HSV-1 and HSV-2 measure approximately 200 nm in diameter and contain a linear, double-stranded DNA core of approximately 150-kilo base pairs (Kbp) enclosed within a protein capsid. The DNA sequence of both HSV-1 and HSV-2 serotypes is similar but they are antigenically distinct because of a difference in the envelope proteins.¹⁰ The majority of orofacial lesions are due to HSV-1 virus, while HSV-2 predominantly causes genital herpes. A notable exception is in neonates where exposure to HSV-2 during childbirth can result in the development of typical skin lesions during the first few days of life. It should be noted that both HSV-1 and HSV-2 are equally distributed in the trigeminal and sacral ganglia; therefore, the regional specificity of recurrent HSV infections is probably due to local host factors rather than a regional distribution of the latent virus.¹²,¹⁴

The chief mode of transmission is by kissing or other forms of intimate contact with an individual who has an active, usually recurrent, herpetic lesion, but asymptomatic patients shed the virus in the saliva as well, and accordingly are a more common source of infection.¹⁰ Once the primary infection is over, HSV-1 ascends in a retrograde manner to the trigeminal ganglion, where the virus, which is now sequestered from host immune surveillance, safely replicates and establishes latency persisting in a dormant state for life. This predisposes the host to recurrent attacks of periodic viral reactivation. Once it is reactivated, the virus travels along sensory neurons to the target sites in the eyelids, conjunctiva, cornea, or the uveal system and retina.¹⁰ These recurrences may be spontaneous or predisposed by a variety of triggers including psychological stress; fatigue; exposure to heat, sunlight, or cold; menstruation; sexual intercourse; fever; diabetes; organ transplantation; immunosuppression; corticosteroid administration (oral, parenteral, topical, or even in inhaled form); and measles or HIV infection.¹⁰,¹¹,¹³,¹⁵

Although direct viral toxicity to the eyelids is probably etiologically responsible for HSV blepharitis, the morbidity in primary HSV infections may also be immunopathogenic in origin.⁷,⁸ After exposure to the viral antigen, there is a massive rise in the number of neutrophils (Gr-1⁺ cells), which is the predominant infiltrating cell type and the likely source of inflammatory cytokines (IL-6, IL-10, IL-12, or IFN-γ), and therefore it could be a major effector of eyelid morbidity.⁸ Shortly after that, the viral load begins to clear and CD4⁺ T-cell count significantly increases in number. Although this immune response is essentially the same in the cornea and eyelids, it may play a different role in recurrent infections.⁶ While an already primed immune system in recurrent HSV may cause an immune-mediated, potentially blinding stromal keratitis, the same immune mechanism may limit the spread of herpetic blisters in recurrent HSV, which may explain why herpetic blepharitis is an unusual occurrence in recurrent disease.⁶,⁷,⁸

Incidence and prevalence data about HSV blepharitis are not directly available in the literature, but the data can be inferred indirectly from epidemiologic studies concerned with corneal HSV. Between 45% and 98% of the world population is seropositive for HSV-1,¹² the majority of whom are seroconverted by adolescence, particularly in children of lower socioeconomic groups.¹³ Primary infections are typically subclinical and may go unrecognized, although they may be associated with constitutional signs and symptoms. However, even in the absence of symptoms, primary infections are associated with a longer duration of viral shedding.¹²

The first presentation of ocular HSV may not necessarily represent the primary site of infection in the body.⁵,¹³ Clinical manifestations of ocular HSV may start at any age, but it generally is a disease of the young (mean age, 34 years). HSV-related blepharoconjunctivitis is one of the presenting signs in 35% to 54% of primary (initial) ocular attacks,⁵,¹⁰,¹¹,¹²,¹³ but monosymptomatic involvement of the eyelids and conjunctiva occurs only in 21% of patients.¹⁰ However, recurrent HSV blepharoconjunctivitis is infrequent, and the incidence was as low as 4% in some studies.² The disease is predominantly unilateral, but bilateral occurrence is encountered in 7.5% to 29% of patients, particularly in children or in those with atopy.¹³

Two major presentations of HSV blepharitis are observed.¹⁶ The classic presentation is with an acute onset of eyelid swelling, erythema, and a tingling sensation with local periocular tenderness in the involved side. This inflammatory swelling may cause mechanical ptosis if the upper eyelid is involved, or it may be accompanied by a red, tearing eye and conjunctival follicles if HSV simultaneously infects the conjunctiva (Figure 67.1).⁶ This is quickly followed by the appearance of a cluster of relatively large umbilicated vesicles with a yellowish content that are usually grouped together with an underlying erythematous and edematous base along the eyelashes (Figure 67.2A-C). These vesicles eventually crust and then dry out causing spontaneous unroofing of the lesions.⁵,¹⁷ In rare situations, particularly in atopic patients, these infections can be quite severe and could be secondarily infected. This is especially true when it is associated with eczema, where the condition has been termed eczema herpeticum (also referred to as Kaposi varicelliform eruption).³,⁵ Regional lymph nodes are usually involved, and the condition may be associated with pathognomonic follicles around the mouth or the nasal cavity.

The second and reportedly more common type of eyelid infection is intermarginal HSV blepharitis (erosive-ulcerative type),¹⁷ which is characterized by single or multiple eyelid margin ulcers or erosions each measuring 1 to several millimeters in length. These ulcers may be associated with localized swelling and tenderness but without the characteristic cutaneous follicular lesions or the acute inflammatory signs that hallmark the more typical presentation described above.⁵,¹⁶,¹⁷,¹⁸,¹⁹ The absence of cutaneous vesicular eruptions on the palpebral surface and the presence of a crust that usually covers these lesions may make the diagnosis difficult.¹⁸ If in doubt, staining the eyelid margin with fluorescein or rose bengal may help identify the ulcers and clinch the diagnosis.¹⁸ Whether this is a distinct clinical type of HSV blepharitis or a normal sequela of deroofing of herpetic vesicles which later coalesce is unknown.⁶ Of note is that the predilection of HSV to involve the eyelid margin is not unusual, and this is the typical behavior of a virus that favors orifices and mucocutaneous junctions.¹⁸ Both forms of presentation (large blisters/eyelid margin ulcers) discussed above are a reliable sign of clinically manifest primary HSV blepharitis, since both are rare in recurrent disease, and even when encountered, they are usually observed in a milder clinical form.⁶,¹⁷ As we mentioned earlier, this is likely due to immune reactions, which would limit the extent of HSV blepharitis.⁶ Other rarer eyelid presentations include acquired entropion in children, complete acquired ankyloblepharon, and punctal or canalicular scarring.¹⁵,²⁰,²¹,²²,²³