Ehlers Danlos Syndrome

By: Hannah Roller

Description

Ehlers - Danlos syndrome (EDS) is defined as a group of hereditary disorders that effect connective tissues due to a defect in collagen. The collagen deficiency can effect the strength of muscles, joint mobility, skin elasticity, and support of the organs and vascular structures.1 The severity of the symptoms can vary from musculoskeletal defects to life threatening complications such as major organ and blood vessel rupture.2 Originally there were 10 different classifications, but in 1997 they were reorganized into 6 major types: classical, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparxis.3


Anatomy

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Collagen is the major structural unit of connective tissue. It is described as a strong fibrous protein, and is characterized as having increased elasticity and strength. The different types of collagen give stability to healing tissue, strength to muscles and tendons, and elasticity to skin. At least 27 different types of collagen have been identified. The organizational structure of the collagen will define its specific purpose. If it is laid down in parallel sheets it will contribute to the strength of tendons, if it is distributed randomly it will help to provide flexibility of the skin, and if it is arranged in a tubular pattern it will contribute to the elasticity of the blood vessels.4

When there is a mutation in the collagen the consistency of the fiber is thin and weak, and therefore will fail under an increased compressive load. This causes weakened connective tissue, bones, dermis, and joints, leading to manifestations of joint hypermobility, joint instability, chronic pain, cutaneous fragility, and dermal hyperextensibility. 1

There are 5 main types of collagen that are effected by EDS. Type I constitutes about 90% of the total amount of collagen, and is found in structures such as tendons, ligaments, and bones. Type II is a component of hyaline cartilage, type III is found in vascular structures such as the liver and blood vessels, and is also the first type of collagen to appear in the healing process. Type IV and V are located in the basement membrane and the connective tissue matrix. 6


Incidence/Prevalence

An overall combined frequency of all types of Ehlers - Danlos Syndrome is estimated to be about 1 in 5,000 individuals worldwide. 2 The most common types of this disease are hypermobility and classic with the hypermobility type affecting around 1 in 10,000 to 15,000 people, and the classic form occurring approximately every 1 in 20,000 to 40,000 people. Vascular EDS occurs in roughly 1 in every 250,000 people. The more rare form of the disease include the arthrochalasia and the kyphoscoliosis type. There have only been 30 to 60 cases of these types reported worldwide. The dermatosparaxis form of EDS is the most rare with only a dozen cases reported worldwide. It has been reported that Caucasians are slightly more prone to this disease over other races, and there are no gender related tendencies found with this syndrome.1


Clinical Presentation

Many types of EDS share universal symptoms. A common symptom that occurs in most forms of Ehlers - Danlos is hypermobility of the joints. These loose joints are classified as being unstable, which leaves them susceptible to dislocation, chronic pain, and the early onset of arthritis.2 Dislocations of the clavicle, digits, hip, patella, radius, and the shoulder have been the most often reported area of dislocation. Another general characteristic involves features of the skin. Ehlers - Danlos patients have skin that is often very fragile and is characterized as being soft and elastic, which leaves them prone to bruising and abnormal scarring.1

Classic (Type I and II)

Clinical features include skin hyper extensibility with a tendency to bruise easily, joint hypermobility, redundant skin folds commonly found on the eyelids, and the presence of spongy tumor like structures found on the skin. Skin is characterized as being thin and fragile, which causes abnormal wound healing leaving behind "cigarette paper" scars. This form has also been reported to have heart problems such as mitral valve prolapse and aortic root dilation. 6

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Hypermobility (Type III)

This form is usually seen from infancy. Most commonly, effected infants are born with dislocated hips due to increased joint hypermobility. This increased joint mobility leads to the occurrence of multiple dislocations throughout the lifespan. This form of EDS is also associated with TMJ dysfunction as well as severe chronic pain. Chronic degenerative joint disease such as premature osteoarthritis and heart issues are also common occurrences with this type of EDS.5

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Vascular (Type VI)

This is a more serious form of the disease, and can lead to potentially life threatening complications. Blood vessels can spontaneously rupture causing internal bleeding, stroke, and shock. Vascular EDS patients are also more prone to organ rupture, with an increased risk of occurrence during pregnancy.2 The most common structures prone to rupture include the intestinal, uterine, and arterial walls. Distinctive facial features are also present and include, protruding eyes, thin nose and lips, sunken cheeks and a small chin. Skin is thin and translucent, especially over the chest and abdomen leading to an increased visibility of veins. Respiratory distress from pneumothorax is also a common occurrence.6 The hypermobility of joints that are characteristic of other types are not as common in this form. Prognosis is poor for this type, and patients typically die before their fourth decade of life, with survival beyond age 50 being extremely rare.7 The most common causes of death are from a rupture of the aorta, colon perforation, or cerebral bleeding.8

Kyphoscoliosis (Type VI)

This form of the disease, like the vascular type, is also prone to blood vessel rupture. Along with this complication people experience a severe progressive curvature of the spine that can interfere with respiration. This form of EDS is congenital, and is associated with severe muscle hypotonia, scleral fragility, placing the globe at an increased risk for rupture, and severe joint laxity in addition to the scoliosis.9

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Arthrochalasia (Type VII A/B)

Congenital bilateral dislocations of both hips, severe generalized joint hypermobility with recurrent subluxations, skin hyperextensibility, tissue fragility, osteopenia, and small stature are a major characteristics of this type of EDS.8

Dermatosparaxis (Type VII C

This form is characterized by having severe skin fragility that bruises easily. The skin also has a decreased skin elasticity that give it a sagging appearance, often leading to extra folds of skin. Blue sclera, short fingers, and short statue are also common in this form of EDS.4

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Potential Etiologies

Ehlers-Danlos is said to be a genetic disorder. It is proposed that mutations in the genes ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1, and TNXB cause this syndrome. 1 These genes are responsible for producing the different types of collagen. The different forms of this disorder are inherited in different patterns.

The classic, hypermobility, vascular, and arthrochalsia form are inherited through an autosomal dominant pattern. This type of inheritance means that it only takes one copy of the altered gene to cause the disorder. This can occur by inheriting the gene from a parent, or it can be caused by a sporadic mutation with no previous history found. 2

The kyphoscoliosis, dermatosparaxis and some cases of the classic forms are inherited in an autosomal recessive pattern. In these cases it takes two copies of the gene in order to cause this disorder.

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Diagnostic Tests10

1. Genetic tests: DNA testing is conducted for classical type EDS, Vascular type EDS, kyphoscoliosis type EDS and arthrochalasis type EDS. A prenatal DNA testing can be done in families in which disease causing mutations have been identified.

2. Urine test: A urine test helps in identifying the kyphoscoliosis type by measuring the level of an enzyme produced by the gene associated with kyphoscoliosis type.

3. Skin biopsy: A skin biopsy may reveal abnormal collagen fibers in the skin. The vascular type of EDS can be diagnosed by analyzing the amount of type III collagen produced by the body.

4. Heart ultrasound: A heart ultrasound is conducted to detect mitral valve prolapse that can occur with classical and hypermobility EDS subtypes. This test helps identify abnormalities in the heart muscle and valves


Evaluation/Special Orthopedic Tests

Joint hypermobility is a major factor in determining the diagnosis of EDS. The presence of this symptom can be evaluated clinically by utilizing the Beighton Scale. An individual must score 5 or more of the 9 possible points in order to confirm joint hypermobility. 13 This scale consists of the following criteria:

  • Passive dorsiflexion of each fifth finger greater then 90 degrees
  • Passive apposition of each thumb to the flexor surface of the forearm
  • Hyperextension of each elbow greater then 10 degrees
  • Hyperextension of each knee greater then 10 degrees
  • Ability to place the palms on the floor with knees fully extended
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Another factor to examine when considering the diagnosis of EDS is skin hyperextensibility. This is assessed at a site lacking excess skin, and is performed by gently pulling until resistance is met. An ideal testing location is the volar surface of the forearm, where the normal range is said to be 1-1.5 cm. 9

New research has also indicated that the presence of Gorlin's Sign:

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and Reverse Namaskar sign:

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have been increasingly expressed in patients with EDS.11

The last important component to consider is patient history. Some key things to look for are reports of prior dislocations or subluxations, and reports of frequent bruising without associated trauma.


Conservative Treatment

Physical Therapy

Due to the complex nature of EDS a physical therapy program is specifically tailored to meet the needs of the individual. The increased amount of hypermobility present in a patient with Ehlers-Danlos Syndrome causes them to be more prone to experience joint effusion, pain, degenerative joint changes, gait deviations, and functional impairments. These symptoms will be the main focus of physical therapy.12

Building muscular strength is often an important goal for the EDS patient. The increased amount of hypermobility found at joints often leads to instability and subluxations. By increasing the muscular strength around the joint it will allow it to become more stable. Strength building needs to be done in the mid -range, stable zone of the joint in order to decrease the risk of dislocation. Low resistance muscle toning exercises can improve joint stability and reduce future subluxations, dislocations, and pain. In this patient population it is advised to increase the number of repetitions of an exercise rather than to increase the resistance due to the high prevalence of pain.13

Swimming is an excellent activity to suggest in order to promote muscular strength and to increase overall fitness. It is a non weight bearing activity that places little stress on the joints.

Improving joint proprioception is another key component to the physical therapy program. Excessive joint mobility is thought to damage joint receptors, leading to increased instability.14 Increasing proprioception is done through utilization of wobble boards, trampolines, and manual rhythmic stabilization exercises.

Patient education is the last essential element of the program. The patient needs to be educated about their diagnosis so they fully understand the risks associated with EDS. This will also help them to determine which activities they do that exacerbate their symptoms, and allow them to make the appropriate lifestyle modifications to ensure the health of their joints. Explain to the patient the normal range of motion for the affected joints, and how important it is to avoid any hyperextension.Younger children especially need to be made aware of the importance of not stretching a joint beyond its limits due to the detrimental effects it may have on the body later in life.

Modalities

The use and efficacy of modalities for the management of symptoms in the Ehlers Danlos patient has not been extensively researched. Given what is known about the mechanism behind certain interventions postulations can be made about their clinical usefulness in this patient population. The major concerns from a physical therapy view are pain management and joint hypermobility, but in treating these symptoms the therapist has to be aware of the unique skin characteristics such as hyperextensible skin, dystrophic scarring and the high tendency of bruising of these patients.15

Many of the modalities work by way of the gate theory. This theory works to explain the presence of pain. There are both large and small nerve fibers in the spinal cord, and when there is no stimulation an inhibitory neuron is present to block any signals from reaching the projection neuron. The gate is said to be closed and no pain is felt. When normal (somatosensory) input occurs large nerve fibers are activated. Both the projection neuron and the inhibitory neuron are activated which blocks the signal to the brain and no pain is felt. When a painful stimulation occurs small nerve fibers are active. This activates the projection neuron and blocks the inhibitory neuron. Since the signal from the projection neuron is not blocked the signal is released and travels to the brain via the spinalthalamic tract. The gate is said to be open and pain is experienced. Many modalities try and send in somatosensory input to activate the inhibitory neuron and block the sensation of pain.

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The following interventions may be found to be beneficial in this patient population.

  • Heat - Heat is a useful tool in increasing the pain threshold. It does this by increasing the skin temperature which can reduce the sensation of pain by altering nerve conduction or transmission.16 Caution needs to be taken when administering heat in this population. These patients have extremely thin skin which may leave them more apt to develop burns. Heat is also used to increase collagen extensibility, and these patients already suffer from hypermobile joints. Using heat may further exacerbate this symptom.
  • Cold - Crytotherapy has also been found to alter nerve conduction velocity to help in the management of pain. When the temperature of the nerve is decreased the velocity also decreases. These effects can be felt after only 5 minutes of application of the cold stimulus. Cryotherpay can also work to increase the pain threshold. This mechanisms works by way of the gate theory as explained previously. By applying cryotherapy for 10 to 15 minutes it can control pain for up to one hour.16 As with the application of heat, the fragile sklin should be monitored for adverse reactions to the intervention
  • Neuromuscular Electrical Stimulation (NMES) - Many patients who suffer from joint hypermobility have a decreased joint position sense and often wear orthosis to help stabilize their joints. Electrically stimulated muscle contractions have been found to assist with joint positioning, and can function like an orthosis. It has also been found that due to the presence of skin laxity enhancing sensory input via the skin may have a beneficial effect on pain, joint stability, and proprioception.17
  • Transcutaneous electrical nerve stimulation (TENS)- Application of TENS can reduce the sensation of pain by interfering with the gate theory previously discussed. It has been theorized that TENS may also control pain by stimulating the production and release of endorphins and enkephalins, which act similarly to morphine to change the perception of pain. Due to this mechanism the pain reducing effects last only while the stimulation is being applied. The electrode pads are placed in such a manner to surround the area of pain and should be atleast 1 inch apart from each other. The stimulation is delivered continuously and should be applied whenever pain is experienced. 16
  • Hydrotherapy - This form of therapy has been highly recommended to decrease the amount of stress experienced by the patient. Hydrotherapy is thought to control pain by “providing a high level of sensory stimulation to the peripheral mechanoreceptors to gate the transmission of pain sesnations at the spinal cord.” 16 Hydrotherapy also helps to decrease stress, and compression on weight bearing joints, muscles and connective tissue. Submersion helps the weakened patient to move against gravity in both therapeutic and functional activities. Good technique during swimming is essential for this patient to prevent strain of the cervical and lumbar spine. Deep water running or walking with the use of a buoyancy belt has also be found to be a beneficial cardiovascular exercise. 15 Some types of EDS patients have cardiac complications. Take caution in exercising these patients in water because upon immersion cardiac volume and right atrial pressure increases. These may place too high of a demand on these patients hearts.

Caution needs to be taken when administering any type of modality in this patient population. These patients have extremely fragile skin, and should be closely monitored for any adverse reactions to any of the above interventions.18

Assistive Devices

  • Crutches, canes, and walkers should be used cautiously as they put increased stress on the upper extremities.
  • Braces can be used to improve stability
  • A soft neck collar may help decrease neck pain
  • A wheelchair may help offload stress on lower extremity joints.
  • Silver ring splints to prevent hyperextension of the digits

Medication

  • NSAIDS as tolerated by gastrointestinal symptoms
  • Topical lidocaine for localized areas of pain
  • Skeletal muscle relaxants for relief of myofascial spasm
  • Glucosamine and chondroitin may help treat osteoarthritis - like symptoms.

Preventative Measures

  • Younger children who have fragile skin should wear pads over the forehead, knees, and shins in order to reduce tears.
  • For individuals who are prone to bruising, it has been reported that ascorbic acid, or vitamin C, may reduce prevalence of bruising.3
  • For individuals who are suffering from types of EDS that are known for heart complications, a yearly echocardiogragm is advised to determine the presence of aortic dilation or mitral valve prolapse. 8

Surgery & Post-Op Treatment

Surgical intervention is complicated in the EDS patient. Correction of one joint may lead to an increased instability of another. These patients also typically exhibit poor wound closure, mechanical problems with anesthesia, and are at high risk for hemorrhaging.

The most common type of EDS that will require surgery is the vascular form. This is usually the result of a vascular or gastrointestinal emergency. Wound closure and healing can be quite difficult with vascular EDS. Dermal wounds should be closed without tension, and cutaneous stitches need to be left in place twice as long as usual in order to promote proper healing. 3


Current and Ongoing Research

Information can be found on current and ongoing research being supported by Ehlers-DanlosSyndrome Network C.A.R.E.S Inc at this link - http://www.ehlersdanlosnetwork.org/Research.html


Additional Web Based Resources

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