Outcomes of orthopaedic surgery in Ehlers-Danlos syndromes: a scoping review

Abstract

Background

Patients with Ehlers-Danlos syndromes (EDS) often experience high rates of joint subluxations and dislocations, and associated pain that may require surgical interventions. Orthopaedic surgical management is challenging in this population, and patients will often undergo multiple unsuccessful surgeries. Outcomes data specific to patients with EDS are sparse in the orthopaedic surgery literature. We conducted a scoping review to evaluate the evidence and outcomes for orthopaedic surgery specifically for the EDS population.

Methods

PubMed MEDLINE, Embase, The Cochrane Library, Cochrane Controlled Register of Trials (CENTRAL), CINHL, and Scopus from their inception to February 28, 2024 for all studies that reported outcomes for orthopaedic surgery in patients with EDS. Two reviewers independently determined study eligibility, rated study quality, and extracted data. Methodology followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The studies in this scoping review include Level III (retrospective cohort and case control) and Level IV (case series) evidence.

Results

The literature search yielded a total of 71 citations published between 1990 and 2023. All were primary studies. 38 were single case studies, 14 were case series, and 19 were retrospective cohort studies. No randomized clinical studies or systematic reviews were identified. Overall, the reported findings for the various anatomical sites and procedures indicated that surgery outcomes were inconsistent. Our review highlights the need for future research to determine whether currently established surgical approaches for various orthopaedic conditions offer long-term clinical benefit in patients with EDS. This is clearly a challenging diagnosis, and more rigorous clinical studies are required to identify optimal treatment approaches.

Conclusions

Our review found little evidence-based research to guide optimal surgical treatment in EDS. Established surgical techniques that have been shown to be successful in the wider orthopaedic population should be studied to determine their efficacy in the EDS population.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12891-024-07937-6.

Introduction

The Ehlers-Danlos syndromes (EDS) are a group of heritable disorders of connective tissue characterized by skin hyperextensibility, tissue fragility, and joint hypermobility. There are 13 types of EDS [1] and all have some orthopaedic manifestations including ligamentous laxity, joint instability, and scoliosis [2, 3]. EDS affects men and women disproportionately (70% female, 30% male) [4].

The prevalence of EDS differs for each of the 13-types. Vascular EDS (vEDS) is estimated to be 1 in 50,000 [5]; while Classical EDS (cEDS) is estimated to be 1 in 20,000–40,000. Hypermobile EDS (hEDS) is the most common, but the exact prevalence has been difficult to estimate due to changes in categorization. A recent paper by Demmler, et al. (2019) reports a combined prevalence of hEDS and Hypermobility Spectrum Disorder (HSD), a related diagnosis, in Wales of 1 in every 500 [4].

The most prevalent type, hypermobile type (hEDS), accounts for 90% of EDS [6, 7], but currently lacks a clear genetic marker [8]. A diagnosis of hEDS currently relies on criteria published in 2017 that include assessing joint hypermobility, systemic manifestations, and absence of signs or symptoms indicative of other established connective tissue disorders [1]. Patients with hypermobile type EDS have higher rates of subluxations and joint pain [6, 9] and often pursue surgical options when non-operative treatment fails [8]. For example, in a study of 2,491 patients enrolled in a genetic study from May 2021 to July 2023, 90% of participants self-reported joint subluxations, 60% reported joint dislocations, and 89% reported chronic pain [8]. Likewise, in a smaller study, Morlino et al. (2017) reported that 70% of the 189 patients seen in an EDS/hypermobility clinic had dislocated a joint at least once, most often the shoulders (54%), temporomandibular joint (45%), and hips (38%), and that 83% had spine problems [10].

Surgical management of EDS is challenging due to abnormal connective tissue resulting in structural insufficiency of the skin and other soft tissues, and fragile blood vessels. Intraoperative bleeding, delayed healing of surgical incisions, and infections are among the known complications [6, 11–14]. There are insufficient reports to provide evidence of the effectiveness of surgery [15], and no clear guidelines for addressing orthopedic concerns in this population [8].

Wright et al. (2020) noted the limited evidence regarding orthopaedic interventions in patients with hypermobility. Their retrospective analysis of medical records for one year at a single institution included 350 patients with hypermobility, of which 37% had EDS, compared to 134 patients with chronic pain syndrome but without hypermobility. The authors concluded that patients with significant hypermobility had more surgeries, multiple joint sites and at a younger age [16]. Yonko et al. (2021) in their retrospective chart review of orthopedic surgical outcomes in EDS (150 patients) drew attention to the challenges in this population. The authors reported a 91% complication rate for the most common musculoskeletal complications. In addition, the infection rate in this EDS cohort was more than 18 times the baseline infection rate at their institution in 2017 [6].

We conducted a scoping review [17] of the published literature of orthopaedic surgery in EDS. Our objectives were to provide an overview of the types of surgical procedures and outcomes reported, and to identify knowledge gaps. Our primary research question was the long-term success of orthopedic surgery in this population.

Materials and methods

The protocol for this scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) [18].

Study eligibility criteria

To be included, original manuscripts were focused on specific study dimensions pre-specified by the PICO elements (Population, Intervention, Comparison, Outcome) [19]. The authors defined the PICO framework as follows:

P (Population)

Patients of any sex or age with a diagnosis of EDS.

I (Intervention)

Orthopaedic surgery of shoulders, knees, hips, spine, elbows, hands, ankles/feet, and pelvis. Our review excluded neurosurgical procedures that involved the brainstem (e.g., atlanto-axial instability, craniocervical instability, Chiari malformation, tethered cord).

C (Comparison)

Either a non-surgical cohort or non-EDS comparison cohort.

O (Outcome)

Follow-up surgical outcomes, short and long-term.

Literature search

The following databases were searched: PubMed MEDLINE, Embase, The Cochrane Library, Cochrane Controlled Register of Trials, CINHL, and Scopus from inception to February 28, 2024. The search strategy is included in Appendix 1. All types of studies were included. Abstracts and conference proceedings were included. Editorials, errata, commentaries, and general discussion papers were excluded.

We abstracted data on article characteristics including year of publication, study design, and patient population. We limited our review to published documents in the English language. Two authors (SEM, JRS) independently assessed study eligibility and extracted relevant data. We grouped the studies by anatomical site and summarized the results (Tables 1, 2, 3, 4, 5, 6, 7 and 8).

Table 1.

Shoulders

Author (Year)	Title	Study Design, Follow-up	Population	Intervention	Reported Outcomes
Jerosch & Castro (1990) Germany [20]	Shoulder instability in Ehlers-Danlos syndrome: An indication for surgical treatment	Case FU: not given	19 y/o F, special needs patient	Multiple stabilization shoulder surgeries	Surgeries failed; raised issue of voluntary self-manipulation of shoulders/dislocations.
Aldridge et al. (2003) USA [21]	Thermal capsulorraphy of bilateral glenohumeral joints in a pediatric patient with Ehlers-Danlos syndrome	Case FU: 2 yr	9 y/o F, 2 shoulders	Thermal capsulorraphy for severe MDI	Only occasional subluxation 2 years post-op in one shoulder; patient satisfied and back to sporting activities.
Galano et al. (2008) USA [22]	Arthroscopic shoulder suture capsulorrhaphy in a patient with Ehlers-Danlos syndrome	Case FU: 21 mos	16 y/o F	Suture anchor capsulorhraphy for right shoulder stabilization	No subluxation or dislocations at 21 months, pain free, & able to do usual activities.
Chaudhury et al. (2012) USA [23]	Bilateral anterior and posterior glenohumeral stabilization using Achilles tendon allograft augmentation in a patient with Ehlers-Danlos syndrome	Case FU: 3 yrs	28 y/o F 2 shoulders	Open inferior capsular shift, anterior capsular reconstruction with Achilles allograft, after numerous failed prior stabilization attempts	No recurrent instability at 3 yrs.
Dewing et al. (2012) USA [27]	Two-year outcomes of open shoulder anterior capsular reconstruction for instability from severe capsular deficiency	Retrospective chart review of patients with collagen disorder or multiple failed stabilization surgeries FU: mean 3.8 yrs, range 2–6 yrs	15 patients, 20 shoulders 2 groups: EDS Type 3 (n = 5) & “hyperlaxity syndromes” (n = 10) 3 M and 12 F, ages 18–38	Anterior capsulolabral reconstruction.	14 of 20 shoulders were stable at post-op FU, and 6 failed progressing to further surgery. In 8 of 14 non-failed surgeries patients were highly satisfied. Of the 6 failed, mean # of prior surgeries was 8 (range 3–15). EDS patients had significantly lower post-op ASES (mean 71, range 58–92) compared to the hyperlaxity syndrome group (mean 92, range 78–97); pre-op scores were similar.
Skedros et al. (2015) USA [24]	Complex scapular winging following total shoulder arthroplasty in a patient with Ehlers-Danlos syndrome	Case FU: 2 yrs	45 y/o F	Complex scapular winging after failed total shoulder arthroplasty (TSA)	“Mild improvement” in pain, no improvement in function; remaining problems at 2 yrs and patient was highly dissatisfied with surgery.
Vavken et al. (2016) USA [28]	Open inferior capsular shift for multidirectional shoulder instability in adolescents with generalized ligamentous hyperlaxity or Ehlers-Danlos syndrome	Retrospective chart review; FU: mean 7.5 yrs	15 adolescents, 18 surgeries 4 M, 11 F EDS (n = 5) Hyperlaxity (n = 10)	Open inferior capsular shift surgery for MDI	13 were satisfied; 9 returned to sports; 1 was dissatisfied with pain and recurrent instability; 7 of 15 patients reported no further instability. Mean ASES at FU = 88 (+/- 10).
Armstrong et al. (2018) Canada [25]	Arthroscopic anterior and posterior glenoid bone augmentation with capsular plication for Ehlers-Danlos syndrome with multidirectional instability	Case	Adult Sex not stated	Shoulder arthroscopy for MDI	Implied good outcome; details not reported. Paper mainly describes the surgical technique.
Rogers et al. (2021) USA [29]	Shoulder arthroplasty is a viable option in patients with Ehlers-Danlos syndrome	Retrospective chart review (11 yrs of data); Matched comparison 2:1 to non-EDS patients FU: mean 5 yrs, range 25–97 mos	10 adult females (mean age: 55 yrs) with EDS & osteoarthritis or rotator cuff arthropathy	Arthroplasty for instability (for rotator cuff arthropathy or primary osteoarthritis)	Improved VAS pain scores and range of motion (no differences between groups); 3 of 10 had post-op complications (2 continued to have instability, 1 acromial stress fracture).
Schoorl et al. (2021) Netherlands [26]	Capsulorraphy with Achilles allograft augmentation for shoulder instability in patients with Ehlers-Danlos syndrome	Case series EDS Type III FU: mean 3.6 yrs, range 2–5 yrs	4 adult females, 5 shoulders	Arthroplasty for instability (superior capsular reconstruction); Achilles allograft augmentation	4 of 5 were stable; improvement in pain; 1 of 5 required further revision (patient had intervening injury). ASES: post-op mean = 84 in the 4 stable shoulders VAS: mean improved from 7 to 2.

Notes: ASES: American Shoulder and Elbow Surgeons (score 0-100, lower is worse); MDI: Multi-directional instability; VAS: Visual Analog Scale

Table 2.

Knees

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Simonian & Luck (1993) USA [43]	Synthetic posterior cruciate ligament reconstruction and below knee prothesis use in Ehlers-Danlos syndrome	Case FU: 3 yrs	21 y/o F, who had prior amputation due to occlusion of popliteal artery	Reconstructive procedures of knee using Gor-tex PLC graft due to history of left knee dislocation	No further dislocations or subluxations at 3 yrs; able to ambulate all day without support.
Rose et al. (2004) USA [12]	Total knee arthroplasty in Ehlers-Danlos syndrome	Retrospective case series 1987–1998 FU: mean 65 mos, range 24–156 mos	10 adult females (mean age: 43.3, range 22–65 yrs) 12 knees	TKA due to tibiofemoral or patellar instability, arthritis	9 of 10 patients reported satisfaction with stability; 3 were dissatisfied with the outcome and would not have surgery again. KSK Functional Score: pre-surg = 29.6; post-surg = 51.3; follow-up = 70 (Authors state that while favorable these are lower than in other patients.)
Moretti et al. (2008) Italy [46]	Spontaneous bilateral patellar tendon rupture: a case report and review of the literature	Case Hypermobile type FU: 10 wks, and 1 yr	13 y/o M	Bilateral patellar tendon repair due to injury (fell while walking)	Stairs w/o pain at 10 wks; gradual resumption of athletics at 1 year and full recovery; diagnosed with hypermobile type EDS after surgery when he developed complication.
Iacono et al. (2010) Italy [47]	Reconstruction of chronic patellar tendon tear with allograft in a patient with Ehlers-Danlos syndrome	Case Vascular type FU: not stated	23 y/o M	Patella tendon repair	Knee surgery successful; patient died of aortic dissection while waiting for contralateral knee surgery.
Shubert & McDonough (2012) USA [35]	Bilateral medial and lateral patellofemoral ligament reconstruction in a patient with hypermobility type Ehlers-Danlos syndrome	Case Hypermobile type FU: 2 yr	35 y/o F	Patellofemoral ligament reconstruction	Patient reported 0 out of 10 on pain scale and no further dislocations at 2 year FU.
Cermak et al. (2013) Belgium [32]	Total knee arthroplasty after former knee fusion in a patient with Ehlers Danlos syndrome	Case FU: 42 mos	46 y/o F	TKA following prior knee fusion	Pain free at 42 mos and patient very satisfied.
Williams, et al. (2015) UK [40]	Anterior cruciate ligament reconstruction in Ehlers-Danlos syndrome	Case FU: 2 yr	18 y/o M	Arthroscopic ACL reconstruction with notchplasty, following soccer injury	At 2 yrs, LKS: 90 of 100; returned to playing soccer, tennis, and cricket.
Takata et al. (2015) Japan [48]	Repair and augmentation of a spontaneous patellar tendon rupture in a patient with Ehlers-Danlos syndrome: a case report	Case FU: 12 mos	27 y/o M	Repair & augmentation patella tendon, with hamstring tendon after spontaneous rupture	Stabilization good at 1 year, able to move without pain; active range of motion.
Erdman et al. (2017) USA [41]	Revision pediatric anterior cruciate ligament reconstruction after failure of iliotibial band technique treated with all-epiphyseal technique in a prepubescent with Ehlers-Danlos syndrome: a case report	Case EDS Type IV FU: 10 mos, 28 mos	10 y/o F Had multiple prior injuries surgery (same knee) at age 8 yrs	ACL revision surgery after injuries with all-epiphyseal technique	Stable Lachman test at 10 and 28 mos FU, whereas the contra-lateral knee was unstable. Both the Lachman and Pedi-IKDC scores were well within the range of an excellent outcome. No appreciable disruption to the femoral or tibial physes, or boney bar in either physes.
Farid et al. (2018) Netherlands [34]	Knee joint instability after total knee replacement in a patient with Ehlers-Danlos syndrome: the role of insert changes as practical solution	Case Hypermobile EDS FU: 2010–2017	53 y/o F	Indication: Prior bilateral TKA surgeries due to valgus osteoarthritis; developed bilateral hypermobility of both knee replacements after surgery. Treated with insert changes to both knees to avoid another total TKA.	Revision of left knee insert, right knee required 2 insert exchanges. Instability persisted, and revision to a constrained prosthesis was performed.
Choi et al. 2018) Korea [42]	Anterior cruciate ligament reconstruction with Achilles tendon allograft in a patient with Ehlers-Danlos syndrome	Case FU: 2 yrs	25 y/o M EDS diagnosed by the surgeon (previously undiagnosed)	Reconstruction with Achilles tendon allograft, due to femur fracture & knee injury after being hit by a car	At 9 mos returned to normal activity. At 2 yrs patient reported no instability able to run/pivot in sports; IKDC score = 100, Cincinnati score = 100.
Tibbo et al. (2019) USA [33]	Outcomes of primary total knee arthroplasty in patients with Ehlers-Danlos syndromes	Retrospective 2001–2016 Matched 2:1 comparison group: OA FU: 2 year minimum	13 F, 3 M (mean age 57 yrs, range 39–76) 20 knees	TKA	No difference between groups. Patients with EDS were not at increased risk of revision compared to the control cohort although EDS cohort had more prior knee surgeries; 4 EDS and 9 comparison cohort underwent re-operation.
Imerci et al. (2022) Turkey [36]	Outcomes of medial patellofemoral ligament reconstruction and tibial tubercle osteotomy in syndromic adolescents with patellar dislocation	Case series FU: mean 2 years	11 adolescent patients w/ various diagnoses (4 had EDS); mean age: 14.8 yrs 17 knees	Medial patellofemoral ligament reconstruction and tibial tubercle osteotomy (MPFL/TTO)	Diagnostic groups were not separated; outcomes improved in total (i.e., knee flexion increased), but cannot draw conclusions about the 4 EDS patients.
Conte et al. (2022) USA [45]	Anterior cruciate ligament agenesia in a patient with Ehlers-Danlos syndrome and open physes	Case FU: 2 yrs	11 y/o M	ACL reconstruction, with Achilles tendon allograft modification due to severe joint instability	“Good” right knee stability with a negative Lachman test and anterior drawer test; the patient was satisfied, no further subluxation.
Hishimura et al. (2022) Japan [44]	Double-bundle anterior cruciate ligament reconstruction using autologous hamstring tendon hybrid grafts in a patient with hypermobile Ehlers-Danlos syndrome: a case report	Case Hypermobile EDS (hEDS) FU: 36 months	18 y/o M	Anatomic double-bundle ACL reconstruction using hamstring tendon hybrid autografts, due to a twisting injury	“Excellent clinical and functional outcomes”. Multiple measures of pain & function (incl. Lachman test, pivot-shift test, IKDC & LKS) indicated full range of motion, improved anterior side-to-side laxity. Patient returned to pre-injury activity levels.
Amemiya et al. (2022) [37]	Proximal tibiofibular joint (PTFJ) dislocation due to Ehlers-Danlos syndrome: posterolateral open-wedge high tibial osteotomy combined with medial closed-wedge distal femoral osteotomy can correct the severe valgus deformity with a markedly increased tibial posterior slope	Case FU: 2 yr	40 y/o F severe valgus deformity caused by longstanding PTFJ dislocation due to EDS; prior surgery	Indication: increase in pain & dislocation PLOWHTO, tibiofibular	Improvement in all 5 subscales of the KOOS, 4 of 5 exceeded minimal clinically significant differences (symptom scale did not).
Nemunaitis & Parikh (2022) USA [38] 2022 PRISM 9th Annual Meeting	Outcomes of isolated medial patellofemoral ligament reconstruction for recurrent patellar instability In Ehlers-Danlos Syndrome	Retrospective 2010–2016 EDS, hypermobility type FU: 2 year min	16 F (mean age: 15 yrs) 21 knees	MPFL-R, some with hamstring autograph, some allograft	3 of 21 (14%) knees had recurrent dislocation; patient reported outcomes scores & dislocation rates were similar between autograft & allograft.
35Parikh et al. (2023) USA [39] Journal of ISAKOS S121-8 ISAKOS CONGRESS, 2023 MEETING	Outcomes of isolated medial patellofemoral ligament reconstruction for patellar instability in Ehlers-Danlos syndrome	Retrospective (time period not stated) hEDS confirmed by Genetics Div FU: 2 year min, mean 7.2 yrs	27 F 4 M, mean age: 14.9 yrs 47 knees	MPFL-R	Restored patellar stability with 19.1% failure rate (9 of 47 knees) at midterm follow-up. Failure was more likely in younger patients, bilateral involvement and in those who can touch the palm to the floor with knees extended. Allograft had less failure rate than autograft. Postoperative PROs were inferior compared to non-EDS population.

Notes: ACL: Anterior cruciate ligament; IKDC: International Knee Documentation Committee; Pedi-IKDC; KOOS: Knee Injury Osteoartritis and Outcome Score (subscales: symptoms, pain, ADLs, sports, QOL); KSK: Knee Society Score; LKS: Lysholm Knee Scale; PLOWHTO: Posterolateral open-wedge high tibial osteotomy; MPLR, MPFL-R: Medial Patellofemoral Ligament Reconstruction; TKA: Total knee arthroplasty

Table 3.

Hips

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Badelon et al. (1990) France [52]	Congenital dislocation of the hip in Ehlers-Danlos syndrome	Case series, 1964–1973 Type 7 EDS Rare type, arthrochalasia FU: mean 17 yrs, range 8–22 yrs	5 F, 4 M, 8 of 9 patients had surgery Intake age: 5 mos to 8 yrs	Closed reduction (16 hips) due to lateral congenital dislocation of hip; 1 not suitable for surgery	Only 1 hip had excellent result at FU; others either fair or poor; vascular necrosis with central physeal developed in 5 hips; 1 hip had wound infection.
Chang et al. (2012) Korea [50]	Obturator hip dislocation with intrapelvic migration of the femoral head in Ehlers-Danlos syndrome	Case FU: 10 yrs	24 y/o F	Complicated surgical repair capsulorrhaphy and posterior repair to prevent dislocation due to hip fracture after falling	No limping, pain or dislocation at 10 yrs.
Larson et al. (2015) USA [53]	Ehlers-Danlos syndrome: arthroscopic management for extreme soft tissue hip instability	Retrospective chart review (Dec 2005-Jan 2014) FU: mean 45 mos, range 12–99 mos	11 F, 1 M 16 hips Mean age: 26 yrs, range 17–40	Hip arthroscopy, various procedure types due to pain & instability	Dramatic improvements in HHS & VAS; 1 patient needed further THA revision.
Guier et al. (2020) USA [54]	Primary total hip arthroplasty in patients with Ehlers-Danlos syndrome: a retrospective matched cohort study	Retrospective matched case-control 1997–2017 FU: mean 7.3 yrs, range 2–20 yrs	10 F 3 M with EDS, matched 1 to 3 osteoarthritis controls Mean age (EDS cohort): 54 yrs	THA, included first hip operated on only for the 4 patients who had bilateral surgery	2 patients in each cohort had a post-op dislocation (Cases: 15%; Controls: 5%). No significant differences in reoperation or revision rates; no differences in post-op HHS.
Rosinsky et al. (2020) USA [55]	Arthroscopic ligamentum teres reconstruction: Minimum 2-year patient-reported outcomes with sub-analysis of patients with Ehlers-Danlos syndrome	Retrospective 2012-16 FU: 2 yrs (minimum)	EDS sub-analysis 5 patients, 7 hips	Ligament reconstruction, (Ligamentum Teres)	Favorable outcomes reported in 4 hips; inferior outcomes in 3 hips.
Moore et al. (2022) USA [56]	Patients with Ehlers-Danlos syndromes experience higher rates of prosthetic dislocation after total hip arthroplasty and worse implant survival at 5 years	Retrospective Pearl diver Mariner database 2010–2018 FU: 5 yrs	354 EDS cases, matched controls 1:10 Mean age: 56 years	THA	EDS patients had higher rates of perioperative dislocation & lower implant survival at 90 days and at 5 yrs. At 5 yrs, 92.7% EDS cases and 96.1% controls remained unrevised (Odds Ratio: 2.64; p = 0.004).
Powell et al. (2023) USA [51]	Obturator anterior dislocation after direct anterior total hip arthroplasty in a patient with Ehlers-Danlos syndrome: a case report	Case EDS rare type FU: not known	71 y/o F	Closed reduction to reduce the femoral prosthesis out of the pelvis and back into an appropriate position after a rare atraumatic obturator dislocation after THA	Successful at reducing the femoral prothesis out of the pelvis & back into the appropriate position.

Notes: HHS: Harris Hip Score; THA: Total hip arthroplasty; VAS: Visual Analog Scale (pain)

Table 4.

Spine

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
el-Shaker et al. (1991) Saudi Arabia [58]	Acute brachial plexus neuropathy secondary to halo- gravity traction in a patient with Ehlers-Danlos syndrome	Case FU: 9 mos	14 y/o F	Anterior spinal release & fusion due to thoracic scoliosis	Progressive improvement at 9 mos.
McMaster et al. (1994) Scotland/UK [59]	Spinal deformity in Ehlers-Danlos syndrome: five patients treated by spinal fusion	Case series Classical type (5 patients); 2 also had vascular type FU: not stated	5 adolescents Mean age: 11 yrs 8 mos	PSF for scoliosis	“Satisfactory” healing of fusion.
Vogel et al. (1996) USA [60]	Neurologic and vascular complications of scoliosis surgery in patients with Ehlers-Danlos syndrome	4 cases EDS FU: varied	3 F, 1 M Age: 8–13 years	Spinal fusion for scoliosis	All had complications: 3 neurologic, 1 vascular complication, 2 developed paraplegia.
Akpinar et al. (2003) Turkey [61]	Surgical management of the spinal deformity in Ehlers-Danlos syndrome type VI	Case series FU: mean 4 yrs	5 F adolescents Type 4 (vascular) Case 1: 11 y/o Case 2: 8 y/o Case 3: 20 y/o, prior spine surgeries Case 4: 17 y/o Case 5: 13 y/o	Anterior or posterior fusions for scoliosis	Outcomes mixed due to vascular complications. At 4 years, spinal fusions radiographically solid, with no implant failure. Case 1: correction maintained at 6 yrs FU; Case 2: correction maintained, 2 yrs, 7 mos; Case 3: correction maintained at 2 yrs; Case 4: pulmonary post-op complications that improved at ~ 5 yrs, curve improved; Case 5: correction maintained, 4 yrs, 7 mos.
Qureshi et al. (2005) USA [75]	Using the semitendinosus tendon to stabilize sternoclavicular joints in a patient with Ehlers-Danlos syndrome: a case report	Case FU: 5 yrs	37 y/o F	Novel sternum reconstruction for pain and dislocation of sternoclavicular joints	Excellent function reported at 5 yrs without pain or subluxation.
Yang et al. (2009) USA [62]	Vascular complications from anterior spine surgery in three patients with Ehlers-Danlos syndrome	Case series FU: Case 1: 5 yrs Case 2: 3 yrs Case 3: 2 yrs	Case 1: 13 y/o M Type I Case 2: 7 y/o F Type II Case 3: 9 y/o M Type IV (vascular)	Anterior & posterior release, followed by PSF due to scoliosis	Vascular complications peri-operatively in all 3; all stable at FU.
Jasiewicz et al. (2010) Poland [63]	Spine deformities in patients with Ehlers-Danlos syndrome, type IV - late results of surgical treatment	Retrospective 1990–2007 Type IV (vascular) FU: mean 5.5 yrs (range 1–10)	5 F, 6 M Mean age at surgery 14 yrs (range 7–18); Mean age latest exam: 19 yrs (range 14–25	Fusion for spinal deformity included posterior alone (n = 6), anterior and posterior (n = 5); 2 also had thoracoplasty	Mixed results, 4 required reoperations (instrumentation failure, increasing imbalance).
Liu et al. (2011) USA [64]	Posterior spinal fusion for scoliosis in Ehlers-Danlos syndrome, kyphoscoliosis type	Case series 2000–2005 kEDS FU: 4–6 yrs	3 adolescents 13 y/o F 14 y/o F 13 y/o F	PSF for scoliosis	Correction maintained for all at FU.
Rabenhorst et al. (2012) USA [14]	Posterior spinal fusion in patients with Ehlers-Danlos syndrome: a report of six cases	Case series Various types, diagnosed by geneticist FU: 1 month to 9 yrs	3 F, 3 M Age: 4–18 yrs	PSF due to spinal deformity	4 had no complications; 1 death from intra-abdominal bleeding ~ 2–3 weeks later; 1 infection requiring implant removal 1 year later.
Lindley et al. (2012) USA [72]	Lumbar artificial disc replacement in Ehlers-Danlos syndrome: A case report and discussion of clinical management	Case Type 3 (hypermobility type) FU: 1 yr	51 y/o F	ADR (L4-5) due to degenerative disk disease not alleviated by prior surgery	No complications at 1 year; no back pain and radicular symptoms.
Jahangiri et al. (2016) Saudi Arabia [65]	Vertebral column resection for kyphoscoliosis in a patient with Ehlers-Danlos syndrome: An intraoperative neurophysiological monitoring alert	Case FU: 4 weeks	16 y/o M	2 stage vertebral column resection, multiple level fusions due to kyphoscoliosis	Satisfactory recovery reported at 4 wks; no further followup available.
Working et al. (2017) USA [66]	Spontaneous fatal intraoperative rupture of great vessel during Growing rod lengthening: Do children with Ehlers-Danlos syndrome require the availability of vascular expertise? A case report and review of the literature	Case kEDS	8 y/o F high risk patient	Growing rod expansion (GRE) for kyphoscoliosis	Spontaneous rupture of superior vena cava, died immediately following surgery.
Uehara et al. (2018) Japan [67]	Spinal manifestations in 12 patients with musculocontractural Ehlers-Danlos syndrome caused by CHST14/D4ST1 deficiency (mcEDS‐CHST14)	Case series of 2 of the 12 cases that underwent surgical correction mcEDS FU: Case 1: 106 mos Case 2: 31 mos	16 y/o F and 17 y/o M	Case 1 PSF with pedicle screws (T10-L4) Case 2 2-staged PSF with pedicle screws (T4-L3)	Case 1: wound fistula infection, screw removed, walked with hand rail. Case 2: no complications; independent gait at FU.
Matur et al. (2020) USA [68]	Complications in children with Ehlers-Danlos syndrome following spine surgery: analysis of the pediatric national surgery quality improvement program database	Retrospective, NSQIP database 2012-16 FU: 30 day outcomes reported	56 pediatric EDS compared with non-EDS Mean age = 11 yrs (2–17 yrs)	Various spine procedures, with most common being arthrodesis (n = 37) for severe sciolosis	No differences between EDS vs. non-EDS in reoperations, wound infection, and overall 30-day complications.
Uehara et al. (2020) Japan [69]	Posterior spinal fusion for severe spinal deformities in musculocontractural Ehlers-Danlos syndrome: detailed observation of a novel case and review of 2 reported cases *Note: the review of the 2 cases are covered in Uehara et al.	Case FU: 1 yr	19 y/o F mcEDS	PSF (T4-L4) due to progressive kyphoscoliosis	At 1 year, correction maintained, able to walk, improvement in lower back pain and other outcomes (post-operative SRS-22, Scoliosis Research Society).
Gouzoulis et al. (2022) USA [76]	Single-level posterior lumbar fusions in patients with Ehlers Danlos syndrome not found to be associated with increased postoperative adverse events or five-year reoperations	Retrospective, MSpine Pearldiver dataset (2010–2020) FU: 90 days & 5 yrs	4 adults Age/sex not stated Matched controls 1:4	PLF, single level	No differences between EDS v non-EDS at 90 days (adverse events or readmissions) or at 5 years (reoperations).
Chi et al. (2023) USA [74]	Outcomes following anterior cervical discectomy and fusion in patients with Ehlers-Danlos syndrome	Retrospective, Mariner PearlDiver database	533 cases EDS; 2634 matched controls 90% F Age 18–84	ACDF, 1 or 2 levels	EDS cases had signif. diff in 90 day complications (wound, SSI, pseudoarthristis, instrument failure), and revision surgeries at 2 yrs, with EDS presenting with a 15-fold increase in anterior revision rates compared to matched controls.
Prabhakar et al. (2023) USA [71]	Vascular injury after scoliosis correction in Ehlers-Danlos syndrome: Proceed with caution.	Case FU: 3yr	20 y/o M Type 2	Spinal fusion with growing rods, pedicle screws due to progressive deformity, scoliosis	Improvement reported at 1 month and at 3 yrs; gait improved, no foot drop, pain score = 0, back to normal school activities.
Toumia et al. (2023) Tunisia [70]	Growing rods for early-onset scoliosis in Ehlers-Danlos disease	Retrospective chart review FU: varied	4 cases 6 y/o M, 11 y/o F, 14 y/o F, 15 y/o M Early onset scoliosis	TGR due to scoliosis, hip dislocations	2 of 4 needed additional leg lengthening procedures; 1 bleeding complication.
Halayqeh et al. (2023) USA [73]	Delayed cerebrospinal fluid (CSF) leak following anterior cervical discectomy and fusion surgery	Case FU: 1 yr	43 y/o F	2 procedures: ACDF for spinal cord compression C6/C7; Revision at 1 yr	At 6 mos, improvement from 1st procedure reported. At 1 year, revision of original surgery for CSF leak; hardware (screws) replaced & CSF leak patch; at 2 & 6 weeks CSF leak resolved
Wu et al. (2023) China [77]	Ehlers-Danlos syndrome is associated with increased rates of adjacent segment disease following TLIF: A propensity matched study	Retrospective review PearlDiver Mariner database (2010–2022); propensity score matched 1:1	85 EDS cases (all types), 78.8% F	1–3 level TLIF due to degenerative disk disease	EDS patients had higher risk of adjacent segment disease at 36 mos; No differences in all-cause medical or surgical complications, and pseudoarthrosis.
Uehara et al. (2023) Japan [57]	Spinal deformity in Ehlers-Danlos syndrome: Focus on musculocontractural type	3 cases Musculocontractural (mckEDS) FU: varied	Case 1 16 y/o F Case 2 12 y/o M Case 3 19 y/o M	PSF due to scoliosis and thoracolumbar kyphosis (case 2 also has thoracic lordosis) Case 1 (T10-L4) Case 2 (T4-L3) Case 3 (T4-L4)	Case 1: pedicle screw caused a fistula, which required surgical removal; after nearly 9 yrs, fistula remained & kyphosis worsened SR-22 Score: pre-op = 2.6, post-op = 3.4 Case 2: positive post-op outcomes; remained favorable at 2.6 yrs SR-22 Score: preop = 4.2, post-op = 4 Case 3: Positive outcome remained at 1 yr SR-22 Score: pre-op score not available, post-op = 4.45

Notes: ACDF: Anterior cervical discectomy and fusion surgery; ADR: Artificial disk replacement; PLF: Posterior lumbar fusion; PSF: Posterior spinal fusion; SR-22: Preoperative Scoliosis Research Society-22 (scale: 1 (worst) to 5 (best) for domains, pain, function, mental health, self-image, satisfaction; TGR: Traditional growing rods; TLIF: Transforaminal lumbar interbody fusion

Table 5.

Elbows

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Rames & Strecker (1991) USA [78]	Recurrent elbow dislocations in a patient with Ehlers-Danlos syndrome. Orthopedics	Case FU: 24 mos. EDS	9 y/o F	Stabilization for recurrent elbow dislocation	Gradually regained function; “doing well” at FU.
Cole et al. (2000) UK [79]	Recurrent instability of the elbow in the Ehlers-Danlos syndrome: a report of three cases and a new technique of surgical stabilization	Case series (n = 2) EDS	Case 1: 38 y/o F FU: 1 yr Case 2 & 3 (bilateral): 34 y/o F FU: 18 mos & 1 yr	Elbow stabilizing surgery & bone block limiting extension due to recurrent dislocation	Both satisfied with surgery; functional range improvement. Full range of flexion; no instability.
Schneider et al. (2019) USA [80]	Stabilization of recurrent elbow instability in a patient with Ehlers-Danlos syndrome: A case report	Case FU: 1 yr EDS	22 y/o F	Elbow ligament reconstruction (medial & lateral) due to elbow instability	Elbow stable, asymptomatic, excellent range of motion reported at FU.
Onode et al. (2021) Japan [81]	Divergent dislocation of the Elbow in an adult with Ehlers-Danlos syndrome: A case report	Case FU: not stated	32 y/o M Snowboarding accident	Elbow reduction repair to correct transverse divergent dislocation	Good clinical results reported.
Christie et al. (2022) USA [82]	Use of tendon allograft for recurrent extensor carpi ulnaris instability in Ehlers-Danlos syndrome: A case Report	Case FU: 1 yr	20 y/o M	Indication: Gracilis tendon allograft to reconstruct extensor carpri ulnaris (ECU) due to subluxation	No pain at FU; ECU stable w/o recurrent subluxation.

Table 6.

Hands

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Cheung et al. (2010) China [83]	Multiple triggering in a girl with Ehlers-Danlos syndrome: case report	Case FU: 2 yrs	17 y/o F Type 1 and Type 2 EDS overlap	Debridement of tendons due to triggering in multiple digits due to tendon fibrillations	Good functional outcome at 2 years, but may need follow-up procedures.
Krijgh et al. (2014) Netherlands [85]	Surgical technique: hemi-extensor carpi radialis brevis tenodesis for stabilizing the midcarpal joint in Ehlers-Danlos syndrome	Case series (2009–2011) EDS HT FU: 1–3 yrs	5 F Age 20–38	Extensor carpi radialis brevis lunocapitate tendoesis due to midcarpal instability	Complication in 2 patients: 1 case had dislocation of the lunate and capitate that was successfully corrected at a second operation; 1 had edema that resolved.
Breahna & Meads (2015) Australia [84]	Thumb carpometacarpal joint stabilization in Ehlers-Danlos syndrome: Case report	Case FU: 2 yrs	18 y/o F	Trapezial wedge osteotomy combined with volar ligaments reconstruction due to thumb carpometacarpal ligament laxity	Carpometacarpal joint stable and pain free at 2 yrs.
Hevesi et al. (2019) USA [86]	Thumb carpometacarpal arthritis in patients with Ehlers-Danlos syndrome: Non-operative and operative experiences	1999–2016 Institutional retrospective review FU: median 6 yrs (range 1–15)	8 F, 1 M 14 thumbs # surgical = 6 thumbs # nonsurgical = 8 thumbs	Thumb carpal stabilization due to carpometacarpal arthritis	Operative thumbs showed a trend towards improved pain and grip strength; non-operative patients had decreased thumb range of motion over time.

Table 7.

Ankles and feet

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Solomon et al. (2002) USA [87]	Surgical treatment pes planovalgus foot secondary to Ehlers-Danlos syndrome with the Maxwell-Brancheau subtalar arthroereisis	Case EDS Type 3 FU: timing of visits not stated	15 y/o F	Indication: pes planovalgus Procedure: Maxwell-Brancheau subtalar arthroereisis	No complications, advised to wear orthotics.
Larholt & Bowling (2014) UK [88]	The surgical management of ankle instability in hypermobile type Ehlers-Danlos syndrome	Case EDS-HT FU: 8 mos	55 y/o F	Augmentated plantaris graft with Brostrom Gould procedure to stabilize right ankle due to lateral ankle instability	Mild discomfort when walking; patient satisfied; planning left ankle procedure.
Dermatis et al. [poster] (2018) USA [90]	Minimally invasive surgical technique for ankle and rearfoot stabilization in patients with hypermobile Ehlers-Danlos syndrome	Retrospective chart review hEDS FU: >6 mos	15 patients	Subtalar joint arthroereisis & lateral ankle ligament supplementation due to lateral ankle instability and pes planjs	At > 6 mos, 73% reported improvement in pain and function, 53% no limitation in activity, & 80% no longer used assistive devices. All reported decreased frequency of ankle sprains (80% had no sprains). One patient required custom-made shoes after surgery.
Hasegawa et al. (2023) Japan [89]	Ankle skin defects with vascular Ehlers-Danlos syndromes treated by posterior tibial artery perforator flap: A case report	Case Vascular type FU: not given	46 y/o M	Open reduction and internal fixation; coverage skin defect with postural tibial artery perforated flap	Successful outcome reported despite tissue fragility.

Table 8.

Sacroiliac joint

Author (Year)	Title	Study Design	Population	Intervention	Reported Outcomes
Beijk et al. (2021) USA [92]	Sacroiliac joint fusion in patients with Ehlers Danlos Syndrome: A case series	Case series 2012-18 FU: mean 36 mos	16 female adults Age: median 46 yrs, range: 20–60 yrs	Sacroiliac joint fusion	8 of 10 patients were satisfied with surgery; 2 underwent revision surgery.

Results

Our scoping review found 71 manuscripts published 1990 to 2023 that described the outcomes of orthopaedic procedures in EDS patients and met the inclusion ciriteria. (Fig. 1) Most were single cases or case series. We found no randomized controlled trials or systematic reviews, and most studies lacked standardized and validated measures. The follow-up times varied and were often inconsistent within the individual studies. Most papers did not define the criteria used for EDS diagnosis.

Fig. 1.

Identification of Studies

Shoulders

Limited literature details the management of shoulder problems in EDS patients. Our review (Table 1) found six single case reports [20–25], one case series [26], and three small retrospective chart reviews [27–29]. In a small case series of patients undergoing arthroplasty for instability, Rogers et al. reported that three of the ten patients with EDS experienced post-operative complications, although no statistically significant differences were found when compared to controls. The EDS patients had improved mean pre- to postoperative visual analog scale (VAS) pain scores (6.5 to 1.7), and range of motion; however, long-term follow-up was lacking [29].

EDS patients often have multidirectional shoulder instability due to global shoulder capsular laxity. If conservative management fails to control symptoms, surgical intervention is pursued. Arthroscopic or open techniques may be performed; however, there is lack of consensus about the optimal approach. Minimally invasive arthroscopic procedures may not provide adequate reinforcement of weak underlying soft tissue. Arthroscopic procedures typically involve plication of the capsule to remove excessive redundancy. Arthroscopic thermal capsulorrhaphy was described in a case published in 2003 as a less-invasive approach with a good outcome [21], but has since fallen out of favor. Galano et al. reported a successful outcome in an adolescent using suture anchor capsulorhraphy. The patient was able to engage in usual activities at 21 months [22].

In patients with prior failed surgeries, especially those with poor quality connective tissue, open surgical capsular reconstruction is recommended. This may involve open tightening of the native shoulder capsule (“capsular shift procedure”) [30] and/or capsular augmentation with allografts [31]. EDS patients who have multidirectional instability may require both anterior and posterior capsular procedures. Closure of a defect in the rotator interval capsule is another approach sometimes used [31].

Given underlying abnormalities in microstructure and composition of the shoulder capsule, allograft tendons (cadaveric, donor tissue) has been used to reconstruct both the anterior and posterior capsule in EDS patients. Chaudhury et al. (2012) describe a successful augmentation using Achilles tendon allografts in a young adult who had failed stabilization surgeries. She reported no recurrent instability at 3 years [23]. Dewing et al. evaluated 2-year outcomes in 15 patients following open capsular reconstruction with soft tissue grafts and reported that 14 of 20 shoulders were stable at post-operative follow-up, and six failed progressing to further surgery [27]. Vavken et al. reported generally favorable outcomes using open inferior capsular shift, including decreased pain and instability. Thirteen of 15 patients were satisfied with the surgery, and seven patients reported no further instability [28]. Schoorl et al. reported improvement in pain and stability after allograft-based open capsular reconstruction in four of the five patients [26].

Other surgical options for recurrent shoulder instability include bone grafting procedures to augment bone loss on the glenoid. Armstrong et al. describe an arthroscopic bony reconstruction technique using capsular plication with iliac crest autograft. The article implies a good outcome, however, details were not reported [25]. For patients who have failed all attempts at surgical shoulder stabilization, shoulder arthrodesis (fusion) may be considered as a last resort.

Collectively, these published studies included 50 patients who had stabilization surgeries, some of which were revision procedures. In most studies, nonsurgical treatments had been tried and failed prior to surgery. The studies used various outcome measures, including measures of joint stability, pain, and patient satisfaction. Chaudry et al. (2012) in one case and Schoorl et al. (2021) in five cases described successful use of Achilles allograft for multidirectional instability but larger cohorts with longer follow-up are needed to confirm these findings. We did not find convincing evidence supporting a specific choice of bone graft, however, bone graft procedures are rarely required in EDS shoulder surgery.

Knees

Our review (Table 2) found 13 single case reports and four retrospective chart reviews describing knee surgery in EDS. Procedures reported were total knee arthroscopy (TKA) for tibiofemoral or patellar instability associated with arthritis, patellofemoral ligament reconstruction, anterior cruciate ligament (ACL) reconstruction, patellar tendon repair, and realignment osteotomy.

Four studies reported TKA in adults [12, 32–34]. Rose et al. reported a case series of TKA in EDS in 2004. Although arthroplasty appeared to be effective for instability in this sample, results and patient satisfaction were lower than for conventional arthroplasty indications [12]. In a single case study, Cermak et al. reported that a 46-year old female patient was very satisfied and pain free at the 42 months [32]. In the only study with a matched comparison group, Tibbo et al. (2019) found no differences in the need for revision surgery or reoperation following TKA at 2-year follow-up [33]. However, the authors noted that constrained components were more likely to be needed in EDS patients to provide adequate stability [33]. Farid et al. (2018) included the patient’s statements about her satisfaction with the stability of her knees, and the authors recommended consideration for use of a more constrained polyethylene insert in patients with instability after TKA. The authors note that it is important to distinguish between EDS patients with osteoarthritis due to other causes since this influences implant selection [34].

Three studies report patellofemoral ligament reconstruction surgeries for patellar instability. Shubert and McDonough (2012) report no further patellar dislocations or pain in an adult at 2 years [35]. Imerci et al. (2022) included four adolescents with EDS in a larger case series; because diagnostic groups were not separated, the outcomes for the EDS patients are not certain [36]. Amemiya et al. described using posterolateral open-wedge high tibial osteotomy technique after all conservative treatments failed. The authors note improvement in all subscales of the Knee Injury Osteoartritis and Outcome Score at two-year follow-up [37]. The largest retrospective review to date, published by Parikh and Nemunaitis (2022 and 2023), reported outcomes in 31 patients with EDS using patellofemoral ligament reconstruction to restore patellar stability. A 19% failure was reported at a mean follow-up of 5 years [38, 39].

Six case studies reported ACL surgeries, all in pediatrics or young adults, five from injuries [40–44], and one from congenital knee malformation [45]. All reported good outcomes, including no further knee instability and return to normal activity. Three studies reported good outcomes following ligament repair [46–48] in one adolescent and two young adults, including satisfactory stability, pain free and active range of motion.

Conte et al. (2022) note that consensus on the optimal treatment has not yet been established for ACL reconstruction [45]. In EDS patients, local tissue may not withstand the normal stresses of surgery [47]. Surgical technique may require a modification of approach. Hishimura et al. (2022) mention their concerns about using native autograft tissue due to intrinsic changes in peri-articular connective tissues that compromise strength and stiffness of local autograft tendon [44]. Technical difficulties can have more serious consequences in people with EDS, and laxity of other peri-articular tissues may compromise outcomes [49].

Collectively, these studies included 78 patients. Overall, outcomes were favorable for the majority of patients, including pain reduction, improved patellar stabilization and ACL stability, and return to normal activity. Comparison groups were lacking. Follow-up times were generally short, and standardized outcomes measures were inconsistent across studies.

Hips

There is minimal published literature describing surgical management of hip problems in EDS patients and outcomes are inconsistent, even within studies. Our review (Table 3) found two case reports [50, 51], one case series [52], three retrospective reviews of institutional registries [53–55], and one large administrative database [56]. Procedures included a closed reduction surgery [52], a repair fracture/dislocation [50], and five total hip arthroplasties (THA) [51, 53–56].

Moore et al. (2022) reported a higher rate of perioperative dislocation following hip arthroplasty [56]. Guier et al. also reported a higher rate of dislocation, but found no differences in reoperation, revision rates, or post-operative Harris Hip Scores (HHS) [54]. Larson et al. (2015) reported improvement in HHS and pain [53]. Rosinsky et al. (2020) reported mixed outcomes in a sub-analysis of 5 patients undergoing ligamentum teres reconstruction [55]. Chang et al. (2015) reported a “reasonable and recommendable” outcome of a relatively rare procedure at 10 years follow-up [50]. The authors note that these results appear to show that surgical treatment may provide meaningful improvement but were too mixed to draw firm conclusions [50].

Collectively, these studies included 394 patients who had various procedures. Outcomes appear to be largely favorable overall. For example, although 5-year THA revision rates were higher for EDS patients compared to non-EDS controls, 93% of EDS patients remained unrevised [56].

Spine

Our review (Table 4) found 22 publications describing spine surgery in patients with EDS. Sixteen of the 22 publications [14, 57–71] reported outcomes for pediatric and adolescent patients with scoliosis undergoing anterior and/or posterior spinal fusion surgery. In a recent study of three cases with musculocontractural type EDS (mcEDS), Uehara et al. (2023) concluded that posterior spinal corrective fusion is a viable treatment for severe spinal deformity, with caution to avoid massive blood loss [57]. Standardized measures were used; however, follow-up times varied between one and ten years.

Spine surgery in adult EDS patients included disk replacement [72], anterior cervical discectomy and fusion surgery (ACDF), [73, 74] and a novel sternum reconstruction [75]. Four publications report outcomes using large databases. Matur et al. (2020) report short-term outcomes in various spinal procedures using the NSQIP database [68]. Three studies used the PearlDiver Mariner database [74, 76, 77] Chi et al. (2023) report outcomes of ACDF using the Mariner database and found that patients with EDS had a 15-fold increase in revision rates compared to matched controls [74].

Collectively, these studies included 732 patients. The population was mainly pediatric with various EDS types, including vascular and musculocontractural types. Most of the surgeries were for kyphoscoliosis. The largest study (533 EDS cases) found a 15-fold increase in anterior revision rates following cervical discectomy compared to controls.

Elbows

Our review (Table 5) found five manuscripts describing the surgical management of instability of elbow problems in six patients. Collectively, these studies included 16 patients. All reported good outcomes, including functional improvement, no recurrent subluxations and excellent range of motion [78–82].

Hands

Our review (Table 6) found two single case reports [83, 84], one case series [85], and one retrospective institutional review of hand surgery in persons with EDS [86]. Of the 16 patients reported, two had complications that were resolved. Overall, the outcomes of surgery appear favorable, including improved pain and grip strength and good function; however, standardized measures and validated questionnaires were not used.

Ankles and feet

Our review (Table 7) found three published manuscripts [87–89] and one poster [90], representing three single case reports and one retrospective review of foot and ankle surgery in EDS. This small set of studies suggest favorable outcomes, including improved pain and function, in the short-term. All follow-up times were less than one year or not stated. Erickson and Wolman (2017) reported that soft tissue procedures involving the ankle and ligamentous repair and joint stabilization have relatively high failure rates and recurrent instability in EDS; [49] however, there is limited evidence supporting the use of surgical intervention to correct foot deformities in EDS [91]. Further research is needed to determine both short- and long-term outcomes of foot deformities in persons with EDS.

Pelvis and other

Our review (Table 8) found one publication reporting on pelvic surgery in EDS. In a case series, Beijk et al. (2021) describe fusion surgery for sacroiliac joint (SI) joint dysfunction using a proprietary fusion device [92]. SI joint fusion appears to be a viable and minimally invasive option for EDS patients with sacroiliac joint pain [93]; however, further research is needed to understand the benefits and risks of implant procedures in EDS to avoid poor clinical outcomes.

Discussion

Surgical considerations in EDS

People with EDS have compromised shoulder function, significant pain, and decreased quality of life scores, compared to healthy controls. Laxity and insufficiency in supporting joint capsules and ligaments can lead to symptomatic shoulder instability, with recurrent subluxations/dislocations contributing to generalized shoulder symptoms and dysfunction [94, 95].

Due to the generalized hyperlaxity characteristics, patellar instability is common in EDS patients, with patellar subluxation/dislocation and associated pain. This has the potential to lead to premature patellofemoral arthritis. Knee instability can also result in a much higher incidence of meniscal and articular cartilage injury [49]. The most common surgical procedures are patellar stabilization, patellar tendon repair or reconstruction, anterior cruciate ligament reconstruction, and total knee arthroplasty. Patellar stabilization includes medial patellofemoral ligament reconstruction, with or without tibial tubercle osteotomy to correct patellofemoral malalignment.

Patients with EDS may have complex hip pathologies due to underlying biomechanical and tissue healing factors that impact their treatment outcomes. Ligamentous laxity is common in the hip joint of EDS patients. Instability and excessive motion of hip joints may result in impingement and labrum tears requiring surgery. Mild acetabular dysplasia combined with a degree of hip joint instability due to the connective tissue disorder may require correction by peri-acetabular (Ganz) osteotomy, which may also require concomitant allograft labral reconstruction. It has been reported that labral reconstruction is more reliable than labral repair [96].

Spinal deformity in EDS is a challenging clinical problem that can lead to deterioration of trunk balance and posture, respiratory dysfunction, and digestive disorders as the deformity progresses, thereby reducing a patient’s quality of life and activities of daily living [57]. Management of scoliosis in immature patients with connective tissue diseases is challenging, as curves can progress rapidly due to generalized ligamentous laxity and muscle hypotonia. Underlying tissue fragility places these patients at risk for increased intraoperative blood loss. Using a multicenter prospective registry, the Pediatric Spine Study Group evaluated casting and bracing for early onset scoliosis in patients with connective tissue disorders including EDS and concluded that non-operative management postponed surgical intervention in a small sample of patients with moderate early onset scoliosis [97].

Surgeons need to be aware of all types of EDS. Surgery should be a last resort following conservative management given the high rate of complications following surgery in these patients [49]. For example, knee surgery is often discouraged in people with EDS due to high rates of failure [38, 96]. As noted by Homere et al. (2020), surgical management of instability in EDS can be challenging due to the likely inferior biomechanical properties of the collagen-containing structures [98].

Summary of evidence

We did not find convincing evidence of long-term success of orthopedic surgery in this population. Published manuscripts often focused on surgical techniques and challenges that may be specific to EDS such as hardware fixation failure, excessive bleeding, wound infections, and need for reoperation. Unfortunately, it was not possible to assess how trends and methods of approach have changed.

Future Research

Surgery is an option for a select number of specific orthopedic conditions in EDS, but there remains very little in the surgical literature to support this approach. The rate of failure of surgical intervention is clearly higher in persons with EDS, particularly for conditions where ligaments are repaired [49]. People with EDS have multiple joint problems for which surgery may be the only reasonable option [49]. Homere et al. (2020) suggest that more research is needed to determine potential differences in tissue material properties and joint mechanics between patients with joint instability and EDS versus those without connective tissue disorders [98]. Unfortunately randomized clinical trials (RCTs) are difficult to conduct in patients with EDS. Multi-site studies using defined inclusion criteria and standardized outcomes measures are needed. Outcome measures should establish a priori minimal important differences to determine improvement.

A correct diagnosis is important. For example, the cause of patients’ pain may be due to reasons other than the purpose of the surgery. Also, it is noteworthy that while the Beighton Score is used as a standard assessment method of generalized joint hypermobility in the diagnostic criteria for EDS and the hypermobility syndromes [99], it has limitations for both surgical decision-making and measuring the outcomes of surgery. The Beighton Score defines a joint that exceeds its normal range of motion and but does not address functional stability. In the knee, for example, another approach might be to use the knee assessment components in the Lower Limb Assessment Score [100] which captures more than just hyperextension.

Selection of the appropriate outcomes measure is an important consideration in designing prospective studies. For example, several of the shoulder studies included in this scoping review used the ASES, a measure of functional improvement. Other measures may be more useful for decision-making in patients with multiple directional instability, for example the Oxford Shoulder Instability Score (OSIS), a patient-reported outcome measure that assesses the severity of shoulder instability and its impact on the patient’s quality of life [101].

Future research is needed to determine the incidence and prevalence of orthopaedic manifestations that may require surgical interventions, the short and long-term outcomes of conservative management and surgery, and the rate of complications associated with each procedure. Ideally, future studies should include accurate diagnosis of the specific type of EDS studied, using stated criterion. Studies are needed to understand the stages of progression to surgery, including efficacy of physiotherapy and other nonsurgical interventions. Studies are also needed to determine the efficacy of postsurgical rehabilitation plans, ideally studies identifying measurable functional parameters of outcomes that are of practical relevance.

Conclusion

Conclusions to be drawn from this scoping review are limited by the underlying published literature on the topic. Ideally, the studies would lend themselves to a systematic review enabling us to address specific questions about outcomes defined a priori. The results of orthopaedic surgical procedures are somewhat variable in all joints but there is sparse comparative literature. A consensus process such as modified Delphi process could be used to determine the tradeoff between benefit and risk of harm [102].

Established surgical techniques that have been shown to be successful in the wider orthopaedic population require further examination to determine their efficacy in the EDS population. Because orthopedic complications for people with EDS may be different, patients should be counseled accordingly, and research should be conducted to further elucidate these differences.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

JRS and SEM conceptualized the study, abstracted data for the review, synthesized the results and wrote the draft manuscript. SAR and CAF were primary contributors in writing the manuscript. All authors read and approved the final manuscript.

Funding

This study did not have funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.