Common Pediatric Lip Lesions: Herpes Simplex/Recurrent Herpes Labialis, Impetigo, Mucoceles, and Hemangiomas Janna M

Clinical Pediatrics http://cpj.sagepub.com

A Review of Common Pediatric Lip Lesions: Herpes Simplex/Recurrent Herpes Labialis, Impetigo, Mucoceles, and Hemangiomas Janna M. Bentley, Benjamin Barankin and Lyn C. Guenther Clin Pediatr (Phila) 2003; 42; 475 DOI: 10.1177/000992280304200601

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Downloaded from http://cpj.sagepub.com at ALBERTA UNIVERSITY on May 24, 2008 © 2003 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. A Review of Common Pediatric Lip Lesions: Herpes Simplex/Recurrent Herpes Labialis, Impetigo, Mucoceles, and Hemangiomas

Janna M. Bentley, BSc1 Benjamin Barankin, MD' 2 Lyn C. Guenther, MD, FRCPC3

Summary: Lip lesions are a common presentation to the pediatrician's office. These lesions are often benign in children, without significant functional morbidity. However, owing to the prominent placement of lips and their role in communication, lip lesions can be alarming to patients as well as to their parents. For these reasons the pediatrician has an important role in recognizing, diagnosing, and treating the various types of labial dermatoses that commonly present to a pediatric practice. Four of the most common lip lesions a pediatrician will see are herpes simplex/recurrent herpes labialis, impetigo, mucoceles, and hemangiomas. This paper reviews the current literature on the diagnosis, treatment, and management of these 4 lesions. Clin Pediatr. 2003;42:475-482

Introduction important, not only to prevent lip is semi-elliptical. At the com- disease morbidity and mortality, missure, the lips meet laterally. L ips provide entrance to the but also to restore social accep- Each lip is attached to the adja- oral cavity and are promi- tance and self-esteem. cent alveolus by the frenulum. nently placed in the center During the 7th week of in- The orbicularis oris muscle circles of the face. They help manipulate trauterine life the lips start to de- both lips. A number of other mus- ingested food into the oral cavity, velop; by the 9th week, they are fully cles interdigitate with this muscle are involved with speech articula- developed. The upper lip is the re- and move the lips in other direc- tion and communication, reflect sult of fusion of the medial nasal tions. The 7th cranial nerve in- sexuality, and are important iden- prominences and maxillary promi- nervates these muscles. The tifying facial features. Any abnor- nence. The lower lip comes from mandibular branch of the 5th cra- mality or blemish is easily notice- the mandibular prominence of the nial nerve supplies the sensory in- able and a potential source of first branchial arch with the upper.' nervation. Lips are highly vascu- embarrassment. Diagnosis and The upper lip has the shape of larized and hairless. The vascular treatment of lip abnormalities is a "Cupid's bow," while the lower supply is from the labial branches of the facial artery. Lips have a "wet" internal mucosa and "dry" external mucosa. 'Department of Medicine; 2Division of Dermatology, University of Alberta; and 3Division of The junction appears as a "white Dermatology, Univeristy of Western Ontario, London, Ontario, Canada. line." The mucosa has a number of labial glands. Unlike other ar- Correspondence to: Lyn C. Guenther, MD, FRCPC, The Guenther Dermatology Research eas of the body covered by skin, 835 Richmond Ontario N6A 3H7 Canada. Centre, St., London, the external mucosa lacks the 2003 Westminster Publications, Inc., 708 Glen Cove Avenue, Glen Head, NY 11545, U.S.A. tough keratin covering, has a

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thinner epithelium, less melanin, matic. An infected mother can these patients seroconverting by and lacks sebaceous and sweat transmit viral particles to her fetus age 5 years.5f6 Similarly, a British glands, all of which have a protec- vertically during delivery, due to study in 1999 reported a preva- tive function. These characteris- asymptomatic cervical shedding. lence of almost 100% seroconver- tics cause the lips to be more sus- The ensuing neonatal infection is sion by the age of 15 years.7 It has ceptible to damage from the difficult to diagnose clinically as been estimated that up to 40% of elements, environment, trauma, the symptoms are very nonspe- seropositive individuals develop and infection. cific and may not be recognized. recrudescent disease, resulting in A comprehensive English lan- It has been shown that mothers site-specific, recurrent ulcera- guage literature search of MED- who experience a primary genital tions such as herpes labialis, or LINE from 1966 to 2002 was per- herpes simplex virus (HSV)-infec- "cold sores."8 formed. Initially, the following tion in the third trimester of their On initial infection, oral her- MeSH terms were used: "lips," pregnancy, who are seronegative pes classically presents as a gin- "pediatrics," and "prevalence," to at delivery, have a 33-50% chance givostomatitis, affecting the oral establish 4 of the most common of transmitting the virus to their mucosa with small vesicles that lesions. An informal survey of pri- infant.2 Conversely, secondary re- rapidly break open releasing a yel- mary care physicians in Edmon- activation of HSV in a seropositive lowish exudates (Figure 1). The ton, Alberta, Canada, was also woman during the intrapartum vesicles are replaced by painful ul- performed to identify which le- period incurs a 3% risk of vertical cerations, along with edematous, sions were most commonly seen transmission to her infant.2 punched-out lesions of the gingi- clinically, and these results fur- Herpes simplex virus type 1 val margin. Primary oral herpes ther reinforced the MEDLINE (HSV-1) classically causes the infection can occur on the inner search. Following the determina- "above the waist" lesions, includ- mucosal border of the lips, but tion of common pediatric lip le- ing the oral and perioral lesions, the pathognomonic "cold sore," sions, the term "pediatrics," and keratoconjunctivitis.3 It is which manifests extraorally on along with "recurrent herpes labi- thus implicated in most cases of the vermilion border of the lip, is alis," "impetigo," "mucocele," or recurrent herpes labialis, while a recurrent herpes simplex infec- "hemangioma" were searched. HSV-2 is responsible in 10% to tion, or "herpes labialis." It occurs The majority of the papers in- 15% of recurrent oral ulcera- following reactivation of latent cluded in this review were cur- tions.4 Ninety percent of the US herpes virus in the cells of the rent randomized, controlled tri- population is seropositive for trigeminal ganglia. als, prospective or retrospective HSV-1 by the time they reach their Unlike the primary gingivos- population-based studies, case re- teenage years, with at least 90% of tomatitis, recurrent herpes labi- ports, and reviews. This paper reviews 4 common pediatric lip lesions: herpes simplex/recurrent herpes labialis, impetigo, mucoceles, and hemangiomas.

Herpes SiWmlex/ Rcurrent Herpes Labialis

The herpes simplex viruses are responsible for a large number of cutaneous infections in hu- mans. There are 2 types of herpes infections recognized clinically: primary and recurrent. The primary infection is often missed as it commonly occurs during ado- lescence and may be asympto- Figure 1. Primary herpes simplex gingivostomatitis.

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alis is much milder in its manifes- the physician's discretion.'2 To been performed in children at tation, without the systemic symp- date, no studies directed at the this point. Application of topical toms. A tingling, burning, or itch- benefits of acute treatment of 1% penciclovir cream every 2 ing feeling may occur such lesions have been completed hours when awake for 4 days was prodromally at the site of the im- in the pediatric population. How- shown to decrease the duration of pending lesions, 12-36 hours be- ever, if the decision to treat an healing (1-day reduction in heal- fore eruption.4 Classically, a sin- acute eruption is made, first line ing time as compared to vehicle), gle, well-localized cluster of 3-5 treatment is generally an oral an- pain, and viral shedding in adult vesicles appears containing the tiviral medication such as acy- patients. 16 virus.9 With recruitment of in- clovir. In children less than 12 Controlled studies have been flammatory cells the vesicles ul- years of age, the recommended performed in adults showing that cerate and crusting occurs within dose of oral acyclovir is 20 mg/kg prophylactic treatment for herpes the first 24-48 hours after appear- every 8 hours.'2 In postpubertal labialis is beneficial using oral acy- ance of the initial lesions.4 It is at children (>12 years old), adult clovir or famciclovir.12'17'8 Adult the time of vesicular rupture that dosing schedules can be fol- studies show that short-term pro- lesions are most contagious9 and lowed.12 Besides acyclovir, fami- phylactic therapy is warranted in the lesions remain contagious un- clovir and valacyclovir have also some situations such as when the til healed. In order for transmis- been found to be efficacious in affected individual experiences sion of HSV to occur between a adult patients. In adult patients, episodes of herpes labialis seronegative and a seropositive in- Spruance et all3 showed that once monthly, or if the individual is an- dividual, shed virus must come the lesions of herpes labialis have ticipating an unavoidable known into direct contact with mucosal erupted, early treatment with trigger, or if the patient experi- surfaces or abraded skin on the high-dose famciclovir (250 mg 3 ences erythema multiforme fol- susceptible individual. Transmis- times per day for 5 days) de- lowing herpes labialis attacks.'7'18 sion between a seropositive and a creases the size and duration of Prophylactic doses of oral acy- seronegative individual can still the lesions. Similarly, a double- clovir 400 to 1,000 mg per day occur even without the presence blind study of 3,151 patients with were recommended, taken at the of active lesions. One study of oth- cold sores showed a reduction in time of exposure to known trig- erwise healthy adults in Japan the duration of the eruption by gers.'7"18 In children prophylaxis found that active shedding of 1.3 days in the group using 2 g of is rarely indicated and again, the HSV-1 into saliva occurred and valacyclovir twice daily for 1 day.'4 decision to treat is up to the pedi- persisted on average 1.2 days over Another group in this same study atrician's discretion. the course of 2 months, without had a lesion-time reduction of 1.2 symptomatic lesions.'0 There was days after receiving 2 g of valacy- no demonstrable causative link to clovir twice daily for 1 day, then 1 Impetigo the shedding in these subjects.10 day of 1 g valacyclovir twice Recurrences of herpes labialis in daily.'4 Approximately half of the Impetigo is a contagious bac- affected individuals typically oc- 3,151 patients in this study were terial infection of the superficial cur 2 or 3 times a year, with ultra- prevented from progressing to layers of the epidermis, often oc- violet (UV) light, trauma, and the macular/papular stage of the curring periorally. There are 3 physical and emotional stress herpes eruption following admin- clinical presentations, all of which serving as possible triggers.4,11 istration of the valacyclovir.14 are most often observed in the pe- Vesicles usually heal in 8 to 10 Besides oral antiviral treat- diatric population: impetigo con- days in immunocompetent peo- ment, some benefit has been tagiosa (nonbullous), bullous im- ple, without leaving a scar."I shown following topical adminis- petigo, and common impetigo.'9 The diagnosis of recurrent tration of acyclovir, but only for Impetigo contagiosa is the most herpes labialis is clinical, owing to primary infection. This method is common skin infection in chil- the classic presentation of the le- slightly less efficacious than oral dren,'9 especially between the sions and lack of constitutional formulations owing to the primar- ages of 2 to 5 years old.20 Bullous symptoms. Followinig diaginosis, ily neural nature of HSV infec- impetigo is usually an infection of early treatment of erupted recur- tions and less opportunity for the neonates and more commonly oc- rent lesions is of questionable topical treatment to exert its ef- curs on the trunk and the extrem- benefit in children and is up to fects.'5 Again, no studies have ities.19 Common impetigo occurs JUYAGS.03CINCLPDARC 7 JULY/AUGUST 2003 Downloaded from http://cpj.sagepub.com at ALBERTA UNIVERSITY on May 24, 2008 CLINICAL PEDIATRICS 477 © 2003 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. Bentley, Barankin, Guenther

in adults as a complication of der- tion,21 and a lack of normal-flora otic.25 Cloxacillin (40-50 mg/kg/ matological conditions causing a lipophilic bacteria.2' More aggres- day, q.i.d.) or cephalexin (40 break in the skin or systemic dis- sive treatment is warranted in mg/kg/day, q.i.d.) is used as oral eases such as diabetes mellitus these instances. therapy for 7 days in generalized and acquired immunodeficiency There are 2 pathogens impli- cases.26 Erythromycin is no longer syndrome (AIDS).19 cated in impetigo, Staphylococcus the treatment of choice owing to Impetigo contagiosa and com- aureus and Streptococcus pyogenes.20 emerging resistance.20 Lesions mon impetigo present initially as In the past, most cases of impetigo should resolve without scarring. If a single 2 to 4 mm erythematous contagiosa were caused by S. pyo- the impetigo does not resolve af- macule that rapidly turns into a genes; however, more recent stud- ter a 7- to 10-day course of antibi- vesicle or a pustule. The vesicles ies have shown that S. aureus is otics, it is important to test for na- rupture and a "honey-colored" now the organism most fre- sopharyngeal carriage of S. crusted exudate remains. Spread quently cultured from lesions.22,23 aureus.24 Elimination of the car- to adjacent skin occurs rapidly as Mixed Staphylococcus and Strepto- rier state can be accomplished the lesions extend and coalesce, coccus infections are common as empirically by application of producing eroded macules in well. Penicillin and ampicillin re- mupirocin, until the infection patches (Figure 2). It has been sistance have been shown in most clears.24 speculated that the site prefer- Staphylococcus infections of this One important complication ence for impetigo eruption in the mixed nature.22,23 of impetigo caused by S. pyogenes is perioral and nare areas is due to Cultures of impetigo are nec- acute poststreptococcal glomeru- their high exposure to environ- essary only when treatment has lonephritis. This occurs in ap- mental trauma.19 Insect bites, failed and methicillin-resistant proximately 2-5% of cases of contact dermatitis, or minor abra- Staphylococcus aureus is suspected. streptococcal impetigo, most sions are often found demonstrat- In localized cases, topical commonly in children 2 to 4 years ing the portal of entry for the bac- treatment with fusidic acid or 2% old.20 Antibiotic treatment of the teria. Secondary infection with mupirocin applied 3 times daily infection does not alter the impetigo in children suffering for 7 to 10 days24 is sufficient. Re- course of this form of glomeru- from atopic dermatitis often removal of crusts before application lonephritis. Fortunately, there is sults in rapid spread of the lesions is controversial. Emerging resis- usually resolution without seque- to other cutaneous sites, owing in tance to mupirocin has been lae in children.20 part to the compromised nature noted with S. aureus, especially in of their skin barrier,'9,21 de- cases of prolonged use, warrant- pressed cutaneous immune func- ing judicious use of this antibi- Mucoceles

Mucoceles are common mucous membrane lesions associated with minor or accessory salivary glands. There are 2 types of mucoceles: mucous extravasation cysts and mucous retention cysts.2728 Mucous extravasation cysts are the most common and are found in children and adoles- cents, most commonly in the 2nd decade of life.27'29 These lesions are much more likely to occur on the lower lip, with 1 study report- ing a site predilection for the lower lip of 58% over all other oral mucous membranes.30 Mu- cous retention cysts are less common, with an incidence of ap- Figure 2. Impetigo. proximately 3% of mucoceles.29

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Mucoceles of the extravasation lesions is pathognomonic, and pal- develop in 2.6% of neonates, with type are caused by trauma that pation helps to confirm the freely the prevalence increasing to 10% shears a minor or accessory sali- movable, soft nature of mucoce- by 12 months of age.35,36 Females vary gland duct. This results in les.27 Biopsy is unnecessary but are most often affected, with re- saliva accumulating between the would confirm the diagnosis. ported rates 2 to 5 times greater epithelium and the adjacent soft Following diagnosis, treat- than males.37 Prematurity and low tissue. A pseudocapsule of fibrous ment is often not needed as the birth weight (500 to 1,000 g) are connective tissue forms, walling off smaller and more superficial mu- associated with the development the mucocele. Extravasated muco- coceles are likely to rupture spon- of these lesions as well, with a 1.5 celes are not true cysts, for they do taneously and then heal.27 The to 2 times greater occurrence rate not have an epithelial lining.28 most common treatment of larger than in normal infants.37 Infants Mucoceles will most often pre- or recurrent mucoceles is surgical weighing 1,500 g or more at birth sent opposite the upper incisor excision, with subsequent re- have the same incidence as regu- on the lower lip as painless, moval of the associated salivary lar birth weight babies.37 smooth, freely movable, soft, fluc- glands.32 This helps to prevent re- There are 2 types of heman- tuant masses, measuring on aver- currences. Prognosis of mucoce- giomas, defined by the depth of age approximately 1 cm (Figure les is good, whether treatment is their penetration into the der- 3).31 They can be found on the up- needed or not. mis.34 The superficial lesions are per lip as well. Mucoceles on the bright red, blanchable nodules lower lip are often bitten by the with well-defined borders, and patient, and consequently they Hemangiomas these comprise approximately drain and heal; however, the 65% of all hemangiomas.34 Deep swelling eventually recurs.31 The Hemangiomas are vascular lesions represent 15% of these more superficial lesions can have anomalies cited as the most com- vascular anomalies, and they ap- a bluish tinge, while deeper mu- mon benign, neoplastic lesions in pear as bluish nodules with less coceles are more likely to be the infants. They are noted most com- distinct borders.34 The remaining color of normal mucosa.27 The monly on the head and neck 20% are considered 'mixed' and fluid-filled nature of the deeper (50-60%), and this site prefer- present as a combination of su- mucoceles is less obvious. ence is most likely due to the un- perficial and deep lesions.34 An The diagnosis of mucoceles is derlying intricate vasculature of example of a superficial (straw- made clinically, with the patient this region.33,34 They are a fre- berry) hemangioma is shown in describing some traumatic event quent cause of presentation to the Figure 4. to the lip. The appearance of these pediatrician since hemangiomas There are typically 5 stages in the development of hemangiomas including eruption, prolif- eration, plateau, involution, and regression. At approximately 2 to 4 weeks of age the nodules erupt, ap- pearing either red in color with telangiectasia, or hypopigmented.33 From approximately 6 to 12 months, the endothelial cells pro- liferate, with the hemangioma reaching a maximal size at around 12 months of age.34 A plateau is reached and the lesion remains sta- tionary from roughly 12 to 15 months of age.33'34 Approximately 50% will involute and regress by age 5 years, 70% by age 7 years, and 90% by age 9 years.34 Residual at- rophic or redundant skin may fol- Figure 3. Mucocele on the lower lip (photo courtesy of Dr. Wysocki). low involution and regression.

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rate has been reported in infants treated with this method.42 How- ever, interferon alpha-2a has a mean time to regression of 7 months and requires monthly complete blood counts, as well as hepatic and renal function tests.42 Laser therapy and surgical treatment are also possibili- ties if deemed necessary to remove the lesion, with a 60%43 response rate of superficial strawberry hemangiomas to fast- pulsed dye laser (FPDL).34 This laser can also be used to remove residual telangiectasias after regression of a hemangioma.34 Sur- Figure 4. Strawberry hemangioma on the upper lip. gical excision is the treatment of choice in lesions extending to in- volve the eyes, which are unre- Superficial hemangiomas are ity of hemangiomas are small and sponsive to corticosteroids, and composed of blood vessels resem- superficial. However, some may is also useful in removal of re- bling capillaries, with thin walls grow rapidly and impinge on or- dundant skin after spontaneous and a thin endothelium lining, gan systems, resulting in life- involution of hemangiomas.44 while the deep variant of heman- threatening complications. In The prognosis is good with su- giomas results from dilatation of particular, hemangiomas of the perficial hemangiomas as most vascular channels at a deeper head and neck are worrisome if spontaneously involute and level.38 they have the potential to ob- regress with minimal residual atro- The diagnosis of heman- struct the infant's airway or im- phy. The outcome is worse with giomas is clinical, with distressed pair vision at a crucial time in the deep or mixed hemangiomas as parents presenting to their pedia- development of visual pathways. If the likelihood of incomplete invo- tricians with infants in the early the decision is made to treat the lution, with residual redundant stages of lesion development. hemangioma, options include sys- skin that is wrinkled and telang- Ninety percent of hemangiomas temic corticosteroids (pred- iectatic in appearance is greater. are diagnosed in the 1st month of nisone 2-4 mg/kg/day for 2-3 Restoration of normal skin follow- life.34 Parents will often express weeks) for rapidly growing, life ing spontaneous regression occurs feelings of guilt, shame, disbelief, threatening, or functionally im- in only 50% of cases.45 If residual mourning, and anxiety.39 Support pairing lesions.34 The rate of re- skin with telangiectasia remains, and reassurance must be given at sponse to prednisone is 30% to laser or surgical treatment is ap- the time of diagnosis. 90% and is expected within 7 to propriate and the final result is As a result of the psychosocial 10 days of initiating treatment; a more cosmetically pleasing.34 stressors of hemangiomas and the good response is characterized by Table 1 summarizes the cur- high rate of spontaneous involu- a fading of the color or slowed rent treatment options for recur- tion, education, reassurance, and growth, as well as softening of the rent herpes labialis, impetigo, monitoring are the mainstays of hemangioma.34 Intralesional in- mucoceles, and hemangiomas. treatment. It is useful to show par- jection of corticosteroids can also ents photos of before and after le- be safe and effective in properly sions following spontaneous invo- selected infants with heman- Conclusion lution, and a wait-and-see giomas.40,41 If the hemangioma is approach is often best. Decisions unresponsive to corticosteroids, Lip lesions are a common pre- to treat are based on prevention therapy with subcutaneous inter- sentation to the pediatrician's of- of loss of life or function, and the feron alpha-2a is the next line of fice, often necessitating consulta- possibility of scarring. The major- treatment.42 A 50% regression tion. In children, most lesions are

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8. Scott DA, Coulter WA, Lamey P-J. Oral shedding of herpes simplex virus abl e; t type 1: a review. J Oral Pathol Med. 1997;26:441-447. SUMMARY OF TREATMENT OPIONS --FOR PEDATI LIP LE1S 9. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Lip Lesion TreNtment Options Dis. 1998;26:541-553. 10. Kameyama T, Sujako C, Yamamoto S. Recurrent herpes lWbialis t*atpediatricians discretion Shedding of herpes simplex virus type : <12 years old orl acycloVir20 mg/kg q8h'2 1 into saliva.jOralPathol. 1988;17:478- * >12 years old (postpubertal) 481. Use adult dosing schedues12 11. Emmert DH. Treatment of common cutaneous herpes simplex virus infec- Prophylaxis: ora acylovir 400100 mg q.i.du. tions. Am Fam Physician. 2000;61: started at tmh time Of exosure to known trigger 718 1697-1708. Earl tretmenit of erupted lSions:orlW iclovir 12. Whitley RJ. Herpes simplex virus in 250mg t.i.d.0 for 5 days13 ayclovir 2 m b.id. children. Curr Treat Options Neurol. for 1 day or1%lpenciclovir cream q2h for 4 days16 2002;4:231-237. Impetigo *swabs forCS before commening treatment 13. Spruance SL, Rowe NH, Raborn GW, funcmlicated-custn op removal a applicton of et al. Perioral famciclovir in the treat- fusidic acid or 2% mupircin for 7-110 days t.i.d.24 ment of experimental ultraviolet radi- * complicated -> cloxacillin 050 t m aq.i.d. ation-induced herpes simplex labialis: or cephalexin 40 m g q.i.d., for67 days26 a double-blind, dose-ranging, placebo-controlled, multicenter trial. Mucoceles : usual no treatment required JInfectDis. 1999;179:303-310. * if largerecurrent -+ surgical extiston32 14. Tyring S. Single-day, oral valacyclovir Hemangiomas * most spontaneously involute in the treatment and prevention of 0* psychosocial suport andclose fbllow-up cold sore lesions. Poster presentation. :if necessary to trt, consider meral to Am AcadDermatol Summer Meeting. New dertmato s: 1 penitsone 2-4 m /a for York City, August 1-3, 2002. 2-3 weeks; expect response in 7-10 days;34 15. Vander Straten M, Carrasco D, Lee P. 2. intralesional[steroids;404'3. interferon et al. A review of antiviral therapy for a04Alpa- subcutaneously;42 4. laser therapy;34 herpes labialis. Arch Dermatol. 2001; 5. surgical excision34 137:1232-1235. 16. Spruance SL, Rea TL, Thoming C. Penciclovir cream for the treatment of herpes simplex labialis: a randomized, multicenter, double-blind, placebo- benign and should not cause sig- ternal infection at the time of labor. controlled trial. JAMA. 1997;277: nificant morbidity. Treatment is NEnglJMed. 1991;324:1247-1252. 1374-1379. often conservative, with reassur- 3. Balciunas BA, Overholser CD. Diag- 17. Spruance SL. Prophylactic chemo- ance being paramount. For these nosis and treatment of common oral therapy with acyclovir for recurrent herpes simplex labialis. J Med V7irol. reasons it is necessary to be able lesions. Am Fam Physician. 1987;35: 1993;PMID8245889:27-32. to recognize, diagnose, and treat 206-220. 18. Raborn GW, McGaw WT, Grace M, et the various types of labial der- 4. Glick M, Siegel MA. Viral and fungal infections of the oral cavity in im- al. Oral acyclovir and herpes labialis: a matoses that commonly present randomized, double-blind, placebo- munocompetent patients. Infect Dis to a pediatric practice. controlled JAm Denzt Assoc. 1987; Clin North Am. 1999; 13:817-831. study. 115:38-42. 5. Corey L, Spear PG. Infections with 19. Shriner DL, Schwartz RA, Janniger REFERENCES herpes simplex viruses: I. NEnglJMed. CK. Impetigo. Cutis. 1995;56:30-32. 1986;314:686-691. 1. Sadler TW. Head and neck. In: Lang 20. Rhody C. Bacterial infections of the mans MedicalEmbryology, 7th ed. Balti- 6. Corey L, Spear PG. Infections with skin. Prim Care. 2000;27:459-473. II. N more: Williams Wilkins; 1995:312-346. herpes simplex viruses: Engl J 21. Rystedt L, Stranngard IL, Stran- Med. 2. Brown ZA, BenedettiJ, Ashley R, et al. 1986;314:749-757. negard 0. Infections as contributing Neonatal herpes simplex virus infec- 7. Marsh P, Martin MV. Oral microbiology. factors to atopic dermatitis. Allergy. tion in relation to asymptomatic ma- 4th ed. Oxford: Wright; 1999:147-152. 1989;44(suppl 9):79-83.

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