Hereditary epidermolysis bullosa: Oral manifestations and dental therapy

Hereditary epidermolysis bullosa: Oral manifestations and dental therapy E. G. Crawford, Jr., D.D.S.,* E. Jeferson Burkes, Jr., D.D.S., M.S., and Robert A. Brigganmn, M.D., Chapel Hill, N. C. DEPARTMENT MENT TISTRY

OF ORAL

OF DERMATOLOGY, AND

SURGERY,

SECTION

UNIVERSITY

OF ORAL

OF NORTH

PATHOLOGY, CAROLINA

AND

SCHOOLS

DEPARTOF DEN-

MEDICINE

The oral and dental manifestations of epidermolysis bullosa hereditaria were evaluated in seventeen patients with this disorder. Clinical findings were correlated with the electron microscope-documented diagnosis of each variant of epidermolysis bullosa hereditaria Significant differences in the dental and oral presentations of each variant indicate the importance of considering these findings in differential diagnosis of the variants and in treatment planning for dental disease in these patients. A rationale for surgical and restorative intervention based on experience with these seventeen patients is presented.

T

he designation hereditary epidermolysis bullosa is given to that rare group of mechanobullous disorders manifesting genetic transmission. Hereditary epidermolysis bullosa affects the integument, the teeth, and the mucous membranes of the oral cavity and genitourinary system, and is occasionally reported to involve the gastrointestinal system.1-3 Classified as to modes of inheritance, the autosomal dominant disorders include epidermolysis bullosa simplex (EBS) , recurrent bullous eruption of hands and feet ( Weber-Cockayne) , and epidermolysis bullosa dystrophica dominant (EBDD) . Autosomal recessive inherited disorders include junctional bullous epidermatosis (JBE) , also known as epidermolysis bullosa hereditaria letalis and epidermolysis bullosa dystrophica recessive (EBDR) .3 Since the initial reports by von Hebra in 1871 numerous labels and groupings have been applied to each disorder, some of which have created confusion in *Formerly

490

Chief

Resident,

Oral Surgery;

now in private

practice

in Greenville,

N. C.

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interpretation of the literature. Lowe5 followed the European trend, considered the letalis form to be a severe variant of the dystrophic recessive form, and simply ignored the Weber-Cockayne form. Other authors have offered variations of this trend. From a viewpoint of simplicity, this classification is convenient, but the work of Pearson,3 Arwill, Bergenholtz, and O1sson,GBriggaman and Wheeler,’ suggests that at least five separate and clearly definable entities do exist and may be realized through utilization of the electron microscope. FORMS

OF

EPIDERMOLYSIS

Epidermolysis

bullosa

BULLOSA

simplex

EBS is manifested at birth or shortly thereafter by bullous eruptions at sites of friction although, as life progresses, the lesions are usually localized to the hands and feet. Nails are affected in only a small percentage of cases. Milia and esophageal involvement are not seen. Oral mucosal and dental involvement occur rarely. The prognosis is good for a normal life span as the lesions heal without scarring. Histologically, the defect appears to be the result of acute degeneration of the basal cells of the epidermis3 Weber-Cockayne

Recurrent bullous eruption of hands and feet has a variable onset, usually being seen in the first 2 years, but is occasionally delayed until later in life. Bullous lesions are confined to the hands and feet and are related to frictional trauma. Nail involvement is rare and no milia are formed. Esophagus, oral mucous membranes, and teeth are not affected. The prognosis for survival is good and the lesions heal without scarring, Intraepithelial clefts are seen in the spinous cell layer. Epidermolysis

bullosa

dystrophica

dominant

This disorder is usually noted soon after birth as bullous lesions which scar the extensor surfaces of the extremities and the hands and feet. Milia occur frequently. Nails usually become thick and dystrophic or are lost. Esophageal complications are rare, as is involvement of oral mucous membranes. Teeth are not involved.3 The work of Anton-Lamprecht and Schnyder* indicates that the separation occurs under the basal lamina in this disorder. Junctional

bullous

epidermatosis

Originally described as epidermolysis bullosa hereditaria letalis, this disorder affects all areas of the integument with nonscarring bullous lesions which are apparent at birth or soon thereafter. Although healing is slow, it usually occurs without signifiant scarring or milia formation. Nail beds are involved and frequent loss of nails is experienced. Although esophageal lesions occur, stricture is not a common problem. Heretofore, one of the criteria for diagnosis of the disorder has been death within the first 3 months of life.Q It is with this criterion that perhaps the greatest

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Oral Surg. October, 1976

confusion has resulted regarding the bullous disorders. It is possible that some cases of EBDR have been misdiagnosed as letalis because of early death and some cases of JBE have been misdiagnosed as EBDR as a result of survival past 3 months.“, lo The electron microscopy of Pearson11 demonstrating a dermal-epiderma1 cleft in the intramembranous space between the plasma membrane and basal lamina has been supported recently by Arwill, Bcrgenholtz, and Thi1ander.l’ Without this aid, it is extremely difficult to ascertain an accurate diagnosis of this disorder during the early months of life. The publications of Arwill and associate@ and Gardner and Hudsonl” describe nicely the histologic appearance of tooth buds in epidermolysis letalis (dBD) . Arwill and associates” summarize the clinical changes in teeth as follows : (1) the teeth may be rudimentary; (2) they may be congenitally absent or fewer in number ; (3) they may be irregular and overspaced; (4) the crowns may contain enamel defects and be uneven; (5) the teeth are soft, and may be worn down to the roots; (6) caries activity is high. Arwill and associates” and Brain and Wigglcsworth14 described the enamel histologically as thin, lamellar, and uneven with free globular structures adjacent and attached to the surface of the enamel. Areas of poor mineralization were apparent throughout and enamel thickness may be as little as 50 microns. Oral mucosal changes commonly include bullous lesions without scarring. Epidermolysis

bullosa

dystrophica

recessive

Epidermolysis bullosa dystrophica recessive is manifested by bullous lesions at birth that heal slowly and scar. The course of the disease from that time onward is progressively debilitating. Involvement increases to include virtually all epidermal and mucosal structures with resultant esophageal structures2 and mitten-like hand and foot dcformities.l” Marked 1’ dysphagia and fecal impactions are common clinical problems necessitatin g bland liquid and pureed diets.’ Neoplastic changes of the integument have been rep0rted.l” vestibular sulci are obliterated Intraoral changes arc severe and debilitating; by scarring,l’ ankyloglossia is common, and the tongue becomes atrophic and shiny except where affected by active blistering. Teeth are cariously involved, often to the point of being destroyed to the gingiva. Some authors have reported congenital enamel defects similar to those seen in ,JBE with this variant but have not documented their cases with electron microscope diagnosis of the cutaneous defect,.“, I0 The electron microscopy of Pearson’l and Briggaman and Wheeler’ indicates there is a regular split just beneath the basal lamina and that anchoring fibrils are absent or greatly decreased, thereby providing a significant diagnostic criterion for this disorder. CASE

REPORTS

Over the past 2 years, we have evaluated the oral manifestations of seventeen patients with epidermolysis bullosa. Of these cases, electron microscopy proved four to be junctional bullous epidermatosis or epidermolysis bullosa hereditaria letalis, eight to be epidermolysis bullosa dystrophica recessive, one to be epidermolysis bullosa dystrophica dominant, and two to be epidermolysis hullosa simplex. Although two patients refused biopsy, their clinical picture was consistent with that of epidermolysis bullosn dystrophica dominant. Ages ranged from 6 months to 41 years at first examination.

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Hereditary

42

Number 4

Fig. 1. Glohular

Fig. b. Radiograph hullous epidermatosis.

Junctional

bullous

and pockmarked

enamel in patient

illustrating

rough enamel surfaces

epidermolysis

with junctional

hullous

bullosa

493

epidermatosis.

and missing teeth seen in junctional

epidermatoris

Of those patients with junctional hullous epidermatosis examined, the most striking similarity in addition to the electron microscopic finding was the loose cobblestoned appearawe of the teeth. In the older patients, shearing of this globular enamel on the occlusal surfaces had caused dentinal exposure and in several teeth occlusal caries had resulted. Oral mucous membranes exhibited bullac following minimal trauma but esophageal strictures were not present. Regular diets were employed and the teeth were subjected to normal mastiCatory stresses. Degrees of cutaneous involvement varied widely among patients but bore no correlation to enamel defects which affected all teeth in all cases. Globular and pockmarked enamel was evident both clinically in erupted teeth (Fig. 1) and radiographically in unerupted teeth (Fig. 2). Succedaneous teeth were occasionally noted to be missing (Fig. 2).

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Oral Surg. October, 1976

Fig. 3. Deciduous tooth from patient with junctional hullous epidermatosis. Note the globular enamel formations (E) and the irregular dentinoenamrl junction (DEJ). (Hematoxylin and eosin stain. Magnification, x100.)

Fig. 4. Mitten

hands resulting

from

scarring

in epidermolysis

bullosa dystrophica

recessive.

The tooth removed from one person was decalcified and stained with hemntoxylin and eosin. It displayed highly abnormal enamel formation. Prismatic enamel was replaced almost entirely by thin, irregular, laminar depositions interrupted by ovoid globular inclusions. The dentinoennmel junction was irregular with little evidencr of normal scalloping. The dentin appeared regular in size and tubular configuration (Fig. 3). Of these four patients, two died of the disease (ages 9 months and 21 months, respectively) and the other two are 6 and 11 years of age.

Hereditary

Volume 42 Number 4

Piy. 5. Scarring

alopecia in epidermolysis

Fig. 6. Smooth, homogenous epidermolysis bullosa dystrophica

Epidermolysis

bullosa

dystrophica

enamel surfaces recessive.

epidermolysis

bullosa dystrophica

of teeth with

rampant

bullosa

495

recessive.

caries in patient

n-ith

recessive

Patients afflicted with epidermolysis bullosa dystrophica recessive bore several distinctive clinical similarities to each other in addition to electron microscopic findings of a dermal cleft under the basal lamina. They all exhibited multiple areas of bullae formation and crusting superimposed on virtually total body scarring. Numerous milin were evident. Mitten or claw hands with fingernail loss were seen on all patients, although the degree of involvement of the feet and hands was variable (Fig. 4). Most could still ambulate, but the scarring of the feet and flexion contractures of the legs made walking impossible in one patient and extremely uncomfortable in another.

496

Crawford,

Oral Surg. October, 1976

Burkes, and Briggama?l

Fig. 7. Radiograph demonstrating molysis bullosa dystrophica recessive.

typical

rampant

caries in Zl-year-old

patient

with epider-

The degree of esophageal stricture and dysphagia was variable in these patients, but all required purred or liquid diets. Common problems included fecal impaction, secondary infcction, and scarring alopecia in areas involved with primary disease (Fig. 5). Intraoral findings were similar in all patients. Kepratrtl cicatrix formation had caused ankyloglossia, atrophy of the dorsal tongue surface, elimination of buccal vestibules, and perioral stricture. Heavy plaque and calculus were evident on all v-isible surfaces of all teeth. Although rampant dental caries was evident in these patients, there was no clinical (Fig. 6) or radiographic (Fig. 7) evidence of any type of congenital hypoplasia or maturation defect of enamel. Caries was interproximal or occlusal in nature, and enamel Iv-as not destroyed by the usual shearing defects seen in hypoplasias. The remaining enamel surfaces were smooth, translucent, and homogenous (Fig. 6). The teeth removed were examined 11y ground sections. The eoamrl appeared regular in thickness; however, in numerous areas near the dentinoenamel junction there were accentuations of enamel tuft formation. Extending from these area.s to the surfaec were bands of enamel prisms cut in varying planes and resembling cnnmel tufts present in smooth surface areas. In addition there were irregular foldings and indentations in the dentin at the dentinoenamel junction all along this interface. Between these areas there was regular scalloping (Fig. 8). Epidarmolysis

bullosa

dyrtrophica

dominant

Tho series included one documented and two clinically probalAe pnt,ients with epidermolysis bullosa dystrophies dominant. Although hands, feet, and extensor surfaces of the extremities were affected and nails were usually lost, there \vere no facial, oral mucous mem Inane, or enamel changes other than those of usual dental neglect and deterioration. One patient had worn dentures for several years and had done so without difficulty, even though the denture fit was less than ideal. Epidermolysis

bullosa

simplex

Two patients with epidermolysis bullosa simplex had teeth which were clinically normal limits and demonstrated an absence of any intraoral mucosal changes.

within

COMMENTS

Accurate differential diagnosis among the variables of EBH has been a problem since the recognition of the disorder as an entity in 187L4 The electron mi-

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Fig. 8. Ground section of tooth from patient with epidermolysis bullosa dystrophica recessive showing an irregular dentinoenamel junction (DEJ) and enamel rod twisting in facial enamel (El. (Magnification, x100.)

croscope findings of Pearsonll and Briggaman and Wheeler7 have alleviated some of the problem, but electron microscopy is an expensive, specialized endeavor requiring a biopsy specimen, so diagnostic errors are still being made. Of our four JBE patients, one was thought to have EBDR and one thought to have EBS prior to electron microscopy determination, These early diagnoses were probably based on length of survival and degree of cutaneous involvement. We would propose, then, that oral manifestations be strongly weighed in the clinical assessment of these disorders. Based on our series of four cases of junctional bullous epidermatosis, pathognomonic change% include thin, cobblestone enamel with frequent shearing to expose the dentin and nonscarring intraoral bullae formation following moderate to severe trauma. Eight cases of EBDR indicate that clinically normally developed teeth with early rampant caries, intraoral bullae formation with scarring, loss of vestibular depth, and ankyloglossia are intraoral changes indicative of this disorder. It is likely that the rampant caries resulted from the poor oral hygiene status of these patients. The pureed diets .were often adherent and offered no masticatory cleansing while the scarred inverted buccal gutters packed material onto the buccal surfaces of the teeth. The ankylosed tongues offered no cleaning of the lingual surfaces and none of the patients could manipulate a toothbrush. Three cases of EBDD and two cases of EBS exhibiting no congenital disturbances of enamel formation, no mucosal bullae, and no unusually rapid deterioration of teeth or periodontium indicate that a lack of intraoral signs serves to rule out possibilities of the former two variants. TREATMENT

At present there are few therapeutic modalities to offer the patient afflicted with hereditary epidermolysis bullosa. Vitamin E or vitamin E-steroid therapy has received the greatest attention as a therapeutic aid but the literaure is divided

Oral Surg. October. 1976

on the efficacy of this treatment, with indications that vitamin E offers little or no benefits. Steroids alone have offered some therapeutic value but the risks of therapy must be considered.lx’ I9 Most care has been palliative and is aimed mainly at prevention and treatment of infections of bullae . Although several clinicians have published case reports of anesthetic management of the patients, 20-22few guidelines for dental management have been presented. Views presented here are based on our experiences with dental therapy provided for our patients discussed previously. Rationale for treatment is based on (1) diagnosis of the specific variant of hereditary epidermolysis bullosa, (2) degrees of dental destruction and mucocutaneous scarring, (3) prognosis of the patient, and (4) emotional maturity and attitudes of individual patients. Diagnosis of the variant is important in assessment of future needs. F’or patients with EBDR the prognosis for maintenance of oral hygiene is very poor in view of the progressive scarring of mucosa and hands. Concurrently, masticatory requirements decrease as progressive esophageal stenosis necessitates pureed or blended diets and teeth lose their importance as functional organs. Perioral stricture prevents even adequate intraoral visualization in most of these patients and thereby obviates restorative efforts. Extraction is the treatment of choice for those patients who will accept it. Although some will allow only removal of those teeth that cause pulpal or periapical pain, others are pleased to be relieved of the bullae-forming, knifelike edges of broken teeth. For the young patients, this may represent only three or four teeth, but for the teenagers, the entire dentition is usually destroyed. As a result of limited opening ability, forceps extractions are often impossible, Although pediatric forceps can occasionally be utilized, surgical instruments as well as perioral skin and lips should be well lubricated with a hacteriostatic cream to reduce mucosal adherence and tearing. Even utilizing this precaution in conjunction with careful surgical manipulation, one can anticipate several areas of desquamation. Healing is remarkably rapid and these patients seem to exhibit a high postoperative pain threshold. Complaints of postoperative discomfort and requests for analgesics were virtually nonexistent. Dentures should not be considered for these patients for obvious reasons, but edentulism creates no apparent problem in consumption of the blended diet. Although the number of bullae seems to be diminished on the buccal mucosa and lateral borders of the tongue following full-mouth extraction, they still appear on the dorsal surface, probably as a result of deglutition efforts. One to 2 months postsurgically, there is a complete loss of the vestibule in edentulous areas. The bony alveolar ridge is lost from view and the palate and the floor of the mouth become contiguous with the buccal vestibule. This situation stabilizes and patients evaluated 1 to 2 years postoperatively have changed little from their status 1 to 2 months postoperatively. For patients with JBE, dental management is quite different. Since there is minimal scarring of mucosa and minimal stricture of the orifice, restorative therapy can be effected. Although the thin, friable enamel obviates any attempt at ideal silver alloy restorations, this material can be utilized as a caries control

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measure quite readily. Restorations have provided service 2 to 3 years before requiring replacement with crowns. When sufficient clinical crowns are exposed through normal eruption, steel crowns provide a satisfactory replacement for sheared-off enamel. Although placement of crowns and alloy restorations is somewhat traumatic to the gingiva and buccal mucosa, healing is rapid and without sequelae. The crowns are well tolerated by the gingival tissues when fabricated properly. Maintenance of dental structures is of vital importance in patients afflicted with JBE. They rarely experience the esophageal strictures seen in EBDR and therefore enjoy relatively normal diets requiring masticatory effort. It is doubtful if dentures could be tolerated by the easily traumatized mucosa if the teeth are not maintained and have to be extracted. EBDD and EBS patients have no dental or intraoral abnormality related to their disorder and therefore are treated in the manner of a normal patient. Anesthetic management of these patients was accomplished with either local block and nitrous oxide or local block and intramuscular sedation. For the nitrous technique, gauze sponges were placed around the nose as cushions and a nasal inhaler was situated on these to provide an available nitrous oxide-oxygen mixture. Although these techniques were adequate for most of the patients, a Ketamine method of general anesthesia might have been more desirable in two of the patients, who were somewhat emotionally volatile and immature. The use of force to control behavior is obviously contraindicated. SUMMARY EBH is fortunately a rare disorder but one which requires special therapeutic consideration. Accurate diagnosis is necessary prior to institution of any form of therapy and oral manifestations are invaluable in providing this diagnosis. Although electron microscopy is necessary for absolute diagnosis, utilization of all available clinical considerations can provide a quick and relatively reliable diagnosis when sophisticated equipment is not available or time is a limiting factor. REFERENCES

Gorlin, R. J.: Epidermolysis Bullosa, ORAL SURG. 32: 760-766, 1971. 2. Nix, T. E., and Christianson, H. B.: Epidermolysis Bullosa of the Esophagus, South. Med. J. 58: 612-620, 1965. 3. Pearson, R. W.: In Fitzpatrick, T. B. (editor) : General Medicine, New York, 1971, McGraw-Hill Book Company, Inc., pp. 621-643. 4. Von Hebra, F.: Pemphigus Aerythicker Bericht deo KK Allgemeinen Krankenhouses y Wein vom Jahre 1870, Wein, 1871, p. 363. 5. Lowe, B.: Hereditary Epidermolysis Bullosa, Arch. Dermatol. 95: 587595, 1967. 6. Arwill, T., Bergenholtz, A, and Olsson, 0.: Epidermolysis Bullosa Hereditaria; A Histologic Study of Changes in Teeth in the Polydysplastic Dystrophic and Lethal Forms, ORAL SURG. 19: 724-744, 1965. 7. Briggaman, R. A., and Wheeler, C. E:, Jr.: Epidermolysis Bullosa Dystrophica Recessive : A Possible Role of Anchoring Fibrils m the Pathogenesis, J. Invest. Dermatol. 65: 203-211, 1975. F-3.Anton-Lamprecht and Schnyder, U. : Epidermolysis Bullosa Dystrophica Dominans-ein Detekt der Anchoring Fibrils? Dermatologica 147: 289-298, 1973. 9. Bergenholtz, A., and Olsson, 0.: Epidermolysis Bullosa Hereditaria. 1. A Survey of the Literature and Report of 11 Cases, Acta Pathol. Microbial. Stand. 74: 311-314, 1968. 1.

Oral Surg. October, 1976 10. Howden, 11. 12.

13. 14. 75.

16. 17. 18. 19. 20. 21. 22.

E. F., and Oldenburg, T. R.: Epidermolysis Bullosa Dystrophica: Report of Two Cases, J. Am. Dent. Assoc. 85: 1113-1118, 1972. Pearson, R. W.: Studies on the Pathogenesis of Epidermolysis Bullosa, J. Invest. Dermatol. 39: 551575, 1962. Arwill, T., Brrgenholtz, A., and Thilander, H.: Epidermolysis Bullosa Hereditaria. The Ultrastructure of Oral Mucosa and Skin in Four Cases of the Letalis Form, Acta Pathol. Microbial. Stand. 74: 311-314, 1968. Gardner, D. G., and Hudson, C. I).: The Disturbances in Odontogenesis in Epidermolysis Bullosa Hereditaria Letalis, OR-IL SURG. 40: 483-493, 1975. Brain, E. B., and Wigglesworth, J. S.: Developing Teeth in Epidermolysis Bullosx Hereditaria Letalis; A Histologic Study, Br. Dent. J. 1‘24: 255-260, 1968. Brinn, L. B., and Khilnani, M. T.: Epidermolysis Bullosa With Characteristic Hand Deformities. RadioloKv 89: 272-274. 1967. Wechsler, H. G., I%gh, F. J., Dbmonkos, A. N., Schern, S. R., and Davidson, C. L.: Polydysplastic Epidermolysis Bullosa and Development of Epidermal Neoplasms, Arch. Dermato1.-102: 374.380, 1970. Winstock, D.: Oral Aspects of Epidermolysis Bullosa, Br. J. Dermatol. 74: 432438, 1962. Smith. E. B.. and Michaner. W. M.: Vitamin E Treatment, of Dermolvtic Bullous DermatoY sis, Arch. D&matol. 108: 254-256, 1973. Unger, TV. P., and Nethercott, J. R.: Epidermolysis Bullosa Dystrophica Treated With Vitamin E and Oral Corticosteroids. Can. Med. Assoc. J. 108: 1136-1138, 1973. Endruschat, A, J., and Keenen, D. ‘A.: Anesthetic and Dental Management of a Child with Epidermolysis Bullosa Dystrophica, ORAL SURG. 36: 667-671, 1973. Hamann, R. A., and Cohen, P. J.: Anesthetic Management of a Patient with Epidermolysis Bullosa Dystrophica, Anesthesiology 34: 389-391, 1972. Kelly, A. J. : Epidermolysis Bullosx Dystrophica-Anesthetic Management, Anesthesiology 35: 659, 1971.

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requests

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Dr. E. G. Crawford, Jr. 10 Medical Pavilion Greenville, N. C. 27834