Vascular Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos syndrome (v-EDS) is a connective tissue disease resulting from mutations in COL3A1 gene, coding for type III procollagen, a major protein in vessel walls and hollow organs (1,2). Common clinical features include translucent skin, prominent superficial veins, abnormal facial appearance, easy bruising, and arterial, intestinal, and/or uterine fragility (1,2). In children, it usually presents with sigmoid perforation or vascular rupture (3). A history of chronic constipation with megacolon starting in adolescence can precede intestinal perforation (1). Intestinal failure (IF) requiring long-term parenteral nutrition (PN) has not been reported in children with v-EDS. We report a case of IF in a child with v-EDS because of multiple high-output enterocutaneous fistulae requiring long-term PN. CASE REPORT A 15-year-old boy presented with abdominal pain after a 6-day history of constipation. He was in haemodynamic shock and had radiological signs of a perforated viscus. There was neither a history of chronic constipation nor any treatment for constipation before presentation. Urgent laparotomy revealed faecal peritonitis because of sigmoid perforation. The sigmoid colon was oversewn with formation of an ileostomy. Multiple enterocutaneous fistulae and wound dehiscence developed post-operatively (Fig. 1). On the basis of spontaneous intestinal perforation and marked bowel friability noted at surgery, v-EDS was suspected and confirmed by genetic analysis. A heterozygous missense mutation c.1700G>A was identified in the COL3A1 gene. His parents did not share this mutation. On reflection, this patient exhibited nonspecific features of v-EDS, including translucent skin, pale face, sunken eyes, and easy bruising. Magnetic resonance angiography showed no evidence of vascular aneurysm.FIGURE 1: Enterocutaneous fistulae opening into a wide abdominal wall.The patient had a challenging postoperative course including persistent drainage of 1500 to 2500 ml/day from fistulae with negligible ileostomy drainage. Intestinal rehabilitation team approach included prompt introduction of PN, acid-suppressant and anti-motility agents, and correction of fluid and electrolyte imbalances. Subsequent strategies included enteral nutrition (EN), high-energy oral diet and restriction of hypotonic drinks. The risk of IF-associated liver disease was minimized by optimization of PN to avoid overfeeding, cycled PN, fish oil-containing lipid emulsion, and strategies to improve feeding tolerance. Attempted PN wean after 6 months failed because of weight loss. A combined EN and PN regimen met his nutritional requirements, and his weight gradually improved (−0.75 SD). He required additional micronutrient supplementation to maintain normal serum zinc, magnesium, vitamin D, and carnitine levels. Dual energy X-ray absorptiometry demonstrated low lean body mass and osteopenia. He developed crush spine fractures requiring bisphosphonate treatment. The primary collagen disorder, reduced mobility and sun exposure, and delayed puberty contributed to increased fracture risk. Complications included recurrent large volume leakages from fistulae necessitating drainage bag changes at least twice weekly under general anaesthesia because of severe peristomal skin pain and behavioural issues. The high-output fistulae induced multiple episodes of dehydration, metabolic acidosis, and electrolyte imbalance. Intensive nutritional therapy resulted in wound size reduction; however, the fistulae continued to drain. A year after his initial surgery, the fistulae were surgically resected with formation of an end-to-end anastomosis, a new ileostomy, and closure of abdominal wall. One month later, enterocutaneous fistulae recurred with wound dehiscence, and PN was re-commenced. With lower fistulae output, enteral autonomy was successfully achieved after a few weeks. DISCUSSION v-EDS is a rare connective tissue disorder that usually presents with colonic perforation often without a prior history of constipation. IF requiring long-term PN is not reported in children with v-EDS in the literature. Enterocutaneous fistulae are uncommon in childhood (4) and are associated with sepsis, malnutrition, dehydration, and metabolic disturbances (5). The definition of high-output fistulae is not well documented in children, but in adults is usually defined as above 500 ml/day (6). The output of proximal jejunal fistulae is 3 times greater than that from distal ileal fistulae (4). Our patient had drainage up to 3000 ml/day from 5 proximal jejunal fistulae resulting in a functional short bowel that behaved as a jejunostomy. Nutritional therapy plays a critical role in enterocutaneous fistulae management (6). In the initial phase, PN limits gastrointestinal secretions stimulated by EN while maintaining a positive energy balance (4). EN is paramount in intestinal adaptation (5) and is advanced according to tolerance and fistula output. Fistuloclysis can be an important adjuvant treatment to EN (5), but was technically difficult in our patient. Hypotonic drinks increase output resulting in a vicious circle of dehydration, and should be restricted (6). Strict monitoring of sodium balance is critical (6). Pharmacologic agents have a role in shortening the fistula closure time by reducing intestinal motility, and gastrointestinal secretions (5). In children, the time to fistula closure was reported between 6 and 107 days (7). This patient failed to achieve fistulae closure after 365 days of maximized conservative management, which likely reflects his underlying collagen disorder. Determining the best time for corrective surgery was challenging with little data to direct decision-making in v-EDS. The risk of mortality because of further surgery in the 3-month period following initial surgery (6) is compounded by an increased risk of mortality during surgery in patients with v-EDS (3). Optimizing nutritional status in the perioperative period may limit the contribution of malnutrition to poor outcomes (6). Ideally, diagnosis of v-EDS should be made before complications occur. Although an uncommon cause of constipation, clinicians should consider this rare diagnosis, given its potentially fatal complications especially in the presentation of late-onset constipation (1). Actions that increase perforation risk should be avoided, including enemas and contact sports. Early involvement of an intestinal rehabilitation team is recommended to minimize complications and avoid malnutrition that may impair healing, increase sepsis risk, and mortality (6). Bone health assessment is important in this population (1). Our case of prolonged IF in a child with v-EDS complicated by multiple high-output fistulae highlights the burden of high-output enterocutaneous fistulae and v-EDS on children and medical resources, and emphasizes the value of a multidisciplinary approach in this complex condition.