Skin >

Herpes Simplex

Definition

Infection by the herpes simplex viruses (types 1 and 2).

Clinical Features

Lesions

  • Usually group of clear vesicles:
    • heal without scarring, unless secondary bacterial infection

Recurrent Disease

  • Stimulated by:
    • ultraviolet light1
    • trauma
    • fever
    • HIV infection2
    • menstruation
    • stress3

HSV-1 Infection

  • Primary infection usually:
    • childhood
    • mild
  • Recurrent lesions:
    • usually around lips:
      • herpes labialis (cold sores)
    • other sites:
      • oral cavity
      • pharynx
      • esophagus
      • eye
      • lung
      • brain4–6

Special Clinical Variants12

Pathogenesis

  • Two main types of biologically and serologically distinct herpes simplex virus:
    • type 1 (HSV-1)
    • type 2 (HSV-2)34
  • After infection, virus:
    • is usually harbored for life
    • travels along sensory nerves to infect neurons in sensory ganglia

Histopathology

Earliest Changes

  • Begin focally along basal layer
  • Soon involve entire epidermis35
  • Epidermal cells:
    • nuclei:
      • peripheral clumping of chromatin
      • homogeneous ground-glass appearance
      • ballooning of nucleus35
    • cytoplasm:
      • vacuolization

Established Intraepidermal Vesicle

  • Usually present by time of biopsy
  • Results from two types of degenerative change:
    • ballooning degeneration:
      • peculiar to viral vesicles
      • mainly at base of vesicle
      • affected cells:
        • swell
        • lose attachment to adjacent cells:
          • secondary acantholysis
        • cytoplasm becomes:
          • homogeneous
          • intensely eosinophilic
        • sometimes multinucleate:
          • Tzanck cells
      • sometimes destroys basal layer of epidermis:
        • leading to formation of subepidermal vesicle
    • reticular degeneration:
      • on superficial aspect and margin of vesicle
      • epidermal cells:
        • enlarged and clear with only fine cytoplasmic strands remaining at edge of cells:
          • due to progressive hydropic swelling
        • eventually rupture:
          • contributing to formation of vesicle
      • also seen in allergic contact dermatitis
  • Eosinophilic intranuclear inclusion bodies:
    • particularly in ballooned cells (Figs 1–3
      Herpes simplex. (H&E)

      Fig. 1: Herpes simplex. (H&E)

      Herpes simplex. There is an intraepidermal vesicle containing ballooned, acantholytic keratinocytes in which there are intranuclear inclusion bodies. (H&E)

      Fig. 2: Herpes simplex. There is an intraepidermal vesicle containing ballooned, acantholytic keratinocytes in which there are intranuclear inclusion bodies. (H&E)

      Herpes simplex. The multinucleate keratinocytes have intranuclear inclusion bodies. (H&E)

      Fig. 3: Herpes simplex. The multinucleate keratinocytes have intranuclear inclusion bodies. (H&E)

      )
    • more common in multinucleate cells of lesions present for several days
  • Neutrophils:
    • within established vesicles
    • moderate numbers in underlying dermis:
      • together with lymphocytes36
      • dermal inflammation usually more severe than in zoster
    • prominent in herpetic whitlow
  • Sometimes:
    • marked inflammation
    • vasculitis37
  • Uncommonly:
    • erythema multiforme-like changes in adjacent skin, concurrent with vesicle of herpes simplex

Lichenoid Lymphocytic Vasculitis

  • A related reaction pattern
  • In presumptive cases of herpes simplex with immunological response38
  • Upper dermal infiltrate of lymphocytes and histiocytes
  • Lichenoid changes in epidermis
  • Dermal lymphocytic vasculitis

Involvement of Pilosebaceous Units

  • Often focal in recurrent lesions35
  • Dominant lesion in herpes folliculitis (Fig. 4
    Herpes folliculitis. There is a heavy superficial and deep dermal infiltrate of lymphocytes. A necrotic follicle is present in the upper third of the dermis. (H&E)

    Fig. 4: Herpes folliculitis. There is a heavy superficial and deep dermal infiltrate of lymphocytes. A necrotic follicle is present in the upper third of the dermis. (H&E)

    )39
  • Rarely, eccrine ducts and glands involved:
    • herpetic syringitis40
  • Ballooning degeneration may involve cells of outer root sheath of deep portion of follicle:
    • often a dermal inflammatory infiltrate:
      • heaviest in deep reticular dermis:
        • ‘bottom-heavy’ infiltrate

Dermal Nerves in Lesional Skin

  • Perineural and some intraneural inflammation:
    • also in herpes zoster
  • Viral antigen detected41
  • May be:
    • Schwann cell hypertrophy
    • neuronal necrosis with cytopathic changes41
  • Sometimes perineural infiltration out of proportion to overlying dermal inflammation

Late Lesions

  • Often ulceration
  • On routine staining:
    • may be ghosts of acantholytic, multinucleate epithelial cells with slate-gray nuclei in overlying crust

Lesions That Recur At Site Of Previous Surgery

  • Subepidermal vesicles
  • Inflammatory response with multinucleate giant cells42 in uppermost dermis

Eczema Herpeticum

  • Usually typical features of vesicle of herpes simplex in recently formed lesion
  • Other features:
    • multinucleate epidermal cells
    • intranuclear inclusions
    • heavy inflammatory cell infiltrate of neutrophils
    • early breakdown of vesicles

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Herpes Simplex

(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)
(View full diagnosis)


  • Histological appearances of herpes simplex, varicella and herpes zoster similar
  • Rapid cytological diagnosis of vesicular lesion:
    • make smear from base of freshly opened vesicle
    • stain with Giemsa stain reveals ballooned cells, some multinucleate, in herpes simplex, varicella and zoster
  • Rapid diagnosis of cutaneous infection of herpes simplex:
    • use smear and monoclonal antibodies, with immunofluorescence technique43,44
  • PCR-based methods used routinely in some laboratories

References

1 Perna JJ, Mannix ML, Rooney JF, et al.. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model. J Am Acad Dermatol. 1987;17:473–478.

2 Severson JL, Tyring SK. Relation between herpes simplex viruses and human immunodeficiency virus infections. Arch Dermatol. 1999;135:1393–1397.

3 Pereira FA. Herpes simplex: Evolving concepts. J Am Acad Dermatol. 1996;35:503–520.

4 Vestey JP, Norval M. Mucocutaneous infections with herpes simplex virus and their management. Clin Exp Dermatol. 1992;17:221–237.

5 Spruance SL. The natural history of recurrent oral-facial herpes simplex virus infection. Semin Dermatol. 1992;11:200–206.

6 Whitley RJ, Roizman B. Herpex simplex virus infections. Lancet. 2001;357:1513–1518.

7 Corey L, Vontver LA, Brown ZA. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Semin Dermatol. 1984;3:89–101.

8 Vanderhooft S, Kirby P. Genital herpes simplex virus infection: natural history. Semin Dermatol. 1992;11:190–199.

9 Petersen CS, Larsen FG, Zachariae C, Heidenheim M. Herpes simplex virus-type 2 seropositivity in a Dutch adult population denying previous episodes of genital herpes. Acta Derm Venereol. 2000;80:158.

10 Cliff S, Ostlere LS, Hague K, Harland CC. Segmental scarring following intrauterine herpes simplex virus infection. Clin Exp Dermatol. 1997;22:96–98.

11 Tang WYM, Lo JYC, Yuen MK, Lam WY. Herpes simplex virus type 2 infection in a 5-year-old boy presenting with recurrent chest wall vesicles and a possible history of herpes encephalitis. Br J Dermatol. 1997;137:440–444.

12 Snavely SR, Liu C. Clinical spectrum of herpes simplex virus infections. Clin Dermatol. 1984;2:8–22.

13 Giacobetti R. Herpetic whitlow. Int J Dermatol. 1979;18:55–58.

14 Peutherer JF, Smith IW, Robertson DH. Necrotising balanitis due to a generalised primary infection with herpes simplex virus type 2. Br J Vener Dis. 1979;55:48–51.

15 Long JC, Wheeler CE, Briggaman RA. Varicella-like infection due to herpes simplex. Arch Dermatol. 1978;114:406–409.

16 Leyden JJ, Baker DA. Localized herpes simplex infections in atopic dermatitis. Arch Dermatol. 1979;115:311–312.

17 Boyd AS, Neldner KH, Zemtsov A, Shihada B. Photolocalized varicella. J Am Acad Dermatol. 1992;26:772–774.

18 Beasley KL, Cooley GE, Kao GF, et al.. Herpes simplex vegetans: Atypical genital herpes infection in a patient with common variable immunodeficiency. J Am Acad Dermatol. 1997;37:860–863.

19 Das S, Leonard N, Reynolds NJ. Herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs. Clin Exp Dermatol. 2000;25:119–121.

20 Butler DF, Malouf PJ, Batz RC, Stetson CL. Acquired lymphedema of the hand due to herpes simplex virus type 2. Arch Dermatol. 1999;135:1125–1126.

21 Langtry JAA, Ostlere LS, Hawkins DA, Staughton RCD. The difficulty in diagnosis of cutaneous herpes simplex virus infection in patients with AIDS. Clin Exp Dermatol. 1994;19:224–226.

22 Saijo M, Suzutani T, Murono K, et al.. Recurrent aciclovir-resistant herpes simplex in a child with Wiskott–Aldrich syndrome. Br J Dermatol. 1998;139:311–314.

23 Hillard P, Seeds J, Cefalo R. Disseminated herpes simplex in pregnancy: two cases and a review. Obstet Gynecol Surv. 1982;37:449–453.

24 Vestey JP, Howie SEM, Norval M, et al.. Immune responses to herpes simplex virus in patients with facial herpes simplex and those with eczema herpeticum. Br J Dermatol. 1988;118:775–782.

25 Fukuda M, Kono T, Ishii M, Hamada T. Detection of herpes simplex viral DNA in Kaposi's varicelliform eruption using in situ hybridization method. Clin Exp Dermatol. 1991;16:407–410.

26 Amatsu A, Yoshida M. Detection of herpes simplex virus DNA in non-herpetic areas of patients with eczema herpeticum. Dermatology. 2000;200:104–107.

27 Parslew R, Verbov JL. Kaposi's varicelliform eruption due to herpes simplex in Darier's disease. Clin Exp Dermatol. 1994;19:428–429.

28 Pantazi V, Potouridou I, Katsarou A, et al.. Darier's disease complicated by Kaposi's varicelliform eruption due to herpes simplex virus. J Eur Acad Dermatol Venereol. 2000;14:209–211.

29 Flint ID, Spencer DM, Wilkin JK. Eczema herpeticum in association with familial benign chronic pemphigus. J Am Acad Dermatol. 1993;28:257–259.

30 Ng SK, Ang CB, Tham A. Kaposi's varicelliform eruption in a patient with pityriasis rubra pilaris. J Am Acad Dermatol. 1992;27:263.

31 Fukuzawa M, Oguchi S, Saida T. Kaposi's varicelliform eruption of an elderly patient with multiple myeloma. J Am Acad Dermatol. 2000;42:921–922.

32 Hayashi S, Yamada Y, Dekio S, Jidoi J. Kaposi's varicelliform eruption in a patient with mycosis fungoides. Clin Exp Dermatol. 1997;22:41–43.

33 Nishimura M, Maekawa M, Hino Y, et al.. Kaposi's varicelliform eruption. Development in a patient with a healing second-degree burn. Arch Dermatol. 1984;120:799–800.

34 Rawls WE, Hammerberg O. Epidemiology of the herpes simplex viruses. Clin Dermatol. 1984;2(2):29–45.

35 Huff JC, Krueger GG, Overall JC, et al.. The histopathologic evolution of recurrent herpes simplex labialis. J Am Acad Dermatol. 1981;5:550–557.

36 Resnik KS, DiLeonardo M. Herpes incognito. Am J Dermatopathol. 2000;22:144–150.

37 Cohen C, Trapuckd S. Leukocytoclastic vasculitis associated with cutaneous infection by herpesvirus. Am J Dermatopathol. 1984;6:561–565.

38 Ferguson DL, Hawk RJ, Covington NM, Reed RJ. Lichenoid lymphocytic vasculitis with a high component of histiocytes. Histogenetic implications in a specified clinical setting. Am J Dermatopathol. 1989;11:259–269.

39 Jang K-A, Kim S-H, Choi J-H, et al.. Viral folliculitis on the face. Br J Dermatol. 2000;142:555–559.

40 Sangueza OP, Gordon MD, White CR. Subtle clues to the diagnosis of the herpesvirus by light microscopy. Herpetic syringitis. Am J Dermatopathol. 1995;17:163–168.

41 Worrell JT, Cockerell CJ. Histopathology of peripheral nerves in cutaneous herpesvirus infection. Am J Dermatopathol. 1997;19:133–137.

42 Shelley WB, Wood MG. Surgical conversion of herpes simplex from an epidermal to a dermal disease. Br J Dermatol. 1979;100:649–655.

43 Goodyear HM, Wilson P, Cropper L, et al.. Rapid diagnosis of cutaneous herpes simplex infections using specific monoclonal antibodies. Clin Exp Dermatol. 1994;19:294–297.

44 Goldman BD. Herpes serology for dermatologists. Arch Dermatol. 2000;136:1158–1161.

Last updated: 21 Nov 2006

Herpes Simplex

Back to top