Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options – Pain Physician – 2020
Background: Ehlers-Danlos syndrome (EDS) is a multifaceted disease that can present with a variety of types of pain.
Unfortunately, both the mechanisms and treatments for pain are poorly understood. The proposed treatments for the various musculoskeletal pain syndromes in EDS have had variable success, and it becomes much more imperative to better define and evaluate the current treatment modalities in treating this debilitating disease.
Objectives: The purpose of this study was to investigate the currently available treatment modalities for patients with EDS and their efficacies in pain and symptom relief. Setting: Institutional physical medicine and rehabilitation primary care clinic.
Methods: All patients were seen between January 2015 and April 2019, in which 98 patients with EDS were identified through retrospective chart review. Institutional review board approval was obtained, and all patients provided written consent to be included in the study.
We reviewed various treatment modalities, including
- complimentary/alternative treatments,
- opioids/opioid-like medications,
- nonsteroidal antiinflammatory drugs,
- physical therapy,
- occupational therapy,
- muscle relaxants,
- neuropathic modulators,
- surgery/procedures, and
Treatment methods were extracted from individual patient charts, and efficacy was grouped into 3 categories: improvement, no effect, or worsened symptoms.
The most common treatments used were complimentary/alternative treatments (n = 88).
Occupational therapy and bracing were the most effective options with 70% of patients reporting improvement.
Neuropathic modulators were the least well tolerated with 47% of patients reporting adverse effects.
There is a relative paucity of published literature regarding the various treatment methods for EDS. Although our study is able to identify positive and negative trends with certain modalities, it is vital to understand that EDS is not a uniform diagnosis among patients, and that a combination of several different treatments usually is needed for optimal symptom control.
Above is from the abstract – parts of full-text article below:
E hlers-Danlos syndrome (EDS) is a multifaceted disease that can present with a variety of types of pain. Unfortunately, both the mechanisms and treatments for pain are poorly understood.
Patients with EDS in general report
- higher pain scores,
- decreased quality of life due to sleep distur bance and increased fatigue, and
- lower satisfaction in the social setting.
There are 3 distinct phases of EDS.
- The first “hy permobility phase” presents in the first decade with joint instability and recurrent dislocations. During this period, patients can also exhibit coordination/ fine motor instability, fatigue, incontinence, devel opmental dyspraxia, and hypotonia.
- The second “pain” phase presents in the second to third decade with reduced mobility. This phase is sometimes confused with fibromyalgia and can also present with pelvic pain, headaches, paresthesias, gastrointestinal (GI) disorders, and orthostatic imbalance.
- The final “stiffness” stage, which is seen in the fourth to fifth decade, results from deconditioning and can cause muscle loss, proprioception deficits, and joint damage.
The most common, the hypermobile type (HT), has a higher incidence of pain, which it induces through soft tissue injury. This can lead to joint microtrauma and pain sensitization.
Chronic pain is widespread in the EDS population with an incidence of 90%. In fact, 75% of patients present with symptoms by age 15 years.
There is some debate regarding the contributors to pain, but most experts agree that there are both nociceptive and neuropathic components.
The nociceptive, joint-related pain is often the first presenting symptom in EDS. Joints most commonly affected by EDS, HT in particular, include the neck, shoulders, elbows, hips, knees, and ankles, which may reflect a musculoskeletal distribution of pain.
The proposed treatments for the various musculoskeletal pain syndromes in EDS have had variable success.
At the same time, diagnosis is particularly challenging as imaging and other tests, such as electromyelograms, are frequently negative when trying to identify structural causes of pain.
Because EDS is at its origin a connective tissue defect, the extracellular membrane can also be damaged and can contribute to pain.
In the past, EDS-HT has been treated ineffectively by providing symptomatic treatment to each joint individually.
At the same time, compression neuropathy can occur owing to de ficiencies in collagen in the perineurium and endoneurium.
As a result of the lack of consensus in treatment plans and subsequent delay in treatment, affected patients often live with poorly controlled pain and disrupted quality of life.
Other factors include
- loss of proprioception that can cause joint instability,
- muscle weakness, and
- increased tendon laxity
Other proposed theories explaining EDS pain include
- connective tissue spasm,
- nerve entrapment,
- joint instability secondary to arthritis,
- central sensitization,
- generalized hyperalgesia, and
- chronic regional pain syndrome
Central sensitization in the dorsal horn neurons, for one, can occur when persistent nociceptive input damages extracellular membranes.
With EDS, there can be defects in the membrane of the extracellular matrix, making it that much more prone to damage.
This can lead to diffuse pain, suggesting that the perceived pain is not necessarily related in proximity to nearby joints.
Patients with EDS can also have lower pain thresholds even in pain-free locations, indicating that there may be a degree of central sensitization and that pain is compounded by multiple mechanisms.
This pain causes severe debility even comparable to that of osteoarthritis, rheumatoid arthritis, and low back pain.
Table 2. Efficacy of treatments organized as improvement, no effect, or worsened symptoms.
Opioids and Opioid-Like Medications
Opioid and opioid-like pain medications are some of the most popular analgesic options currently for all types of pain.
This historic and ongoing medical need for opioids negates any claims that they aren’t effective or are less effective than OTC pain relievers. If that were true, opioid medication would never use used or prescribed at all.
In our study, this class of medications showed moderate efficacy with 40% of patients reporting improvement with use. Of these, hydroco done/acetaminophen demonstrated the most statistically significant benefit, relieving pain in 60% of pain patients.
Although notorious for its side effects, opioids can be especially risky in EDS by causing constipation through decreased GI motility, orthostasis throughm peripheral vasodilation and reduced peripheral resistance, dysautonomia, proprioceptive deficits, hyperalgesia, and psychiatric side effects.
How about all the “psychiatric side effects” of dealing with constant pain day in and day out?
Thus, they are not indicated for chronic musculoskeletal pain and should be reserved for acute exacerbations or pain refractory to other treatments.
Before telling a patient “you’ll just have to live with your constant pain”, a doctor should consider that chronically uncontrolled pain leads to psychiatric depression and anxiety and also to brain damage and other physical harms as explained in these previous posts: Bodily Damage from Uncontrolled Chronic Pain.
Muscle relaxants demonstrated moderate efficacy with 42% of patients reporting improvement.
Interestingly, these medications were some of the most well tolerated after acetaminophen, with only 4% of pa tients reporting adverse effects. Of these, Botulinum toxin injections were most effective, benefiting 67% of patients.
As a whole, muscle relaxants can also be helpful for spasm-related pain
There is limited literature on the different treatment modalities used to treat pain in the EDS population.
EDS is a systemic condition that can cause wide- spread, debilitating pain.
Because of the complexity and variability of this condition, there is no one single treatment that works for every patient.
This seems like such an obvious fact that it surprises me that even science-types assume there is one single kind of chronic pain that can be treated by <whatever they believe works>.
These patients often consult with multiple providers and are prescribed many treatments without subjective improvement.
Most times, they will require a combination of treatments. Thus it is important for each patient to undergo a comprehensive evaluation and to create a dynamic, individualized treatment plan.
Pain physicians are unique in their ability to advocate for this patient population. As experts in neuromusculoskeletal medicine and diagnosis, pain medicine physicians are better positioned to more accurately identify EDS and its characteristics. In addition, their specialized training in therapeutic options, such as pain medication management and interventional approaches, make them best suited for managing this debilitating disease.
We found that in addition to prescribing the various treatments seen in our study, providers often spend a sizeable fraction of clinic visits counseling the patient.
Specifically, patients should be educated on the common pain generators, including joint dislocation, subluxation, overuse pain, nerve hypersensitivity, arthritic changes, and central hypersensitivity to pain.
Developing a close physician-patient relationship can facilitate trust and help patients understand that sometimes multiple treatments will be attempted before obtaining relief.
They should also be advised to undergo genetic and clinical testing both themselves and for their children.