The clinical features of patients with EPS at initial presentation can be non-specific, with abdominal pain, weight loss, nausea and vomiting being the most common initial symptoms. It is therefore important to investigate non-specific symptoms in ‘at-risk’ patients, especially patients undergoing peritoneal dialysis. It has been reported that the incidence of EPS is up to 3% in patients undergoing peritoneal dialysis, and is proportional to the amount of time spent undergoing dialysis.6 There have been three major studies regarding incidence and time on dialysis. A Japanese study (6923 peritoneal dialysis patients) demonstrated an incidence of 0.9% of patients on peritoneal dialysis progressing to EPS.7 A Manchester study with 810 dialysis patients, demonstrated an incidence of 3.3%.8 An Australian study showed an prevalence of 0.7%, which increased progressively with the duration of peritoneal dialysis (1.9%, 6.4%, 10.8%, and 19.4% for patients on dialysis for 2, 5, 6 and 8 years respectively).9
With the patients who developed EPS secondary to peritoneal dialysis in our series, the median duration of peritoneal dialysis was 53 months (range 36-78 months).
The aetiology of this difficult condition is unclear, with a two-hit’ hypothesis having been proposed.410 This hypothesis suggests disruption of peritoneal physiology and histology by a long duration of continuous exposure to hypertonic glucose dialysis solutions. A ‘second hit’ then provokes the full syndrome of EPS, with the second hit being due to recurrent peritonitis, exposure to infections such as tuberculosis, or even the paradox of discontinuing peritoneal dialysis (undergoing renal transplantation, or converting to haemodialysis). In this series, two patients suffered frequent attacks of peritonitis and required increasing glucose content in their dialysis solutions.
Augustine and colleagues propose plasma exudation, fibrin deposition and subsequent fibrosis as the basis of the pathogenesis.4 Loss of the peritoneal physiological responses of production of fibrinolytic agents increases the risk of fibrinous adhesions. Furthermore, over-expression of TGF-β1 is also associated with adhesions.
Glucose in dialysis fluid may have a role in peritoneal mesenchymal cell malfunction, stimulating angiogenesis with TGF-β (transforming growth factor β) and vascular endothelial growth factor (VEGF) production by mesothelial cells. This however, does not explain those cases not associated with dialysis.
A high index of suspicion is fundamental to diagnosis, especially with patients undergoing peritoneal dialysis suffering from intermittent sub-acute bowel obstruction and weight loss. The literature supports CT (with a scoring system)11 as the best imaging modality, although dynamic MRI may prove beneficial in the future.12
Management of EPS is complex, requiring a multidisciplinary approach. Nutritional support is central, with involvement of specialist dieticians from the outset. Nutrition can be complemented by oral supplements, enteral, or parenteral feeding. This can be successful in maintaining nutrition and minimising obstructive symptoms. Nutritional support should begin early, and may be required for a prolonged period.10 These patients will most likely also require post-operative nutritional support, as shown in our case series, where 4/7 patients were discharged on home TPN. However, only 1 patient has not been successfully weaned off TPN 24 months post-surgery.
There have been mixed data published regarding medical treatment of EPS. Corticosteroids have been the first line medical management with little evidence to support their use.6 Tamoxifen has been used with some theoretical basis - due to its anti-TGF-β properties - and is now the mainstay of medical therapy even though the controlled data are limited.n
14 A randomised controlled trial has not been carried out probably because of small numbers and difficulty of diagnosis. There is some evidence (mostly case reports), that immunosuppressants, such as Azathioprine or Ciclosporin, are effective in EPS. However, it must be noted, that there is a high incidence of EPS in renal transplant patients, who are immunosuppresed.15
Surgery should be performed prior to complete obstruction, and before the patient becomes nutritionally deplete. It requires a high index of suspicion of EPS, with the role of surgery being to restore gut function, relieve obstructive symptoms, improve nutrition and may be life-saving. It involves undertaking extensive enterolysis and peritonectomy. The aim is to perform the peritonectomy without enterotomy, or bowel resection, and without a stoma. Morbidity can be an issue with these complex cases, with complications of bleeding, intra-abdominal collections, recurrent obstruction, fistula and sepsis. This is difficult, time consuming surgery.
Prognosis is poor, especially with a late diagnosis. There is a mortality rate between 25% and 55% in the first year.616 In our study, two out of seven patients died within 2 years following their initial diagnosis. Emergency surgery for complete intestinal obstruction must be avoided, with a higher mortality of 60-93%.
Augustine and colleagues in both 2009 and 2012, have clearly indicated these complex patients are challenging to manage.410 These patients need access to an experienced nutrition support team for potentially pre- and post-operative TPN. It is important to avoid emergency surgery in these malnourished patients. If they require surgery, this should be done in a dedicated centre with an experienced intestinal failure surgeon with access to a full team of multi-disciplinary specialists (radiology, nursing, dietetics), including access to home TPN. There should be a national registry of these rare patients to collate outcome and research data.
In England, centres in Manchester and Cambridge are designated by the National Specialist Commissioning Group4 for treatment of patients with this rare disorder since 2009.