Encapsulating Peritoneal Sclerosis: Different clinical presentations and their management

Introduction: One of most common treatments of end-stage renal disease is peritoneal dialysis. Encapsulating peritoneal sclerosis is a complication in which the osmotic capacity of the peritoneal barrier is lost, due to infections or the irritating effect of dialysis solutions. This pathology has different clinical presentations, hence the need of different diagnostic and therapeutic methods. Objective: To present a series of three cases with encapsulating peritoneal sclerosis and different clinical pictures, using laparoscopy as the mainstay for diagnosis and treatment. Patients and methods: This work describes the clinical and imaging features of three patients. A systematic approach was utilized which included the delimitation of the affected zone, sterilization, collapse of the cavity, and change of dialysis mode until renal transplantation. Conclusions: Our work suggests that a laparoscopic approach to encapsulating peritoneal sclerosis can be very valuable for the diagnosis and treatment of this condition and controlled clinical trials are warranted to validate this observation. Research Article Encapsulating Peritoneal Sclerosis: Different clinical presentations and their management Jaime Manuel Justo-Janeiro (fi csfacs)1, 2*, Elizabeth Huerta-Calixto2, de la Rosa Paredes René2, Fernando Vázquez de Lara3 and Luis G Vázquez de Lara1 1Faculty of Medicine, Meritorius Autonomous University of Puebla, Mexico 2Department of Organ Transplantation, General Hospital of Puebla “Dr. Eduardo Vázquez Navarro”, Puebla, Puebla, Mexico 3Department of Internal Medicine, Icahn School of Medicine at Mount Sinai West and St. Luke’s, New York, NY, USA Dates: Received: 09 March, 2017; Accepted: 17 May, 2017; Published: 19 May, 2017 *Corresponding author: Jaime Manuel Justo-Janeiro, Department of Organ Transplantation, General Hospital of Puebla “Dr. Eduardo Vázquez Navarro”, Puebla, Puebla, Mexico, Tel: 52 (222) 303-83-91; E-mail:


Introduction
According to The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines for chronic kidney diseases, end-stage renal disease (ESRD) is defi ned as an irreversible decline in kidney function, characterized by a level of glomerular fi ltration rate (GFR) below 15 mL/min/1.73 m2 or by the need of dialysis or transplantation, regardless of the level of GFR [1]. The etiology is diverse and age-related.
Currently, patients with ESRD are offered peritoneal dialysis, hemodialysis or renal transplantation as renal replacement therapies [2,3]. Peritoneal dialysis is the most widely used, because it is inexpensive and can be performed in an ambulatory basis [4]. The fi rst description of this therapy was made by Ganter in 1923, but it was until 1976 when Popovich et al. [5], described the basic concepts of continuous ambulatory peritoneal dialysis (CAPD) as they are known today. Current techniques allow peritoneal fl uid instillation and drainage with minimum disruption in patient's lifestyle [6]. This therapy utilizes the peritoneal membrane's properties for diffusion and ultrafi ltration and its effectiveness depends on the functional and structural integrity of the peritoneum. The peritoneal membrane is a complex and functional structure which is formed by a layer of mesothelial cells, connective tissue, blood vessels, lymphatic vessels and innate immune cells which can be affected by peritoneal dialysis in the long term [3,7].
Encapsulating peritoneal sclerosis (EPS) is defi ned by clinical and pathologic criteria, such as macroscopic honeycomb appearance, fi brin deposits, edema, mononuclear infi ltration, fi broblast activation markers and fi broblast proliferation into the peritoneum [8,9]. EPS impairs the capability of the peritoneum for diffusion and dialysis and it must be suspected in any patient with evidence of ultrafi ltration failure [10,11]. and a cocoon appearance. These fi ndings can be seen with ultrasound, tomography or MRI. Clinically, patients may be asymptomatic or show evidence of intestinal obstruction with nausea, vomiting, abdominal distention, anorexia and weight loss, fever and an abdominal mass [13]. There is not a widely accepted biochemical marker to diagnose EPS; however, some authors have suggested that low levels of CA125 and high concentrations of IL6 in dialysis fl uid have a 70% sensitivity and 89% specifi city in diagnosing EPS. Honda has proposed that a persistently elevated C reactive protein may aid in the diagnosis of EPS [14].
The aim of this work is to describe three clinical presentation patterns found in EPS in a clinical case format along with laparoscopy-based therapeutic options.

Methods
We present the clinical and imaging features of three different patients with EPS. A systematic decision-making process for the resolution of each case was used, which comprised of the delimitation of the affected zone, sterilization, collapse of the cavity, and change of dialysis mode until renal transplantation.

Patient 1
An 18 year-old male with ESRD treated with CAPD for 42 months, was considered for renal transplantation. During the physical exam, a solid and fi xed 20 x 30 cm epigastric mass was found, and laparoscopic exploration was offered.

Discussion
Long term CAPD diminishes solute transport, changes the vascularity and increases blood fl ow to the peritoneum, resulting in a conductance decrease that leads to progressive fi brosis [15].
This mode of renal replacement therapy is not exempt from morbidity. During CAPD the peritoneum is continually exposed to hyperosmotic fl uids with high glucose concentration. The acidity of the fl uids and the degradation products that are formed during CAPD favor a chronic infl ammatory state, which modifi es the peritoneum's immunologic response and predisposes to infections and membrane loss in the long term, even in the absence of episodes of peritonitis [4]. Efforts have been made to develop new biocompatible dialysis fl uids [16] such as Dianeal™ (Baxter Healthcare, Deerfi eld, Il, USA), which increases pH resulting in an alkaline fl uid and 7.5% Morphologic changes observed include loss of mesothelial cells, submesothelial fi brosis, granulation tissue, macrophage infi ltration and neoangiogenesis [18]. Uremia and chronic exposure to these molecules lead to changes in proteoglycan production and alteration of the extracellular matrix. Jiménez-Heffernan et al. [4], observed that myofi broblasts involved in the peritoneum fi brogenesis, originate from local fi broblasts and from transformation of mesothelial cells which acquire contractile ability and produce extracellular collagen, glycosaminoglycans and fi bronectin matrix [19].
Furthermore, it has recently been observed that chronic dialysis promotes chronic infl ammation and adiposity.
Adipocytes affect the metabolism of mesothelial cells through the synthesis of a number of mediators including adipokines (leptin, resistin and other growth factors) and their receptors, forming an autocrine, paracrine and endocrine local web which contribute to systemic infl ammation and decreasing survival [20,21].
After one year with peritoneal dialysis all patients develop peritoneal sclerosis, but only a few will have encapsulating peritoneal sclerosis (EPS). Even though it is a rare complication it carries a high morbidity and mortality. Some authors have observed a 20% death rate after 10 years with dialysis. In children the incidence is approximately 6.6% at 5 years and 22% after 10 years [22].
The clinical picture of EPS has a wide range of symptoms.
We presented three cases which required an individualized diagnostic and therapeutic approach, from simple observation to direct intervention for sealing the sclerotic cavity. We identifi ed four phases for the diagnosis and treatment: 1)   In the presented cases, clinical suspicion began with the visualization or palpation of an abdominal mass, followed by image confi rmation to rule out a solid mass. Hence, the fi rst study should be an abdominal ultrasound and later a tomography to defi ne size, location and organ involvement [23]. In addition, EPS should be ruled out when there is evidence of ultrafi ltration failure.
Diagnostic abdominal paracentesis is mandatory in order to obtain a culture sample to rule out infection. When culture is positive, the treatment must include specifi c antimicrobial therapy and repeated peritoneal lavages through the dialysis catheter with dialysis solutions until the culture is negative.
In case 1, once the culture became negative, the cavity was collapsed with 2% polydocanol trough the dialysis catheter and external compression to avoid further fl uid collection, without complications or adverse reactions.
The use of laparoscopy is helpful to determine the nature of the cavities, allowing the cleaning and curettage of the inner wall under direct vision to remove detritus that may complicate the resolution of infection, while minimally invading the patient [24].
Laparoscopy also aids in the differential diagnosis.
Other diseases such as pseudomyxoma peritonei, peritoneal tuberculosis, mesothelioma and peritoneal carcinomatosis may show similar imaging features, but the distinction can be made with laparoscopic exploration, because of their characteristic visual appearances and the ability of performing a biopsy of the lesion [25].
When the diagnosis is made, the peritoneal dialysis must be suspended and the patient should be switch to hemodialysis.
Nutritional support must be considered because of the risk of protein loss.
Treatment modalities include the administration of drugs to decrease the fi brotic process, which include prednisolone, sirolimus and everolimus [26] or renin-angiotensin blockers.
Other drugs that have shown some benefi t, especially in diabetic patients, are azathioprine, mycophenolate mofetil, acetyl cysteine, colchicine, thalidomide and rosiglitazone. Tamoxifen, an antifi brinolytic agent, has been used intraperitoneally with positive results [27].
Surgical treatment includes peritoneum cleavage, lysis of adhesions and intestinal resection when nonviable tissue is found. Reported mortality ranges from 24 to 53% in some series [28].

Conclusion
EPS is a rare complication in patients with ESRD who undergo peritoneal dialysis. It must be suspected in patients with evidence of ultrafi ltration failure, especially if an abdominal mass is present. The early recognition and adequate treatment of this complication gives the opportunity to switch to other renal replacement therapies, especially renal transplantation.
Our work suggests that the laparoscopic approach to this disease can be of substantial benefi t and controlled clinical trials are warranted to validate this observation.