Describe the herpesvirus group. Discuss herpes simplex and varicella-zoster infections with their complications and treatment.

The Herpesvirus Group

• Large enveloped viruses with double-stranded DNA and icosahedral symmetry, replicating in the nucleus and producing COWDRY type A intranuclear inclusions
• The defining property of the whole family is latency — after primary infection the virus persists for life in a particular cell type and reactivates when immunity falls

Herpes Simplex Virus

• Transmission — by direct contact with lesions or with saliva or genital secretions, including from asymptomatic shedders, which is why most transmission occurs from people who do not know they are infected
• Primary infection — often subclinical. When symptomatic: acute gingivostomatitis in young children (painful vesicles and ulcers in the mouth with fever and refusal to feed), or primary genital herpes, which is more severe and prolonged than recurrences
• Recurrent infection — herpes labialis ("cold sore") preceded by tingling, triggered by fever, sunlight, stress, menstruation or immunosuppression
• Serious forms — herpetic keratitis with a dendritic corneal ulcer, a leading infectious cause of corneal blindness, in which topical corticosteroids are contraindicated as they cause corneal perforation; herpes simplex encephalitis, the commonest sporadic fatal encephalitis, caused by HSV-1 and characteristically affecting the temporal lobes, with fever, confusion, seizures and personality change; neonatal herpes acquired at delivery, which may be localised or disseminated and carries a high mortality; eczema herpeticum; and herpetic whitlow
• Diagnosis — PCR of cerebrospinal fluid is the test of choice in encephalitis and has replaced brain biopsy; TZANCK smear from a vesicle base shows multinucleate giant cells; immunofluorescence, culture and serology
• Treatment — acyclovir, given intravenously and immediately on suspicion in encephalitis, since delay converts a treatable illness into a fatal or disabling one; valacyclovir and famciclovir orally; suppressive therapy for frequent recurrences

Varicella-zoster Virus

• Primary infection is chickenpox (varicella) — highly infectious, spread by respiratory droplets and by vesicle fluid; the patient is infectious from about 2 days before the rash until all lesions have crusted
• The rash is centripetal (denser on the trunk than the limbs) and appears in crops, so lesions at different stages — macule, papule, vesicle, pustule and crust — are present simultaneously. This pleomorphism is the classical distinction from smallpox, in which all lesions were at the same stage and the rash was centrifugal
• Complications — secondary bacterial infection of the skin (the commonest); varicella pneumonia, which is far more serious in adults, in pregnancy and in the immunosuppressed; cerebellar ataxia; encephalitis; and REYE syndrome if aspirin is given
• Congenital varicella syndrome — from maternal infection in the first 20 weeks: limb hypoplasia, cicatricial skin scarring, eye and neurological defects. Perinatal varicella, when the mother develops the rash from 5 days before to 2 days after delivery, is severe and requires immunoglobulin
• Herpes zoster (shingles) — reactivation from a dorsal root or cranial ganglion, producing a painful vesicular rash in a dermatomal distribution that does not cross the midline, often preceded by pain for days
• Important forms and complications of zoster — herpes zoster ophthalmicus (ophthalmic division of the trigeminal nerve; involvement of the nasociliary branch gives hutchinson sign, a lesion on the tip of the nose, which predicts ocular involvement); RAMSAY hunt syndrome (geniculate ganglion, with facial palsy and vesicles in the external auditory meatus); post-herpetic neuralgia, which is common in the elderly and may be intractable; and disseminated zoster in the immunosuppressed
• Treatment and prevention — acyclovir or valacyclovir, most effective within 72 hours; analgesia including amitriptyline, gabapentin or pregabalin for neuralgia; varicella vaccine (live attenuated) and the recombinant zoster vaccine for older adults; and varicella-zoster immunoglobulin for exposed susceptible neonates, pregnant women and immunosuppressed contacts

Comparison of Chickenpox and Smallpox

Applied Aspects

• Start intravenous acyclovir on suspicion of herpes encephalitis and do not wait for imaging or cerebrospinal fluid results
• Never prescribe topical steroids for a red eye without excluding dendritic ulceration; steroid-treated herpetic keratitis can perforate the cornea and blind the patient
• Do not give aspirin to a child with chickenpox or influenza, because of Reye syndrome
• Chickenpox in an adult or in pregnancy is a serious illness, not the trivial childhood disease, and warrants antiviral treatment and assessment for pneumonia
• Treat zoster within 72 hours where possible, and consider it in unexplained dermatomal pain before the rash appears
• Zoster in a young adult should prompt HIV testing; it is a recognised early indicator of immunosuppression and is a common presentation of undiagnosed HIV in India
• Chickenpox is infectious from 2 days before the rash, so exposure has already occurred by the time the diagnosis is made and contact tracing must look backwards
• A pregnant woman exposed to chickenpox needs urgent assessment of her immune status, and varicella-zoster immunoglobulin if susceptible
• Look for Hutchinson sign in ophthalmic zoster — a vesicle on the tip of the nose indicates nasociliary involvement and predicts ocular disease, requiring urgent ophthalmological referral
• Post-herpetic neuralgia is prevented better than it is treated, which is the argument for early antiviral treatment and for zoster vaccination in the elderly
• Disseminated zoster crossing several dermatomes indicates significant immunosuppression and requires intravenous treatment and investigation of the cause
• Neonatal herpes carries a high mortality and may present without skin lesions; caesarean section is advised where the mother has active genital lesions at delivery
• Aspirin is contraindicated in chickenpox because of Reye syndrome, and paracetamol should be used instead — a point worth stating explicitly to families
• Herpes is transmitted by asymptomatic shedders, so the absence of visible lesions does not mean the absence of risk, and this is important in counselling about genital herpes
• Zoster vaccination is recommended for older adults in many countries and reduces both shingles and post-herpetic neuralgia; the recombinant vaccine is preferred to the live one in the immunosuppressed
• Varicella vaccine is live and contraindicated in pregnancy and in significant immunosuppression, which is precisely the group most in need of protection — hence the role of immunoglobulin after exposure
• The Tzanck smear cannot distinguish HSV from VZV, so where the distinction matters clinically, PCR or immunofluorescence is required
• Acyclovir is remarkably safe because it is a prodrug activated by viral thymidine kinase, so it is concentrated only in infected cells — which is why it can be given in high dose with little toxicity
• Ensure adequate hydration with intravenous acyclovir, which can crystallise in the renal tubules and cause acute kidney injury if given rapidly to a dehydrated patient