Viral Skin Disease: Herpes, Warts and Molluscum

Two herpesviruses, one clinical family

The herpesviruses share a signature habit: they never truly leave. Herpes simplex virus (HSV) comes in two types. HSV-1 classically causes orolabial disease — the recurrent cold sore (herpes labialis) — while HSV-2 classically causes genital herpes, though the overlap between the two has grown. After a first infection the virus retreats up a sensory nerve and sleeps in the dorsal root or trigeminal ganglion, reactivating under stress, sunlight, illness or immunosuppression. Varicella-zoster virus (VZV) tells the same story on a bigger stage: the primary infection is chickenpox (varicella), a widespread itchy vesicular rash of childhood; the virus then lies dormant in a dorsal root ganglion for decades and can reactivate as shingles (herpes zoster) — a painful band of blisters confined to one dermatome, the territory of the single nerve it woke in.

The trick: a drug switched on only inside infected cells

Aciclovir is a prodrug — inert until the virus itself activates it. The nucleoside analogues — aciclovir (acyclovir), and its better-absorbed relatives valaciclovir (valacyclovir) and famciclovir — are the backbone of herpes treatment, and their selectivity is a small masterpiece of pharmacology. Aciclovir is a fake building block, a decoy version of the nucleoside guanosine. But it is delivered in an unusable form and must be phosphorylated (switched on) three times before it can act. The crucial first phosphorylation is performed by a viral enzyme, thymidine kinase (TK), which HSV and VZV carry but human cells largely lack. So the drug is activated to any meaningful degree only inside a cell the virus has infected. Host cell enzymes then add the last two phosphates, and the finished drug — aciclovir triphosphate — is ready.

Now the second half of the selectivity. Aciclovir triphosphate does two things at the viral DNA polymerase, the enzyme copying the virus's genome. First, it competes with real guanosine and is preferentially grabbed by the viral polymerase (far more avidly than by our own). Second, once slotted into the growing DNA strand it acts as a chain terminator: it lacks the chemical handle (the 3'-hydroxyl) the next nucleotide needs to attach to, so the chain simply stops dead. Replication halts. Because activation needs viral TK and the target is viral polymerase, the drug is toxic to the virus and remarkably gentle on the patient — the reason aciclovir is one of the safest antivirals ever made. The same chain-termination logic underlies the nucleoside analogues used against other viruses, as covered in the Antimicrobials chapter on antiviral pharmacology.

Shingles, its nerve pain, and a dermatological emergency

Shingles is more than a rash; it is a disease of the nerve. The pain can precede the rash, outlast it, and in older patients persist for months as post-herpetic neuralgia — a burning, lancinating pain in the healed dermatome that is notoriously hard to treat and belongs to the neuropathic-pain drugs (gabapentinoids, tricyclics) discussed in the Neurology/pain chapter. Prompt antiviral therapy blunts this risk, and prevention has moved upstream: the recombinant zoster vaccine now markedly reduces the incidence of shingles in older adults. Two zoster sites are red flags. Ophthalmic zoster (the tip-of-the-nose Hutchinson sign) threatens the eye and needs urgent ophthalmology; zoster near the ear (Ramsay Hunt syndrome) can cause facial palsy. Both demand systemic antivirals, not a topical cream.

One HSV scenario is a true emergency — and it lives in dermatology. Eczema herpeticum is HSV infection spreading explosively across skin whose barrier is already broken by atopic dermatitis. Instead of a tidy cluster of vesicles, the virus disseminates as widespread, monomorphic, punched-out erosions with crusting, often with fever and malaise. Because the compromised skin barrier lets it spread and even become systemic, this is a dermatological emergency treated with prompt systemic (usually intravenous) aciclovir — never dismissed as "infected eczema" and never treated with topical steroids alone, which can make it worse. It is the sharpest reminder that in a patient with eczema (see the Atopic dermatitis chapter), a sudden painful vesicular flare is herpes until proven otherwise.

Warts: no antiviral, so destroy or provoke

Human papillomavirus has no thymidine kinase to exploit and no antiviral to match aciclovir. Warts (verrucae) are driven by human papillomavirus (HPV) hijacking keratinocytes into a thickened, hyperkeratotic overgrowth. There is no direct antiviral drug for them, so treatment follows two very different logics: destroy the wart, or provoke the immune system into recognising and clearing it. The destructive/keratolytic approaches physically remove infected tissue — salicylic acid, applied over weeks, chemically dissolves the built-up keratin layer by layer; cryotherapy with liquid nitrogen freezes and kills the wart tissue. Many warts, especially in children, also simply resolve on their own as immunity eventually catches up — which is why aggressive treatment of a harmless wart is often unnecessary.

The more interesting drug does not touch the virus at all — it calls in the immune system. Imiquimod is the clearest example of the immunomodulatory strategy. It is not an antiviral in any conventional sense: it kills nothing directly. Instead it is an agonist of Toll-like receptor 7 (TLR7), a sensor of the innate immune system that normally detects viral genetic material. By switching on TLR7 in the skin, imiquimod triggers a local burst of interferon-alpha and other pro-inflammatory cytokines — essentially raising a local alarm that summons immune cells to the wart and drives them to clear the HPV-infected tissue. The mechanism is pure immunology, linking directly to the Immunology/Inflammation chapter on interferons and innate-immune sensing. Tellingly, the visible sign that imiquimod is working is inflammation — redness, soreness and erosion at the site — the deliberate immune response, not a side effect to be feared.

Anogenital warts and prevention

Anogenital warts (condylomata acuminata) are caused by low-risk HPV types (commonly 6 and 11) and have their own toolkit, again split between provoking immunity and destroying tissue. Imiquimod recruits the immune system as above. Podophyllotoxin is an antimitotic — it binds tubulin and arrests dividing cells in metaphase, killing the rapidly dividing wart tissue directly (the same tubulin-poisoning principle as the vinca alkaloids in the Oncology chapter). Sinecatechins, a purified green-tea catechin extract, offer a third, gentler option. But the deepest intervention is prevention: HPV vaccination. Because high-risk HPV types (notably 16 and 18) also cause cervical, anal and oropharyngeal cancers, vaccinating before exposure prevents both the warts and the far more dangerous malignancies downstream — a link that carries straight into the Skin cancer and oncology-prevention chapters.

Molluscum contagiosum: mostly, wait

Molluscum contagiosum is caused not by a herpesvirus or HPV but by a poxvirus, and it produces the characteristic small, dome-shaped, pearly papules with a central dimple (umbilication), most often in children. The key teaching point is restraint: in an immunocompetent person it is benign and self-limiting, clearing on its own over months as immunity develops, so no treatment is often the right answer. When treatment is wanted — for spread, discomfort or cosmetic reasons — options include physical/destructive methods and topical agents. Cantharidin, a blistering agent derived historically from the blister beetle, has re-emerged as a newer approved topical formulation applied in the clinic: it raises a controlled blister that lifts the lesion away. As with warts, no drug attacks the poxvirus directly; the approaches either remove the lesion or wait for immunity to win.