Viral Exanthems & Cutaneous Viral Infections

A high-yield cluster covering the viruses that produce rashes and skin lesions: the herpesviruses (HSV, VZV), poxviruses (molluscum), papillomaviruses (warts) and enteroviruses (hand-foot-mouth). NEET PG loves Tzanck smear, dermatomal zoster, HPV typing and antiviral dosing — get these crisp.

Overview & classification

Cutaneous viral infections are conveniently grouped by the offending virus family, because the family predicts morphology, histology and therapy.

Virus family	Member	Classic lesion	Bedside test
Herpesviridae	HSV-1/2	Grouped vesicles on erythematous base	Tzanck smear (multinucleate giant cells)
Herpesviridae	VZV	Dewdrop-on-rose-petal vesicles; dermatomal in zoster	Tzanck smear; PCR
Poxviridae	Molluscum contagiosum virus	Umbilicated pearly papule	Henderson–Paterson bodies
Papillomaviridae	HPV	Verrucous papule / condyloma	Koilocytes on histology
Picornaviridae	Coxsackie A16 / EV71	Oval grey vesicles palms/soles + oral ulcers	Clinical

High-yield: A Tzanck smear is positive (shows multinucleated giant cells / acantholytic cells) in HSV, VZV and pemphigus vulgaris — it cannot distinguish HSV from VZV. PCR or DFA is needed for speciation.

Herpes simplex virus (HSV)

Virology & transmission

Double-stranded DNA viruses. HSV-1 classically causes orolabial disease; HSV-2 causes genital disease — but cross-over is now common (HSV-1 is a leading cause of genital herpes in young adults from oro-genital contact). After primary infection the virus establishes latency in sensory (dorsal root/trigeminal) ganglia and reactivates with stress, fever, UV light, immunosuppression and menstruation.

Clinical syndromes

• Primary herpetic gingivostomatitis — children 1–5 yr; high fever, painful vesicles/erosions over gingiva, tongue, buccal mucosa, perioral skin; tender cervical lymphadenopathy. Most common clinical primary HSV-1 presentation.
• Herpes labialis ("cold sore") — recurrent, prodromal tingling then grouped vesicles at the vermillion border.
• Genital herpes — painful grouped vesicles/ulcers, inguinal nodes; recurrences from HSV-2 are more frequent than HSV-1.
• Herpetic whitlow — vesicles on the finger/distal phalanx; classic in dentists, anaesthetists and thumb-sucking children. Do not incise (worsens it).
• Herpes gladiatorum — wrestlers; head/neck/trunk lesions.
• Eczema herpeticum (Kaposi varicelliform eruption) — disseminated HSV over pre-existing atopic dermatitis; monomorphic punched-out erosions, fever — a dermatological emergency.
• Herpetic keratoconjunctivitis — dendritic corneal ulcer (fluorescein); a top cause of corneal blindness; never give topical steroids alone.
• Herpes encephalitis — HSV-1; temporal lobe involvement; treat empirically with IV aciclovir.

High-yield: Eczema herpeticum + monomorphic punched-out erosions in an atopic child = start IV aciclovir without waiting for confirmation. Bacterial super-infection (Staph) is common.

Diagnosis

• Tzanck smear — quick, scrape base of a fresh vesicle → giant cells (sensitivity moderate; not specific for HSV vs VZV).
• PCR — most sensitive and specific; investigation of choice for CNS disease (CSF PCR) and for speciation.
• Viral culture, DFA, Type-specific serology (HSV glycoprotein G) for chronic counselling.

Management

Indication	Drug & dose
Primary orolabial/genital HSV	Aciclovir 400 mg PO TDS × 7–10 d (or valaciclovir 1 g BD)
Recurrent genital herpes	Aciclovir 800 mg TDS × 2 d / valaciclovir 500 mg BD × 3 d
Suppressive therapy (≥6 recurrences/yr)	Aciclovir 400 mg BD daily
HSV encephalitis / neonatal / disseminated	IV aciclovir 10 mg/kg 8-hourly × 14–21 d
Aciclovir-resistant (TK-deficient, in HIV)	IV foscarnet (or cidofovir)

High-yield: Aciclovir is a guanosine analogue activated by viral thymidine kinase → triphosphate inhibits viral DNA polymerase. Resistance = TK mutation → switch to foscarnet (a pyrophosphate analogue needing no TK activation).

Varicella-zoster virus (VZV)

VZV causes chickenpox (varicella) on primary infection and shingles (herpes zoster) on reactivation. Highly contagious via respiratory droplets and lesion contact.

Chickenpox (varicella)

• Incubation ~14–21 days; infectious from 1–2 days before rash until all lesions crust.
• Prodrome of fever/malaise, then a centripetal (trunk > limbs) rash that evolves macule → papule → vesicle → pustule → crust.
• Hallmark: pleomorphism — lesions in different stages simultaneously (contrast smallpox, where all lesions are in the same stage and centrifugal).
• Vesicle = "dewdrop on a rose petal".

Complications: secondary bacterial infection (Staph/Strep, incl. necrotising fasciitis), varicella pneumonia (worst in adults, smokers, pregnancy), cerebellar ataxia (children, good prognosis), encephalitis, congenital varicella syndrome (limb hypoplasia, cicatricial skin scarring, eye/CNS defects if maternal infection at 8–20 wk), and neonatal varicella (maternal rash 5 days before to 2 days after delivery → give VZIG).

High-yield: Reye syndrome — encephalopathy + fatty liver — is linked to aspirin (salicylate) use during varicella or influenza in children. Never give aspirin in these settings; use paracetamol.

Herpes zoster (shingles)

• Reactivation in a single dermatome, unilateral, does not cross the midline; preceded by pain/paraesthesia.
• Most common site: thoracic dermatomes; risk rises with age and immunosuppression.
• Hutchinson sign — vesicles on the tip/side of the nose (nasociliary branch) → high risk of herpes zoster ophthalmicus → urgent ophthalmology.
• Ramsay Hunt syndrome (herpes zoster oticus) — geniculate ganglion; facial palsy + ear vesicles + ear pain, sometimes vertigo/hearing loss.
• Disseminated zoster (>2 dermatomes or >20 lesions outside primary dermatome) signals immunosuppression — investigate for HIV/malignancy.
• Post-herpetic neuralgia (PHN) — pain persisting >3 months; commonest complication, especially in elderly.

Diagnostic flow for a vesicular rash: Grouped vesicles → Tzanck smear (giant cells confirm herpes group) → PCR/DFA to separate HSV vs VZV → if dermatomal & unilateral, clinical diagnosis of zoster suffices.

Management of VZV

• Varicella in healthy child: symptomatic (calamine, antihistamine, paracetamol); antivirals not routine.
• Varicella in adults / adolescents / immunocompromised / pregnant: oral aciclovir (800 mg 5×/day) or IV if severe — best if started within 24 h of rash.
• Herpes zoster: aciclovir 800 mg 5 times daily × 7 days (or valaciclovir 1 g TDS / famciclovir 500 mg TDS) — start within 72 h of rash to reduce PHN.
• PHN: gabapentin/pregabalin, tricyclics (amitriptyline), topical lidocaine/capsaicin.
• Post-exposure prophylaxis: VZIG within 96 h for susceptible high-risk contacts (neonates, pregnant, immunocompromised).
• Vaccines: live-attenuated varicella vaccine; recombinant zoster vaccine (Shingrix) preferred in ≥50 yr (do not give live vaccine to immunocompromised).

High-yield: Zoster antivirals must begin within 72 hours of rash onset to cut post-herpetic neuralgia. Famciclovir is the dose to remember: 500 mg TDS.

Molluscum contagiosum

A poxvirus (DNA virus) spread by skin contact, fomites and autoinoculation; sexually transmitted in adults.

• Lesion: firm, dome-shaped, pearly/skin-coloured papule with central umbilication; expressing yields a cheesy core.
• Children: trunk, face, limbs. Adults: genitalia/lower abdomen/thighs (consider STI).
• Immunocompromised (HIV with low CD4): giant, numerous, treatment-resistant molluscum, often on the face — a clue to advanced HIV. Differential: disseminated cryptococcosis/histoplasmosis/penicilliosis, which mimic molluscum.
• Histology: intracytoplasmic inclusion bodies = Henderson–Paterson bodies (molluscum bodies).

Management: Often self-limited in immunocompetent (months–2 yr). Active options: cryotherapy, curettage, cantharidin, topical podophyllotoxin/imiquimod, KOH. In HIV the key is antiretroviral therapy (immune reconstitution) clears lesions.

High-yield: Extensive/giant molluscum on the face of an adult = suspect HIV; treat the underlying immunosuppression with ART rather than chasing individual lesions.

Warts (verrucae) — Human papillomavirus

HPV is a DNA virus infecting keratinocytes; >200 types. Histology hallmark = koilocytes (perinuclear halo). Types map to clinical lesion and oncogenic risk.

HPV type(s)	Clinical lesion
1, 2, 4	Common wart (verruca vulgaris); plantar (myrmecia)
3, 10	Flat/plane warts (verruca plana)
6, 11	Anogenital warts (condyloma acuminatum); laryngeal papillomatosis — low oncogenic risk
16, 18	Cervical, anal, oropharyngeal cancer — high oncogenic risk
5, 8	Epidermodysplasia verruciformis → SCC

Verruca vulgaris vs condyloma acuminatum

Feature	Verruca vulgaris	Condyloma acuminatum
HPV types	1, 2, 4	6, 11
Site	Hands, knees, fingers	Genital/perianal mucosa
Surface	Rough, hyperkeratotic; thrombosed capillaries ("black dots")	Soft, moist, cauliflower-like
Transmission	Contact/autoinoculation	Sexual
Cancer risk	Negligible	Low (but co-infection with 16/18 matters)

High-yield: Thrombosed capillaries appear as black dots within a wart and pathognomonically distinguish a plantar wart from a corn/callus (which has a clear central core and skin lines passing through it). Paring a wart obliterates skin lines and reveals the black dots.

Management of warts:

• First line topical: salicylic acid (keratolytic) ± occlusion; cryotherapy with liquid nitrogen.
• Recalcitrant: electrocautery, laser (CO₂), intralesional bleomycin/immunotherapy (MMR/Candida antigen).
• Anogenital warts: imiquimod, podophyllotoxin, trichloroacetic acid, cryotherapy; podophyllin is contraindicated in pregnancy.
• Prevention: HPV vaccines — quadrivalent (6/11/16/18), bivalent (16/18) and 9-valent; best given before sexual debut (9–14 yr, two doses).

High-yield: Buschke–Löwenstein tumour = giant condyloma acuminatum (HPV 6/11) — locally destructive, verrucous carcinoma variant. Epidermodysplasia verruciformis (HPV 5/8) predisposes to SCC on sun-exposed skin.

Hand-foot-and-mouth disease (HFMD)

Enterovirus — chiefly Coxsackievirus A16 (mild, classic) and Enterovirus 71 (EV71) (more severe, neurological).

• Faeco-oral/respiratory spread; outbreaks in young children, summer/autumn.
• Oral enanthem: painful vesicles/ulcers on tongue, buccal mucosa, palate.
• Exanthem: oval grey vesicles with an erythematous halo on palms, soles (and buttocks); lesions tend to run parallel to skin lines.
• Herpangina = a related Coxsackie A illness with posterior oropharyngeal vesicles/ulcers only (soft palate, tonsillar pillars), without the hand-foot component.
• EV71 complications: brainstem encephalitis, aseptic meningitis, myocarditis, pulmonary oedema — can be fatal.
• Onychomadesis (nail shedding) may follow weeks later. Coxsackie A6 causes a more widespread "atypical" eruption.

Management: Supportive — hydration, paracetamol, topical anaesthetic mouth rinses. Self-limiting in ~7–10 days; no specific antiviral. Hygiene to limit spread.

High-yield: Vesicles confined to the posterior oropharynx (soft palate) = herpangina (Coxsackie A); add palm/sole vesicles + anterior oral ulcers = hand-foot-mouth disease. EV71 is the dangerous neurotropic strain.

Other viral exanthems (quick map)

Disease (number)	Virus	Rash clue
Measles (1st)	Measles (paramyxo)	Koplik spots; cephalocaudal morbilliform rash
Scarlet fever (2nd)	Group A Strep (toxin)	Sandpaper rash, strawberry tongue
Rubella (3rd)	Rubella	Pink macules + posterior auricular/suboccipital nodes; Forchheimer spots
Dukes (4th)	(historical)	—
Erythema infectiosum (5th)	Parvovirus B19	"Slapped cheek"; lacy reticular rash; aplastic crisis
Roseola/exanthem subitum (6th)	HHV-6/7	High fever → defervescence then rash; febrile seizures

High-yield: Parvovirus B19 → slapped-cheek + arthropathy in adults, aplastic crisis in sickle cell, and hydrops fetalis in pregnancy. HHV-6 roseola: fever breaks first, rash appears after.

Key differentials

• Vesicular grouped rash: HSV vs zoster (dermatomal, unilateral) vs dermatitis herpetiformis vs contact dermatitis.
• Umbilicated papules in HIV: molluscum vs disseminated cryptococcosis/histoplasmosis (do not assume molluscum if very ill).
• Plantar wart vs corn (clavus): black dots & loss of skin lines vs central keratin plug with preserved lines.
• HFMD vs herpangina vs primary herpetic gingivostomatitis: distribution of oral lesions + presence of acral rash.
• Chickenpox vs smallpox: pleomorphic/centripetal vs monomorphic/centrifugal.

Recently asked / exam angle

• Tzanck smear shows multinucleate giant cells — asked across HSV, VZV and pemphigus; remember it does not differentiate HSV from VZV (need PCR/DFA).
• Drug of choice for herpes zoster / window period — aciclovir/valaciclovir/famciclovir within 72 hours; famciclovir 500 mg TDS.
• Aciclovir mechanism & resistance — viral thymidine kinase activation; resistance → foscarnet.
• Hutchinson sign and Ramsay Hunt syndrome — image-based and one-liner questions.
• HPV oncogenic types 16 & 18 vs 6 & 11 anogenital warts — a perennial favourite.
• Henderson–Paterson (molluscum) bodies; giant molluscum on face → HIV.
• Reye syndrome / aspirin in varicella; congenital varicella syndrome features.
• HFMD = Coxsackie A16; EV71 = neurological complications; herpangina location.
• Koilocytes for HPV histology; dewdrop on rose petal for varicella.
• Eczema herpeticum — punched-out monomorphic erosions in atopic dermatitis → IV aciclovir.

Rapid revision

1. Tzanck smear → multinucleate giant cells = HSV, VZV or pemphigus; can't tell HSV from VZV (use PCR).
2. Aciclovir needs viral thymidine kinase; resistant strains (HIV) treated with foscarnet.
3. HSV encephalitis / neonatal / eczema herpeticum / disseminated → IV aciclovir 10 mg/kg 8-hourly.
4. Herpetic whitlow — don't incise; common in dentists and thumb-sucking children.
5. Chickenpox = pleomorphic, centripetal, dewdrop-on-rose-petal; smallpox = monomorphic, centrifugal.
6. Aspirin in varicella/influenza → Reye syndrome; use paracetamol.
7. Zoster antivirals within 72 h to prevent PHN; famciclovir 500 mg TDS.
8. Hutchinson sign (nose-tip vesicles) → zoster ophthalmicus; Ramsay Hunt = facial palsy + ear vesicles.
9. Disseminated zoster / giant facial molluscum → screen for HIV.
10. Molluscum = umbilicated pearly papule, Henderson–Paterson bodies; ART clears it in HIV.
11. HPV 6/11 = condyloma (low risk); 16/18 = cervical/anal/oropharyngeal cancer; koilocytes on histology.
12. Plantar wart = black dots (thrombosed capillaries) + loss of skin lines; HFMD = Coxsackie A16, EV71 is the neurotropic killer.