Ehlers-Danlos Syndrome & Pain

New Advance in Treating EDS Pain:

Pain is the most common symptom of EDS. It can occur due to multiple causes.

  1. Hypermobile joints may lead to sprains and fractures causing pain.
  2. Hypermobile joints may cause tendinitis and muscular pain.
  3. Sciatic pains from ruptured discs pressing on nerve roots.
  4. Headache is also a common feature; it may be due to temporomandibular joint dysfunction, tension-type headache or due to cervical spine problems.
  5. Neuropathic chronic pain, sometimes resembling fibromyalgia, can also occur.
  6. GI abnormalities like a hiatal hernia, PUD, diverticulitis may cause abdominal pain.

A new method of treating pain, the high-dose pain laser, may be a profound advance in EDS pain treatments.  In our clinic, in a series of EDS patients with pains in their joints, muscles, tendons, lower back, and sciatica, 6 of 7 patients responded very well or extremely well to treatment.  In one patient, two separate instances of impending gastrocnemius calf muscle rupture from its tendon was cured with the pain laser. All of these patients had Classic, Classical-like, or Hypermobile EDS and are 20-50 years old.

As the pain reduction from high-dose laser is genetic, there may be an overlap between being genetically a high responder to laser, and the genetics of EDS.  Schedule an appointment for your EDS pains.

Classification of Ehlers-Danlos Syndrome:

Ehlers-Danlos syndrome or EDS, is a part of the Hypermobility Spectrum Disorder.  EDS is a group of disorders that are genetically transmitted and clinically diverse. It is a heritable disorder which affects the synthesis or structure of fibrillar collagen in the connective tissue. EDS is characterized by joint hypermobility along with hyperextensible and fragile skin which occurs due to abnormal collagen fibers that have reduced tensile strength.

On the basis of clinical features and the molecular level findings, six classes of EDS have been recognized:

  1. Classic (I/II)
  2. Hypermobile (III)
  3. Vascular (IV)
  4. Kyphoscoliosis (VI)
  5. Arthrochalasia (VII a, b)
  6. Dermatosparaxis (VII c)

Note that there is a newer classification system, which is still being hammered out:

Classical-like EDS (clEDS)

Cardiac-valvular EDS (cvEDS)

Vascular EDS (vEDS)

Hypermobile EDS

Arthrochalasia EDS (aEDS)

Dermatosparaxis EDS (dEDS)

Kyphoscoliotic EDS (kEDS)

Brittle cornea syndrome (BCS)

Spondylodysplastic EDS (spEDS)

Musculocontractural EDS (mcEDS)

Myopathic EDS (mEDS)

Periodontal EDS (pEDS)

Genetic basis Ehlers-Danlos Syndrome:

Classic type:

In 30-50 % of cases, genes affected are the ones that encode type IV collagen (COL5A1 and COL5A2). The remaining cases are due to genetic defects in genes not encoding collagen fibers (other extracellular matrix molecules that influence collagen formation indirectly may be involved)

Kyphoscoliosis type:

The best described is the Kyphoscoliosis type, it is caused by mutations in the gene encoding hydroxyl lysyl enzyme, resulting in its deficiency which leads to the formation of collagen that lacks normal structural stability.

Vascular type:

This variant of EDS is caused due to mutations in the COL3A1 gene resulting in abnormalities of type III collagen.

Arthrochalasia and Dermatosparaxis types

The abnormality lies in the conversion of type I procollagen to collagen.
In Arthrochalasia type, the defect lies in the genes COL1A1 and COL1A2 and in Dermatosparaxis type, the defect lies in the genes encoding for the enzyme procollagen-N-peptidase.
These defects interfere with the formation of normal collagen helices leading to weakening of its structure.

The inheritance pattern of various classes of EDS

Classic(I/II)Autosomal dominant
Hypermobile (III)Autosomal dominant
Vascular (IV)Autosomal dominant
Kyphoscoliosis (VI)Autosomal Recessive
Arthrochalasia (VII a,b)Autosomal dominant
Dermatosparaxis (VII c)Autosomal recessive

Clinical features of Ehlers-Danlos Syndrome:

EDS is characterized by

  1. Joint hypermobility.
  2. Hyperextensible skin.
  3. Fragile skin (leading to atrophic scars and reduced wound healing).

Effects of EDS on different organ systems:

Musculoskeletal system:

Hypermobile joints (permitting grotesque contortions like bending the thumb backward to touch the forearm, bending the knee forward to create almost a right angle etc.)
It leads to complications such as joint sprains, dislocations, deformities, early onset osteoarthritis, osteopenia (loss of bone density), fractures, kyphosis and scoliosis (abnormal curvatures of the spine).
Symptoms include joint pain, deformity, reduced function, and power.

Skin:

The skin is extraordinarily stretchable; it becomes fragile and vulnerable to trauma. The wounds don't heal easily and the scars are atrophic.
There are also hyperpigmented areas over shins and extensor surfaces due to hemosiderin deposition.

Neurological:

Neurological pain is also a feature sometimes encountered which manifests as chronic generalized pain.

Gastrointestinal system:

A hiatal hernia (protrusion of organs in the thoracic cavity via the diaphragm from the abdominal cavity) is a common occurrence in EDS.
Other manifestations include gastroesophageal reflux disease, diverticulitis, peptic ulcer disease, irritable bowel syndrome-like symptoms and rupture of viscera.
Some patients of EDS also report constipation or abdominal pain, diarrhea, dysphagia, gastroesophageal reflux, dyspepsia, a feeling of uncomfortable fullness after meals, nausea and vomiting.

Cardiovascular system:

In EDS, Aortic root dilatation leading to aortic regurgitation, mitral valve prolapse leading to mitral regurgitation, aneurysms and arterial ruptures may occur. These are serious conditions which may culminate into compensated or decompensated heart failure, hypotension and hypovolemic shock depending on the severity of the condition.

Eyes:

Thin transparent corneas and floppy eyelids may be a feature.

Diagnostic criteria for Ehlers-Danlos Syndrome:

The diagnostic criteria used to diagnose clinically has 3 major and 9 minor features.

Major featuresMinor features
•Skin hyperextensibility.
•Joint Hypermobility.
•Widened atrophic scars
•Easy bruising.
•Soft, doughy skin.
•Skin fragility (or traumatic splitting).
•Molluscoid pseudotumours (fleshy lesions associated with scars found over pressure points eg. elbows).
•Subcutaneous spheroids (may be calcified and detectable radiologically).
•Hernia (or history thereof).
•Epicanthal folds (mostly in children).
•Complications of joint hypermobility (e.g., sprains, dislocation/subluxation, pain).
•Family history of a first-degree relative who meets clinical criteria.

For establishing diagnosis of EDS, the patient must have at least
1) 1 major and 2 minor features
Or
2) Three minor features

Classes of EDS and their commonly found clinical findings:

Classic (I/II)Skin and joint hypermobility, atrophic scars, easy bruising.
Hypermobile (III)Joint hypermobility, pain, dislocations.
Vascular (IV)Thin skin, arterial or uterine rupture, bruising, small joint hyperextensibility.
Kyphoscoliosis (VI)Hypotonia, joint laxity, congenital scoliosis, ocular fragility.
Arthrochalasia (VII a,b)Severe joint hypermobility, skin changes, scoliosis, bruising.
Dermatosparaxis (VII c)Severe skin fragility, cutis laxa, bruising.

Confirmatory tests for EDS:

  1. Since Ehlers-Danlos syndrome is a genetic disease, molecular analysis of the relevant genes identifies a causal relationship in more than 90% of the cases. Molecular screening by means of targeted resequencing of a gene panel that at least includes COL5A1, COL5A2, and COL1A1 gene is indicated.
  2. Electron microscopy findings of collagen flowers from skin scrapings and biopsy may support the diagnosis.

However, it is important to note that the absence of these confirmatory findings does not exclude the clinical diagnosis of EDS.

Prenatal testing (via chorionic villus sampling or amniocentesis) and pre-implantation genetic diagnosis are possible once the mutation is known, however as it is a condition which does not affect the intellect of the baby with a near normal quality of living, these tests are not usually requested by the parents.

Treatment of Ehlers-Danlos Syndrome:

Ehlers-Danlos Syndrome is a condition which cannot be cured completely but it can be managed. Pain management, physiotherapy and symptomatic management of other organ systems is the mainstay of management along with psychiatric evaluation and support.

Pain management in EDS:

Management of pain requires a multifaceted approach. Following measures can be taken.

  1. High-intensity pain lasers are a new advance and may be able to treat a higher percentage of EDS patients than other therapies.  Schedule an appointment for your EDS pains.
  2. Physiotherapy is particularly useful in the management of painful joints.
  3. Medication: Drugs which can be helpful include:
    1. NSAIDs (eg. naproxen, ibuprofen).
    2. Opioids (reserved for severe pain).
    3. Lidocaine (locally acting short lasting drug for local use, especially useful in painful intercourse)
    4. Hormonal control drugs for dysmenorrhea (painful menstrual bleeding) and menorrhagia (heavy menstrual bleeding) e.g. GnRH analogues, COCPs etc.
  4. TENS (transcutaneous neurostimulator), a device that blocks pain signals.
  5. Special cushions and mattresses to make sitting and lying down comfortable.
  6. Compressive tight stockings and splints to reduce joint hypermobility.
  7. Cognitive behavioral therapy.

Management of skin:

  1. Avoid undue trauma.
  2. Use protective coverings and pads.
  3. Wounds must be expertly closed by sutures without tension.
  4. Avoid excessive sun exposure to delay skin ageing.

Management of the musculoskeletal system:

  1. Physiotherapy, light exercise and swimming are beneficial.
  2. Avoid combat sports.
  3. Avoid showing off the hypermobility of joints.
  4. Compression stockings and splints may be useful to prevent hypermobility of joints.
  5. Pain management has already been described above.

Management of cardiovascular system:

CVS is assessed mainly by echocardiography and conditions like aortic regurgitation and mitral valve prolapse are then managed symptomatically.

Gastrointestinal system management:

Endoscopy and colonoscopy are indicated and then related conditions are managed accordingly.

Psychiatric evaluation and therapy:

EDS is a chronic condition which may alienate the children in their childhood as their parents have to be careful about them and they cannot play that freely with other children. It is a common cause of anxiety, depression and other mental health related issues in children as well as adults. These conditions may also manifest as other symptoms unrelated to the spectrum of EDS. So all the patients of EDS may also undergo a psychiatric evaluation and proper therapy, if indicated.

Pregnancy and EDS:

Increased frequency of prenatal visits is indicated. Preterm premature rupture of membranes leading to preterm delivery is a possibility.

Breech presentation is more common if the baby is affected by EDS.

After delivery, an extension of episiotomy and damage to pelvic floor muscles due to tissue weakness leading to urinary and fecal incontinence and pelvic organ prolapse is a possibility.  

References:

  1. https://patientworthy.com/2016/04/26/types-of-ehlers-danlos-syndrome/
  2. https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.c.31548
  3. https://www.practicalpainmanagement.com/pain/other/ehlers-danlos-syndrome-emerging-challenge-pain-management
  4. https://www.ehlers-danlos.com/2017-eds-classification-non-experts/pain-management-ehlers-danlos-syndromes/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538080/
  6. https://www.theacpa.org/conditions-treatments/conditions-a-z/ehlers-danlos-syndrome-eds/
  7. Robbins and Cotrans, Pathologic Basis of disease (9th edition)
  8. Davidson, Principles and practice of medicine (22nd edition)
  9. https://rarediseases.info.nih.gov/diseases/6322/ehlers-danlos-syndromes
  10. https://www.caringmedical.com/conditions/prolotherapy-eds-hypermobility/
  11. https://www.ehlers-danlos.com/dysawareoct2018/  
  12. https://www.ehlers-danlos.com/what-is-hsd/