Ehlers-Danlos syndrome: recommendations for anaesthesia and perioperative management
Thomas Wiesmann, Marco Castori, Fransiska Malfait and Hinnerk Wulf summarise recommendations for general, obstetric and regional anaesthesia in patients with a rare, heritable connective tissue disorder.
Ehlers-Danlos syndrome (EDS, Orphanumber: ORPHA98249) is an umbrella term for a growing number of heritable connective tissue disorders, mainly featuring joint hypermobility and instability, skin texture anomalies and vascular and internal organ fragility [1–3]. The overall incidence is 1:10,000 to 1:25,000 with no ethnic predisposition [4], resulting in a presumed number of at least 20,000–50,000 EDS patients in North America. However, the real frequency is probably underestimated due to the general lack of awareness among the various disciplines of such a protean condition, especially for the most atypical presentations. Clinical manifestations range from extremely mild phenotypes to life-threatening complications. The current Villefranche nosology recognises six major subtypes, comprising classic (corresponding to EDS type I and II of the ‘old’ Berlin nosology), hypermobile (EDS type III), vascular (EDS type IV), kyphoscoliotic (type VIA), arthrochalasia (types VIIA and VIIB) and dermatosparaxis (type VIIC), most of which are linked to mutations in one of the genes encoding for fibrillar collagen proteins or enzymes involved in post-translational modification of these proteins. Recently, several new EDS variants have been defined clinically and genetically. In addition, there has recently been suggested a possible connection between hypermobile EDS and the joint hypermobility syndrome [5], a relatively neglected rheumatologic condition recognised by specific diagnostic criteria [6]. However, not all researchers and clinicians agree with this view, which may be clarified by future molecular studies [7].
For the purposes of this review, we will use the last Villefranche classification. Most EDS subtypes are transmitted as autosomal-dominant or recessive traits; a general overview is presented in Table 1. For a comprehensive overview of genetic and clinical features, there are several published reviews on EDS [2,7]. Surgery is a concern [8]. Vascular EDS and the other rarer EDS variants with increased vascular fragility, e.g. classic-like EDS with arterial rupture due to arginine-to-cysteine substitutions in type I collagen [9] and kyphoscoliotic EDS, are associated with an increased frequency of arterial aneurysms and dissections. Vascular EDS is associated with spontaneous visceral ruptures. Due to the involvement of peri-articular non-ossified connective tissue, many EDS subtypes, especially the hypermobile and arthrochalasis types, may predispose to the need for orthopaedic surgery.
Methods
A literature search was conducted in PubMed and EMBASE for all published literature on the clinical management of EDS. The searches, performed in November 2013, spanned the literature from 1950 to 2013. The following search string was used: Ehlers-Danlos [OR] EDS [AND] anesthesia [OR] anaesthesia [OR] perioperative management. A supplementary search was performed using the references of the selected papers, as well as from personal literature databases (TW, MC and FM). The retrieved literature was screened for information on anaesthetic and perioperative management. Interventional studies (experimental or quasi-experimental designs) were defined as those in which an investigator determined the treatment regimen. Observational studies were defined as those in which treatment was decided on the basis of the clinical characteristics of each individual patient. Studies were labelled as case reports or case series when patients were individually described.
This review article does not include data obtained in clinical or laboratory animal studies. Thus, no ethical approval by clinical ethical committees or governmental responsibilities was needed for this article.
Results
A Pubmed search retrieved 102 articles, and EMBASE 72 articles. Three further articles were obtained from the personal databases of the authors. There was one clinical trial [10], the rest were case reports (one or more patients undergoing anaesthesia for surgical or obstetric purposes), retrospective case series or reviews, guideline recommendations or expert opinion. Most case reports and case series deal with vascular EDS, a systematic publication bias towards the relatively rare vascular subtype (EDS subtype IV) (5% of all EDS patients). Furthermore, most retrieved case reports focus on peripartal management (i.e. obstetric anaesthesia). Five retrieved papers offered guidelines for EDS, dealing in part with anaesthetic [11], perioperative [12–14] or peripartal [15] topics. Dolan et al. [16] published the first recommendations for anaesthesia in EDS, and Kuczkowski [15] published guidelines for obstetric anaesthesia. Castori [14] summarised the relevant aspects for surgery and anaesthesia in patients with hypermobile EDS. A guideline by Orphanet UK [12] focuses on e