Development of Encapsulating Peritoneal Sclerosis Following Bacterial Peritonitis in a Peritoneal Dialysis Patient

Introduction 

Encapsulating peritoneal sclerosis (EPS) is an uncommon and often fatal complication in patients on peritoneal dialysis (PD) therapy. EPS is a clinical syndrome characterized by symptoms of impaired intestinal motility, such as anorexia, nausea, vomiting, abdominal fullness, abdominal pain, absent bowel sounds, and constipation.1 These presentations result from diffuse peritoneal thickening, sclerosis, calcifications, and encapsulation of the bowel loops.1 Progression of EPS usually is considered to be insidious; however, we describe a patient who developed EPS immediately after an episode of bacterial peritonitis. The diagnosis of EPS requires a high index of clinical suspicion, especially in long-term PD patients with symptoms of ileus. Imaging studies can be very important in confirming the diagnosis.

Discussion 

EPS is an uncommon, but catastrophic, complication of long-term PD therapy in which the peritoneum becomes progressively thickened, causing encasement of the small intestine. Its high mortality rate is related to complications from bowel obstruction (such as malnutrition, sepsis, and bowel perforation) and complications after surgical enterolysis. The incidence of EPS reported in the literature ranges from 0.7%-7.3%.1 Recent studies described the incidence to be 2.5% in Japan2 and 3.3% in a single-center study in the United Kingdom.3 The duration of PD treatment correlates with the risk and mortality of EPS.1 However, EPS had been observed even after discontinuation of PD therapy or kidney transplant in PD patients.1, 4

Clinical presentations of EPS are related to impaired small-intestinal motility and peritoneal inflammation and include abdominal pain, abdominal mass, nausea, vomiting, anorexia, malnutrition, weight loss, low-grade fever, hemorrhagic effluent, and recurring or nonresolving peritonitis. Another common clinical finding in EPS is loss of dialysis efficiency because of progressive increases in the mass transfer area coefficients of creatinine and glucose, leading to high peritoneal permeability and loss of ultrafiltration volume.5 Clinical presentations are variable and nonspecific and therefore cannot be used to establish a diagnosis of EPS.

Radiologic diagnosis had been recommended by the ad hoc committee of the Internal Society for Peritoneal Dialysis.1 A plain abdominal film frequently shows air-fluid level, a dilated small bowel with predominant distribution in the mid-abdomen, and peritoneal calcification (Fig 1).1, 6, 7, 8, 9, 10

Computed tomography can show dilated bowel loops, air-fluid level, intestinal wall thickening, increased mesenteric fat density, loculated peritoneal fluid with some free strands,7 and peritoneal enhancement. Small-bowel tethering to the mesentery may be noted posterior to or within an adjacent loculated fluid collection.11, 12 Peritoneal calcification typically presents on the visceral surface of the small bowel, but also can be seen in the parietal peritoneum,7 and can manifest as a small focal area of calcification, a fine linear pattern, or more extensive conglomerate calcification.11, 12 Peritoneal thickening can be found when the abdominal organs have not attached to the peritoneum (Fig 2).12

Sonographic examination shows tethering of bowel loops to the posterior abdominal wall, fine intraperitoneal echogenic strands, localized fluid collection, and dilated and fixed small bowels.10, 13 Membrane formation, which appears as an echogenic layer, can be found anterior to the bowel.13 In patients with late-stage EPS, the previsceral membrane formation and bowel lumen can be seen as a trilaminar structure consisting of (1) a superficial echogenic membrane, (2) a middle hypoechoic bowel wall, and (3) the inner echogenic bowel content.7 This characteristic appearance can represent peritoneal thickening or membrane formation over the bowel surface (Fig 3).7

Small-bowel series are more characteristic in patients with late-stage EPS and can indicate the separated dilated bowel loops,13 “cocooning” of varying lengths of small intestine enclosed by the thickened peritoneum,9 and increased bowel transit time (Fig 4).

The pathologic findings of EPS include peritoneal mesothelial cell loss, proliferation of fibroblasts, capillary angiogenesis, and deposition of extracellular matrix. However, these findings can result from PD alone, and the laparotomy/laparoscopy procedures are invasive. Laboratory results for patients can indicate anemia, hypoproteinemia, and increased C-reactive protein level. Studies of the dialysis effluent can reveal decreased cancer antigen 125 and increased interleukin 1β, interleukin 6, and interleukin 8 levels.14 However, these markers are not specific and do not serve to identify EPS in patients.

The cause of EPS is not well understood. Various risk factors have been reported and can be separated into 2 categories: PD dependent and PD independent. PD-related factors include PD duration; peritonitis; PD catheter; bioincompatible dialysis solution contents, such as acidity, high glucose concentration, high osmolarity, glucose degradation products, and acetate or lactate buffer; plasticizers; and sterilizing agents, such as chlorhexidine. PD-independent factors include β-blockers and genetic predisposition. However, no single etiologic factor directly related to the development of EPS has been identified.

According to a “2-hit” theory,15 2 factors are required for the onset of EPS. First is a predisposing factor, such as long-term PD therapy with bioincompatible dialysis solutions, resulting in disruption of the peritoneal/mesothelial physiologic state: mesothelial denudation, interstitial fibrosis, fibrin deposition, and neovascularization. Second, an initiating factor, such as infectious peritonitis, is superimposed to trigger the extensive peritoneal lesion characteristic of EPS.

Therapeutic strategies were derived from small case series and case reports. Removal of the PD catheter and transfer to hemodialysis therapy are mandatory. Other management options include immunosuppressant therapy, such as corticosteroid, azathioprine, mycophenolate mofetil, and tamoxifen; total parenteral nutrition for patients with ileus; and surgical enterolysis to free the bowel loops.6, 16

Our patient was maintained on stable long-term PD therapy and was free from peritonitis or gastroenterologic disorders before this hospitalization. However, extended use of PD, bioincompatible dialysis fluid, and β-blockers may have acted as the first hit, making her prone to develop EPS. Alteration of peritoneal transport function from low average to high, as indicated by the peritoneal equilibrium test, denotes her peritoneal damage. Peritoneal calcification is not an uncommon finding in patients such as ours, who receive long-term PD therapy or have hyperparathyroidism,17, 18 and thus peritoneal calcification alone is not indicative of EPS. However, when symptoms and signs of ileus developed although the peritonitis was well controlled, it prompted the need to consider the development of EPS. Such rapid and intense deterioration often can be overlooked,19 and clinical presentations of EPS, such as abdominal pain, nausea, vomiting, and fever, can be masked by the preceding bacterial peritonitis. These will result in delayed recognition of EPS and is a life-threatening crisis for the patient.

In conclusion, early recognition of EPS is imperative and requires a high index of clinical suspicion, especially with patients on long-term PD therapy or with severe nonresolving peritonitis. Imaging studies are noninvasive and useful tools to aid in the diagnosis of EPS.