II. Epidemiology
-
Prevalence
- Worldwide Prevalence: 60-95% (typically acquired by teen years)
- Antibody positive: 37% in U.S. college freshman and 46% in college seniors
- Cold Sore history: 25-28% of U.S. college students
- Age of transmission
- Childhood (most common)
- Young adults
III. Pathophysiology
- Etiology: HSV I (less commonly HSV II)
- Transmission via mucous membranes or open skin
- Kissing
- Fomites (e.g shared towels, utensils)
- Incubation: 2-20 days after contact
- Shedding: 48-60 hour duration (not longer than 96 hours)
- HSV lies dormant after initial infection
- Distributed in the trigeminal Ganglion
- Periodic reactivation with triggers as described below
- Recurrence in 40% of patients
- Triggers for recurrence
- Fever
- Emotional stress
- Sun Exposure
- Trauma
- Immunocompromised state
- Menses
- Fatigue
IV. Symptoms
- Primary (Initial) HSV I: Usually asymptomatic (but first episode is most severe)
- Fever
- Chills
- Malaise
- Cervical Lymphadenopathy
- Ulcers deep in mouth on Gingival surface
- Avoidance of drinking, eating de to pain
- Secondary (Later) HSV I (Recurrent labial lesions)
- Provocative factors for recurrence: See above
- Frequency: Up to 1-6 episodes per year (recurrs in 40% of patients)
- Prodrome before lesions (60% of patients)
- Itching, burning or Paresthesias for 12 to 36 hours before lesions
- Lesions form along vermillion border
- Fever Blisters form on outer vermillion border
- Cold Sores form on inner lip
- Course
V. Signs
- Lesion characterictics
- Painful grouped Vesicles on erythematous base
- Forms on epithelial surface at vermillion border edge
- Vesicular lesions rupture to form painful ulceration
- Distribution: Lips, Gingiva, Hard Palate, Tongue
- Associated findings
VI. Complications
- Herpes Keratitis (Corneal infection)
- Herpetic Whitlow (painful vesicular lesions on fingers)
- Herpetic sycosis (beard area vesicular eruption)
- Herpes gladiatorum (vesicular lesions typically on torso with history of wrestling exposure)
- Erythema Multiforme (HSV is the most common cause)
-
HSV Encephalitis
- Contrast with HSV2 which causes Herpes Meningitis (Mollaret Meningitis) instead of Encephalitis
VII. Differential Diagnosis
- Oral Lesions
- Skin lesions
VIII. Differential Diagnosis: Distinguishing features
- Differs from Aphthous Ulcers in that:
- Found on keratinized (bound-down) intraoral mucosa
- Vesicles rupture into coalescing ulcers
- HSV lesions are anterior compared with:
IX. Labs:
- Viral culture for HSV
- Vesicles are most concentrated with infection within first 48 hours
- Unroof Vesicles with scalpel or needle tip and apply viral culture swab
- Expect viral growth within 5 days
- Test Sensitivity: 50%
-
HSV PCR
- Test Sensitivity: High
- HSV Direct Fluorescent Antibody
- Test Sensitivity: 80%
- HSV IgG
- Antibodies form with weeks of primary infection
- Does not differentiate acute infection from prior
- Rapid Giemsa (Dif-Quik) stain
- Multinucleated giant cells
- Test Sensitivity: 40-77%
X. Management: General Measures
- See Oral Mucositis
-
Magic Mouthwash
- Indicated for analgesia
XI. Management: Antivirals for Primary and Recurrent Outbreaks
- Best efficacy when Antivirals are started at the first signs of recurrence (e.g. local tingling or Paresthesias)
- Systemic Antiviral Agents for primary outbreaks
- Start within 24 hours of lesion onset
- Acyclovir (Zovirax)
- Child: 15 mg/kg (up to 400 mg) orally 5 times per day for 7 to 10 days
- Adult: 400 mg orally 5 times daily for 7 to 10 days
- Efficacy
- Lesions resolved in 4 versus 10 days, and viral shedding decreased to 1 versus 5 days
- Amir (1997) BMJ 314:1800-3 [PubMed]
- Famciclovir (Famvir)
- Adult: 500 mg orally twice daily for 7 to 10 days
- Valacyclovir (Valtrex)
- Adult: 1 g orally twice daily for 7 to 10 days
- Systemic antvirals for recurrent outbreaks (reduce healing time by up to 2 days)
- Acyclovir (Zovirax)
- Adult: 400 mg orally 3 to 5 times daily for 5 days
- Valacyclovir (Valtrex)
- Adult: 2 grams orally twice daily for one day
- Famciclovir (Famvir)
- Adult: 1500 mg orally for one dose (or 750 mg orally twice daily for one day)
- Efficacy
- Shortens healing time by 2 days in UV-induced cases
- Spruance (1999) J Infect Dis 179:303-10 [PubMed]
- Acyclovir (Zovirax)
- Topical Antiviral Agents (reduce healing time by 0.7 days)
- Docosanol (Abreva) cream apply 5 times per day until healed
- Least costly topical ($20 in 2014)
- Topical Acyclovir
- Expensive ($300-600)
- Acyclovir (Zovirax) cream apply 5 times per day for 4 days
- Acyclovir with Hydrocortisone (Xerese)
- Penciclovir (Denavir) 1% cream apply every 2 hours while awake for 4 days
- Very expensive ($500/tube in 2014)
- Sitavig buccal one tablet per episode placed in upper gum on same side of mouth as symptoms
- Very expensive ($300 for 2 tabs in 2014) and only shortens Cold Sore course by <1 day
- (2014) Presc Lett 21(9): 53
- Docosanol (Abreva) cream apply 5 times per day until healed
XII. Prevention: General
- Use Sunscreen
XIII. Prevention: Daily Antiviral Suppression
- Indications
- Recurrence of Herpes Labialis 6 or more times per year
- Preparations
- Acyclovir (Zovirax) 400 mg orally twice daily
- Valacyclovir 500 mg orally once daily to twice daily
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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 |