II. Epidemiology

  1. Prevalence:
    1. Antibody positive: 37% in U.S. college freshman and 46% in college seniors
    2. Cold Sore history: 25-28% of U.S. college students
  2. Age of transmission
    1. Childhood (most common)
    2. Young adults

III. Pathophysiology

  1. Etiology: HSV I (less commonly HSV II)
  2. Transmission via mucous membranes or open skin
    1. Kissing
    2. Fomites (e.g shared towels, utensils)
  3. Incubation: 2-20 days after contact
  4. Shedding: 48-60 hour duration (not longer than 96 hours)
  5. HSV lies dormant after initial infection
    1. Distributed in the trigeminal Ganglion
    2. Reactivation with triggers as described below
  6. Triggers for recurrence
    1. Fever
    2. Emotional stress
    3. Sun Exposure
    4. Trauma
    5. Immunocompromised state
    6. Menses
    7. Fatigue

IV. Symptoms

  1. Primary (Initial) HSV I: Usually asymptomatic (but first episode is most severe)
    1. Fever, chills
    2. Cervical Lymphadenopathy
    3. Ulcers deep in mouth on Gingival surface
    4. Avoidance of drinking, eating de to pain
  2. Secondary (Later) HSV I (Recurrent labial lesions)
    1. Provocative factors for recurrence: See above
    2. Frequency: 1-6 episodes per year
    3. Lesions form along vermillion border
      1. Fever Blisters form on outer vermillion border
      2. Cold Sores form on inner lip
    4. Course
      1. Prodrome: Itch, burn, or tingling for 12-36 hours (60% of cases)
      2. Vesicle forms
      3. Vesicle ruptures, ulcerates and crusts in 48 hours
      4. Lesion heals in 10-14 days

V. Signs

  1. Lesion characterictics
    1. Grouped Vesicles on erythematous base
    2. Forms on epithelial surface at vermillion border edge
    3. Vesicular lesions rupture to form painful ulceration
    4. Distribution: Lips, Gingiva, Palate, Tongue
  2. Associated findings
    1. Cervical Lymphadenopathy

VI. Complications

  1. Herpes Keratitis (Corneal infection)
  2. Herpetic Whitlow (painful vesicular lesions on fingers)
  3. Herpetic sycosis (beard area vesicular eruption)
  4. Herpes gladiatorum (vesicular lesions typically on torso with history of wrestling exposure)
  5. Erythema Multiforme (HSV is the most common cause)
  6. HSV Encephalitis

VII. Differential Diagnosis

VIII. Differential Diagnosis: Distinguishing features

  1. Differs from Aphthous Ulcers in that:
    1. Found on keratinized (bound-down) intraoral mucosa
    2. Vesicles rupture into coalescing ulcers
  2. HSV lesions are anterior compared with:
    1. Herpangina
    2. Hand Foot and Mouth Disease

IX. Labs:

  1. Viral culture for HSV
    1. Vesicles are most concentrated with infection within first 48 hours
    2. Unroof Vesicles with scalpel or needle tip and apply viral culture swab
    3. Expect viral growth within 5 days
    4. Test Sensitivity: 50%
  2. HSV PCR
    1. Test Sensitivity: High
  3. HSV Direct Fluorescent Antibody
    1. Test Sensitivity: 80%
  4. HSV IgG
    1. Antibodies form with weeks of primary infection
    2. Does not differentiate acute infection from prior
  5. Rapid Giemsa (Dif-Quik) stain
    1. Multinucleated giant cells
    2. Test Sensitivity: 40-77%

X. Management: General Measures

  1. See Oral Mucositis
  2. Magic Mouthwash
    1. Indicated for analgesia

XI. Management: Primary Outbreak (Initial)

  1. Acyclovir (not FDA approved)
    1. Dose: 15 mg/kg (max: 200 mg) orally 5 times per day for 7 days
  2. Efficacy
    1. Lesions resolved in 4 versus 10 days, and viral shedding decreased to 1 versus 5 days
    2. Amir (1997) BMJ 314:1800-3 [PubMed]

XII. Management: Recurrent Outbreaks

  1. Systemic antiviral agents (reduce healing time by up to 2 days)
    1. Acyclovir (Zovirax)
      1. Child: 15 mg/kg (max: 200 mg) orally 5 times per day for 5 days
      2. Adult:
        1. 200 mg orally 5 times daily for 5 days or
        2. 400 mg orally 3 times daily for 5 days
    2. Famciclovir (Famvir)
      1. Adult: 1500 mg orally for one dose
      2. Efficacy
        1. Shortens healing time by 2 days in UV-induced cases
        2. Spruance (1999) J Infect Dis 179:303-10 [PubMed]
    3. Valacyclovir (Valtrex)
      1. Adult: 2 grams orally twice daily for one day
  2. Topical antiviral agents (reduce healing time by 0.7 days)
    1. Docosanol (Abreva) cream apply 5 times per day until healed
      1. Least costly topical ($20 in 2014)
    2. Topical Acyclovir
      1. Expensive ($300-600)
      2. Acyclovir (Zovirax) cream apply 5 times per day for 4 days
      3. Acyclovir with Hydrocortisone (Xerese)
    3. Penciclovir (Denavir) 1% cream apply every 2 hours while awake for 4 days
      1. Very expensive ($500/tube in 2014)
    4. Sitavig buccal one tablet per episode placed in upper gum on same side of mouth as symptoms
      1. Very expensive ($300 for 2 tabs in 2014) and only shortens Cold Sore course by <1 day
      2. (2014) Presc Lett 21(9): 53

XIII. Management: Prevent recurrence (daily suppression)

  1. Acyclovir (Zovirax) 400 mg orally twice daily
  2. Valacyclovir 500 mg orally once daily

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Ontology: Herpes Labialis (C0019345)

Definition (MEDLINEPLUS)

Cold sores are caused by a contagious virus called herpes simplex. There are two types of herpes simplex virus. Type 1 usually causes oral herpes, or cold sores. Type 1 herpes virus infects more than half of the U.S. population by the time they reach their 20s. Type 2 usually affects the genital area

Some people have no symptoms from the infection. But others develop painful and unsightly cold sores that last for a week or more. Cold sores usually occur outside the mouth -- on the lips, chin, and cheeks, or in the nostrils. When they do occur inside the mouth, it is usually on the gums or the roof of the mouth.

There is no cure for cold sores. Medicines can relieve some of the pain and discomfort associated with the sores. These include ointments that numb the blisters, antibiotics that control secondary bacterial infections, and ointments that soften the crusts of the sores.

Definition (NCI) A lesion caused by type 1 or type 2 herpes simplex virus, involving the oralfacial region.
Definition (MSH) Herpes simplex, caused by type 1 virus, primarily spread by oral secretions and usually occurring as a concomitant of fever. It may also develop in the absence of fever or prior illness. It commonly involves the facial region, especially the lips and the nares. (Dorland, 27th ed.)
Concepts Disease or Syndrome (T047)
MSH D006560
ICD10 B00.1
SnomedCT 154336005, 186556004, 186548002, 186540009, 1475003
English Herpes Labialis, Herpes Simplex, Labial, Labial Herpes Simplex, HERPES LABIALIS, Blister, Fever, Blisters, Fever, Cold Sore, Fever Blister, Fever Blisters, Sore, Cold, Sores, Cold, herpes labialis, Fever sore, Cold sores lip, Cold sore (herpetic), Herpes on lip, fever blister, herpes febrilis, Herpes Labialis [Disease/Finding], fever sores, lip herpes, herpes lips, herpes on lip, cold sores, fever sore, herpes simplex labialis, cold sore, lip cold sore, fever blisters, lip cold sores, herpes lip, Cold Sores, herpes simplex labialis (diagnosis), Cold sores, Fever blister, Herpes labialis, Cold sore, Herpes simplex labialis, Herpes labialis (disorder), blister fever, coldsore, febrilis; herpes, herpes; febrilis, herpes; labialis, herpes; lip, labialis; herpes, lip; herpes
French HERPES LABIAL, Boutons de fièvre sur la lèvre, Bouton de fièvre (herpétique), Boutons de fièvre, Herpès sur la lèvre, Herpès labial, Herpès simplex labial, Bouton de fièvre
Portuguese HERPES LABIAL, Feridas herpéticas, Ferida da febre, Herpes labial, Feridas herpéticas do lábio, Ferida herpética, Vesícula febril, Boqueira, Herpes Febril, Herpes Labial, Herpes Simples Labial, Ulceração de Resfriado
Spanish HERPES LABIAL, Dolor frío (herpético), Herpes febril, Calentura, Herpes labial, Herpes en labio, Boquera, herpes labial (trastorno), herpes labial, Ampolla Febril, Herpes Labial, Herpes Simple Labial, Llaga del Resfriado
German HERPES LABIALIS, Herpes labialis (herpetisch), Herpes labiales, Herpes an der Lippe, Fieberblase, Herpes labiales der Lippen, Herpes labialis, Herpes simplex febrilis, Herpes simplex labialis, Fieberbläschen
Swedish Munsår
Dutch koortsblaas (herpetisch), koortsblazen, herpes op lip, koude pijnlijke lip, herpes labialis, koortsblaas, febrilis; herpes, herpes; febrilis, herpes; labialis, herpes; lip, labialis; herpes, lip; herpes, Herpes labialis, Herpes simplex labialis, Koortslip
Italian Herpes faciale, Herpes facciale, Herpes Simplex labiale, Herpes labiale
Japanese 熱性疱疹, ネッセイホウシン, コウシンヘルペス, 口唇ヘルペス, 口唇単純ヘルペス, 疱疹-口唇, ヘルペス-口唇, 単純ヘルペス-口唇, 口唇単純疱疹, 口唇疱疹
Czech herpes labialis, Prostý opar rtu, Herpes simplex labialis, Herpes labialis, Opar při horečce, Opar rtu při horečce, Opar rtu, opar rtu
Finnish Huuliherpes
Russian GERPES GUB, GERPES PROSTOI GUB, ГЕРПЕС ГУБ, ГЕРПЕС ПРОСТОЙ ГУБ
Polish Opryszczka wargowa
Hungarian Herpes az ajkon, Száj herpesz, száj-herpesz, ajakherpes, herpesz labiálisz, herpes labialis
Norwegian Herpes labialis, Munnsår, Forkjølelsessår, Leppeherpes

Ontology: Stomatitis, Herpetic (C0038366)

Definition (MSH) Stomatitis caused by Herpesvirus hominis. It usually occurs as acute herpetic stomatitis (or gingivostomatitis), an oral manifestation of primary herpes simplex seen primarily in children and adolescents.
Concepts Disease or Syndrome (T047)
MSH D013283
SnomedCT 186540009, 57920007
English Herpes Simplex, Oral, Herpetic Stomatitides, Herpetic Stomatitis, Oral Herpes Simplex, Simplex, Oral Herpes, Stomatitides, Herpetic, Stomatitis, Herpetic, Herpetic stomatitis, Stomatitis, Herpetic [Disease/Finding], herpes simplex oral, Herpes simplex;mouth, herpetic stomatitis, oral herpes simplex, herpes stomatitis, herpes oral simplex, Stomatitis - herpetic, Herpes simplex oral, Herpes stomatitis, herpes; stomatitis, stomatitis; herpesviral, stomatitis; herpes, herpes simplex in the mouth
Swedish Stomatit, herpetisk
Dutch herpesstomatitis, herpes simplex oraal, herpes; stomatitis, stomatitis; herpesvirus, stomatitis; herpes, Herpes simplex, orale, Stomatitis herpetica
German Entzuendung der Mundschleimhaut durch Herpes, Oraler Herpes simplex, Herpes simplex, oraler, Stomatitis herpetica
Portuguese Estomatite herpética, Herpes simples oral, Estomatite Herpética, Herpes Simples Bucal
Spanish Estomatitis herpética, Herpes simplex oral, Estomatitis Herpética, Herpes Simple Oral
Japanese ヘルペスセイコウナイエン, ヘルペス性口内炎, 口内炎-ヘルペス, 歯肉口内炎-疱疹性, ヘルペス口内炎, 単純ヘルペス-口腔, 疱疹性歯肉口内炎, ヘルペス性歯肉口内炎, 単純疱疹-口腔, 疱疹性口内炎, 歯肉口内炎-ヘルペス性, 口腔単純疱疹, 口腔単純ヘルペス, 口内炎-ヘルペス性, コウコウタンジュンヘルペス, コウクウタンジュンヘルペス
Czech stomatitida herpetická, Herpetická stomatitida, herpetická stomatitida, orální herpes simplex, opar (ústa), Herpes simplex v ústech
Finnish Herpeksen aiheuttama suutulehdus
Russian GERPES PROSTOI POLOSTI RTA, GINGIVOSTOMATIT GERPETICHESKII, STOMATIT GERPETICHESKII, ГЕРПЕС ПРОСТОЙ ПОЛОСТИ РТА, ГИНГИВОСТОМАТИТ ГЕРПЕТИЧЕСКИЙ, СТОМАТИТ ГЕРПЕТИЧЕСКИЙ
Italian Herpes simplex orale, Stomatite erpetica
Polish Zapalenie dziąseł opryszczkowe, Zapalenie jamy ustnej opryszczkowe, Opryszczka zwykła jamy ustnej
Hungarian Stomatitis herpetica, Herpes simplex oralis
Norwegian Herpetisk munnbetennelse, Oral herpes simplex, Stomatitt, herpetisk, Herpetisk stomatitt
French Herpès simplex oral, Stomatite herpétique

Ontology: Human herpesvirus 1 (C0206679)

Definition (CSP) causes cold sores in humans, especially in young children.
Definition (MSH) The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
Concepts Virus (T005)
MSH D018259
SnomedCT 266191005, 154332007, 15302007
LNC LP14821-0, MTHU004636
English Herpes Simplex Virus 1, Herpesvirus 1 (alpha), Human, Herpesvirus 1, Human, HSV-1, HHV-1, Human herpesvirus 1, HERPESVIRUS 1 ALPHA HUMAN, HERPESVIRUS HUMAN 01, HSV 01, HHV 1, HERPES SIMPLEX VIRUS 01, HUMAN HERPESVIRUS 01, human alphaherpesvirus 1, herpes simplex virus 1, HSV 1, herpes virus 1, human, herpesvirus 1, human, 1 herpes simplex virus, 1 hsv, herpes simplex type 1 virus, herpes simplex 1 virus, hhv-1, hsv-1, human herpes virus 1, herpes simplex 1 virus (hsv-1), herpes simplex i, hsv i, herpes virus simplex type 1, hsv 1, virus type 1 herpes simplex, herpes simplex virus type 1, HUMAN HERPESVIRUS 1, Human herpesvirus type 1, herpes simplex virus 1 HSV-1, herpes simplex virus HSV-1, herpes simplex virus type 1 HSV-1, herpes simplex virus type 1 HSV1, herpes simplex virus type-1 HSV-1, Herpes simplex virus type 1, Herpes Simplex Virus Type 1, Herpes simplex virus 1, HSV 1 - Herpes simplex virus 1, Human (alpha) herpes virus 1, Human herpes simplex virus type 1, Human herpes simplex virus type 1 (organism)
Swedish Herpesvirus 1, humant
Czech herpesvirus 1 (alfa) lidský, herpesvirus 1 lidský, herpes simplex virus 1
Portuguese Herpesvirus Humano 1, Herpesvirus Humano Tipo 1, HSV-1, Vírus do Herpes Simplex 1
Spanish Herpesvirus Humano Tipo 1, Herpesvirus Humano 1, HSV - 1, virus del herpes simple humano tipo 1 (organismo), virus del herpes simple humano tipo 1, HSV-1, Virus 1 del Herpes Simple
Finnish Ihmisen herpesvirus 1
Russian GERPESVIRUS 1 (AL'FA) CHELOVEKA, GERPESVIRUS 1 CHELOVEKA, GERPES PROSTOGO VIRUSA 1, ГЕРПЕСВИРУС 1 (АЛЬФА) ЧЕЛОВЕКА, ГЕРПЕСВИРУС 1 ЧЕЛОВЕКА, ГЕРПЕС ПРОСТОГО ВИРУСА 1
Italian HHV-1, Herpes simplex virus 1, Herpes simplex virus di tipo 1, HSV-1, Herpesvirus 1 (alfa) umano, Herpesvirus 1 umano
German HERPES SIMPLEX VIRUS TYP 01, HUMANES HERPESVIRUS 01, HERPESVIRUS HOMINIS TYP 01, HERPESVIRUS HUMANES 01, HSV 01, HSV-1, Herpes-simplex-Virus Typ 1, Herpesvirus 1, humanes, Herpesvirus hominis, Typ 1, Humanes Herpesvirus 1
Polish Wirus opryszczki pospolitej 1, Herpes simplex 1, HSV-1, Herpeswirus 1 ludzki
Japanese 単純ヘルペスウイルス-1, ヒトヘルペスウイルス1型, ヒトヘルペスウイルス1(アルファ), ヒトヘルペスウイルス1, 単純ヘルペスウイルス1, ヒトヘルペスウイルス-1, ヘルペスウイルス1-ヒト, ヘルペスウイルス1型-ヒト
French HHV-1 (Human HerpesVirus 1), Herpes simplex virus 1, HSV-1 (Herpes Simplex Virus 1), Virus de l'herpès simplex de type 1, Herpèsvirus humain de type 1, Human herpesvirus 1
Croatian HERPES SIMPLEKS VIRUS, TIP 1, HERPESVIRUS 1, HUMANI
Dutch HSV 1, HSV-1, Herpes simplex type 1, Herpesvirus 1, Herpesvirus 1, humaan, Herpesvirus hominis type 1, Herpesvirus-1, Humaan herpesvirus 1, Virus 1, humaan herpes-

Ontology: Oral herpes simplex infection (C0341012)

Concepts Disease or Syndrome (T047)
SnomedCT 235055003
English Oral herpes, oral herpes, herpes oral, Herpes, Oral, Oral Herpes, Oral herpes simplex infection, Oral herpes simplex infection (disorder)
Dutch orale herpes
French Herpes buccal
German oraler Herpes
Italian Herpes orale
Portuguese Herpes oral
Spanish Herpes oral, herpes simple oral, infección oral por herpes simple (trastorno), infección oral por herpes simple
Japanese コウコウヘルペス, コウクウヘルペス, 口腔ヘルペス
Czech Herpes úst
Hungarian oralis herpes

Ontology: Gingivostomatitis, Herpetic (C0376379)

Concepts Disease or Syndrome (T047)
MSH D013283
ICD9 054.2
SnomedCT 154334008, 186540009, 57920007
English Gingivostomatitides, Herpetic, Herpetic Gingivostomatitides, Herpetic Gingivostomatitis, Herpetic gingivostomat, herpetic gingivostomatitis, Herpetic gingivostomatitis, Herpetic gingivostomatitis (disorder), gingivostomatitis; herpes, herpes; gingivostomatitis, Primary herpetic gingivostomatitis, Gingivostomatitis, Herpetic
Dutch herpetische gingivostomatitis, gingivostomatitis; herpes, herpes; gingivostomatitis, Gingivostomatitis, herpetische
German Mundfaeule durch Herpes, Gingivostomatitis herpetica, Stomatitis aphthosa
Portuguese Gengivoestomatite herpética, Gengivostomatite Herpética
Spanish Gingivoestomatitis herpética, Gingivoestomatitis Herpética, gingivoestomatitis herpética (trastorno), gingivoestomatitis herpética
Japanese ヘルペスセイシニクコウナイエン, ヘルペス性歯肉口内炎
French Gingivostomatite herpétique, Gingivo-stomatite herpétique
Czech Herpetická gingivostomatitida, herpetická gingivostomatitida
Hungarian gingivostomatitis herpetica
Italian Gengivostomatite erpetica
Norwegian Herpetisk gingivostomatitt, Gingivostomatitt, herpetisk

Ontology: Primary oral herpes simplex infection (C0549208)

Concepts Disease or Syndrome (T047)
SnomedCT 235056002
English Primary oral herpes simplex infection, Primary oral herpes simplex, Primary oral herpes simplex infection (disorder)
Spanish infección primaria bucal por herpes simple (trastorno), infección primaria bucal por herpes simple