A 26-year-old woman recently diagnosed with hypermobile Ehlers-Danlos syndrome (EDS) and pregnant for the first time presents to your office for rheumatologic consultation. Symptoms of low back pain, anterior knee pain, and multiple episodes of subluxation of both hips first presented at age 18. The patient has a history of easy bruising, papyraceous scars, and early-onset striae atrophicae.
Family history included early-onset hip osteoarthritis in her mother and maternal grandmother. Her father has a history of bilateral hip dislocation. No formal diagnosis of EDS had been established for any of the patient’s family members.
The patient was assessed by a maternal-fetal medicine obstetric specialist following a fetal dating ultrasound at 13 weeks. Following the initial evaluation, she was referred for this rheumatologic consultation, as well as hematology, cardiology, and anesthesiology assessments.
What are some precautions you would advise for this patient with EDS, to minimize potential pregnancy-related complications?
EDS Introduction and Types of EDS
Ehlers-Danlos syndrome (EDS) is the term used for a group of genetic connective tissue disorders that are characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. The underlying pathophysiology in EDS involves inherited alterations in genes affecting the synthesis and processing of collagen.1 Patients suspected of having EDS based on their clinical presentation and family history should be referred to an expert in clinical genetics for confirmation of the diagnosis.
Six distinct EDS types are recognized using the Villefranche classification scheme, defined according to clinical features, as well as specific underlying genetic and biochemical defects.2 This revised nomenclature replaced the prior method of identifying the different forms by number. Under this classification, the 6 major types of EDS are identified as: classic, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis. The 2 most frequently diagnosed forms of the condition are the classic and hypermobile types.
Joint hypermobility is the hallmark of most types of Ehlers-Danlos syndromes. This can involve both proximal and distal joints. Assessment of the joints is accomplished using the Beighton hypermobility scale, which assigns points for the ability to perform each of 4 maneuvers, including dorsiflexion of the fifth finger >90 degrees, hyperextension of the elbow >10 degrees, hyperextensibility of the knee >180 degrees, and flexion of the waist with palms on the floor.2
Some forms of EDS are inherited in an autosomal-dominant pattern, including the classic, hypermobile, and vascular types of EDS. Heterozygocity for tenascin X deficiency can be associated with mild features of disease, including joint hypermobility.3
The hypermobile type of EDS is considered the least severe. Skin can appear velvety and hyperextensible. Striae distensae and piezogenic papules are present in classic and hypermobile types of EDS.
Patients with EDS are at increased risk for cardiac valvular disease and aortic dilatation.4 Although no standardized protocols exist for the evaluation of cardiovascular function with echocardiography in Ehlers-Danlos syndrome, a baseline screening echocardiogram is usually performed, with follow-up studies based on the initial results or the development of new symptoms.
Closer monitoring may be required in patients with vascular and kyphoscoliosis EDS, given the higher risk of cardiovascular diseases in these types of EDS and depending upon the severity of the illness. Particular attention should be paid to the aortic root diameter.4
Patients with joint hypermobility should be referred for physical and occupational therapy evaluation. A low-impact, muscle-strengthening program for joint protection and appropriate use of assistive devices, such as orthoses, can have a positive impact on activities of daily living.1
In patients with joint hypermobility, musculoskeletal pain may become chronic and difficult to treat. Pharmacologic treatment of joint pain involves the use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). However, NSAIDS may diminish platelet function and generally should be avoided in patients with a history of easy bruising. This is especially true if bleeding is anticipated during labor and delivery. Additionally, the chronic use of NSAIDs is discouraged in pregnancy when possible due to the possible increased risk of premature closure of the fetal ductus arteriosus and oligohydramnios.5
Increased ligament laxity and risk of tendon rupture are most concerning in patients during their third trimester.
Communication with the obstetric labor and delivery team, the anesthesia providers, and the newborn pediatric team is crucial. The availability of cross-matched blood, especially in patients with higher risk of postpartum bleeding, should be considered prior to surgery due to potential fragility of blood vessel walls.6
Patients with Ehlers-Danlos syndrome can have symptoms of esophagitis and gastroesophageal reflux (GERD); these should be addressed prior to delivery to minimize risk of aspiration while the patient is positioned for vaginal or Cesarean section delivery.
Patients with EDS are high-risk patients and should be followed by a maternal-fetal medicine specialist. They are at increased risk of having rapid progression of labor and delivery, as well as premature delivery due to cervical insufficiency or premature rupture of membranes.7 Currently, there are no clear recommendations favoring vaginal vs Cesarean delivery.
Patients with vascular Ehlers-Danlos syndrome are at higher risk for uterine rupture and postpartum hemorrhage.8
Some further complications of delivery in EDS include abnormal fetal presentations, delayed wound healing, uterus atonia, hemorrhage, pelvic prolapse, deep venous thrombosis, and coccyx dislocation.7
Joints should be kept in neutral positions if a patient receives neuraxial anesthesia for a Cesarean section delivery due to joint hypermobility and the risk of dislocation.
After delivery, postpartum hemorrhage, extension of episiotomy, and uterine/bladder prolapse can occur. Patients with the vascular type of Ehlers-Danlos syndrome are at greatest risk for these complications.8
Special precautions may be required for wound healing in patients with hyperelastic skin. Patients with significant skin fragility may decrease their risk of developing skin lacerations by the use of protective bandages or pads over especially exposed areas, such as the knees, shins, and forehead.
CORRECT ANSWER: C
Routine colonoscopy should be avoided because of the risks of colonic perforation; virtual colonoscopy should be avoided because of the use of insufflation, which may also increase such risks.9 Alternative noninvasive measures for cancer screening, such as testing for occult blood, should be considered unless invasive testing is absolutely warranted.
1. Callewaert B, Malfait F, Loeys B, De Paepe A. Ehlers-Danlos syndromes and Marfan syndrome. Best Pract Res Clin Rheumatol. 2008;22:165-189.
2. Malfait F, De paepe A. The Ehlers-Danlos syndrome. Adv Exp Med Biol. 2014;802:129-43.
3. Malfait F, Wenstrup RJ, De Paepe A. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genet Med. 2010;12:597-605.
4. Atzinger CL, Meyer RA, Khoury PR, et al. Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome. J Pediatr. 2011;158:826-830.
5. Antonucci R, Zaffanello M, Puxeddu E, et al. Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn. Curr Drug Metab. 2012;13(4):474-90.
6. Lindsay H, Lee-kim YJ, Srivaths LV. Perioperative hemostatic management in Ehlers-Danlos syndrome: a report of 2 cases and literature review. J Pediatr Hematol Oncol. 2016;38(2):158-160.
7. Hurst BS, Lange SS, Kullstam SM, et al. Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome. Obstet Gynecol. 2014;123(3):506-513.
8. Murray ML, Pepin M, Peterson S, Byers PH. Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos syndrome. Genet Med. 2014;16(12):874-880.
9. Lum YW, Brooke BS, Black JH 3rd. Contemporary management of vascular Ehlers-Danlos syndrome.Curr Opin Cardiol. 2011;26:494-501.