Surgical Care

Extreme caution is mandatory in any surgical maneuver. Type IV Ehlers-Danlos syndrome (EDS) patients should be carefully monitored because they are at high risk for spontaneous rupture of a large artery (eg, splenic artery, aorta) or perforation of internal organs. These patients should be educated that surgery can pose life-threatening risks.

Plastic re-excision of scars sometimes provides acceptable cosmetic results.

Anesthetic implications, although rare, are very important in Ehlers-Danlos syndrome, especially in the type IV (or vascular) patients. Risk of complications is higher, spontaneous vascular rupture can occur, and cervical spine and airway trauma must be kept in mind. Bleeding is also reported.^[52]Lethal arterial events may occur.^[53] Fernandez-Alcantud reviewed management of anesthesia in vascular type IV Ehlers-Danlos syndrome patients.^[54] Jones reports the use of local anesthesia for elective cesarian delivery in a type III Ehlers-Danlos syndrome woman.^[55]

Recombinant factor VIIa has been successful in the treatment of intractable bleeding in vascular-type Ehlers-Danlos syndrome.^[56]

Activity

Patients with Ehlers-Danlos syndrome (EDS) types IV or VI should avoid participating in dangerous contact sports. Some authors mention risks with activities that can increase intracranial pressure as a result of the Valsalva effect. An example of one such activity is playing the trumpet.

Medication

Castori M, Hakim A. Contemporary approach to joint hypermobility and related disorders. Curr Opin Pediatr. 2017 Dec. 29 (6):640-649. [QxMD MEDLINE Link].
Junkiert-Czarnecka A, Pilarska-Deltow M, Bąk A, Heise M, Haus O. New variants in COL5A1 gene among Polish patients with Ehlers-Danlos syndrome: analysis of nine cases. Postepy Dermatol Alergol. 2019 Feb. 36 (1):29-33. [QxMD MEDLINE Link].
Hamonet C, Frédy D, Lefèvre JH, Bourgeois-Gironde S, Zeitoun JD. Brain injury unmasking Ehlers-Danlos syndromes after trauma: the fiber print. Orphanet J Rare Dis. 2016 Apr 22. 11:45. [QxMD MEDLINE Link].
Umekoji A, Fukai K, Hosomi N, Ishii M, Tanaka A, Murakami K, et al. Vascular type of Ehlers-Danlos syndrome associated with mild haemophilia A. Clin Exp Dermatol. 2009 Jan. 34 (1):101. [QxMD MEDLINE Link].
Leganger J, Fonnes S, Kulas Søborg ML, et al. The most common comorbidities in patients with Ehlers-Danlos syndrome: a 15-year nationwide population-based cohort study. Disabil Rehabil. 2022 Jan. 44 (2):189-193. [QxMD MEDLINE Link].
Rombaut L, Malfait F, De Wandele I, Cools A, Thijs Y, De Paepe A, et al. Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers-Danlos syndrome. Arch Phys Med Rehabil. 2011 Jul. 92 (7):1106-12. [QxMD MEDLINE Link].
Kitagawa T, Matsui N, Nakaizumi D. Structured Rehabilitation Program for Multidirectional Shoulder Instability in a Patient with Ehlers-Danlos Syndrome. Case Rep Orthop. 2020. 2020:8507929. [QxMD MEDLINE Link].
Reina-Bueno M, Vázquez-Bautista C, Palomo-Toucedo IC, Domínguez-Maldonado G, Castillo-López JM, Munuera-Martínez PV. Custom-Made Foot Orthoses Reduce Pain and Fatigue in Patients with Ehlers-Danlos Syndrome. A Pilot Study. Int J Environ Res Public Health. 2020 Feb 20. 17 (4):[QxMD MEDLINE Link].
Grahame R. The multisystemic nature and natural history of joint hypermobility syndrome and Ehlers-Danlos syndrome in children: New research data conflict with widely held views. Rheumatology (Oxford). 2017 Dec 1. 56 (12):2048-2049. [QxMD MEDLINE Link].
Brady AF, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-Seebacher I, et al. The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017 Mar. 175 (1):70-115. [QxMD MEDLINE Link].
Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, et al. Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017 Mar. 175 (1):40-47. [QxMD MEDLINE Link].
Eder J, Laccone F, Rohrbach M, Giunta C, Aumayr K, Reichel C, et al. A new COL3A1 mutation in Ehlers-Danlos syndrome type IV. Exp Dermatol. 2013 Mar. 22 (3):231-4. [QxMD MEDLINE Link].
Ghali N, Baker D, Brady AF, Burrows N, Cervi E, Cilliers D, et al. Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers-Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility. Genet Med. 2019 Mar 6. [QxMD MEDLINE Link].
Schwarze U, Atkinson M, Hoffman GG, Greenspan DS, Byers PH. Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II). Am J Hum Genet. 2000 Jun. 66 (6):1757-65. [QxMD MEDLINE Link].
Bouma P, Cabral WA, Cole WG, Marini JC. COL5A1 exon 14 splice acceptor mutation causes a functional null allele, haploinsufficiency of alpha 1(V) and abnormal heterotypic interstitial fibrils in Ehlers-Danlos syndrome II. J Biol Chem. 2001 Apr 20. 276 (16):13356-64. [QxMD MEDLINE Link].
Wenstrup RJ, Florer JB, Willing MC, Giunta C, Steinmann B, Young F, et al. COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. Am J Hum Genet. 2000 Jun. 66 (6):1766-76. [QxMD MEDLINE Link].
Sun M, Connizzo BK, Adams SM, Freedman BR, Wenstrup RJ, Soslowsky LJ, et al. Targeted deletion of collagen V in tendons and ligaments results in a classic Ehlers-Danlos syndrome joint phenotype. Am J Pathol. 2015 May. 185 (5):1436-47. [QxMD MEDLINE Link].
Yeowell HN, Walker LC. Mutations in the lysyl hydroxylase 1 gene that result in enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome type VI. Mol Genet Metab. 2000 Sep-Oct. 71 (1-2):212-24. [QxMD MEDLINE Link].
Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G, van Vlijmen IM, et al. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001 Oct 18. 345 (16):1167-75. [QxMD MEDLINE Link].
Boudko SP, Engel J, Okuyama K, Mizuno K, Bächinger HP, Schumacher MA. Crystal structure of human type III collagen Gly991-Gly1032 cystine knot-containing peptide shows both 7/2 and 10/3 triple helical symmetries. J Biol Chem. 2008 Nov 21. 283 (47):32580-9. [QxMD MEDLINE Link].
Okamoto O, Ando T, Watanabe A, Sato F, Mimata H, Shimada T, et al. A novel point mutation in type III collagen gene resulting in exon 24 skipping in a case of vascular type Ehlers-Danlos syndrome. Arch Dermatol Res. 2008 Oct. 300 (9):525-9. [QxMD MEDLINE Link].
Viglio S, Zoppi N, Sangalli A, Gallanti A, Barlati S, Mottes M, et al. Wound repair capability in EDS fibroblasts can be retrieved by exogenous type V collagen. ScientificWorldJournal. 2008 Oct 3. 8:956-8. [QxMD MEDLINE Link].
Kuz'mina NS, Shipaeva EV, Semyachkina AN, Vasil'eva IM, Kovalenko LP, Durnev AD, et al. Polymorphism of detoxification genes and cell resistance to mutagens in patients with Ehlers-Danlos syndrome. Bull Exp Biol Med. 2007 Nov. 144 (5):717-21. [QxMD MEDLINE Link].
Murray ML, Yang M, Fauth C, Byers PH. FKBP14-related Ehlers-Danlos syndrome: expansion of the phenotype to include vascular complications. Am J Med Genet A. 2014 Jul. 164A (7):1750-5. [QxMD MEDLINE Link].
Bethea BT, Fitton TP, Alejo DE, Barreiro CJ, Cattaneo SM, Dietz HC, et al. Results of aortic valve-sparing operations: experience with remodeling and reimplantation procedures in 65 patients. Ann Thorac Surg. 2004 Sep. 78 (3):767-72; discussion 767-72. [QxMD MEDLINE Link].
Remvig L, Flycht L, Christensen KB, Juul-Kristensen B. Lack of consensus on tests and criteria for generalized joint hypermobility, Ehlers-Danlos syndrome: hypermobile type and joint hypermobility syndrome. Am J Med Genet A. 2014 Mar. 164A (3):591-6. [QxMD MEDLINE Link].
Castori M, Dordoni C, Morlino S, Sperduti I, Ritelli M, Valiante M, et al. Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. Am J Med Genet C Semin Med Genet. 2015 Mar. 169C (1):43-53. [QxMD MEDLINE Link].
Scheper MC, Nicholson LL, Adams RD, Tofts L, Pacey V. The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study. Rheumatology (Oxford). 2017 Apr 18. [QxMD MEDLINE Link].
Yassin OM, Rihani FB. Multiple developmental dental anomalies and hypermobility type Ehlers-Danlos syndrome. J Clin Pediatr Dent. 2006 Summer. 30 (4):337-41. [QxMD MEDLINE Link].
Kapferer-Seebacher I, Oakley-Hannibal E, Lepperdinger U, Johnson D, Ghali N, Brady AF, et al. Prospective clinical investigations of children with periodontal Ehlers-Danlos syndrome identify generalized lack of attached gingiva as a pathognomonic feature. Genet Med. 2021 Feb. 23 (2):316-322. [QxMD MEDLINE Link].
Cortés-Bretón Brinkmann J, García-Gil I, Lobato-Peña DM, Martínez-Mera C, Suárez-García MJ, Martínez-González JM, et al. The key role of the dental practitioner in early diagnosis of periodontal Ehlers-Danlos syndromes: a rare case report of siblings. Quintessence Int. 2021. 52 (2):166-174. [QxMD MEDLINE Link].
van Bon AC, Kristinsson JO, van Krieken JH, Wanten GJ. Concurrent splenic peliosis and vascular Ehlers-Danlos syndrome. Ann Vasc Surg. 2009 Mar. 23 (2):256.e1-4. [QxMD MEDLINE Link].
Guala A, Viglio S, Ottinetti A, Angeli G, Canova G, Colombo E, et al. Cutaneous metaplastic synovial cyst in Ehlers-Danlos syndrome: report of a second case. Am J Dermatopathol. 2008 Feb. 30 (1):59-61. [QxMD MEDLINE Link].
Vilisaar J, Harikrishnan S, Suri M, Constantinescu CS. Ehlers-Danlos syndrome and multiple sclerosis: a possible association. Mult Scler. 2008 May. 14 (4):567-70. [QxMD MEDLINE Link].
Perrinaud A, Matos M, Maruani A, Mondon K, Machet L. [Absence of inferior labial or lingual frenula in Ehlers-Danlos syndrome: a new diagnostic criterion?]. Ann Dermatol Venereol. 2007 Nov. 134 (11):859-62. [QxMD MEDLINE Link].
Baba CS, Sharma PK, Deo V, Pal S, Sethuraman G, Gupta SD, et al. Association of Ehlers-Danlos syndrome and solitary rectal ulcer syndrome. Indian J Gastroenterol. 2007 May-Jun. 26 (3):149-50. [QxMD MEDLINE Link].
Savasta S, Crispino M, Valli M, Calligaro A, Zambelloni C, Poggiani C. Subependymal periventricular heterotopias in a patient with ehlers-danlos syndrome: a new case. J Child Neurol. 2007 Mar. 22 (3):317-20. [QxMD MEDLINE Link].
Miles SC, Robinson PD, Miles JL. Ehlers–Danlos syndrome and anorexia nervosa: a dangerous combination?. Pediatr Dermatol. 2007 May-Jun. 24 (3):E1-4. [QxMD MEDLINE Link].
Kundu AK, Chattopadhyay P, Kundu S, Choudhury S. Pregnancy in Ehlers-Danlos syndrome. J Assoc Physicians India. 2006 Dec. 54:938. [QxMD MEDLINE Link].
Spiegel E, Nicholls-Dempsey L, Czuzoj-Shulman N, Abenhaim HA. Pregnancy outcomes in women with Ehlers-Danlos Syndrome. J Matern Fetal Neonatal Med. 2022 May. 35 (9):1683-1689. [QxMD MEDLINE Link].
Cortini F, Villa C, Marinelli B, Combi R, Pesatori AC, Bassotti A. Understanding the basis of Ehlers-Danlos syndrome in the era of the next-generation sequencing. Arch Dermatol Res. 2019 Mar 2. [QxMD MEDLINE Link].
Atzinger CL, Meyer RA, Khoury PR, Gao Z, Tinkle BT. Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome. J Pediatr. 2011 May. 158 (5):826-830.e1. [QxMD MEDLINE Link].
Dordoni C, Ritelli M, Venturini M, Chiarelli N, Pezzani L, Vascellaro A, et al. Recurring and generalized visceroptosis in Ehlers-Danlos syndrome hypermobility type. Am J Med Genet A. 2013 May. 161A (5):1143-7. [QxMD MEDLINE Link].
Ayoub S, Ghali N, Angwin C, Baker D, Baffini S, Brady AF, et al. Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers-Danlos syndrome. Am J Med Genet A. 2020 Feb 24. [QxMD MEDLINE Link].
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar. 175 (1):8-26. [QxMD MEDLINE Link].
Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017 Mar. 175 (1):148-157. [QxMD MEDLINE Link].
Sinibaldi L, Ursini G, Castori M. Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised. Am J Med Genet C Semin Med Genet. 2015 Mar. 169C (1):97-106. [QxMD MEDLINE Link].
Aalberts JJ, van den Berg MP, Bergman JE, du Marchie Sarvaas GJ, Post JG, van Unen H, et al. The many faces of aggressive aortic pathology: Loeys-Dietz syndrome. Neth Heart J. 2008 Sep. 16 (9):299-304. [QxMD MEDLINE Link].
Castori M. Ehlers-Danlos syndrome(s) mimicking child abuse: Is there an impact on clinical practice?. Am J Med Genet A. 2016 May 5. [QxMD MEDLINE Link].
Ritelli M, Morlino S, Giacopuzzi E, Bernardini L, Torres B, Santoro G, et al. A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations. Clin Genet. 2018 Jan. 93 (1):126-133. [QxMD MEDLINE Link].
Yang F, Yang RJ, Li Q, et al. Whole-exome sequencing facilitates the differential diagnosis of Ehlers-Danlos syndrome (EDS). Mol Genet Genomic Med. 2022 Mar. 10 (3):e1885. [QxMD MEDLINE Link]. [Full Text].
Alkadhi H, Wildermuth S, Desbiolles L, Schertler T, Crook D, Marincek B, et al. Vascular emergencies of the thorax after blunt and iatrogenic trauma: multi-detector row CT and three-dimensional imaging. Radiographics. 2004 Sep-Oct. 24 (5):1239-55. [QxMD MEDLINE Link].
Monroe GR, Harakalova M, van der Crabben SN, Majoor-Krakauer D, Bertoli-Avella AM, Moll FL, et al. Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1. Am J Med Genet A. 2015 Jun. 167 (6):1196-203. [QxMD MEDLINE Link].
Fernández-Alcantud J, López RC, Osado IR, Castro MR. [Management of anesthesia in vascular-type Ehlers-Danlos syndrome (type IV)]. Rev Esp Anestesiol Reanim. 2008 May. 55 (5):312-3. [QxMD MEDLINE Link].
Jones TL, Ng C. Anaesthesia for caesarean section in a patient with Ehlers-Danlos syndrome associated with postural orthostatic tachycardia syndrome. Int J Obstet Anesth. 2008 Oct. 17 (4):365-9. [QxMD MEDLINE Link].
Faber P, Craig WL, Duncan JL, Holliday K. The successful use of recombinant factor VIIa in a patient with vascular-type Ehlers-Danlos syndrome. Acta Anaesthesiol Scand. 2007 Oct. 51 (9):1277-9. [QxMD MEDLINE Link].
Nourissat G, Vigan M, Hamonet C, Doursounian L, Deranlot J. Diagnosis of Ehlers-Danlos syndrome after a first shoulder dislocation. J Shoulder Elbow Surg. 2018 Jan. 27 (1):65-69. [QxMD MEDLINE Link].

Media Gallery

Patient with Ehlers-Danlos syndrome. Note the abnormal ability to elevate the right toe. Courtesy of Enrico Ceccolini, MD.
Girl with Ehlers-Danlos syndrome. Dorsiflexion of all the fingers is easy and absolutely painless. Courtesy of Enrico Ceccolini, MD.
Patient with Ehlers-Danlos syndrome mitis. Joint hypermobility is less intense than with other conditions. Courtesy of Enrico Ceccolini, MD.
Dorsal view of a patient with Ehlers-Danlos syndrome. Note the S-curved spinal column. Courtesy of Enrico Ceccolini, MD.
Cigarette-paper–like scars over the knees of a patient with Ehlers-Danlos syndrome. Note also the deformity of the left knee. Courtesy of Enrico Ceccolini, MD.
Criteria for Ehlers-Danlos syndrome are shown in Media Files 6-11. Dorsiflexion of the little finger by more than 90°with the forearm flat on the table.
Passive apposition of the thumb to the flexor forearm.
Hyperextension of the elbow by more than 90°.
Hyperextension of the knee by more than 10°.
Forward flexion of the trunk until the palms of the hands rest easily on the floor.
Evaluation of skin extensibility.

of 11

Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Enrico Ceccolini, MD Consulting Staff, Department of Dermatology, University of Bologna; Private Practice, Pesaro, Italy

Enrico Ceccolini, MD is a member of the following medical societies: American Academy of Dermatology, International Society of Dermatology, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Noah S Scheinfeld, JD, MD, FAAD † Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Ehlers-Danlos Syndrome Treatment & Management

Surgical Care

Activity

References

Tables

Contributor Information and Disclosures

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