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Review Article

Indian J Med Res 145, March 2017, pp 294-298

DOI: 10.4103/ijmr.IJMR_1622_16

Variations in herpes zoster manifestation

Uwe Wollina

Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt,

Dresden, Germany

Received October 3, 2017

Herpes zoster (HZ) is a neurocutaneous disorder due to endogenous reactivation of the varicella-zoster
virus (VZV). The typical clinical manifestation is an acute segmental eruption of herpetiform umbilicated
vesicles associated with malaise, pain, dysaesthesia, allodynia and probably fever. This review focuses on
other possible clinical manifestations of the disease to sensitize physicians not to overlook HZ since only
an early antiviral treatment can reduce the risk of post-zosteric neuralgia.

Key words Clinical findings - herpes zoster - varicella-zoster virus

Introduction clinical presentation of herpetiform umbilicated

vesiculation within a dermatoma allows a visual
Herpes zoster (HZ) is a viral disease caused
diagnosis without the need for extensive diagnostic
by endogenous reactivation of an infection by the
procedures. Later on, crusts develop that disappear
varicella-zoster virus (VZV). Clinically, the disease
within one or two weeks without leaving scars (Fig. 1).
is characterized by an acute segmental (dermatomal)
eruption of herpetiform vesicles on the skin The classical feature, however, may not always be
and/or mucosa1. Epidemiologic data from Europe and present making diagnosis more challenging. A typical
the US suggest a yearly incidence rate of 4 to 5 per prodromal stage of HZ ophthalmicus is Hutchinson’s
1000 person-years. Incidence increases with age. HZ sign: vesicles develop on the tip of the nose or on the
is more common among females in all age groups2,3. In side of the nose due to the involvement of the nasociliary
Germany, HZ morbidity has been reported to be 0.29 for branch of the trigeminal nerve, which innervates both
females and 0.10 for males per 100,000 patient-years4. the cornea and the nose. Hutchinson’s sign is more
Patients at risk for HZ are those with one of the following common among patients with immunosuppression or
underlying disorders and treatments: autoimmune immunodeficiency5.
diseases, asthma, diabetes, treatment with biologics or
Herpes zoster with extended prodrome
immunosuppressants, cancer or HIV/AIDS1.
HZ prodrome extending five days and up to
Clinical presentation
18 days have been reported. Extended prodrome is
The prodromal phase of about one to five days is not necessarily associated with immunosuppression or
characterized by malaise, fever and pain. The classical immunodeficiencies6.
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WOLLINA: HERPES ZOSTER 295

Herpes zoster not respecting dermatoma borders head-and-neck region1. The development of keloids
after HZ has been reported in a pregnant woman8.
Some aberrant vesicles are not uncommon.
However, HZ not respecting the borders of a dermatoma Herpes zoster with vascular manifestations
may be due to viraemic spread indicating a more
VZV vasculopathy covers a broad range of
severe subtype. HZ duplex is crossing the midline of
vascular manifestations in both immunocompetent and
the body. This subtype is seen more often in Asia than
immunocompromised patients. Ischaemic stroke and
in Europe7. An association to immunologic aberrations
intracerebral aneurysms may develop after VZV infection
is present in <50 per cent of patients7. Multi-segmental
of cerebral arteries9. In patients ≥65 yr of age, HZ increases
HZ and generalized HZ represent a continuum of more
the risk of myocardial infarction 1.7-fold and of ischaemic
severe manifestations (Fig. 2A, B)1.
stroke 2.4-fold during the first week of disease10.
Herpes zoster leaving scars
Leucocytoclastic VZV vasculitis can be a
If the inflammation is very strong, protracted consequence of HZ11. VZV can even trigger the onset of
scars may develop. This can be seen in haemorrhagic temporal arteriitis12. Erythema multiforme (EM)-linked
and necrotic HZ (Figs 3 & 4). Healing is delayed and lesions have been observed in HZ patients13. HZ has
bacterial superimposed infection is an additional risk been reported to increase the risk of peripheral arterial
(Fig. 5). Necrosis can also develop after unremarkable disease by 13 per cent14.
HZ due to delayed nervous and vascular compromise.
This subtype is most commonly seen in the Herpes zoster associated with neurologic impairment
An overview of specific neurological consequences
of HZ is summarized in the Table. The central nervous

A B

Fig. 2. Generalized herpes zoster. (A) Milder form, (B) more severe
manifestation with haemorrhagic lesions.
Fig. 1. Classical presentation of herpes zoster thoracicus.

Fig. 4. Extensive necrosis after complete remission of herpes zoster

Fig. 3. Haemorrhagic-necrotizing herpes zoster ophthalmicus. ophthalmicus.
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296 INDIAN J MED RES, MARCH 2017

Table. Subtypes of herpes zoster associated with specific neurological consequences

Subtype Affected nerve Findings Complications
Zoster First trigeminal nerve branch Keratitis, blepharitis, keratoconjunctivitis Uveitis anterior, orbital
ophthalmicus phlegmon, retinal necrosis,
superior orbital fissure
syndrome, blindness
Zoster oticus Vestibulocochlear and facial Pain localized to the ear may also be Bell’s palsy
nerve affected
Ramsay‑hunt Vestibulocochlear and facial Vesiculation in auditory canal, buccal Tinnitus, hearing loss,
syndrome nerve mucosa, cheeks laryngitis, failure of lid
closure
Source: Ref 1

represent a locus minoris resistentiae, on which other

disorders may develop. The phenomenon has been
called Wolf’s isotopic response. The phenotypical
variety is extraordinarily large. Such postherpetic
disorders with Wolf’s response include granuloma
annulare, lupus erythematosus, morphoea, lichen
planus, molluscum contagiosum or B-cell chronic
lymphocytic leukaemia17. In such cases, histologic
investigations are indispensable.
Pathergic phenomenon
Pathergy describes a skin condition, in which a
minor trauma leads to the development of ulcerations
or other skin lesions that may be resistant to healing.
Pathergy can also lead to ulcerations at the site of
Fig. 5. Herpes zoster ophthalmicus with ocular involvement and
superimposed bacterial infection. surgical incisions. Pyoderma gangrenosum of the scalp
has been observed as a pathergic response to HZ18.
system can be affected by HZV. Such patients Herpes zoster as a marker for occult cancer
suffer from headache, neck stiffness, behavioural
In a systematic review and meta-analysis19 of
abnormalities and somnolence. Typical manifestations
46 eligible studies, the pooled relative risk for any cancer
are encephalitis and meningitis in addition to VZV
was 1.42 and 1.83 at one year after zoster. The highest
vasculopathy. The diagnosis is hampered in particular
estimates were noted for haematological malignancies
in elderly patients with multiple comorbidities.
(Fig. 6). A study from Taiwan investigated the hazard
Cerebrospinal fluid analysis is not always helpful since
rates for cancer after HZ infection in elderly people.
pleocytosis can be found even in uncomplicated HZ,
Within the first two years after HZ, the risk of subsequent
but increased virus load is characteristic15.
cancer was significantly increased, particularly lung
A study conducted in Taiwan investigated HZ cancer20. On the other hand, metastases may resemble
in 10,296 elderly people (≥65 yr of age). Data were HZ. This has been reported for metastatic melanoma21,
compared with 39,405 randomly selected individuals lung cancer22, rectal adenocarcinoma23, breast cancer24
aged ≥65 yr without a diagnosis of HZ. The HZ group and nasopharyngeal cancer25 among others.
showed a hazard rate of 1.17 for the development of
Erythema multiforme (EM) after herpes zoster
Parkinson’s disease16. This is important to recognize
(HZ)
early symptoms of Parkinson’s disease among elderly
people affected by HZ. EM is commonly associated with herpes simplex
virus infections. It is considered as a hypersensitivity
Wolf’s isotopic response
reaction with polymorphous eruptions of macules,
Even after clinical remission, former HZ lesions papules and targetoid lesions symmetrically distributed.
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WOLLINA: HERPES ZOSTER 297

6. Zerngast WW, Paauw DS, O’Connor KM. Varicella zoster

with extended prodrome: A case series. Am J Med 2013; 126 :
359-61.
7. Son JH, Chung BY, Kim HO, Cho HJ, Park CW. Herpes zoster
duplex unilateralis: Two cases and brief literature review.
Ann Dermatol 2016; 28 : 757-61.
8. Verma SB, Wollina U. Herpes zoster in pregnancy leading
to keloids and post herpetic neuralgia: A double whammy?
Indian Dermatol Online J 2013; 4 : 158-9.
9. Nagel MA, Gilden D. Developments in varicella zoster virus
vasculopathy. Curr Neurol Neurosci Rep 2016; 16 : 12.
10. Minassian C, Thomas SL, Smeeth L, Douglas I, Brauer R,
Langan SM. Acute cardiovascular events after herpes zoster:
A self-controlled case series analysis in vaccinated and
unvaccinated older residents of the United States. PLoS Med
Fig. 6. Necrotic disseminated herpes zoster in occult chronic 2015; 12 : e1001919.
lymphatic leukaemia. 11. Wollina U, Schönlebe J. Segmental leukocytoclastic vasculitis
in herpes zoster. Int J Dermatol 2012; 51 : 1351-2.
12. Gilden D, Nagel MA. Varicella zoster virus triggers the
In contrast, EM has rarely been observed after HZ. immunopathology of giant cell arteritis. Curr Opin Rheumatol
Weisman et al26 reported on four patients with HZ with 2016; 28 : 376-82.
marked increase in VZV antibodies and development 13. Wollina U, Gemmeke A. Herpes zoster – associated erythema
of bullous EM about 10-14 days after resolution of multiforme. J Dermatol Case Rep 2009; 3 : 11-3.
HZ. Another patient was reported from Kyoto, Japan, 14. Lin TY, Yang FC, Lin CL, Kao CH, Lo HY, Yang TY. Herpes
who developed EM after HZ treated successfully with zoster infection increases the risk of peripheral arterial
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Conclusions
15. Grahn A, Bergström T, Runesson J, Studahl M. Varicella-zoster
HZ is a common disease caused by VZV. Although virus (VZV) DNA in serum of patients with VZV central
easily recognized by clinical features in the majority of nervous system infections. J Infect 2016; 73 : 254-60.
cases, the clinical presentation is variable. The suspicion 16. Lai SW, Lin CH, Lin HF, Lin CL, Lin CC, Liao KF. Herpes
of HZ in such cases is of particular importance since zoster correlates with increased risk of Parkinson’s disease
early treatment is warranted i.e. within 72 h after onset in older people: A population-based cohort study in Taiwan.
of vesicular eruption28. Medicine (Baltimore) 2017; 96 : e6075.
17. Wollina U, Schönlebe J. Disseminated specific cutaneous
Conflicts of Interest: None. infiltrates of B-cell chronic lymphocytic leukemia – Wolf’s
isotopic response following herpes zoster infection. J Dtsch
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Reprint requests: Dr U. Wollina, Department of Dermatology and Allergology, Academic Teaching Hospital
Dresden-Friedrichstadt, Friedrichstrasse 41, 01067 Dresden, Germany
e-mail: [email protected]