Encapsulating Peritoneal Sclerosis Leading to Small Bowel Obstruction in a Young Woman with End-Stage Renal Disease: A Case Report

Introduction

Peritoneal dialysis (PD) is a home-based treatment option with noteworthy quality-of-life benefits for patients with end-stage renal disease (ESRD) [1]. In PD, the peritoneal membrane acts as the dialyzing membrane, through which water and solutes are exchanged [2]. One of the concerns with long-term PD is the unavoidable fibrotic transformation of the peritoneum [1]. Within 1–2 years of starting PD, signs of peritoneal fibrosis can be detected in 50–80% of patients [3]. In several cases, a serious and life-threatening complication called encapsulating peritoneal sclerosis (EPS) may develop [1]. The International Society for Peritoneal Dialysis defines EPS as “a syndrome continuously, intermittently, or repeatedly presenting with symptoms of intestinal obstruction caused by adhesions of a diffusely thickened peritoneum” [4]. Owtschinnikow first described EPS in 1907 as “peritonitis chronica fibrosa incapsulata” [5]. Since then, it had been referred to as abdominal cocoon and sclerosing encapsulating peritonitis prior to being coined EPS [5]. The incidence of EPS secondary to PD varies considerably across the globe, at 0.5–7.3%, with recent students showing a decrease in the incidence, likely due to improved dialysis techniques [1,6]. Duration of PD is the largest risk factor for EPS development [5]. Incidence gradually increases with time, such that by 8 years, 10–20% of patients on PD develop EPS [5]. Mortality approaches 50% at 1 year after diagnosis, although, it is difficult to ascertain how much is related to EPS versus other ESRD-associated comorbidities [5,6]. Here, we report a case of a 37-year-old woman with ESRD and history of PD who presented with a small bowel obstruction (SBO) secondary to EPS. We aim to shed light on EPS, its pathogenesis, diagnosis, and management.

Case Report

A 37-year-old woman with a medical history of 10 years of ESRD secondary to uncontrolled hypertension and heart failure with reduced ejection fraction presented to the emergency department for evaluation of intractable nausea and vomiting onset 1 week ago, which was preceded by 1 week of diffuse abdominal pain. She reported having 2–3 episodes of postprandial nonbilious, non-bloody emesis that contained mostly food particles. She denied any weight loss, diarrhea, or constipation. She also denied any recent medication or diet changes. She reported having minimal urine output due to her ESRD. Ten years ago, she was started on PD, which she continued for 8.5 years until being transitioned to hemodialysis (HD) following an intraperitoneal catheter infection (Figure 1). She denied any alcohol use, tobacco use, or recreational substance use.

Vitals signs were notable for tachycardia at 106 beats per min. Physical examination was notable for a palpable thrill over the arteriovenous graft on her left upper extremity and mild suprapubic tenderness to palpation. Initial lab work revealed a potassium of 3.7 mEq/L, chloride of 82 mEq/L, blood urea nitrogen of 26 mg/dL, creatinine 10.91 mg/dL, alkaline phosphatase 125 U/L, normal alanine aminotransferase, and normal aspartate aminotransferase. Computed tomography (CT) of the abdomen with and without contrast showed large-volume ascites with a rind of peripheral enhancement (Figure 2) and mild circumferential bowel wall thickening (Figure 3). No high-grade obstruction was seen. Additionally, an upper gastrointestinal small bowel follow-through was obtained, which revealed a partial mechanical SBO with marked dilatation of the stomach, duodenum, and proximal jejunum. She received a mineral oil-glycerin-water (HOG) enema, with a resultant large bowel movement. Given her abdominal CT findings and SBO, she was subsequently diagnosed with secondary stage 3 EPS due to PD and was started on tamoxifen 10 mg 3 times a day and a 14-day course of prednisone 40 mg daily, with quick resolution of her nausea and vomiting.

She was then discharged home with instructions to follow-up with her primary care physician, nephrologist, gastroenterologist, and cardiologist. Upon follow-up with her primary care physician 1 week after discharge, her symptoms had completely resolved and she was doing well. Unfortunately, over the next 2 years, she has required numerous hospital admissions for recurrent SBOs despite being compliant with medications. As a result, she is being evaluated by general surgery for more invasive treatment options.

Discussion

The aim of this case report is to improve physicians’ understanding of EPS and help them diagnose and initiate treatment without delay. We will discuss the types of EPS, risk factors, pathophysiology, presentation, and management. EPS is divided into either primary or secondary [5]. The etiology of primary EPS is still unclear but it appears to affect men twice as often than women and has an equatorial geographic predilection [7,8]. The etiology of secondary EPS is either a local or a systemic trigger [5]. Some of the known triggers include medications, infection, cirrhosis, mechanical or chemical intraperitoneal irritants, endometriosis, organ transplantation, gynecologic neoplasms, dermoid cyst rupture, and systemic rheumatologic and inflammatory disorders [5]. As our patient developed secondary EPS due to PD, we will only focus on this etiology for the remainder of the discussion. As mentioned earlier, the largest risk factor for the development of EPS is the duration of PD [5]. Other risk factors include a history of renal transplantation, the use of high-glucose concentrations and icodextrin-based PD fluids (as glucose and glucose breakdown products increase inflammation), the number of peritonitis episodes, and the presence of high peritoneal permeability, which can be assessed using a peritoneal equilibration test [9].

The development of EPS in patients on PD is believed to be caused by the “two-hit” hypothesis, which states that the “first hit” is the repeated PD sessions causing a non-inflammatory peritoneal sclerosis [5,10], and the “second hit” then causes a cascade of cytokines involving both proinflammatory [transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6), connective tissue growth factor 2 (CCN2)], and proangiogenic [vascular endothelial growth factor (VEGF)] cytokines [5]. This cascade of cytokines results in the formation of a fibrocollagenous cocoon [11]. For our patient, the “first hit” was her 8.5 years of PD and the “second hit” was likely the intraperitoneal catheter infection, which resulted in her switching to HD.

Interestingly, most patients develop EPS after PD has been stopped, with symptoms occurring up to 5 years later [12]. Unlike our case, many reports of EPS secondary to PD involve a prior history of renal transplant, as described by Al-Lawati et al [13]. Taguchi et al presented a similar case to ours, in which their patient received 5 years of PD, was transitioned to HD, and then developed EPS 5 year later [14]. Most patients with EPS present malnourished, likely from intractable nausea and vomiting and poor oral intake [7]. Although our patient presented with abdominal pain, nausea, and vomiting, she was not malnourished, likely because this was her first presentation with SBO.

There are no specific laboratory tests for diagnosing EPS [5]. Imaging can often help delineate EPS from other causes of intestinal obstruction [5]. CT scan is the most definitive imaging technique for EPS [15]. It usually shows small bowel loops tethered together in an enveloping, thickened peritoneum, typically accompanied with proximal bowel dilation [15]. Abdominal plain films and a small bowel follow-through may also be helpful [5]. Abdominal plain films can demonstrate peritoneal calcification and dilated loops of bowel with air-fluid levels, which suggest advanced EPS [5]. Small bowel follow-through will reveal distension proximal to small bowel adhesions, delayed transit, and a compression of tightly adherent bowel loops giving a “cauliflower” appearance [8].

There are 4 stages of EPS, which have been categorized by Nakamoto et al based on abdominal symptoms and inflammation, encapsulation, and intestinal findings [16]. Stage 1 (pre-EPS) includes loss of ultrafiltration capacity, increase in the transport rate, hypoproteinemia, bloody dialysate, ascites, and peritoneal calcifications [16]. Stage 2 (inflammatory) includes increased C-reactive protein and a leukocytosis accompanied by fever, chills, weight loss, anorexia, diarrhea, and ascites [16]. Stage 3 (encapsulating) involves resolution of the inflammation seen in stage 2 with the clinical signs of SBO [16]. Stage 4 (chronic) entails a complete SBO associated with an abdominal mass and anorexia [16]. Our patient has secondary stage 3 EPS, as she presented with the clinical signs of SBO but showed no evidence of acute inflammation.

The goal of treating EPS is to relieve the symptoms and decrease the chance for recurrence. The treatment of EPS secondary to PD should initially involve treating the underlying condition [5]. This involves cessation of PD and transitioning to HD with optimization of nutrition [5,7]. Although nutrition in itself does not treat EPS, ensuring adequate nutrition – even total parenteral nutrition (TPN) if enteral feeding is not tolerated – has been shown to decrease hospital complications [7]. The next aspect of treatment is immunosuppression [5]. The most studied medication is corticosteroids, which should be used in patients with an active inflammatory component, but only after infection has been ruled out [5]. It is often difficult to determine which patients have active inflammation, and dosing and duration have not been well established [5]. Following immunosuppression, tamoxifen, a selective estrogen receptor modulator (SERM), can be used for its strong anti-fibrotic properties involving inhibition of TGF-β [5]. This can be used alone or in combination with corticosteroids [5]. The first use of tamoxifen in EPS was described by Allaria et al in 1999 [17]. A specific treatment dose for tamoxifen has not been well defined, but most studies use 10–40 mg daily for at least 1 year, with a clinical response typically seen in 1–6 months [5]. In patients who fail conservative management, surgical techniques such as enterolysis or bowel resection may be required, but these are time-consuming, hazardous, and technically difficult procedures [5]. In our case, our patient had already been transitioned off PD and was not found to be malnourished on examination. Therefore, she was started on prednisone and tamoxifen, but because of her repeated SBOs over the next 2 years, she is now being evaluated by surgery for more invasive treatment options. Taguchi et al differed from our case in that their management involved only glucocorticoid use and not tamoxifen [14].

Conclusions

This report presents a case of EPS, a rare complication of PD, which requires early diagnosis and management to prevent potentially fatal consequences. Management should be geared towards treating the underlying condition, optimizing nutrition, and using corticosteroids or tamoxifen (alone or in combination), depending on disease state and contraindications. The aim is to reduce recurrent SBOs. Failure of conservative and medical management may require surgical evaluation.