Primary herpetic gingivostomatitis is caused by herpes simplex virus 1 (HSV-1) infection in children and characterized by painful vesicular lesions of the mouth.
INSIGHT 
Any oral ulceration should be evaluated for herpes infection.
SYNONYMS Herpes, herpes simplex, cold sore, fever blister, herpes febrilis, herpes labialis.
AGE 1 to 10 years. Peak incidence between 6 months and 5 years age.
GENDER M = F.
INCIDENCE 90% HSV-1 seropositive by age 10.
ETIOLOGY HSV-1 >> HSV-2.
Transmission and primary infection of HSV occurs through close contact with a person shedding the virus at a peripheral site, mucosal surface, or through secretion. HSV is inactivated promptly at room temperature; thus, aerosolized or fomite spread is unlikely. Infection occurs via inoculation onto susceptible mucosal surface or breaks in skin. Subsequent to primary infection at the inoculation site, HSV ascends peripheral sensory nerves and enters the sensory or autonomic nerve root ganglia, where latency is established. Latency can occur after either symptomatic or asymptomatic primary infection.
Three to seven days after exposure, primary herpetic infections may be asymptomatic (the majority) or symptomatic with gingivostomatitis, high fever, sore throat, and lymphadenopathy. The pain may be so debilitating that hospitalization is necessary for intravenous (IV) hydration.
TYPE Plaque, vesicles, ulcerations (Fig. 23-1).
ARRANGEMENT Herpetiform (grouped) vesicles.
DISTRIBUTION Oral mucosa, oropharynx.
FEVER, LAD.
OTHER Headache, fever, nuchal rigidity, ± positive HSV cerebrospinal fluid culture in severe disease.
The differential diagnosis for primary HSV gingivostomatitis includes aphthous stomatitis, hand-foot-and-mouth disease (HFMD), herpangina, erythema multiforme, or Behçet’s disease, oral candidiasis, and chemotherapy mucositis.
TZANCK SMEAR Cells from the base of an intact vesicle are smeared thinly on a microscope slide, dried, stained with Wright’s or Giemsa’s stain, showing multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or varicella-zoster virus (VZV).
DIRECT IMMUNOFLUORESCENCE Cells from the base of an intact vesicle can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
VIRAL CULTURE HSV can be cultured in 2 to 5 days from early vesicular fluid or from scraping the base of an erosion.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
SEROLOGY Primary HSV-1 infection can be documented by seroconversion.
Episodes of primary herpetic gingivostomatitis are self-limited within 2 to 6 weeks but can range in severity from mild asymptomatic infection to severe debilitating disease requiring hospitalization.
The treatment of choice for primary herpetic gingivostomatitis is oral or IV acyclovir and symptomatic measures. Initiation within the first 4 days of symptoms has been demonstrated to reduce symptom duration. Acetaminophen and 2% viscous lidocaine can be used for oral pain and IV fluids may be needed to prevent dehydration.
In older children, immunocompromised patients, or more refractory cases, oral valacyclovir or oral famciclovir may be used. Topical 1% penciclovir or 5% acyclovir ointment can be used in conjunction with oral therapy. Acyclovir-resistant HSV-1 requires IV foscarnet or topical cidofovir. Individuals with severe HSV gingivostomatitis and those with active secretions not yet on treatment should be placed on contact precautions and limit interaction with other children.
Recurrent facial–oral herpes is a reactivation of latent herpetic infection caused by HSV-1 and characterized by grouped blisters, typically on the vermillion border.
SYNONYMS Cold sores, fever blisters, herpes, herpes simplex, herpes labialis.
AGE Any age. Most common in young adults.
GENDER M = F.
PREVALENCE Common. One-third of population.
INCIDENCE 90% of population serologically positive for HSV-1 infection.
ETIOLOGY HSV-1 >> HSV-2.
Herpes virus is transmitted by skin-to-skin, skin-to-mucosa, or mucosa-to-mucosa contact. Subsequent to the primary HSV-1 infection, HSV ascends the peripheral sensory nerves and enters the ganglion where latency is established. Recurrences occur at the same site each time and may be clinically asymptomatic or symptomatic.
Sunlight, stress, illness, or local trauma may precipitate blistering episodes.
Recurrent HSV-1 episodes are typically heralded by a prodrome of tingling, itching, or burning, which usually precedes any visible skin changes by 24 hours. The skin then flares with a small, localized crop of blisters followed by healing in 1 to 2 weeks. Systemic symptoms are usually absent.
TYPE Plaque, papules, vesicles, crust (Fig. 23-3).
COLOR Pink, red.
SIZE 1 to 2 mm.
ARRANGEMENT Herpetiform (i.e., grouped) vesicles.
DISTRIBUTION Vermillion border >> any other mucocutaneous site.
LYMPHADENOPATHY Rarely present in immunocompetent individuals.
The differential diagnosis for recurrent facial–oral herpes includes varicella zoster, aphthous ulcers, and contact dermatitis.
TZANCK SMEAR Cells from the base of an intact vesicle are smeared thinly on a microscope slide, dried, stained with Wright’s or Giemsa’s stain, showing multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or VZV.
DIRECT IMMUNOFLUORESCENCE Cells from the base of an intact vesicle can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
VIRAL CULTURE HSV can be cultured in 2 to 5 days from early vesicular fluid or from scraping the base of an erosion.
SEROLOGY Recurrent HSV-1 infections can be detected by immunoglobulin M (IgM) and IgG antibody titers.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
Recurrent facial–oral herpetic outbreaks are localized, self-limited, typically number one to four per year, are milder, and have shorter duration than the primary infection. They tend to become less frequent as the individual gets older. Oral antiviral agents, if used early (during prodromal period), may abort or minimize symptoms.
In recurrent facial–oral herpes, patients who start oral antiviral therapy (acyclovir, valacyclovir, or famciclovir) at the beginning of the prodrome or within 2 days after onset of lesions may experience diminished symptoms and faster resolution. Topical 1% penciclovir or 5% acyclovir ointment can be used in conjunction with oral therapy. Impetiginized lesions may benefit from topical antibiotics (mupirocin). Acyclovir-resistant HSV requires IV foscarnet or topical cidofovir.
For individuals with multiple recurrences (six to eight or more annually), chronic suppressive therapy with one of the oral antiviral agents listed above may decrease viral shedding and prevent frequent recurrences.
Eczema herpeticum is a widespread HSV-type infection superimposed on diseased skin (most commonly atopic dermatitis). It is characterized by widespread vesicles and erosions, fever, and malaise and can be a severe, recurrent problem.
INSIGHT 
An area of eczema that “just won’t seem to heal” can be a sign of eczema herpeticum and should be evaluated for herpes infection.
SYNONYMS Kaposi’s varicelliform eruption, pustulosis varioliformis acute, Kaposi– Juliusberg dermatitis.
AGE Children > adults.
ETIOLOGY HSV-1, less commonly HSV-2.
RISK FACTORS Increased incidence in individuals with filaggrin mutation.
On abnormal skin (atopic dermatitis >> Darier’s disease, burns, pemphigus vulgaris, ichthyosis vulgaris), the barrier function of the skin is impaired and viral or bacterial superinfection can easily become widespread. In the case of eczema herpeticum, frequently a child with atopic dermatitis becomes inoculated with HSV-1 from a parent or other caregiver with a clinical or subclinical case of recurrent facial–oral herpes. The disease then becomes widespread because of the infant’s uncontrolled scratching, autoinoculation, and impaired skin barrier function.
Herpetic skin lesions begin on inoculated, impaired skin and extend rapidly during primary infection. Systemic symptoms include fever, malaise, and irritability.
TYPE Vesicles, erosions (Fig. 23-4), pustules, crust (Fig. 23-5). Monomorphic appearance, may appear “punched-out.”
FIGURE 23-5
Eczema herpeticum
Widespread crusted lesions on a child with atopic dermatitis kissed by a parent with active HSV-1 recurrent facial–oral herpes infection with resultant eczema herpeticum. Clinical picture is complicated by Staphylococcus aureus superinfection causing yellow-brown crusted appearance.
DISTRIBUTION Common sites: face, neck, trunk.
FEVER, LAD.
The differential diagnosis of eczema herpeticum includes varicella zoster with dissemination, disseminated (systemic) HSV infection, widespread bullous impetigo, staphylococcal folliculitis, pseudomonal (hot tub) folliculitis, and Candida folliculitis. A similar-appearing eruption may also be caused by coxsackie A16 virus (the virus responsible for HFMD).
TZANCK SMEAR Cells from the base of an intact vesicle are smeared thinly on a microscope slide, dried, stained with Wright’s or Giemsa’s stain, showing multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or VZV.
DIRECT IMMUNOFLUORESCENCE Cells from the base of an intact vesicle can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
CULTURE HSV-1 > HSV-2 can be cultured in 2 to 5 days from early vesicular fluid or from scraping the base of an erosion. Frequently, superinfection with Staphylococcus aureus or Streptococcus pyogenes is present.
SEROLOGY HSV infections can be detected by IgM and IgG antibody titers.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
Eczema herpeticum self-resolves in 2 to 6 weeks. Recurrent episodes tend to be milder and not associated with as severe systemic symptoms as in the primary episode. The risk of systemic dissemination is possible, especially in immunocompromised patients.
Eczema herpeticum may be considered a pediatric dermatologic emergency and early recognition can prevent significant sequelae. Preventative measures aimed at controlling the underlying chronic dermatosis (e.g., atopic dermatitis) will improve the skin’s barrier function and prevent widespread cutaneous viral and bacterial infection.
Mild cases of eczema herpeticum can be managed on an outpatient basis with acyclovir, valacyclovir, or famciclovir. Topical 1% penciclovir or 5% acyclovir ointment can be used in conjunction with oral therapy. Impetiginized crusted lesions may benefit from topical antibiotics (mupirocin).
In more severe cases with high fever or marked prostration, hospitalization may be needed with IV acyclovir, antibiotics, IV fluids, and pain medications.
Acyclovir-resistant HSV eczema herpeticum requires IV foscarnet or topical cidofovir.
Herpetic whitlow is a cutaneous herpetic infection of the distal fingertip, usually caused by recurrent HSV-1 or HSV-2, inadvertently inoculated onto the hand.
AGE Children > adults.
GENDER M = F.
INCIDENCE Common.
Herpetic whitlow is typically seen in physicians, dentists, dental hygienists, nurses, and children. HSV, from infected mucosa with clinical or subclinical herpes, gets inoculated onto a finger, and herpetic whitlow ensues. After the primary infection, the herpes virus becomes dormant in the nerve and can recur in the same location.
Two to eight days following exposure, painful vesicular lesions appear on the fingertips of the infected individual, often in association with swelling and surrounding erythema. Systemic symptoms are rare but can include fever and regional lymphadenopathy. Lesions take 1 to 3 weeks to resolve, and recurrences are possible.
TYPE Vesicles.
COLOR Whitish-red or blue (Fig. 23-6).
SIZE 2- to 4-mm vesicles.
ARRANGEMENT Herpetic (grouped vesicles).
DISTRIBUTION Distal fingertips.
The differential diagnosis of herpetic whitlow includes dyshidrotic eczema, contact dermatitis, orf, or other paronychial infection.
TZANCK SMEAR Cells from the base of an intact vesicle stained with Wright’s or Giemsa’s stain show multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or VZV.
DIRECT IMMUNOFLUORESCENCE Cells from the base of an intact vesicle can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
CULTURE HSV-1 > HSV-2 can be cultured in 2 to 5 days from early vesicular fluid or from scraping the base of an erosion.
SEROLOGY HSV infections can be detected by IgM and IgG antibody titers.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
Herpetic whitlow will self-resolve without treatment, but recurrences are possible.
Much of the treatment of herpetic whitlow is symptomatic with analgesics for pain, topical penciclovir cream, or 5% acyclovir ointment. More severe or refractory cases may require treatment with oral acyclovir, valacyclovir, or famciclovir.
Herpes gladiatorum is an infection seen primarily in contact sports players (e.g., wrestlers, rugby players) who abrade their skin and come into direct contact with an active HSV infection.
SYNONYMS Scrumpox, herpes rugbiorum, wrestler’s herpes, mat pox.
AGE Any age.
GENDER M > F.
INCIDENCE Common, up to 67% of wrestlers/rugby players.
ETIOLOGY HSV-1 >> HSV-2.
HSV-1 is transmitted during infected skin-to-skin exposure in rough contact sports. Of note, studies have shown negative oropharyngeal swabs for active mucosal HSV-1; thus, saliva seems not to be a major source of infection. The virus then becomes latent in the sensory nerve ganglia, and recurrences at the ectopic site are possible.
Two to eight days after contact, herpetic lesions can occur at atypical sites (head, trunk, extremities; sites of skin-to-skin contact during sports) and are often associated with edema, pain, and regional lymphadenopathy.
TYPE Grouped vesicles.
COLOR White, pink, red (Fig. 23-7).
SIZE 2 to 5 mm.
NUMBER One lesion >> multiple sites.
DISTRIBUTION Head (73%), trunk (28%), and extremities (42%).
FEVER Malaise and lymphadenopathy.
The differential diagnosis of herpes gladiatorum includes contact dermatitis and varicella zoster.
TZANCK SMEAR Cells from the base of an intact vesicle stained with Wright’s or Giemsa’s stain show multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or VZV.
DIRECT IMMUNOFLUORESCENCE Cells from the base of an intact vesicle can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
CULTURE HSV-1 > HSV-2 can be cultured in 2 to 5 days from early vesicular fluid or from scraping the base of an erosion.
SEROLOGY HSV infections can be detected by IgM and IgG antibody titers.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
The primary episode of herpes gladiatorum may last 2 to 6 weeks but does self-resolve. Recurrences are less painful and resolve more quickly.
Wrestlers, rugby players, parents, and coaches need to be made aware of the transmission of HSV-1, and active lesions should be covered to prevent spread. Much of the treatment of herpes gladiatorum is symptomatic with analgesics for pain, topical penciclovir cream, or 5% acyclovir ointment. For crusted impetiginized lesions, a topical antibiotic should be added (mupirocin). More severe or refractory herpes gladiatorum cases may require treatment with oral acyclovir, valacyclovir, or famciclovir. Athletes with active lesions should occlude the areas or avoid competing in events with skin-to-skin contact to minimize disease spread.
Disseminated herpes simplex infection is a potentially fatal, systemic HSV infection, characterized by widespread mucocutaneous vesicles, pustules, erosions, and ulcerations. It is associated with signs of pneumonia, encephalitis, and hepatitis, as well as involvement of other organ systems. Disseminated HSV infection usually occurs in an immunocompromised host.
AGE Any age.
INCIDENCE Uncommon, but increasing because of immunosuppressive therapies.
ETIOLOGY HSV-1 or HSV-2.
Disseminated herpes typically occurs in immunocompromised states (organ transplantation, cancer chemotherapy, corticosteroid therapy), hematologic and lymphoreticular malignancies, and in the setting of severe malnutrition. Eighty percent of HSV seropositive transplant recipients and patients undergoing chemotherapy for hematologic malignancies will reactivate HSV. Following viremia, disseminated cutaneous or visceral HSV infection may follow.
Disseminated herpes simplex infection is typically seen in hospitalized patients with underlying disease. It presents as tender and painful mucocutaneous erosions with systemic fever, malaise, and organ involvement.
TYPE Vesicles, crusts, erosion, ulcers.
DISTRIBUTION Generalized, disseminated (Fig. 23-8).
MUCOUS MEMBRANES Oropharyngeal erosion, HSV tracheobronchitis with erosions.
HSV pneumonitis, hepatitis, or encephalitis may be present.
The differential diagnosis of disseminated HSV includes eczema herpeticum, varicella, and cutaneous disseminated zoster.
TZANCK SMEAR Cells from infected mucocutaneous sites or infected body fluids stained with Wright’s or Giemsa’s stain show multinucleated giant keratinocytes (Fig. 23-2). Tzanck smear is positive in 75% of early cases, but does not differentiate HSV-1 from HSV-2 or VZV.
DIRECT IMMUNOFLUORESCENCE Cells from a mucocutaneous lesion or infected body fluids can be smeared on a glass slide and immunofluorescent antibodies can be used to stain specifically for the presence of HSV-1 or HSV-2.
DERMATOPATHOLOGY Ballooning and reticular epidermal degeneration, acanthosis, and intraepidermal vesicle formation. Intranuclear inclusion bodies, multinucleate giant keratinocytes, and multilocular vesicles may be present.
ELECTRON MICROSCOPY Can detect HSV particles.
CULTURE HSV-1 > HSV-2 can be cultured in 2 to 5 days from scraping the base of a mucocutaneous erosion or from infected body fluids.
SEROLOGY HSV infections can be detected by IgM and IgG antibody titers.
POLYMERASE CHAIN REACTION Scrapings from the base of an erosion or patient serum can also be tested using real-time HSV PCR to diagnose and differentiate between HSV-1 and HSV-2. May be particularly useful in diagnosis of asymptomatic viral shedding.
When widespread, visceral dissemination of HSV may occur to liver, lungs, adrenals, gastrointestinal (GI) tract, and central nervous system. Severe cases can be complicated by disseminated intravascular coagulation. Untreated, the mortality rate of disseminated HSV with organ involvement approaches 70% and residual neurological defects are common.
Early recognition and treatment are essential in the treatment of disseminated herpes which can be considered a dermatologic and medical emergency.
Prophylaxis with acyclovir is recommended for seropositive patients undergoing bone marrow transplantation; induction therapy for leukemia; and solid organ transplantation from the day of conditioning, induction, or transplantation lasting for 4 to 6 weeks. For disseminated HSV infection, systemic acyclovir, valacyclovir, or famciclovir is necessary. In more severe cases with high fever or marked prostration, hospitalization may be needed with IV acyclovir, antibiotics, fluids, and pain medications.
Acyclovir-resistant disseminated HSV requires IV foscarnet.
Varicella is a highly contagious primary infection caused by VZV, characterized by successive crops of pruritic vesicles that evolve to pustules and crusts, and can heal with scarring. The rash is often accompanied by constitutional symptoms such as fever and malaise.
SYNONYM Chickenpox.
INSIGHT 
The live attenuated VZV vaccine is 90% effective in preventing chickenpox and currently recommended for all children in the United States.
AGE Before vaccine and in unvaccinated populations: 90% younger than 10 years.
GENDER M = F.
INCIDENCE Before vaccine: nearly universal in the United States. Common worldwide.
SEASON Winter, spring.
ETIOLOGY VZV, a herpesvirus.
GEOGRAPHY Worldwide.
Varicella virus is highly contagious and spreads via airborne droplets between persons or, less commonly, through direct contact with the vesicle fluid. Patients are contagious several days before exanthem appears and until the last crop of vesicles crusts over. Varicella virus enters the host through the mucosa of upper respiratory tract and oropharynx, replicates in the lymph nodes, and causes primary viremia. VZV then replicates in organs with subsequent secondary viremia and dissemination of the virus to the skin and mucous membranes. Once crusted over, the skin lesions are no longer infectious.
Primary attack usually confers lifelong immunity. Second episodes of varicella have been documented but are rare. As with all herpesviruses, VZV enters a latent phase, residing in sensory ganglia, and reactivation of VZV later in life results in herpes zoster (shingles).
Varicella is usually transmitted by exposure to a sick contact at day care, school, an older sibling, or even an adult with zoster. The rash appears following an inoculation period of 14 days (range, 10–23 days), a mild prodrome of headache, general aches and pains, and malaise. Crops of vesicles with an erythematous base appear (“dewdrops on a rose petal”) and crust over an 8- to 12-hour period. With subsequent crops, all stages of evolution may be noted simultaneously: papules, vesicles, pustules, crusts. The exanthem appears within 2 to 3 days (Fig. 23-9).
TYPE Vesicles (Fig. 23-10), pustules, crusts, scars.
COLOR Clear, white, yellow, red.
SIZE 2 to 5 mm.
NUMBER Few to >100 lesions.
DISTRIBUTION Face, scalp, then trunk, extremities. Palms/soles spared.
MUCOUS MEMBRANES Vesicles or erosions on palate, nasal mucosa, conjunctivae, GI, genitourinary, or respiratory tract.
FEVER Low grade.
The differential diagnosis of varicella includes disseminated HSV infection, cutaneous dissemination of zoster, eczema herpeticum, Coxsackie virus, enteric cytopathic human orphan virus, pityriasis lichenoides et varioliformis acuta, rickettsialpox, drug eruption, contact dermatitis, insect bites, scabies, bullous impetigo, and historically, smallpox.
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