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Introduction
Ehlers-Danlos Syndrome (EDS) is a group of hereditary connective tissue disorders that affect the body’s ability to produce or process collagen. While each subtype is distinct, all share features like joint hypermobility, tissue fragility, and musculoskeletal pain. For many patients, these symptoms emerge early in life and can progress over time, leading to complications such as joint instability, chronic fatigue, or gastrointestinal problems. The symptoms present as a wide range of co-occuring conditions that are called commorbidities.
One area of growing interest is the connection between EDS and different forms of arthritis. Many people with EDS experience joint pain, but not all joint pain is due to arthritis. In fact, arthritis and EDS can overlap in subtle ways that complicate diagnosis and treatment.
This article explores which types of arthritis are most likely to occur in people with EDS, why those overlaps may exist, and how patients and clinicians can work together to manage both conditions.
EDS and the Musculoskeletal System
Joint hypermobility is a defining feature of many EDS subtypes. While some flexibility is normal—especially in children and athletes—EDS-related hypermobility is more extreme and often causes pain, instability, or injury. Over time, repetitive subluxations (partial dislocations), joint strain, and altered biomechanics can lead to structural wear-and-tear, especially in weight-bearing joints like the hips, knees, and spine.
Pain is a near-universal symptom in hEDS, but it doesn’t always mean arthritis is present. Mechanical pain from joint instability or muscle overuse is more common than inflammatory joint pain, but that doesn’t mean arthritis should be ruled out—especially in patients whose symptoms evolve or worsen over time.
Types of Arthritis Associated with EDS
Osteoarthritis (OA)
Key takeaway: Early-onset osteoarthritis is significantly more common in EDS patients due to joint instability and biomechanical stress.
Osteoarthritis is a degenerative condition characterized by the breakdown of cartilage and the development of bony changes in the joints. In the general population, OA is more common with age. However, in EDS—especially classical and hypermobile types—it often shows up earlier.
A 2022 case report documented a young adult with classical EDS who developed severe hip osteoarthritis after a history of developmental dysplasia of the hip (Tran et al., 2022). Another study found radiographic signs of early hand osteoarthritis in over 40% of EDS patients, with thumb joints most frequently affected (Rombaut et al., 2021). These findings align with clinical experience: when joints move more than they should, the surrounding tissues and cartilage bear the brunt.
While some earlier reports questioned whether hypermobility might protect against OA by distributing force across larger joint surfaces, newer research shows the opposite—repetitive trauma, ligament laxity, and poor joint alignment likely increase the risk of early degeneration.
Rheumatoid Arthritis (RA)
Key takeaway: Rheumatoid Arthritis is more common in hEDS than in the general population, with an estimated prevalence of 6.8% among patients.
Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation of the joints, particularly in the hands, feet, and wrists. Unlike OA, RA affects the joint lining (synovium), causing pain, swelling, and long-term joint damage if untreated.
A 2017 study published in Scientific Reports found that 6.8% of individuals with hEDS also had RA—more than ten times the rate in the general population (Rodgers et al., 2017). A 2021 review by Makol et al. confirmed the association and suggested that dysregulation of inflammatory pathways in hEDS may increase susceptibility to autoimmune diseases like RA.
For patients, this overlap can be tricky. Joint pain and swelling from RA may be mistaken for hypermobility-related pain, and vice versa. Some hEDS patients with undiagnosed RA are treated for years with physical therapy alone, without appropriate immunomodulatory medication. Conversely, healthy individuals with joint hypermobility may be misdiagnosed with RA if inflammation is not thoroughly assessed.
A detailed discussion of this overlap—including common diagnostic pitfalls—is available in our article: Can You Have Rheumatoid Arthritis and EDS? (Harris, 2024).
Ankylosing Spondylitis (AS)
Key takeaway: AS is more prevalent in hEDS patients, especially those who test positive for HLA-B27.
Ankylosing spondylitis is a form of inflammatory arthritis that primarily affects the spine and sacroiliac joints. It causes stiffness, pain, and, in advanced cases, fusion of the vertebrae. It often begins in young adulthood and may initially be mistaken for mechanical back pain.
In a study of hEDS patients, 24% tested positive for HLA-B27, a genetic marker strongly associated with AS. By comparison, HLA-B27 occurs in only 6.1% of the general U.S. population (Makol et al., 2021). This suggests a potentially heightened risk in hEDS, though more research is needed to clarify the nature of this association.
Systemic Lupus Erythematosus (SLE)
Key takeaway: Rare case reports suggest that SLE can co-occur with EDS, though the mechanisms are not fully understood.
Lupus is a systemic autoimmune disease that can affect the skin, joints, kidneys, and nervous system. It is known to cause arthritis-like symptoms, especially in the small joints.
A classic case report from 1978 described a young woman diagnosed with SLE, myasthenia gravis, and EDS—an unusual trio of conditions that suggest overlapping autoimmune and connective tissue dysfunction (Branch & Swift, 1978). While SLE is not commonly linked to EDS, clinicians should consider autoimmune workups in patients with unexplained symptoms like rashes, fevers, or multi-system involvement.
Sjögren’s Syndrome
Key takeaway: Patients with EDS, particularly those with chronic fatigue and dry eyes/mouth, may meet criteria for Sjögren’s syndrome.
Sjögren’s is an autoimmune condition that targets the salivary and lacrimal glands, causing dry mouth, dry eyes, and often systemic symptoms like fatigue and joint pain. While it is under-recognized, a subset of hEDS patients, especially those with overlapping mast cell activation or autonomic symptoms, may also meet criteria for Sjögren’s. Links between MCAS, Dysautonomia, and Sjogren's are widely observed including in celebrities like Solange. The co-occurrence appears to be more than coincidence.
A Note on Juvenile Arthritis
Many children with EDS experience joint pain, fatigue, and hypermobility. These symptoms can be mistaken for juvenile idiopathic arthritis (JIA), especially when inflammation is suspected. However, unlike true autoimmune arthritis, hEDS in children does not usually present with persistent joint swelling or erosive changes on imaging.
Nonetheless, a rheumatologic evaluation is crucial to rule out true inflammatory disease and to guide safe treatment plans, including physical therapy, joint protection, and activity modification.
Why Do These Overlaps Exist?
The mechanisms linking EDS with various forms of arthritis are still being studied, but several theories are emerging:
- Myofibroblast activation in hEDS may lead to low-grade tissue inflammation and pain (Makol et al., 2021).
- Dysregulation of TGF-β and Wnt signaling pathways in EDS may contribute to both fibrotic and inflammatory processes.
- Certain genetic markers, such as HLA-B27 and anti-citrullinated protein antibodies, appear more frequently in hEDS populations than in the general public.
- Chronic mechanical stress due to joint instability may increase susceptibility to degenerative arthritis.
What Patients and Providers Can Do
For patients living with EDS, awareness is key. Not all joint pain means arthritis—but if symptoms are persistent, asymmetrical, or associated with swelling, morning stiffness, or systemic symptoms, further workup may be warranted.
If arthritis is suspected, referral to a rheumatologist and imaging (e.g., X-rays, MRI) may help clarify the diagnosis. Blood tests for inflammatory markers and autoantibodies can also guide treatment.
A multidisciplinary team is ideal for patients with both EDS and arthritis. This may include:
- Rheumatologists (for autoimmune arthritis)
- Orthopedic surgeons (for structural issues or severe OA)
- Physical therapists (for strengthening and mobility)
- Pain management specialists
- Genetic counselors and primary care providers
Next Steps
Living with EDS is already complex, and the added burden of arthritis—whether inflammatory or degenerative—can significantly impact quality of life. Fortunately, research is shedding new light on the overlap between these conditions, leading to earlier diagnosis and more personalized care.
If you're experiencing joint pain that seems beyond hypermobility—or if your symptoms are evolving—it may be time to revisit the possibility of coexisting arthritis. With the right team and a proactive approach, it’s possible to manage both conditions effectively.
References:
- Tran, S., Thakkar, R., Gillie, M., & Anderson, J. (2022). A case of early osteoarthritis in a patient with Ehlers-Danlos Syndrome. Cureus, 14(7), e27069. https://doi.org/10.7759/cureus.27069
- Rodgers, K., Gui, J., Dinulos, M., et al. (2017). Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases. Scientific Reports, 7, 39636. https://doi.org/10.1038/srep39636
- Makol, A. K., Chakravorty, B., Heller, M. B., & Riley, B. (2021). The association between hypermobility Ehlers-Danlos syndrome and other rheumatologic diseases. EMJ Rheumatology. https://doi.org/10.33590/emj/21-00078R2
- Harris, D. (2024, October). Can You Have Rheumatoid Arthritis and Ehlers-Danlos Syndrome? The Ehlers-Danlos Clinic. https://www.eds.clinic/articles/ehlers-danlos-syndrome-comorbidities
- Reinstein, E., Pariani, M., Lachman, R. S., Nemec, S., & Rimoin, D. L. (2012). Early-onset osteoarthritis in Ehlers-Danlos syndrome type VIII. American Journal of Medical Genetics Part A, 158A(4), 938–941. https://doi.org/10.1002/ajmg.a.35261
- Branch, C. E., & Swift, T. R. (1978). Systemic lupus erythematosus, myasthenia gravis, and Ehlers-Danlos syndrome. Annals of Neurology, 4, 374–375. https://doi.org/10.1002/ana.410040415
- Rombaut, L., De Baere, K., Debacker, E., et al. (2021). Early stage hand osteoarthritis in patients with the Ehlers-Danlos syndrome: An explorative study. Annals of the Rheumatic Diseases, 80(Suppl 1), 275.1. https://doi.org/10.1136/annrheumdis-2021-eular.1351
- Rath, L. (2024, January 11). Ehlers-Danlos Syndrome. Arthritis Foundation. https://www.arthritis.org/health-wellness/about-arthritis/related-conditions/other-diseases/ehlers-danlos-syndrome
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