Inflammatory Diseases of the Skin
Moderator: Dr. Lorenzo Cerroni
Case 14 -
Exclusive Involvement of Folliculosebaceous Units by Herpes:
A Reflection of Early Herpes Zoster
Noreen Walsh, MD
Although clinical overlap exists between the vesicular cutaneous and muco-cutaneous eruptions of
herpes simplex (HS), zoster (HZ) and varicella(VZ), these infections are usually distinguishable from one
another on careful evaluation of the patient, with or without the benefit of additional investigations.
The same is not true of the microscopic manifestations of these conditions which are regarded as being
identical to one another.
Case 14 - Slide 1
They are characterized by intraepithelial vesiculation due to acantholyis and/or reticular
degeneration, accompanied by characteristic cytopathic changes. The latter include ballooning of cells,
steel grey nuclei due to intranuclear inclusions, multinucleation with nuclear moulding and
mummified/necrotic remnants of such cells. That folliculosebaceous and eccrine units can also display
herpetic cytopathic features is well recognized. In fact, when epidermal features of the disease are
obliterated by ulceration, detection of adnexal involvement can serve as the sole clue to the diagnosis.
As a rule, the purpose of histopathological examination of a biopsy from a patient with a particular
vesicular eruption is to confirm or refute its herpetic nature. If necessary, adjunctive investigations
such as serology, tissue culture and/or molecular biology will serve to hone the specific diagnosis.
Following primary infection by herpes simplex I or II, the virus (HSV) is transported via sensory
nerves to dorsal root and/or trigeminal ganglia where it is stored, in a latent state, for variable
periods of time. Subsequently, there is periodic reactivation and replication of the virus, triggered by
a variety of poorly understood factors. This is followed by axonal spread of the virus to the original
cutaneous or mucocutaneous site, resulting in recurrent, pauci-lesional, self limited episodes of disease
throughout life. Similarly, following primary infection with varicella zoster (chicken pox), the virus
(VZV) travels via sensory neurons to dorsal root and/or trigeminal ganglia where it remains latent for an
indefinite period of time. Under certain circumstances, for example, in the setting of severe
immunosuppression, the virus is reactivated. Following its replication and expanded involvement of the
ganglion, it is transported via sensory nerves to the skin and/or mucous membranes. This results in a
further episode of disease, usually confined to one or more dermatomes. Most commonly thoracic or lumbar
dermatomes are involved by the characteristic unilateral vesicular eruption but the dermatomal area of
the trigeminal nerve is sometimes affected. In states of severe debilitation both herpes simplex and
zoster can manifest themselves as a disseminated, life threatening disease.
There is compelling scientific evidence in the literature indicating that, in herpes zoster, the
reactivated virus is transported from dorsal root or trigeminal ganglia via myelinated nerves to the
skin. These terminate at the isthmus of hair follicles and primary infection of follicular and sebaceous
epithelium occurs. Spread of infection to the epidermis follows. In contrast, data pertaining to
recurrent herpes simplex indicates that axonal transport of the reactivated virus from sensory ganglia to
the skin is directed primarily to the epidermis, via terminal non-myelinated nerve twigs. Clinical
studies and scientific data in the literature indicate that exclusive folliculosebaceous involvement by
herpes, in the setting of a non-vesicular eruption, represents early herpes zoster. This point was
reinforced by findings outlined in an oral presentation at the 41st Annual Meeting of the American
Society of Dermatopathology, where 8 of 8 patients whose biopsies showed exclusives folliculosebaceous
involvement by herpes proved to have infection by varicella zoster virus on molecular analysis [PCR].
Recognition of the fact that folliculosebaceous units are the first cutaneous epithelial structures to be
targeted in HZ, enables a specific histopathological diagnosis of HZ to be made in the pre-vesicular
stage of the disease, when administration of antiviral agents may be most advantageous.
- Muraki R, Baba T, Iwasaki T, et al. Immunohistochemical study of skin lesions in herpes zoster. Virchows Archiv A Pathol Anat 1992; 420:71-76.
- Nikkels AF, Debrus S, Sadzot-Delvaux C, et al. Comparative immunohistochemical study of herpes simplex and varicella-zoster infections. Virchows Archiv A Pathol Anat 1993; 422:121-126.
- Nikkels AF, Debrus S, Sadzot-Delvaux C, et al. Localization of varicella-zoster virus nucleic acids and proteins in human skin. Neurology 1995; 45(Suppl 8):S47-S49.
- Muraki R, Iwasaki T, Sata T, et al. Hair follicle involvement in herpes zoster: pathway of viral spread from ganglia to skin. Virchows Arch 1996; 428:275-280.
- Iwasaki T, Muraki R, Kasahara T, et al. Pathway of viral spread in herpes zoster: detection of the protein encoded by open reading frame 63 of varicella-zoster virus in biopsy specimens. Arch Virol Suppl 2001; 17:109-19.
- Walsh N, Boutilier R, Glasgow D and Shaffelberg M. Exclusive folliculosebaceous involvement by herpes: A reflection of early herpes zoster. Am J Dermatopathol 2005; Jun; 27(3): 189-194.
- Blair J, Kutzner H, McCalmont T. Herpetic folliculitis is usually a consequence of varicella zoster virus infection. Oral presentation (Oral Abstract Session 1), 41st Annual Meeting of the American Society of Dermatopathology, October 15, 2004, Boston, Massachusetts.