Oral Manifestations and Dental Management J

REVIEW ARTICLE

Hereditary epidermolysisbullosa: oral manifestations and dental management J. TimothyWright, DDS, MSJo-David Fine, MDLorraine Johnson,ScD Abstract Epidermolysis bullosa (EB) is a diverse group of disorders that have as a commonfeature blister formation with tissue separation occurring at variable depths in the skin and~ormucosa depending on the specific EBtype. There maybe markedoral involvement, potentially creating devastating alterations in the soft and hard tissues. Oral tissue fragility and blistering is commonto all EBtypes. However,oral debilitation as a result of soft tissue scarring is primarily limited to the recessive dystrophic EBsubtypes. Generalized enamelhypoplasia appears to be limited to junctional EB, although rampantdental caries is associated with manyindividuals having generalized recessive dystrophic EB. While systemic treatment remains primarily palliative, it is possible to prevent destruction and subsequentloss of the dentition throughappropriate interventions and dental therapy. The majority of individuals with mild EBsubtypes may receive dental treatment with only minor modifications in approach. Even the most severely affected individuals with EB can retain their dentition using general anesthesia and conventional restorative techniques. With aggressive preventive interventions and managementof developing malocclusions using serial extraction, it also is possible to reducethe likelihood of rampantcaries, achievean acceptableocclusion without the need for active tooth movementor appliancetherapy, and allow these individuals to benefit from maintaininga natural healthy dentition. (Pediatr Dent 15:242-47, 1993)

Introduction Fragility and skinblistering are the hallmark features of discuss the implications and approaches for managingthe the hereditary disorders classified as epidermolysis bul- systemic and oral manifestations. losa (EB). While the specific pathogenesis of these disor- Classification ders remains unknown, bullae formation has been associated with numerous basic defects including structural As many as 23 distinct types of EB now have been and/or biochemical abnormalities of keratin, recognized, each varying in its clinical appearance, hemidesmosomes,anchoring fibrils, anchoring filaments, extracutaneous involvement, mode of inheritance, and and physicochemically altered skin collagenase. 1~ Recent level of tissue cleavage. These subtypes are classified into genetics studies have linked one EB type to a keratin three main groups based on the level of tissue separation defect, while another type has been linked previously to that develops following mechanical trauma to the skin the type VII collagen gene. 6, 7 Although tremendous (Table 1 ).s.12 Blistering occurs within the epidermis, within progress has been made toward understanding this di- the basement membrane, or beneath the basement mem- verse group of disorders, they continue to present a formi- brane in simplex, junctional, and dystrophic forms of in- dable challenge to medical and dental practitioners. Dur- herited EB, respectively. The ultrastructural level of sepa- ing the 1980s, the National Institutes of Health established ration in blistered tissue is determined using transmission four regional institutional centers that were designated as electron microscopy and/or immunofluorescence anti- clinical sites for the National EpidermolysisBullosa Regis- genic mapping23 Characterizing morphologic features-- try (NEBR). These centers were charged with advancing including the hemidesmosomes, anchoring fibrils, and our understanding of the clinical, diagnostic, and labora- subbasal dense plates and the relative expression of nu- tory characteristics of EB. Since the NEBRbecame opera- merous basement membrane-specific antigens, such as tional in 1986 approximately 1600 affected individuals type VII collagen, GB3,19DEJ-1, and chondroifin 6-sulfate have been evaluated. As a result of these and other inves- proteoglycan--also are useful diagnostic aids in further tigations our knowledgeconcerning the clinical character- delineating EBtypes and subtypes. 13’ 14 istics and oral manifestationsof the 23 different EBsubtypes Modeof inheritance and clinical features, such as the has increased markedly,s During the past decade there severity and distribution of cutaneous and extracutaneous also has emerged a growing body of dental literature findings, also are considered in the final classification of presenting successful anesthetic and dental management each EB subtype25 Hereditary EB subtypes may exhibit for9- individuals having even the most severe forms of EB. autosomal dominant or recessive modes of transmission, n In this manuscript we will review the current classifica- with the possible exception of the MendesDa Costa vari- tion and clinical findings of the different EB types and ant of EB simplex, which is reported to be X linked, s To

242 Pediatric Dentistry: July/August 1993 - Volume15, Number 4 Table 1. Ultrastructural site of tissue separationand common morphologic may include the eyes, teeth, featuresof the majorEB types oral mucosa, esophagus, in- testinal tract, anus, genito- Major EB Type Site of Tissue Separation CommonMorphologic Features of Tissue urinary tract, and/or mus- culoskeletal system. 16 In EB Simplex Within or just above the stratum Cytolysis of basilar or suprabasilar basalis Cepidermolytic") keratinocytes general, specific EB subtypes will have characteristic com- Junctional EB Within dermoepidermal Absence of or rudimentary appearing binations of cutaneous and junction (intralamina lucida; hemidesmosomes; reduced or absent extracutaneous features, al- "lamina lucidolytic") subbasa| dense plates though there may still be Dystrophic EB Beneath the entire dermo- Reduced numbers of or absent considerable clinical varia- epidermal junction (sublamina anchoring fibrils tion in the type and severity densa; "dermolytic") of manifestations (Table 2). Someclinical features are characteristic of one or a few develop an accurate prognostic prediction and treatment specific EBsubtypes such as the pathognomonicfinding approach it is imperative that clinicians managing EB of extensive perioral granulation tissue seen in the Herlitz patients are familiar with each subtype and its particular variant of generalized junctional EB (Fig I and Fig 2). 17’ 18 clLnical presentation. These lesions develop during infancy and may heal with atrophic scarring without specific treatment during young General clinical features or mid-adulthood. In some severely affected individuals Cutaneous findings vary considerably and may include these lesions may encompass nearly the entire face, ex- blisters, crusted erosions, milia, scarring, granulation tis- tending as far as the eyes and nasal bridge and may even sue, pigmentation changes, cicatricial alopecia, and ab- lead to partial or complete obstruction of the nares. The sence or dystrophy of nails, s Extracutaneous involvement development of digital webbing with mitten-type defor-

Table2. Clinical featuresof inheritedepidermolysis bullosa variants"

EB Type Subtype Inheritance Age of Onset Distribution Scarring Mechanical Growth Fragility Retardation

Simplex Localized AD 0-4 yr Palms/soles Rare Rare Absent (Weber-Cockayne) Simplex Generalized AD 0-2 yr Extremities > Rare Rare Absent (Koebner) elsewhere Simplex Herpetiformis AD Birth Generalized Variable Variable May be (Dowling-Meara) delayed Simplex Localized with AR 3 mo - 1 yr Hands/feet Absent ? Absent Hypodontia (Kallin) Junctional Generalized AR Birth Generalized Common Moderate Severe (Herlitz; Gravis) to severe Junctional Generalized AR Birth Generalized Common Moderate Absent (Mitis; Non-Herlitz) but focal or mild Junctional Localized AR Birth Hands, feet, Absent Absent Absent (minimus) pretibial Dystrophic Generalized AD Birth Generalized Common Variable Absent (Pasini; Cockayne-Touraine) Dystrophic Localized AD Early Acral Absent ? Absent (Minimus) childhood Dystrophic Generalized AR Birth Generalized Common Severe Severe (Gravis; Hallopeau-Siemens) Dystrophic Generalized AR Birth Generalized Present Moderate Absent (Mitis) ¯ Listedare 12of the possible23 described EB subtypes. The reader is referredto morecomplete listings for a comprehensivereview of the EB subtypesand their clinical features(Fine et al. 1991).

PediatricDentistry: July/August 1993 - Volume15, Number4 243 tion may be seen occasionally in several EB subtypes it is most often seen with the Herlitz variant of junctional EB and severe generalized recessive dystrophic EB. Patients with the latter are at particularly high risk during early adulthood of developing aggressive cutaneous squamous cell carcinomas, which may eventually lead to metastasis and death.21 Oral features The character and extent of oral involvement varies greatly from one EB type to the next. In the milder forms of inherited EB the oral mucosa may suffer only occasional blistering with small discrete vesicles that heal rapidly without scarring and do not significantly alter the patient's life. In more severe cases, however, the entire oral mucosa is af- Fig 1. This 2-year-old female has the Fig 2. The same patient shows the fected and may be characterized by severe Herlitz variant of generalized perioral lesions have healed with no intraoral blistering with subsequent scar for- functional EB demonstrating the specific therapy by age 11 years, mation, microstomia, obliteration of the oral characteristic perioral lesions unique leaving the nares occluded due to vestibule, and ankyloglossia. Table 3 reviews to this specific subtype. scarring. the predominant oral features of the major EB subtypes. Oral mucosa fragility, with subsequent development of intraoral soft tissue lesions, is common to all major EB types.22 Prospective evaluation of enrollees in the South- eastern Clinical Center NEBR has demonstrated a much higher frequency of oral blistering with even mild forms of EB simplex than reported previously.22"24 Although 35% of the localized and 59% of the generalized EB simplex patients develop intraoral blistering, these lesions tend to be few and small in size (< 1 cm), and tend to heal without scarring.22 Whereas oral involvement in EB simplex appears to occur most commonly during the perinatal pe- riod, some individuals experience continued blistering into or beyond infancy or even late childhood.22 Most individuals with junctional or dominant dystro- Fig 3. Digital webbing and severe mitten deformities result phic forms of inherited EB develop lesions involving their from the continual process of blistering and scarring around oral mucosa that are characteristically larger (> 1 cm), and the digits. Complete enclosure of the digits in an ectodermal more numerous than those observed in EB simplex, often sac is characteristic of severe generalized recessive dystrophic become erosive, and are usually quite painful. Despite this EB. propensity to develop clinically significant oral lesions, mities of the hands and feet is characteristic of severe patients with these two major inherited EB forms usually generalized recessive dystrophic EB (Fig 3), although rare heal without extensive intraoral scarring and, therefore do patients with cicatrical junctional EB may exhibit similar not typically develop ankyloglossia or vestibular oblitera- or identical findings. tion (Fig 4). In some cases extracutaneous involvement can be so Individuals with generalized recessive dystrophic EB severe that it significantly alters an individual's lifestyle. exhibit the most severe oral involvement, which is charac- For example esophageal involvement, most frequently terized by complete obliteration of the vestibule and associated with Herlitz junctional and severe generalized ankyloglossia (Fig 5). With increasing age, structures such recessive dystrophic EB, may potentially lead to signifi- as the palatal rugae and lingual papilla typically become cant strictures, making the passage of food impossible.19 unrecognizable because of the presence of continuous blis- Severe multifactorial anemia also is seen commonly in ter formation and scarring. In contrast, localized or mildly both of these EB types and is presumed to be secondary to affected generalized recessive dystrophic cases do not show malabsorption and chronic iron (blood) loss through mu- the same severity in oral scarring, loss of lingual papillae, cosal erosions and ulcerations.8-20 While growth retarda- and/or ankyloglossia observed in the severe generalized

244 Pediatric Dentistry: July/August 1993 - Volume 15, Number 4 Table 3. Oral manifestations of inherited epidermolysis bullosa variants'

EBType Subtype ^ucosal °ral Ankyloglossia Microstomia fmu"el. Hypodontia Rampant Erosions Scarring______tHypolasia Anodonha Canes' Simplex Localized Occasional Absent Absent Absent Absent Absent Absent (Weber-Cockayne) Simplex Generalized Occasional Absent Absent Absent Absent Absent Absent (Koebner) Simplex Herpetiformis Common Absent Absent Absent Absent Reported Absent (Dowling-Meara) Simplex Localized with Present? Absent Absent Absent Absent Present Absent Hypodontia (Kallin) Junctional Generalized Common Mild/ Absent/ Moderate Severe Absent Severe (Herlitz; Gravis) Variable Mild Junctional Generalized Common Absent/ Absent/ Absent Moderate/ Absent Moderate (Mitis; Non-Herlitz) Mild Mild Severe Junctional Localized Common Absent Absent Absent Mild/ Absent ? (Minimus) Moderate Dystrophic Generalized Mild/ Absent Absent Absent Absent Absent Absent (Cockayne-Touraine) Moderate Dystrophic Generalized Severe Severe Severe Severe Absent Absent Severe (Gravis & Pasini; Hallopeau-Siemens)

•Oral features are listed for 10 of the EB subtypes. The following references provide more complete reviews of all subtypes (Fine et al. 1991). f Moderate and Severe indicates relative risk for developing dental caries. By no means will all individuals in a subtype listed as severe have rampant caries.

viduals with the Herlitz variant of Junctional EB.22 In these two EB subtypes, microstomia apparently results from either inrraoral or perioral blistering with subsequent scar formation. In generalized recessive dystrophic EB, microstomia appears to be the result of chronic, severe inrraoral blistering. In Fig 4. The lesions on the tongue of Fig 5. This individual with severe generalized recessive contrast, while the this individual with the Herlitz variant dystrophic EB has lost all the papillae on the tongue which is Herlitz variant of of generalized functional EB are large ankylosed and will not extend beyond the incisal edges of the Junctional EB also and painful but heal without scarring mandibular incisors. Marked microstomia and dental caries demonstrates leaving the tongue with normal also are clearly evident. microstomia, vestibu- mobility. lar obliteration and forms.22 Squamous cell carcinoma of the tongue has been severe, inrraoral scarring are characteristically absent. In- reported in several cases of recessive dystrophic EB, pre- stead, this EB subtype is classically associated with se- sumably due to the analogous tendency for such tumors vere, chronic, perioral erosions and exuberant granula- to arise on skin sites subjected to repeated ulceration and tion tissue.17 re-epithelialization.21-22 The dentition may be affected severely by enamel hyp- Microstomia is most profound in severe generalized oplasia and/or dental caries depending on the EB type. recessive dystrophic EB, but also may be common to indi- Examination of more than 100 individuals with EB by

Pediatric Dentistry: July/August 1993 - Volume 15, Number 4 245 30 Eroded skin surfaces are best covered with nonadherent dressings after applying a topical antibiotic such as baci- tracin, silver sulfadiazine, or mupirocin.12 Oral nutritional supplements including iron and zinc may be partially beneficial in managing individuals suffering from anemia, and liquid preparations high in protein and calories may help patients with growth retardation.31"32 Nutritional counseling also should take into account and address the control of dietary cariogenicity since individuals with severely affected oral mucosa and/or esophageal strictures usually consume soft or pureed foods high in calories; in addition they frequently eat very slowly, thereby further extending the dentition's exposure to potentially caries- promoting substrate. Surgical intervention helps to correct mitten deformi- Fig 6. This scanning electron micrograph shows the diverse size ties and digit webbing, although webbing usually recurs, and shapes of the hypoplastic pits seen in the enamel of a necessitating repeated surgeries.33 Esophageal stenosis may permanent molar removed from an individual affected with the be managed with dilatation, which again usually must be Herlitz variant of generalized junctional EB (Original repeated to maintain luminal patency.19 Although most magnification 25x). interventions remain palliative and temporary, collectively they have permitted many severely affected EB patients to Gedde-Dahl indicated that all patients with junctional EB live beyond early childhood, thus producing a population suffered from enamel hypoplasia.25 It has since been con- of individuals requiring refined and aggressive dental firmed in a large prospective study that generalized enamel treatment and interventions.12 hypoplasia is limited to junctional EB types.26 Among the junctional EB patients, however, considerable variation Oral management may be noted in the nature of the enamel hypoplasia with Individuals with milder forms of EB require few alter- some individuals having generalized pitting hypoplasia ations in their dental care and may be treated much like while others display very thin enamel with marked fur- any other patient. For example, the majority of individuals rows (Fig 6). Rampant dental caries in patients with junc- with EB simplex will tolerate dental procedures without tional EB seems to occur, at least in part, as a result of difficulty. The practitioner should, however, carefully enamel hypoplasia, which decreases the tooth's intrinsic question any individual with EB as to their mucosal fragil- disease resistance. ity, since dental therapy can precipitate oral blistering Rampant dental caries is frequently seen in patients even in some mildly affected patients. Conversely, an with severe generalized recessive dystrophic EB despite altered approach to oral rehabilitation and anesthetic appearing to have normal dentition development.26 It has management may be required in individuals with enamel been hypothesized that excessive dental caries is a result hypoplasia or rampant caries, extreme fragility of the of the presence and severity of the soft tissue involvement, mucosa, and/or the presence of microstomia (eg. Herlitz which leads to alterations in the diet (soft and frequently junctional EB and severe generalized recessive dystrophic high carbohydrate), increases oral clearance time (second- EB).9 Routine outpatient dental treatment with local anes- ary to limited tongue mobility and vestibular constric- thesia is possible in patients with minimal soft tissue in- tion), and creates an abnormal tooth /soft tissue relation- volvement or limited treatment needs. Individuals with ship (i.e., buccal and lingual mucosa, which is firmly severe soft tissue involvement requiring multiple restor- positioned against the tooth.)27 Furthermore, these indi- ative and/or surgical procedures typically are best man- viduals often lack the ability to routinely practice normal aged with general anesthesia. preventive measures such as oral hygiene or the use of When administering intraoral local anesthesia, the an- oral rinses. esthetic solution should be injected deeply into the tissues slowly enough to prevent tissue distortion, which may General management cause mechanical tissue separation and blistering. In our Treating inherited EB still consists primarily of pallia- experience, nerve blocks are far less likely to form blisters tive topical care. There are no known cures and most since they do not place the mucosal surface under pres- systemic therapeutic approaches have proved to be inef- sure by depositing a bolus of fluid near the tissue surface. fective. For example, although initial reports suggested When manipulating tissues of individuals with those EB that phenytoin might prove to be beneficial in reducing types most prone to mucosal blistering (severe general- the tissue collagenase levels in recessive dystrophic EB ized recessive dystrophic EB), only compressive forces and thereby reduce blistering, a subsequent double-blind should be applied because these are less likely than lateral study failed to confirm the efficacy of this particular agent.28" traction or other shear forces to induce tissue separation.

246 Pediatric Dentistry: July/August 1993 - Volume 15, Number 4 Lubricating the patient’s lips and any tissue to be con- able to perform routine preventive procedures. In pa- tacted also will reduce the likelihood of shear forces and tients prone to oral blistering oral hygiene maybest be tissue9 damage. accomplished with a soft-bristled, small-headed tooth- General anesthesia allows for extensive reconstructive brush. In addition to systemic administration of fluorides, dental treatment and/or multiple extractions despite the fluoride rinses also mayhelp control caries. 27 However, severe soft tissue fragility. Clinicians have approached manyEB patients with mucosallesions are sensitive to the anesthetic managementwith great caution; their concern strong flavoring agents and alcohol in most rinses; spe- is the possiblility of developingairway obstruction due to cially formulated rinses lacking these ingredients maybe blister formation and tissue damage. Anesthetic manage- required. Chlorhexidine mouth rinses also mayhelp con- ment for dental care has therefore varied greatly and in- trol dental caries, but again the patient maybe sensitive to cluded such techniques as IV ketamine, insuffiation, and the high alcohol content of commerciallyavailable rinses. orotracheal and nasotracheal intubations. 3~-37 It is dear, This may be overcome by swabbing the chlorhexidine however, that even the most severely affected individuals directly on the teeth. Diet constitutes a major difficulty in may be treated using tracheal intubation, an approach caries control. Due to the complex systemic nutritional that provides optimal airway protection during dental demandsof these patients, diet maybest be managedwith treatment.9-38 the help of a dietician. The generalized enamel hypoplasia characteristic of Summary junctional EB often is best managedin the child with stainless steel crownsso as to protect all of the teeth. This While this diverse group of potentially debilitating in- therapy maybe necessary at a very early age in individu- herited diseases remains a tremendouschallenge for health als prone to rapid attrition and caries formation.17 Adults care professionals, enormousstrides have been madedur- with junctional EB also frequently benefit from conven- ing the past decade toward partially unraveling some of tional fixed prostheses that allow them to maintain their the manyquestions and issues related to EB. Although dentition and have optimal esthetics. Tissue-borne remov- specific therapies are not yet available for the cure or able prostheses usually canbe tolerated in those junctional prevention of blisters in any of the EB types, the oral EBpatients whohave lost their dentition. ravages associated with these diseases certainly can be Patients with severe generalized recessive dystrophic controlled. If treatment is instituted early enough, even EBwho develop extensive dental caries frequently require individuals with the most severe forms of EBcan retain a stainless steel crowns on all of the primary teeth. Simi- functional dentition by using appropriate combinations larly, because of marked mucosal abnormalities, of available anesthetic, restorative, and preventive mea- microstomia,and vestibular obliteration, severely affected sures. Maintaining the dentition not only reduces the individuals with marked dental involvement often will be potential for soft tissue trauma to the mucosa--andpossi- best served by placement of stainless steel crowns on the bly the esophagus through more efficient mastication-- permanentdentition. 9 Patients with generalized recessive but also mayallow better nutrition. There is no question dystrophic EB rarely are considered candidates for re- that dentists have the ability to help these patients keep a movableprostheses, although occasionally even severely positive self image by providing them with optimal oral affected22 patients will tolerate tissue-borne appliances. health. While most individuals with EB can tolerate orthodon- Dr. Wrightis associateprofessor, Department of PediatricDentistry; tic therapy with only minor modifications designed to Dr. Fine is professor,Department of Dermatology;and Dr. Johnsonis reduce soft tissue irritation, individuals with severe gen- clinical assistant professor, Departmentof Dermatology;schools of eralized recessive dystrophic EBare unlikely candidates Dentistryand Medicine,The University of NorthCarolina at Chapel for such treatment. Unfortunately, these patients are prone Hill. to develop a severely crowded dentition, apparently re- 1. TidmanMJ, Eady RAJ: Evaluation of anchoringfibrils andother sulting from small alveolar arches (secondary to general- componentsof the dermal-epidermaljunction in dystrophicepi- ized growthretardation), and collapsed dental arches (sec- dermolysisby a quantitativeultrastructural technique. J Invest ondary to soft tissue constriction) although no specific Dermato184:374-77,1985. studies have critically addressed this hypothesis. The inci- 2. TidmanMJ, EadyRAJ: Hemidesmosome heterogeneity in junctional epidermolysisbullosa revealed by morphometricanalysis. sors often are inclined lingually and if the malocclusion J Invest Dermato186:51-56,1986. remains untreated, severe crowding is likely to result. A 3. Fine JD: The skin basementmembrane zone. AdvDermatol program of serial extraction in those patients unable to 2:283-303,1987. receive other orthodontic therapy can greatly improve 4. BauerEA, Tabas M: A perspective on the role of collagenasein dental alignment if instituted during the appropriate stage recessive dystrophic epidermolysisbullosa. Arch Dermatol 124:734-36,1988. of dental development. 5. EadyRAJ: The basement membrane: interface betweenthe epi- Preventing dental caries is most challenging in indi- theliumand the dermis: structural features. ArchDermatol viduals with severe mucosal involvement since they often 124:709-12,1988. are faced with an extremely cariogenic diet and are least 6. CoulombePA, Hutton ME, Letai A, HebertA, Paller AS,Fuchs E: Point mutationsin humankeratin 14 genes of epidermolysis

PediatricDentistry: July/August 1993 - Volume15, Number4 247 bullosa simpler patients: genetic and functional analyses. Cell MA, Sneddon IB: Epidermolysis bullosa dystrophica with epi- 66:1301-11, 1991. dermal neoplasms. Arch Dermato1110:894-902, 1974. 7. Ryynanen, M, Knowlton RG, Parente MG, Chung LC, Chu M-L, 22. Wright JT, Fine JD, Johnson LB: Oral soft tissues in hereditary Uitto J: Humantype VII collagen: genetic linkage of the gene epidermolysis bullosa. Oral Surg Oral Med Oral Patho171:440- (COL7A1) on chromosome 3 to dominant dystrophic epider- 46, 1991. molysis bullosa. AmJ HumGenet 49:797~803, 1991. 23. Touraine MA:Classification des epidermolyses bulleuses. Ann 8. Fine JD, Bauer EA, Briggaman RA, Carter DM, Eady RAJ, Esterly DermatolSyphiligr (Ser~es 2) 2:309-12, 1942. NB. Holbrook KA, Hurwitz S, Johnson L, Andrew L, Pearson R, 24. Sedano HO, Gorlin RJ: Epidermolysis bullosa. Oral Surg Oral Sybert VP: Revised clinical and laboratory criteria for subtypes of Med Oral Path 67:55~63, 1989. inherited epidermolysis bullosa: a consensus report by the Sub- 25. Gedde-DahlT Jr: Epidermolysis Bullosa: A Clinical, Genetic, and committee on Diagnosis and Classification of the National Epi- Epidemiologic Study. Baltimore: John Hopkins Press, 1971. dermolysis Bullosa Registry. J AmAcad Dermatol 24:119-35, 26. Wright J, Capps J, Fine JD, Johnson L: Dental caries variation in 1991. the different epidermolysis bullosa diseases. J Dent Res 68:416 9. Wright JT: Comprehensive dental care and general anesthetic (Abst 1878), 1989. management of hereditary epidermolysis bullosa: a review of 27. NowakAJ: Oropharyngeal lesions and their management in epi- fourteen cases. Oral Surg Oral MedOral Patho170:573-78, 1990. dermolysis bullosa. Arch Dermato1124:742--45, 1988. 10. Lanier PA, Posnick WR, Donly KJ: Epidermolysis bullosaMen- 28. Bauer EA, Cooper TW,Tucker DR, Esterly NB: Phenytoin therapy tal managementand anesthetic considerations: case report. Pedi- of recessive dystrophic epidermolysis bullosa. N Engl J Med atr Dent 12:246-49, 1990. 303:776-81, 1980. 11. CammJH, Gray SE, Mayes TC: Combined medical-dental treat- 29. Cooper TIN, Bauer EA: Therapeutic efficacy of phenytoin in ment of an epidermolysis bullosa patient. Spec Care Dentist 11:148- recessive dystrophic epidermolysis: a comparison of short- and 50, 1991. long-term treatment. Arch Dermato1120:490-95, 1984. 12. Fine JD, Johnson LB, Wright JT: Inherited blistering diseases of 30. Fine JD, Johnson L: Efficacy of systemic phenytoin in the treat- the skin. Pediatrician 18:175~7, 1991. ment of junctional epidermolysis bullosa. Arch Dermatol 13. Fine JD: Altered skin basement membraneantigenicity in epider- 124:1402M)6,1988. molysis bullosa. Curr ProblDermatol 17:111-26, 1987. 31. Gruskay DM:Nutritional managementin the child with epider- 14. Fine JD: Antigenic features and structural correlates of basement molysis bullosa. Arch Dermato1124:760-61, 1988. membranes;relationship to epidermolysis bullosa. Arch Dermatol 32. Fine JD, Tamura T, Johnson L: Blood vitamin and trace metal 124:713-17, 1988. levels in epidermolysis bullosa. Arch Dermato1125:374-79,1989. 15. Pearson RW:Clinicopathologic types of epidermolysis bullosa 33. Greider JL, Flatt AE: Surgical restoration of the hand in epider- and their nondermatological complications. Arch Dermatol molysis bullosa. Arch Dermato1124:76~67, 1988. 124:718-25, 1988. 34. Reddy ARR, Wong DHW:Epidermolysis bullosa: a review of 16. Holbrook KA: Extracutaneous epithelial involvement in inher- anaesthetic problems and case reports. Can Anaesth Soc J 19:536- ited epidermolysis buliosa. Arch Dermato1124:726-31, 1988. 48,1972. 17. Gedde-DahiT Jr: Sixteen types of epidermolysis bullosa: on the 35. HamannRA, Cohen PJ: Anesthetic management of a patient with clinical discrimination, therapy and prenatal diagnosis. Acta epidermolysis bullosa dystrophica. Anesthesiology 34:389-91, Derm Venerol Suppl 95:74-87, 1981. 1971. 18. Wright JT: Epidermolysis bullosa: dental and anesthetic manage- 36. Yonfa AE, Thomas JP, Labbe R, Roebuck BL, Hoar KJ, Gutierrez ment of two cases. Oral Surg Oral MedOral Pathol 57:155-57, JF: Epidermolysis bullosa: a protocol for general anesthesia and 1984. successful dental rehabiiitation. Anesthesiol Rev 9(6):20-25,1982. 19. Gryboski JD, Touloukian R, Campanella RA: Gastrointestinal 37. Marshall BE: A comment on epidermolysis bullosa and its manifestations of epidermolysis bullosa in children. Arch anaesthetic managementfor dental operations: case report. Br J Dermato1124:746-52, 1988. Anaesth 35:724-27, 1963. 20. Hruby MA,Esterly NB: Anemiain epidermolysis bullosa letalis. 38. James I, Wark H: Ainvay management during anesthesia in AmJ Dis Child 125:696-99,1973. patients with epidermolysis bullosa dystrophica. Anesthesiology 21. Reed WB,College J Jr, Francis MJO, Zachariae H, MohsF, Sher 56:323-26, 1982.

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