antimicrob Agents Chemother 2000;44:873-878.

27 Breuer J, Harper DR, Kangro HO, Zuckerman A, Banatvala JE, Pattison JR (eds): Principles and Practice Of Clinical Virology, ed 4. Varicella Zoster. Baffins Lane, Chichester, West Sussex PO19 1UD, England, John Wiley and Sons, 2000, vol 2B, pp 47-78.

28 Schirm J, Meulenberg JJ, Pastoor GW, Voorst Vader PC, Schroder FP: Rapid detection of varicella-zoster virus in clinical specimens using monoclonal antibodies on shell vials and smears. J Med Virol 1989;28:1-6.

29 West PG, Aldrich B, Hartwig R, Haller GJ: Increased detection rate for varicella-zoster virus with combination of two techniques. J Clin Microbiol 1988;26:2680-2681.

30 Brinker JP, Doern GV: Enhancement of varicella-zoster virus detection in A-549 shell vials by use of freeze-thawed specimens, extended incubation, and 'a centrifuged, not incubated' direct detection method. Diagn Microbiol Infect Dis 1998;31:555-558.

31 Brinker JP, Doern GV: Comparison of MRC-5 and A-549 cells in conventional culture tubes and shell vial assays for the detection of varicella-zoster virus. Diagn Microbiol Infect Dis 1993;17:75-77.

32 Weinberg A, Hayward AR, Masters HB, Ogu IA, Levin MJ: Comparison of two methods for detecting varicella-zoster virus antibody with varicella-zoster virus cell-mediated immunity. J Clin Microbiol 1996;34:445-446.

33 W├╝ltzer P, Porstmann T (eds): Virusdiagnostik. Varicella-Zoster-Virus. Berlin, Wien, Blackwell Wissenschafts-Verlag, 1996, pp 291-302.

34 Doerr HW, Rentschler M, Scheifler G: Serologic detection of active infections with human herpes viruses (CMV, EBV, HSV, VZV): diagnostic potential of IgA class and IgG subclass-specific antibodies. Infection 1987;15:93-98.

35 Wittek AE, Arvin AM, Koropchak CM: Serum immunoglobulin A antibody to varicella-zoster virus in subjects with primary varicella and herpes zoster infections and in immune subjects. J Clin Microbiol 1983;18:1146-1149.

36 Arvin AM, Koropchak CM: Immunoglobulins M and G to varicella-zoster virus measured by solid-phase radioimmunoassay: antibody responses to varicella and herpes zoster infections. J Clin Microbiol 1980;12:367-374.

37 Schmidt NJ: Further evidence for common antigens in herpes simplex and varicella-zoster viruses. J Med Virol 1982;9:27-36.

38 Gilden DH, Dueland AN, Devlin ME, Mahalingam R, Cohrs R: Varicella-zoster virus reactivation without rash. J Infect Dis 1992;166(suppl 1):S30-S34.

39 Hayward AR, Zerbe GO, Levin MJ: Clinical application of responder cell frequency estimates with four years of follow up. J Immunol Methods 1994;170:27-36.

40 Zhang Y, Cosyns M, Levin MJ, Hayward AR: Cytokine production in varicella zoster virus-stimulated limiting dilution lymphocyte cultures. Clin Exp Immunol 1994;98:128-133.

41 Zhang Y, White CJ, Levin M, Hayward A: Cytokine production in varicella-zoster virus-stimulated lymphocyte cultures. Neurology 1995;45(suppl 8):S38-S40.

42 Warnatz K, Draeger R, Schlesier M, Peter HH: Successful IL-2 therapy for relapsing herpes zoster infection in a patient with idiopathic CD4+ T lymphocytopenia. Immunobiology 2000;202:204-211.

43 Asanuma H, Sharp M, Maecker HT, Maino VC, Arvin AM: Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression. J Infect Dis 2000;181:859-866.

44 Svahn A, Linde A, Thorstensson R, Karlen K, Andersson L, Gaines H: Development and evaluation of a flow-cytometric assay of specific cell-mediated immune response in activated whole blood for the detection of cell-mediated immunity against varicella-zoster virus. J Immunol Methods 2003;277:17-25.

45 Smith JG, Liu X, Kaufhold RM, Clair J, Caulfield MJ: Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus. Clin Diagn Lab Immunol 2001;8:871-879.

Professor H.W. Doerr, MD

Institute of Virology, University of Frankfurt

Paul-Ehrlich-Strasse 40

DE-60596 Frankfurt am Main (Germany)

Tel. +49 69 63015219, Fax +49 69 63016477, E-Mail [email protected]

Spectrum of Clinical Manifestations and Outcome

Gross G, Doerr HW (eds): Herpes Zoster. Monogr Virol. Basel, Karger, 2006, vol 26, pp 20-36

Clinical Picture and Complications of Herpes Zoster: The View of the Dermatologist

G. Gross

Department of Dermatology and Venereology, University of Rostock, Rostock, Germany

Herpes zoster (shingles, zoster) is a common neurocutaneous disease resulting from reactivation of latent varicella-zoster virus (VZV) infection acquired during primary VZV-infection (varicella, chickenpox). Herpes zoster presents as a painful characteristically unilateral cutaneous rash in the sensory innervation region of a spinal nerve or a cranial nerve. Unlike varicella herpes zoster is a sporadic disease with an estimated lifetime incidence of 10-20% [1]. Whereas, varicella is generally a disease of childhood, herpes zoster becomes more common with increasing age. Factors that decrease immune function, such as human immunodeficiency virus infection, chemotherapy, malignancies and chronic corticosteroid use may also increase the risk of developing herpes zoster. The main risk factor for the development of herpes zoster, however is increasing age, leading to a decline of VZV-specific cell-mediated immunity. Incidence of zoster rises steadily until adulthood and remains constant with about 2-3 cases per 1,000 per year until the end of the fourth decade of life. In persons older than 50 years of age the incidence strongly increases to approximately 5 cases per 1,000 persons per year. Individuals in the sixth to seventh decade have an incidence rate of 6-7 cases per 1,000 and individuals beyond the age of 80 have an incidence of more than 10 cases per 1,000 per year. According to Hope-Simpson [2] more than half of all people who reach 85 years of age will develop herpes zoster at any point of their life.

Persons older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These persons and immunocompromised individuals of any age are at increased risk for severe complications involving the skin, the eye, internal organs and the peripheral and central nervous system.

About 20% of patients with shingles develop prolonged pain and postherpetic neuralgia (PHN). The most established risk factor for PHN is again age. This complication occurs nearly 50 times more often in patients older than 50 years of age. Other possible risk factors for the development of PHN are ophthalmic zoster, zoster oticus and a history of prodromal pain before appearance of the rash. Growing life expectancy and the increasing number of elderly in Europe has resulted in a higher population risk for herpes zoster and chronic zoster pain. HIV-infected individuals and adults suffering from cancer have a much higher herpes zoster incidence than immunocompetent persons of the same age [3, 4]. The occurrence of herpes zoster in HIV-infected patients, however does not appear to increase the risk of acquired immunodeficiency syndrome (AIDS) and is less dependent on the CD4-count than AIDS-related opportunistic infections [5]. Furthermore, there is no evidence that herpes zoster heralds the onset of an underlying malignancy [6].

Clinical Picture

Herpes zoster presents in about 80% with a prodrome consisting of hyper-aesthesia, paraesthesia, burning disaesthesia, sometimes itching along the affected dermatome (figs. 1, 2). In rare cases these symptoms may be localized to more than one, sometimes several overlapping dermatomes. In general the prodrome lasts only 1-5 days. Rarely, it may precede the appearance of skin lesions by up to 3 weeks. During the prodromal phase herpes zoster may be misinterpreted as cardiac disease, herniated nucleus pulposus or as various gastrointestinal disorders such as cholecystitis, biliary colic, renal colic, appendicitis or even as a gynecologic disorder. A rare condition seen in patients having prodromal symptoms and later dermatome-dependent pain without developing the characteristic rash is called zoster sine herpete [7].

Cutaneous Manifestations

The characteristic zoster rash is unilateral and crossing of the bodies midline is a extremely rare condition, called zoster duplex. Unusually several skin segments may be affected asymmetrically on both sites of the body [8, 9]. As a rule discrete pale to erythematous spots start to develop into a painful asymmetrical unilateral erythema in the affected nerve segment known as 'belt-like pattern' (figs. 2, 3). Normally after a period of about 12-24h grouped vesicles appear and become confluent (fig. 3). In general, the vesicles are painful and may lead to anxiety and flu-like symptoms in the patients. The subsequent

Fig. 1. Herpes zoster of the right ophthalmic nerve (V-1 dermatome) (first branch of the trigeminal nerve) with dissemination of vesicles to V-2-dermatomes (note: severe oedema of the right eye-lid).

stages involve pustulation, erosion, ulceration and crusting (fig. 2). New vesicles may continue to arise during a period of 1-7 days. In immunologically healthy patients duration of rash until disappearance of the crusts takes usually 2-3 weeks. Scarring with hypo- or hyperpigmentation may result [10]. Particularly if the rash is complicated by haemorrhagy and necrosis scarring may be pronounced. In these cases dysaesthesia may develop. The rash is known to be most severe and to last longest in older persons and least severe and shows clearing soonest in children. In immunocompromised patients chronic courses of zosteric skin lesions may last up to several months and development of repeated vesicular and pustular eruptions may be seen [11-13].

Fig. 2. Early herpes zoster rash: dermatomal erythema at the lower right abdominal skin (TH 11-12 dermatome). Unilateral asymmetrical erythema with initial vesicles limited by the midline of the body (TH 10-12 dermatome). Grouped vesicles and blisters become confluent and erosive.

Fig. 2. Early herpes zoster rash: dermatomal erythema at the lower right abdominal skin (TH 11-12 dermatome). Unilateral asymmetrical erythema with initial vesicles limited by the midline of the body (TH 10-12 dermatome). Grouped vesicles and blisters become confluent and erosive.

Localization of Herpes Zoster

Although any dermatome may be involved, dermatomes of the trunk from Th3 to L1 are most frequently affected (figs. 3, 4). The second most frequently involved nerve dermatome is the ophthalmic division of the trigeminal nerve.

Fig. 4. Disseminated herpes zoster: Thoracic herpes zoster involving the Th 5-6 dermatomes combined with disseminated partially umbilicated vesicles in a 69-year-old woman suffering from Hodgkin's disease.

Herpes zoster of cervical, lumbal and sacral segments is observed in a declining frequency [14]. Haematogenous spread of VZV results in disseminated zoster which is seen in only 1-2% of immunocompetent herpes zoster patients, but which is a particularly more frequent finding in immunodeficient patients [15, 16]. Disseminated herpes zoster (fig. 4) appears in a non-dermatomally pattern of nodules and vesicules and needs sometimes to be differentiated from chicken-pox. Involvement of visceral organs such as the lungs and the nervous system is occasionally found in these cases.

According to Meister et al. [14], there is an age-specific predilection of zoster localization. Whereas affection of thoracic segments is preferentially seen in younger patients, the trigeminal nerve (especially the ophthalmic division) and sacral segments are increasingly involved in individuals older than 50 years of age.

Differentiating zoster from other circumscribed rashes may be possible by the characteristic asymmetrical zoster rash and synchronous development of skin lesions starting with erythema followed by vesicular, pustular and finally crustous lesions. Lesions not developing synchronously such as varicella-like lesions, especially reported from AIDS patients, may create a special problem for differential diagnosis [17, 11]. In such cases, virus detection by virus culture, antigen detection by direct immunofluorescence or polymerase chain reaction (PCR) should be made (see chapter: Laboratory confirmation of Herpes Zoster, pp 13-19).


Characteristically the clinical appearance of herpes zoster is accompanied by dermatomal pain, which may be continuous or intermittent and presenting with varying intensity. By definition, pain occurring before and after the dermatomal rash is called zoster-associated-pain. Postzoster neuralgia or PHN is defined as pain, which appears or continues after cutaneous symptoms have disappeared (see chapter: Postherpetic Neuralgia and Other Neurologic Complications, pp 69-80). PHN is the most frequent and important complication of herpes zoster affecting the nervous system [18].

Herpes Zoster Ophthalmicus

Herpes zoster ophthalmicus involves the ophthalmic branch (V-1 dermatome), which is the first division of the trigeminal nerve. According to several studies about 7-18% of reported herpes zoster cases affect the ophthalmic division of the trigeminal nerve [19-21]. While cases of zoster ophthalmicus occur approximately in 10% of zoster patients under the age of 10 years, almost 30% of 80-year-old and older patients suffer from this condition. There is no doubt that ophthalmic zoster is seen particularly more frequently in patients older than 50 years of age [14, 22, 23]. The rash of ophthalmic zoster may extend from the level of the eye to the vertex of the skull. Characteristically it does not cross the midline of the forehead. About 50% of patients with herpes zoster ophthalmicus will develop ocular complications if they do not receive antiviral therapy [12]. Involvement of the nasociliary branch of the ophthalmic nerve which is evidenced by a zosteric rash on the tip and side of the nose (Hutchinson's sign) is seen in about one-third of patients and is usually accompanied by ocular symptoms (fig. 5).

Thus, when ophthalmic zoster affects the side and the tip of the nose, careful attention must be given to the condition of the eye and immediate ophthal-mologic consultation is necessary in order to prevent complications of the eye and central nerve system (see chapter: Ophthalmic Manifestations of Herpes Zoster Infection, pp 37-46) [24].

Herpes Zoster Oticus

Herpes zoster affecting the second and third division of the trigeminal nerve and other cranial nerves is likely uncommon. When it occurs, however it may produce symptoms and lesions in the mouth, ear, pharynx or larynx. The Ramsay

Fig. 5. a Herpes zoster ophthalmicus with involvement of the left tip and side of the nose (nasociliary branch of V-1 (Hutchinson's sign)) in a 84-year-old woman. b Severe ulceration despite optimal intravenous acyclovir therapy.

Hunt syndrome consists of facial palsy combined with ipsilateral herpes zoster of the external auditory meatus or tympanic membrane. Severe facial pain, facial palsy, decreased hearing or even deafness, tinnitus, vertigo and loss of taste in the anterior part of the tongue may coexist resulting from the involvement of the geniculate ganglion (compare chapter: (Herpes) Zoster Oticus, pp 47-57).

Herpes Zoster in Children

Herpes zoster can develop in immunocompetent children as young as a few weeks of age and should be considered in the differential diagnosis of vesicular eruptions in infants. Zoster in children most frequently involves the thoracic dermatomes (65%). In contrast to adult zoster patients, cranial sites are rarely affected (13 vs. 5%, respectively). Sacral and disseminated zoster are very rare findings (<5%) [25-27].

Herpes zoster certainly occurs in pediatric populations, although by far less frequent compared with adults [28]. Affected children are almost exclusively those, who had an intrauterine exposure to VZV, VZV exposure until the fourth year of age or who are immunosuppressed [25] (fig. 6). Pediatric malignancies most frequently associated with zoster are leukaemia and Hodgkin's lymphoma. As a rule zoster does not precede the clinical manifestations of these malignancies but is associated with chemotherapy or relapse [29]. If immunocompetent children are affected, the course of the disease is rather mild and pain and PHN are extremely uncommon findings. It is quite likely that the vesicular lesions of herpes zoster in this age group are misdiagnosed as impetigo or other cutaneous disorders [30].

Fig. 6. a Herpes zoster affecting dermatomes S1-S2 in a 10-months-old girl. b Grouped vesicles on the left S2 dermatome.

With the increasingly widespread use of varicella-vaccine the frequency of herpes zoster in children will probably continue to decrease. Studies of herpes zoster in normal children [26] have not shown underlying problems and have resulted in the conclusion that laboratory studies in healthy children with herpes zoster are not helpful. The majority of children presenting with herpes zoster is not infected with HIV Undocumented HIV infection in a young child should however be considered when herpes zoster develops with a short interval after an eruption of chickenpox. This is particularly true if there are no data about the HIV serologic status of the mother [12].

Herpes Zoster in Immunodeficient Patients

Individuals with pathologic or iatrogenic immunodeficiency may present atypical zoster. In some cases, the rash may appear mitigated with only few symptoms. More often the rash shows severe inflammation in part with haemorrhages and necrosis of the skin. Involvement of more than one dermatome may be seen and the rash may persist for a longer period than in immunocompetent persons. Disseminated zoster with varicella-like lesions (fig. 4) combined with involvement of inner organs and the nervous system is more common in immunodefi-cient persons [16, 31] than in immunocompetent individuals. In persons suffering from lymphocytic leukaemia or Hodgkins disease zoster rash with atypical vari-celliform or papular and even verrucous lesions was reported [11, 17]. Since herpes zoster is regarded as an early marker for HIV-infection [32], it is generally accepted to serologically test zoster patients under the age of 50 for HIV infection (see chapter: Herpes Zoster in the Immunocompromised Host, pp 93-106).

Herpes Zoster during Pregnancy

Maternal zoster is hardly considered a risk for the unborn. This is in contrast to maternal varicella (see chapter: Varicella-Zoster Virus Infections during Pregnancy, pp 81-92). Zoster during pregnancy should only be treated with intravenous acyclovir in exceptional cases. In general local and symptomatic treatment is sufficient.

Pregnant zoster patients in a gynaecologic practice, however should be treated in such a way that non-pregnant women without immune protection are not put at risk of varicella [13].

Clinical Diagnosis

The clinical picture of herpes zoster is almost always distinctive enough for diagnosis and laboratory diagnosis is not required. Characteristically, the asymmetrical rash with grouped vesicles is located on inflamed and erythematous dermatomal skin. This and limitation of the rash by the midline as well as prodromal and zoster-associated segmental pain are mostly sufficient to establish the diagnosis. Diagnostic difficulties may arise during the prodromal period and the early phase of zoster and also when atypical skin lesions appear or an atypical site of the body is affected. In such situations laboratory confirmation is required. Equally laboratorial diagnosis is important for VZV infections of pregnant women, newborn infants and particularly if a VZV-infection of the central nervous system is suspected.

The golden standard of laboratorial diagnosis is viral culture (see chapter: Laboratory Confirmation of Herpes Zoster, pp 13-19). The PCR is a useful method to detect VZV-DNA in fluids and in tissues. In case of neurological manifestations PCR is the test of choice to detect VZV in cerebro-spinal fluid [18]. Detection of VZV in blood by the PCR can be predictive of PHN or even diagnostic in some cases of zoster sine herpete. In everyday practice, direct immunofluorescence assays using labelled VZV-specific monoclonal antibodies are a diagnostic approach suitable in terms of low costs and the option to distinguish VZV-infection from HSV-infection. The Tzanck test can be of help to examine the cytopathic effect of VZV in the epidermis with multinucleated giant cells and intranuclear inclusions (fig. 7). The test is done by taking a swab from the base of a blister, transferring the cells to a microscopic glass, and observing the cells under the light-microscope after giemsa staining. This

Fig. 7. Histology of a zoster vesicle: subcorneal vesicle with multinuclear giant squamous cell. Tzanck-test: multinuclear giant cells. Features of a herpes virus infection.

simple assay can be done easily at bed-side and may be helpful to establish the diagnosis of herpes virus infection of the skin quickly. Unfortunately, the Tzanck-test is unable to distinguish between VZV- and HSV-infection. Diagnosis of zoster is exceptionally done by histopathological means. The histopathological features with focal intercellular oedema, ballooning degeneration of keratinocytes and multinucleated giant cells as well as intranuclear inclusions (fig. 7) are not characteristic enough to differentiate VZV-infection (herpes zoster and varicella) from HSV-infection.

Serologic tests can provide a retrospective diagnosis when acute and convalescent sera are available. The detection of IgM- and high-titered IgA-anti VZV-antibodies are of some help since they indicate VZV-reactivation whether lesions are present or not [33] (see chapter: Laboratory Confirmation of Herpes Zoster, pp 13-19). In the future detection of lowered VZV-specific cellular immunity might be a very early marker for reactivation of latent VZV-infection indicating zoster eruption.

Differential Diagnosis

Particularly in the prodromal period, herpes zoster is easily confused with other causes of pain. Herpes simplex lesions may be reminiscent of herpes zoster and therefore it may be very difficult to differentiate clinically [12] (figs. 8, 9). The same holds true for bullous or haemorragic erysipelas (fig. 10), contact dermatitis, pannicalitis and insect bites [10]. Autoimmune bullous dermatoses such as bullous pemphigoid or pemphigus may pose special differential diagnostic problems which have to be resolved by specific immunofluorescence tests.

Penis Schingles
Fig. 8. a 23-year-old male with vesicular and crusted zoster lesions on the penile shaft (S2 dermatome) reminiscent of genital herpes. b Asymmetrical grouped erythematous and crusted lesions on the left buttock (S2 dermatome) indicating herpes zoster (same patient).
Fig. 9. Zosteriform herpes simplex of the right cheek of a young adult male (no dermatome-associated lesions).
Fig. 10. Facial erysipelas: non-dermatomal patchy infiltrated erythema (note: no limitation of the lesions by the midline).


While acute and chronic zoster complications affecting skin, eye and central nervous system are quite frequent, complications of visceral organs are very rare findings. At cutaneous and mucocutaneous sites additional secondary bacterial infections may lead to ecthymiform ulcerations and delayed healing which finally may result in either hyper- or hypopigmented scarring (fig. 11a; table 1). Manifestation of psoriasis within the affected dermatomes and also granulomatous reactions may appear [34]. The most important and most frequent complication of shingles is acute pain and particularly chronic pain, also known as PHN. The latter is defined as pain persisting more than 12 weeks after rash healing. Elderly and immunocompromised herpes zoster patients of any age are at increased risk for PHN and also for complications of the central nervous system such as myelitis, encephalitis and motor neuropathy (fig. 11; table 1), (see chapter: Postherpetic Neuralgia and Other Neurologic Complications, pp 69-80). The latter can occur with or without cutaneous manifestations. VZV-infection of cerebral arteries can present as unifocal or multifocal vasculopathy. While unifocal large-vessel vasculopathy (granulo-matous arteritis) usually affects elderly immunocompetent persons, multifocal vasculopathy occurs primarily in immunocompromised persons [35, 36]. PHN shows a clear age-dependency. In herpes zoster patients over 70 years its incidence may be as high as 73%. Patients with zoster ophthalmicus and women seem to have a certain increased risk to develop PHN [14, 23]. Immunodeficiency alone, however appears to be no risk for development of chronic pain [25, 37]. Chronic zoster pain in children being immunocompetent or

Fig. 11. Complications of herpes zoster: a Hypopigmented postzosteric scars on the left lower abdominal skin (Th 10 and 12 dermatomes). b Ramsay-Hunt Syndrome with paralysis of facial muscles (Bell's palsy). c 75-year-old woman: Blindness of the left eye with zos-teric scars on the left forehead and nose (V-1 dermatome).

Fig. 11. Complications of herpes zoster: a Hypopigmented postzosteric scars on the left lower abdominal skin (Th 10 and 12 dermatomes). b Ramsay-Hunt Syndrome with paralysis of facial muscles (Bell's palsy). c 75-year-old woman: Blindness of the left eye with zos-teric scars on the left forehead and nose (V-1 dermatome).

immunosuppressed is extremely rare [38]. Ocular complications may present as zoster lesions of the eyelid with subsequent scar formation, conjunctivitis, corneal erosions, episcleritis, iritis, stromal keratitis and ulcers (see chapter: Ophthalmic Manifestations of Herpes Zoster Infections, pp 37-46). A severe complication with visual impairment is acute retinal necrosis, which has been described both in immunocompetent and in immunocompromised patients. Finally it may lead to blindness (fig. 11c). This condition is regularly preceded by zoster ophthalmicus. However, it may also develop in combination with

Table 1. Complications of zoster

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