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Hereditary
epidermolysis bullosa: Report of two cases
Asma Al-Jobeir, BDS, MSc
Department of Preventive Dental Sciences
College of Dentistry, King Saud University, P.O. Box 60169, Riyadh 11545, Saudi Arabia
Epidermolysis bullosa (EB) describes a group of
genetically determined disorders, characterized by blistering of the skin and
mucosa. It is of dental interest because of its specific oral manifestations
and management problems. Oral manifestations and management outline of two different types of EB are
described.
Hereditary
epidermolysis bullosa (EB) is a group of rare genetically transmitted disorders
that have several methods of inheritance with various degrees of severity and
expression.1, 2 It is a multiracial disorder that is
characterized by the formation of vesicles and bullae on the skin and mucous
membranes. The vesicles may arise spontaneously or from minor trauma. In some
varieties of EB, high room temperature may precipitate blisters.3
The pathogenesis of these disorders is unknown. Bullae formation has to
do with various basic defects including structural and biomechanical
abnormalities of keratin, hemidesmosomes, anchoring fibrils, anchoring
filaments, and altered skin
collagenase.4
Hereditary EB is classified into three major categories which have been
further subdivided on the basis of their clinical phenotypes and modes of
inheritance.1,4 The three types of hereditary EB are simplex,
dystrophic and junctional. In simplex EB, the disease appears at birth or
shortly after and is characterized by the development of bullae, mainly limited
to the hand and feet. Extracutaneous organs and nails are rarely involved. The
lesions heal without residual scarring or pigmentation.2
In the dystrophic form of EB, the disease also appears at birth. The skin
lesions appear on the ankles, knees, elbows, hands, and feet. The nails are
severely dystrophic or absent. Oral lesions are also observed and the mucosal
lesions tend to heal with scar formation in the mouth, oropharynx and
conjunctiva. These patients present with microstomia and ankyglossia.2
In junctional EB, lesions tend to appear at birth, bullae and erosions usually
form on the side of trauma on hands and feet resulting in atrophic scars.
Dystrophy of nail and oral lesions is common.2
Nowadays, there is an increased knowledge about clinical
characteristics of different hereditary EB subtypes including oral and dental
involvements. Clinicians managing patients with EB must be familiar with
different subtypes of this disease so that they may accurately predict the
prognosis and develop an optimal treatment approach. Recessive dystrophic EB
presents the most severe oral involvement which complicates optimal dental
treatment delivery, while patients with simplex EB can be treated as normal
patients. Dental literature has described successful dental management under
general anesthesia for patients having even the most severe forms of EB.5-7
The purpose of this study was to present the oral and dental
manifestations of two different cases of EB, namely recessive dystrophic EB and
EB simplex, and to discuss the dental management as well as the different
problems confronting the dentist in the
management of the conditions.
Case
1
A 10-year-old Saudi girl presented for dental care at
the Pediatric Dentistry Clinic of the College of Dentistry, King Saud
University in Riyadh, Saudia Arabia. Medical history revealed that the patient
is a known case of recessive dystrophic EB. The patient was anemic and
suffering from multiple eye infections as well as upper respiratory tract
infection. The patient had been managed only by palliative treatment of the
skin with Flumazine cream. She had only one dental visit for incomplete root
canal treatment of the upper central incisors, which was done in a private
clinic. Family history revealed that there was no previous history of family
skin disorders or consanguinity. The patient has two siblings (8-year-old
sister and 6-year-old brother) who are severely affected by dystrophic EB.
Extra-oral examination showed multiple bullae and vesicles all over the body
with severe hands and legs involvement (Fig. 1a). The vesicles were large, red
and infected. In addition, there were multiple scarrings and pigmentation (Fig.
1b). There was complete absence of finger nails (Fig. 1c), but the face was not
severely involved although there were multiple skin milia (Fig. 1d). The
patient was underweight. Intra-oral examination showed diminished oral opening,
multiple vesicles and bullae, obliteration of the sulcus, ankyloglossia and
tongue atrophy (Fig. 1e). Oral hygiene was very poor with thick plaque
deposition. The teeth were hypoplastic with severe rampant caries affecting the
permanent upper and lower incisors and the remaining primary teeth (Fig. 1f).
The patient had class III malocclusion, the upper incisors and upper molars
were in crossbite (Fig 1f). OPG examination
revealed that all permanent teeth were present except the third molars, with
pulp involvement of the upper centrals, lower centrals and lateral incisors.
Treatment was planned to extract all the remaining
roots of the upper and lower primary molars, to use fissure sealant and
preventive resin restorations as indicated for all newly erupted teeth, to
apply topical fluoride, to carry out composite restorations of small caries and
to do root canal treatment for all pulpally involved permanent teeth. Oral
hygiene instructions were given to the patient to use small-headed soft
toothbrush and to use chlorhexidine mouth rinse twice a day. On the second
visit, the father said that the patient could not use chlorhexidine mouthwash
since it "burns the tongue and mucosa". Fissure sealant, preventive resin
restorations and composite restorations were performed with difficulty since
the patient could not open her mouth wide. Isolation and suction were achieved
with caution. Formation of vesicles occurred after using saliva ejector (Fig.
1e). In the third visit, one extraction was done under intraligamentry injection
of local anesthesia with some difficulties because the patient was
uncooperative and could not be restrained. Then the patient failed to come for
two visits. There was consultation with the anesthesiologist to continue
treatment under general anesthesia. The anesthesiologist advised not to use
general anesthesia approach because the case was severe and there was a
possibility of developing airway obstruction due to blister formation and also
due to recurrent upper respiratory tract infections. Patient was given
appointment to complete extraction and to be referred to the endodontist for
treating pulpally involved teeth but the patient failed to attend subsequent
appointments.
Case 2
A 6-year-old Saudi girl presented for dental care at the Pediatric
Dentistry Clinic, College of Dentistry, King Saud University in Riyadh. Medical
history revealed that the patient is a known case of simplex EB. She had only
been managed by palliative treatment for the skin lesions with fucidin ointment
and potassium permanganate. Family history revealed that there was no previous
history of family skin disorders or consanguinity. The patient had two previous
emergency dental visits. Extraction of two teeth was done at these visits with
some management difficulty. Then the patient was referred to the Pediatric
Dentistry Clinic.
Extra oral examination showed multiple bullae and vesicles scattered on
the face (Fig. 2a). They are maximal in the upper and lower limbs which ended
up with erosions but no scarring (Fig. 2b). Some lesions had post healing
hypopigmentation. There were no milia and no nail dystrophy (Fig. 2c). The
patient was underweight. Intraoral examination showed no bullae on the oral
mucosa at the time of the first examination (Fig. 2d). The mother gave history
that oral bullae decreased as the child got older. Permanent upper central
incisors were mildy hypoplastic with multiple carious lesions of other teeth
(Fig. 2e). OPG examination showed that all permanent teeth were present except
the third molars. There was an apical radiolucency around the lower primary
canines and molars.
Treatment was planned to extract non-restorable primary teeth, to do
composite restorations for small carious lesions and fissure sealant for all
first permanent molars, to construct upper Nance and lower lingual arch space
maintainers to be inserted and to apply fluoride therapy. Oral hygiene
instructions were given to the patient.
Treatment was carried out as planned after behavior modification. Extraction was done under
infiltration injection. Suction was used with caution to avoid formation of
bullae. Treatment was completed without bullae formation. Patient was put on
recall program every 3 months (Figs. 2 f, g, h).
Signs and symptoms of the first case were
pathognomonic of dystrophic EB, a recessive type since the eye involvement and
the presence of cutaneous milia or small epidermoid cysts can be distinguished
from the dominant type.2 Nails are usually involved often being
dystrophic or absent. Bullae are usually manifested at or shortly after birth
arising at the site of pressure or trauma or appearing spontaneously. In older
children, hands, feet, knees and elbows are most often involved. The fluid contained
in the bullae is sterile at first but it may become secondarily infected and
then contain blood. Upon healing, the bullae are often followed by keloidal
scars causing contraction and pigmentation. The scars may lead to the loss of
the bony structure or to interference with growth.2,8 Severe anemia
is commonly seen in recessive dystrophic EB and is presumed to be secondary to
malabsorption and chronic iron loss through mucosal erosions and ulcerations.2,910,11 Eroded skin surfaces are best covered with
nonadherent dressings after applying a topical antibiotic such as bacitracin,
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.13,14
Individuals with recessive dystrophic EB exhibit most severe oral
involvement, which is characterized by complete obliteration of the sulcus,
ankyloglossia and the absence of lingual papilla as a result of continuous
blistering and scarring.15 Microstomia is often severe with this
type of EB which result from either intraoral or peri-oral blistering with
subsequent scar formation.8 Oral milia do not usually occur in this
form of EB despite their widespread prevalence on the skin and despite the
presence of severe oral involvement.15 Regarding enamel hypoplasia
and rampant caries, it was shown that dental enamel from patients with
recessive dystrophic EB is essentially normal in terms of its chemistry.16
Caries prevalence among patients with dystrophic EB is significantly
higher than among healthy people.17,18 The high caries experience is
probably related to some factors such as the presence of the soft tissue
involvement, which leads to alterations in the diet (soft and frequently high
carbohydrate). This increases oral clearance time due to limited tongue
mobility and vestibular constriction, and creates an abnormal tooth/soft tissue
relationship as the buccal and lingual mucosa is firmly positioned against the
tooth. Furthermore, these individuals often lack the ability to routinely
practice normal preventive measures such as oral hygiene or the use of oral
rinses.8 Class III malocclusion may result from atrophy of maxilla with
resultant relative mandibular prognathism, secondary to generalized growth
retardation. Patients with severe recessive dystrophic EB are prone to develop
crowded dentition. The incisors often are inclined lingually. This may result
from small alveolar arches secondary to generalized growth retardation and
collapsed dental arches which are secondary
to soft tissue constriction.8
Dental management of patients with recessive dystrophic EB includes
some difficulties. The presence of microstomia prevents adequate examination
and delivery of dental treatment.5 Formation of bullae after simple
dental procedures and the use of suction also added to these difficulties.
Preventive measures which included fissure sealants, preventive resin
restorations, dietary advice and oral hygiene instructions were delivered to
this patient with very hard approach. Extraction of one remaining root was done
under intraligamentry injection of local anesthesia to avoid infiltration,
which might cause tissue separation and bullae formation.8 Patient
was uncooperative during this procedure although the extraction was very simple
but the patient could not be restrained to avoid formation of skin bullae.
Consultation with anesthesiologist was done to treat the patient under general
anesthesia. Successful dental management under general anesthesia had been
reported in the dental literature,5-7 but due to the presence of
recurrent upper respiratory tract infection and the possibility of developing
airway obstruction during or after the operation, which may require emergency
tracheostomy,19,20 the anesthesiologist advised against the use of
tracheal intubation. Intubation was reported as extremely difficult in a case
of severe microstomia which limited oral accessibility and visibility and
resulted in the swelling of the epiglottis.16 It appears that due to
the complications of treatment required by patients with HEB, there is a
tendency for such patients to lose interest in regular dental appointments.
Sucralfate which is a complex salt of sucralfate and aluminum hydroxide
has proven to be an effective prophylactic and therapeutic modality in the
treatment of pain and blisters in the oral cavity on patients with dystrophic
EB. It is also attributed to a decreased cariogenic potential and the inhibition of the growth of
cariogenic streptococci.21
The goal of dental therapy is preservation of the dentition.
Unfortunately, this may not be possible because many of these patients are not
brought to the dentist or do not seek dental care until acute dental problem
arises as in these cases. This is mainly because too much concentration has
been placed on the patient's medical status.22
Preventing dental caries is most challenging in patients with recessive
dystrophic EB since they often are faced with an extremely cariogenic diet and
are least able to perform routine preventive procedures. Preventive measures
can be best accomplished by using soft bristled, small-headed toothbrush with
fluoride containing tooth paste, systemic fluoridation when appropriate, daily
fluoride rinse, chlorhexidine mouth rinse and diet counseling.23
Initiating a preventive program when the patient is young will allow the oral
health to be successfully managed before the development of problems become so
severe that treatment is difficult to accomplish. All patients with recessive
dystrophic EB should be referred for dental evaluation by the age of one year,
and such patients should be maintained on a frequent recall schedule so that
preventive measures and treatment strategies can be monitored and modified to
the patient's needs. Diet constitutes a major difficulty in caries control. Due
to the complex systemic nutritional demand of these patients, diet may best be
managed with the help of a dietitian.5
The second patient is a case of EB simplex. Skin blisters and vesicles
were present all over the body and concentrated in the extremities which
ruptured and healed without scar leaving hypopigmented areas. Extraoral and
intraoral milia were not seen in this patient and neither was nail dystrophy which are
characteristic of EB simplex.2,3,5 No oral bullae were seen at the
time of examination. Oral blistering tends to be few and small in size and
tends to heal rapidly without scarring.12 In addition, oral
involvement in EB simplex appears to occur most commonly during the early
childhood period.12,24 As the child matures, less oral involvement
usually occurs and this disease becomes self-limiting.3,25 This
patient did not develop ankyloglossia or vestibular obliteration because oral
lesions when they existed, healed without scarring. The teeth were mildly
hypoplastic although earlier, there were reports of severe enamel hypoplasia in
cases of EB simplex.25 Generalized severe enamel hypoplasia is
limited to junctional EB types.14,23 Rampant caries involved primary
teeth, while newly erupted permanent teeth were free of caries.
Treatment was carried out as planned. This included the use of local
anesthesia, extraction, composite restorations, fissure sealants and
cementation of space maintainers. Patients with EB simplex have no intraoral abnormalities
related to their disorder and therefore are treated in the manner of a normal
patient.5,26 Individuals with this form of EB require few
alterations in their dental care and maybe treated much like any other patient.
The practitioner should, however, carefully question any individual with EB as
to the fragility of the mucosa because dental therapy can precipitate oral
blistering even in some mildly affected patients.25
Treating hereditary EB still consists of palliative topical care. There are no
known cures. Phenytoin was suggested for treatment but its efficacy has not
been proven.
-
Wright JT, Gantt DG. Epidermolysis
bullosa. J Oral Pathol 1983; 3:73-83.
-
Fine JD, McGrath J, Eady RAJ. Inherited
epidermolysis bullosa comes into the new millenium: A revised classification
system based on
current knowledge of pathogenetic mechanisms and the clinical, laboratory, and
epidemiologic findings of large, well-defined patients cohorts. J Am Acad
Dermatol 2000;43: 135-137.
-
Hochberg MS, Ivan A, Vasquez-Santiago, Sher M.
Epidermolysis bullosa: Case report. Oral Surg Oral Med Oral Pathol 1993;
75:54-75.
-
Coulombe P, Hutton ME, Letai A, Hebert A, Paller AS,
Fuchs E. Point mutations in human 14 genes of epidermolysis bullosa simplex
patients. Genetic and functional analysis. Cell 1991; 66:1301-1311.
-
Wright JT. Comprehensive dental care and general anesthetic
management of hereditary epidermolysis bullosa: A review of fourteen cases.
Oral Surg Oral Med Oral Pathol 1990; 70:573-578.
-
Wright JT. Epidermolysis bullosa: Dental and
anesthetic management of two cases. Oral Surg Oral Med Oral Pathol 1984;57:
155-157.
-
Block MS, Gross BD. Epidermolysis bullosa dystrophica
recessive: Oral surgery and anesthetic considerations. J Oral Maxillofac Surg
1982; 40:753-758.
-
Wrigth JT, Fine JD, Johnson L. Hereditary
epidermolysis bullasa: Oral manifestations and dental management. Pediatr Dent
1993;15:242-248.
-
Hruby MA, Esterly NB. Anemia in epidermolysis bullosa
letalis. Am J Dis Child 1973;125:696-699.
-
Cooper TIN, Bauer EA. Therapeutic efficacy of
phenytoin in recessive dystrophic epidermolysis: A comparison of short- and
long-term treatment. Arch Dermatol 1984;120:490-495.
-
Fine JD, Johnson L. Efficacy of systemic phenytoin in
the treatment of junctional epidermolysis bullosa. Arch Dermatol
1988;124:1402-1406.
-
Fine JD, Johnson LB, Wright JT. Inherited blistering
diseases of the skin. Pediatrician 1991;18:175-187.
-
Gruskay DM. Nutritional management in the child with
epidermolysis bullosa. Arch Dermatol 1988;124:760-761.
-
Fine JD, Tamura T, Johnson L. Blood vitamin and trace
metal levels in epidermolysis bullosa. Arch Dermatol 1989;125:374-379.
-
Wright JT, Fine JD, Johnson LB. Oral soft tissues in
hereditary epidermolysis bullosa. Oral Surg Oral Med Oral Pathol
1991;71:440-446.
-
Kirkham J, Robinson C, Strafford SM, Shore RC, Bonass
WA, Brookes SJ, et al. The chemical composition of tooth enamel in recessive
dystrophic epidermolysis bullosa: Significance with respect to dental caries. J
Dent Res 1996;75:1672-1678.
-
Wright J, Capps J, Fine JD, Johnson L. Dental caries
variation in the different epidermolysis bullosa diseases. J Dent Res
1989;68:416.
-
Harris JC, Lucas VS. Dental disease and caries related
microflora in children with dystrophic epidermolysis bullosa. Pediatr Dent
2001; 23:438-443.
-
Milne B, Rosales JK. Anaesthesia for correction of
oesophageal structure in a patient with recessive epidermolysis bullosa
dystrophica: Case report. Can Anaesth Soc J 1980;27:169-17l.
-
James MB, Wark MB. Airway management during anesthesia
in patients with epidermolysis bullosa dystrophica. Anesthesiology
1982;56:323-326.
-
Marini I, Vecchiet F. Sucralfate: A help during oral
management in patients with epidermolysis bullosa. J Periodontol 2001;
72:691-695.
-
Martinez CR. Esthetic anterior restoration in a child
with epidermolysis bullosa: Case report. J Dent Handicapped 1978;3: 29-30.
-
Nowak AJ. Oropharyngeal lesions and their management
in epidermolysis bullosa. Arch Dermatol 1988;124:742-745.
-
Gazi Ml. Epidermolysis bullosa simplex. Quintessence
Int 1987;18:655-658.
-
Sipahier M. Epidermolysis bullosa: A case report.
Quintessence Int 1994; 25: 839-843.
-
Crawford EG, Burkes EJ, Briggaman RA. Hereditary
epidermolysis bullosa: Oral manifestations and dental therapy. Oral Surg Oral
Med Oral Pathol 1976;42:490-500.

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