SpecialCareDentistry Enhanced CPD DO C

Samina Nayani Joanna Dick

Charlotte Curl

Ehlers-Danlos Syndrome: a Review

Abstract: Ehlers-Danlos Syndrome (EDS) affects the metabolism of collagen which can have implications throughout the body, impacting
on not only the skin, but also the joints, muscles, cardiovascular and gastrointestinal systems. The condition can have dental implications
such as poor wound healing, mucosal fragility, prolonged bleeding, temporomandibular joint dislocation and, in some forms, periodontal
disease. Three clinical cases of patients with EDS will be discussed and their dental management described. The patient with EDS may be
seen in primary care and, if input from secondary care is required, a multidisciplinary, shared care approach will ideally be utilized.
CPD/Clinical Relevance: Ehlers-Danlos Syndrome is a condition that can be multifactorial, with medical implications as well as dental;
depending on the manifestations of the condition, the patient may be seen in primary and/or secondary care with or without a shared
care approach.
Dent Update 2019; 46: 634–644

Ehlers Danlos Syndrome (EDS) is a rare
syndrome characterized by 13 types of
connective tissue disorders which manifest
primarily in dermatological and joint conditions.
EDS affects collagen metabolism, leading
to deficiency and/or disordered deposition
of collagen.1 Within the literature there is
an overlap between the EDS subtypes and
other connective tissue diseases, including
hypermobility disorders, for example Joint
Hypermobility Syndrome (JHS), which is often
referred to interchangeably with EDS.2
Samina Nayani, BDS(Hons), MFDS
RCSEd, Specialty Registrar in Special Care
Dentistry, King’s College Hospital (email:
samina.nayani@nhs.net), Joanna Dick,
BDS, MJDF RCSEng, DipDSed, Specialty
Registrar in Special Care Dentistry, The
Royal London Dental Hospital, Turner
Street, Whitechapel, London E1 1BB and
Charlotte Curl, BDS(Hons), FDS RCS(Eng)
DSCD RCS(Eng), PgDipClinEd FHEA,
Consultant in Special Care Dentistry,
Department of Community and Special
Care Dentistry, King’s College Hospital,
Denmark Hill, London SE5 9RS, UK.
634 DentalUpdate
The condition was first described
in 1657 when a young Spanish man was found
to be able to stretch the skin overlying his
right pectoral muscle over the left angle of his
mandible.3 Further descriptors were added
in 1901 by Ehlers, 1908 by Danlos, and then
by Poumeau-Delille and Soulie in 1934 when
the condition was described as Ehlers-Danlos
Syndrome.4
Epidemiology and diagnosis
The prevalence of EDS is reported
to be 1 in 5,000,5 however, recent clinical
studies suggest that joint hypermobility
syndromes are under diagnosed6 and the
condition is more common than these ratios
indicate. EDS is equally distributed throughout
the world and theoretically affects men and
women equally without racial predilection,7,8
however, in practice a greater proportion of
females appear to be affected.9,10
Classification of EDS
Each phenotype of EDS has a
unique collagen defect which may lead to
different symptoms and signs. The most
recent criteria, produced in 2017, recognizes
13 subtypes10−12 (Table 1). Each subtype
has a set of clinical criteria that help guide
diagnosis; a patient’s physical signs and
symptoms are matched up to the major and
minor criteria to identify the subtype that is
the best fit. This classification also recognizes
the type of collagen involved and the genetic
basis.12
Characteristics of EDS
The classic signs of EDS are:
 Hypermobility of the joints; joints are often
loose and unstable resulting in frequent
subluxations and dislocations. Chronic
musculoskeletal pain and early onset arthritis
are common;7
 Hyperelasticity, fragility and softness of the
skin;7
 Deficient wound healing with the
development of scars with a ‘cigarette-paper
like quality’;13
 Tendency to excessive bleeding manifested
by bruises, ecchymoses and haematomas.4
Oral and dental implications of
Ehlers-Danlos Syndrome
Oral and facial manifestations
of EDS are variable depending on the type
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Clincal EDS Subtype
1 Classical EDS
2 Classical-like EDS
3 Cardiac-valvular
4 Vascular EDS
5 Hypermobile EDS
6 Athrochlasia EDS
7 Dermatosparaxis EDS
8 Kyphoscholiotic EDS
9 Brittle Cornea Syndrome
10 Spondylodysplastic EDS
11 Musculocontractural EDS
12 Myopathic EDS
13 Periodontal EDS
Table 1. Clinical classification of Ehlers Danlos Syndrome (EDS) (adapted from Malfait et al)12
of disease present, but in all types defects of
the collagen-processing enzymes or collagen
structure lead to collagen fragility throughout
the body. Table 2 outlines the main extra-oral
7
and intra-oral manifestations of EDS, which may mouthwash to prevent premature breakdown
be present.
Dental considerations
When treating patients with EDS
there are many medical and dental factors to
consider. Medical conditions and their effect
on the provision of dental care are outlined in
Table 3.
Oral surgery
Failure of anaesthesia has been
reported in some patients with EDS, and so
when treating these patients the clinician
should be mindful of the risk of LA failure.14,15
This could lead to increased levels of dental
anxiety. Conscious sedation or general
anaesthesia may need to be considered.
Bleeding can occur with all types
of EDS but is more common with the vascular
and kyphoscoliotic types.7 Excessive gingival
haemorrhage is commonly seen during
toothbrushing and hygiene therapy.7 When
undertaking extractions, care must be taken
when raising mucoperiosteal flaps and sutures the periodontal destruction in pEDS often
must be tied only under slight tension due to
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SpecialCareDentistry
Abbreviation Inheritance Pattern inflammation with minimal plaque,17 and
the absence of attached keratinized gingiva
cEDS Autosomal Dominant leading to greater fragility and increased risk
(AD) of breakdown.18 When managing patients with
cIEDS Autosomal Recessive (AR) pEDS, strict adherence to oral hygiene and
regular non-surgical debridement is advised.
cvEDS AR
vEDS AD Oral medicine
As well as deficiency/
hEDS AD
ineffectiveness of collagen leading to collagen
aEDS AD fragility in the skin, this is also reflected in the
oral mucosa, with even minor trauma leading
dEDS AR
to oral ulceration or haematoma formation.7,16
kEDS AR Patients may have to be advised regarding
oral ulceration and care should be taken to
BCS AR
minimize trauma with dental instruments
spEDS AR during dental treatment.
mcEDS AR
Orthodontic
mEDS AD or AR Orthodontic treatment is not
contra-indicated in patients with EDS but
pEDS AD
it has been reported that the teeth move
more rapidly and that there is greater tooth
mobility during the migratory phase, thus
leading to unpredictable results.7,19 Lighter
mucosal fragility.16 If excessive bleeding occurs forces should be used as it is believed that
following an extraction, haemostatic agents stressed periodontal fibres on the tension
must be placed in the socket and consideration side may tear during treatment and be
should be given to the use of a tranexamic acid slow to repair. 19
This, in addition to the
disorganized arrangement of collagen fibres
of the blood clot. in the periodontium, results in the need for a
Some patients with EDS suffer from prolonged period of retention.
19
recurrent TMJ dislocation. If this is known,
7 Patients undergoing orthodontic
therapy may also be at higher risk of
the clinician must be careful not to open the
patient’s mouth too wide as this may increase ulceration from fixed and removable
the risk of dislocation.16 Allow the patient appliances.7,20
frequent respites during lengthy treatment and
the use of a small mouth prop may be helpful. Case study 1
A 58-year-old Caucasian female
Restorative patient, Patient A, was referred to the
When carrying out endodontic department of special care dentistry by her
treatment, it may be complicated by the rheumatologist due to recurrent failed local
presence of pulp stones or calcification of the anaesthesia (LA), and having experienced
pulp chamber or abnormal root morphology.7 prolonged bleeding times following dental
The new EDS classification system extractions in the past. The patient reported
formally identified peridontal EDS (pEDS) as that she had developed anxiety relating to
subtype 13.12 Although the exact prevalence dental treatment following repeated failed
of pEDS is unknown, the key features include LA and requested if it would be possible to
extensive intra-oral periodontal destruction, be treated under sedation. The patient had
the presence of pretibial plaques on the legs been diagnosed with EDS in 1990 following
and generalized tissue fragility.17 Diagnosis of repeated dislocations of her shoulders and
true pEDS can be difficult as some patients will TMJ. EDS had also manifested as irritable
present with an EDS diagnosis and separate bowel syndrome, recurrent bruising, poor
coincidental periodontal disease. However, wound healing, asthma and osteoarthritis
in her hips and knees; this necessitated the
manifests as recession, extensive gingival use of crutches so her mobility was impaired.
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Characteristics Associated Type of EDS (if applicable)

Hyperelastic skin on the face and neck.7,23 Classical

Hypermobile
Arthrochalasia
‘Cigarette-paper’ scarring of the face and Classical
forehead7,23
Recurrent Temporomandibular Joint (TMJ)
dislocation7,23

Epicanthic folds (folds extending from the Kyphoscoliotic

bridge of the nose to the upper eyelids)7,23 Classical
Extra-oral
Strabismus7,23 Classical
Blue sclera 7,23
Classical
Kyphoscoliotic
Arthrochalasic
Myopia7,23 Classical

Lack of earlobes7,23 Vascular

Gorlin’s Sign (ability to touch the tip of their
nose with their tongue)24
Fragile mucosa16
Increased risk of haemorrhage7 Vascular

Periodontitis (primary and permanent Periodontal

dentition)4
Enamel hypoplasia and hypomineralization
− increased caries risk4,25
Deep fissures and long cusps of premolar
and molar teeth16
Intra-oral
Pulp stones7

Short deformed roots7

Increased incidence of congenitally absent,
microdont or supernumerary teeth7,16
High arched palate7
Absence of the inferior labial and lingual
frena7

Odontogenic keratocysts (rare)1,26

Table 2. Extra-oral and intra-oral characteristics of EDS.

Additionally, she reported recurrent oral
ulceration and a dry mouth. She had also
been recently diagnosed with mild angina.
Patient A reported that there was a family
history of EDS; although she was single and
had no children, all of her seven nieces and
nephews were affected by EDS to varying
degrees.
636 DentalUpdate
On intra-oral examination,
there was an ulcer on her soft palate
approximately 5−6 mm in diameter with
a surrounding ring of erythema and a
further ulcer in her right buccal mucosa
approximately 4 mm in diameter. Patient A
gave a history of oral ulceration occurring
frequently, lasting between 8 and 14 days
and resolving spontaneously. Oral hygiene
was good, but the patient was found to have
occlusal caries on her lower left first and
second molars (LL6, LL7) and a vertical root
fracture on her non-vital upper left second
premolar (UL5).
The initial treatment plan was as
follows:
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 SpecialCareDentistry

Associated Medical Conditions Impact on Dental Care

Impaired Mobility • Access to dental clinic and surgery

Mobility problems are frequent • Wheelchair recliner or hoist may be required
• May need hospital transport
• Positioning in dental chair − may require pillows or need to be
treated upright
Cardiac Considerations • Potential risk of infective endocarditis
Aortic and mitral valve prolapses are common in the Cardiac-Valvular • Follow NICE/SDCEP guidelines28,29
type of EDS27 • Contact cardiologist if concerned
Postural Orthostatic Tachycardia Syndrome (POTS) • Increased risk of palpitations, dizziness and syncope30
POTS is characterized as a significant increase in heart rate of 30 beats • Stress and anxiety can bring on episodes
per minute or greater occurring within 10 minutes of standing or a • Treat in supine position
heart rate when upright of greater than 120 beats per minute, but with • Manage as per current resuscitation council guidelines
no decline in blood pressure30
Asthma • Increase risk of asthma attack
Due to underlying connective tissue defects affecting the lungs27,31 • Take a thorough history and ensure patients bring inhalers to
appointments
Migraines • Stress or anxiety associated with dental treatment may
Increased incidence of TMJ disorder, atlantoaxial and craniocervical precipitate a migraine
instability, fibromyalgia, POTS, sleep disorders and anxiety are all • Patients may cancel at short notice
associated with EDS and can all lead to migraines32-35
Chronic Pain and Fatigue • Patient may tire easily
Causative factors include: • Lying back in the dental chair for long periods may be
• Muscle weakness uncomfortable
• Respiratory insufficiency • Chronic pain may affect manual dexterity and therefore oral
• Unrefreshing sleep hygiene
• Headaches • Conscious sedation – strong analgesics may interact with
• Reactive depression and anxiety sedative drugs
• Increased use of analgesics
• Frequent joint dislocations33,36,37
Psychiatric Disorders • Possible associated dental anxiety
Increased prevalence of depression and anxiety38 • Drug-induced xerostomia as a result of anti-depressant
medication

Mast Cell Disorders • Enquire regarding potential triggers

Increased number and/or activity of mast cells. Signs and symptoms • Dental treatment, drugs, stress, infection can all trigger an
include:39 episode
• Skin urticaria • Refer to current anaphylaxis guidelines
• Flushing
• Hypotension
• Asthma
• Diarrhoea
• Abdominal bloating or cramping
• Rhinitis
• Anaphylaxis
Table 3. Medical co-morbidities and their impact on dental care.

1. Restoration of carious teeth under LA
with inhalation sedation (IHS). This was
the preferred modality of anxiolysis as
the patient was anxious but did not have
July/August 2019
a suitable escort for intra-venous sedation
(IVS).
2. Extraction of UL5 under LA with IHS.
3. Referral to the department of oral medicine
regarding oral ulceration.
Upon the first episode of treatment,
IHS with nitrous oxide and oxygen, titrated
up to 50%, was used for the restoration of
DentalUpdate 639
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a Postural Orthostatic Tachycardia Syndrome
b felt to be inappropriate due to the tissue
Figure 1. (a) Right bitewing radiograph, patient
B. (b) Left bitewing radiograph, patient B.
Figure 2. Patient B in intercuspal position
illustrating anterior open bite.
the LL6 and LL7. Although adequate LA was
achieved using an inferior dental block with
2.2 ml lidocaine hydrochloride with 1:80,000
adrenaline, Patient A was extremely anxious
throughout. Following discussion with the
patient, it was felt that IHS would not provide
sufficient anxiolysis for the extraction of the
UL5, therefore the patient found a suitable
escort to have the treatment carried out under
LA and IVS with midazolam to achieve greater
anxiolysis.21 At the next appointment, the
extraction was carried out under IVS and LA
and local haemostatic measures were applied
without any complications.
Patient A’s oral ulceration was
reviewed by the oral medicine department
but, on investigation, no obvious causative
640 DentalUpdate
Figure 3. Flowchart illustrating recommended
management of patient collapse.22
factors were found. Appropriate medication was hydrochloride 4% with adrenaline 1:100,000.
prescribed to provide symptomatic relief.
Patient A was regularly reviewed at degree of pain, but chose to continue with the
6-monthly intervals following her initial referral extraction, which was then carried out without
and continues to have her dental treatment
carried out under LA with inhalation sedation.
LA has been effective, and the patient is now far GDP for routine recall appointments.
less anxious about receiving dental treatment.
Case study 2
A 26-year-old female patient,
Patient B, was referred to the department of
special care dentistry by her rheumatologist
as LA had been previously unsuccessful
during dental treatment by her general dental
practitioner (GDP). The patient also reported
that she frequently had short periods of loss
of consciousness in the dental surgery without
warning.
Her medical history included
Hypermobile EDS, which was diagnosed in
2007 following multiple shoulder dislocations
and the patient having an awareness of
increased flexibility. Patient B reported that
she has frequent flare-ups of the condition
causing her to become immobile and reliant
on a wheelchair for long periods. She also had
(POTS) and asthma, which was well controlled
with inhalers. Patient B had two children,
aged 3 and 4 years, both of whom had been
diagnosed with EDS.
On examination, Patient B had
carious lesions in several teeth, including
the upper right third molar (UR8), which was
unrestorable (Figures 1a and b). The patient’s
primary concern was an anterior open bite
(Figure 2). She had previously been referred
for orthodontic treatment but treatment was
challenges with EDS19 and her frequent
episodes of loss of consciousness associated
with POTS.
Towards the end of the initial
examination, the patient suddenly lost
consciousness. She was managed as per
current guidelines,22 as outlined in Figure
3. Within 90 seconds she had regained
consciousness and was fully alert. Following
discussion with the patient, all restorations
were carried out without local anaesthetic
(LA). Despite suffering some minor discomfort,
she was able to tolerate treatment. When
extracting the UR8, 6.6 ml of lidocaine
hydrochloride 2% with 1:80,000 adrenaline
was administered followed by 2.2 ml articaine
Unfortunately, the patient could still feel a
further complications. When treatment was
completed, she was discharged back to her
Case study 3
A 47-year-old Caucasian female
patient, Patient C, was referred to the
department of special care dentistry by
the department of oral medicine due to a
history of fainting during dental treatment.
She had a complex medical history which
included paroxysmal atrial fibrillation,
and supraventricular tachycardia (SVT)
secondary to re-entry tachycardia, for which
she underwent radioablation in 2001. This
was initially thought to be the cause of the
episodes of fainting. Her medical history
included Hypermobile EDS, thoracic outlet
syndrome, depression, gastro-oesophageal
reflux disease, irritable bowel syndrome, stress
incontinence, and chronic fatigue syndrome.
On examination, a cuspal fracture
was noted on the lower right first molar (LR6),
July/August 2019

which was subsequently restored under local
anaesthetic. Towards the end of her treatment
she suffered from palpitations and loss of
consciousness lasting several minutes. Vital
signs were monitored and she was managed
conservatively,22 following which she was
transferred to the Emergency Department
for further monitoring. While an inpatient,
she was found to have self-terminating SVT,
diagnosed on Echocardiogram (ECG), as well as
postural hypotension. She was discharged with
appropriate follow-up.
At a later appointment with
her GDP, the patient collapsed again whilst
undergoing a routine scale and polish. Due to
the risk of collapse during dental treatment, a
shared care protocol was agreed. It was agreed
that the patient should attend the dental
hospital for recalls and treatment, as required,
but maintain contact with the GDP for dental
emergencies.
Over the subsequent 4 years,
patient C continued to attend dental recalls
without any significant issues. During this
period, outside of the dental setting, the patient
continued to suffer from episodes of fainting
and was finally diagnosed with POTS. Several
months later she was also diagnosed with
Mast Cell Activation Syndrome and Addison’s
Disease. Following an episode of Addisonian
Crisis during a routine urology procedure, it
was advised that planned dental treatment
should be carried out in a theatre setting
with a 24-hour hydrocortisone infusion post-
operatively.
She attended the department
of special care dentistry 6 months later with
multiple carious lesions. An inpatient general
anaesthetic was arranged alongside the
Endocrinology and Oral and Maxillofacial
Surgery (OMFS) teams, to provide
comprehensive care. The treatment was carried
out uneventfully, and the patient was admitted
under the OMFS team, whilst the Endocrinology
team managed her steroid cover.
When the patient attended
several months later with a cracked tooth, the
Endocrinology and Cardiology teams were
contacted for advice prior to treatment. As she
was on a reducing dose of steroids, no steroid
cover was required. To prevent episodes of
collapse associated with POTS, the patient was
treated in a supine position.
The patient continues to attend for
routine recalls in the department of special care
dentistry, and episodes of collapse associated
with POTS have been managed as before.
July/August 2019
Contact is maintained with her medical teams
to ensure that she is managed appropriately
when undergoing treatment.
Conclusion
As demonstrated by the clinical
cases presented, EDS patients can present
with a range of complications of their disease 10.
which may affect provision of their dental care.
The clinician should be aware of the intra-oral
manifestations of the disease as well as the
concurrent medical conditions, all of which may
complicate provision of care. As EDS impacts 11.
multiple aspects of care, a multidisciplinary
approach is required, including good
communication with medical teams. Referral to
tertiary level care may be required for complex 12.
procedures, with the GDP playing an integral
role in the shared dental care of the patient.
Compliance with Ethical Standards
Conflict of Interest: The authors declare that
they have no conflict of interest.
Informed Consent: Informed consent was
obtained from all individual participants
included in the article.
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Genet − Seminars in Medical Genetics 2017;
175C: 226−236.

COLLEGE OF
MEDICAL AND
DENTAL SCIENCES

Restorative Dentistry
MSc/PGDip/PGCert
Distance-learning, two years, part-time
This innovative, two-year, blended learning
programme uses the University of
Birmingham School of Dentistry’s state-
of-the-art, award-winning, e-learning
technology to deliver a flexible, interactive,
advanced training programme suitable
for both UK and international dentists at all
stages of their clinical careers.
The course has a very high level of
practical content and is designed to deliver
progressive study through Certificate,
Diploma and MSc levels, providing you with
detailed understanding and clinical skills
for high-quality predictable and enjoyable
advanced restorative dentistry across a wide
range of subject areas.
Learn more
For detailed course information and online
application, please visit our dedicated web
pages, or contact our programme team
with your questions.
T: +44 (0)121 466 5477
E: L.Mackenzie@bham.ac.uk

www.birmingham.ac.uk/restorativedentistry

644 DentalUpdate July/August 2019