Encapsulating peritoneal sclerosis (EPS) is a chronic clinical syndrome with an insidious onset that manifests as chronic

undernourishment Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...

accompanied by sporadic, acute, or subacute gastrointestinal obstruction symptoms.

Peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...

is most commonly linked to encapsulating peritoneal sclerosis, especially when

peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...

is stopped. The diagnosis is verified by macroscopic and/or radiological observations of intestinal encapsulation, calcification, thickening of the

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of meso ...

, or sclerosis. Treatments that have been reported include the use of antifibrotic drugs like tamoxifen, immunosuppressant drugs like corticosteroids, nutritional support, and surgery to remove the fibrotic material.

Signs and symptoms

Patients usually present with abdominal symptoms such as altered bowel habits,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

, and early satiety. In the early stages, these symptoms can be linked to signs of

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

such as

pyrexia Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

and elevated CRP, and/or blood-stained

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

Abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

, fullness, overt bowel obstruction, and the presence of an

abdominal mass An abdominal mass is any localized enlargement or swelling in the human abdomen. Depending on its location, the abdominal mass may be caused by an enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), protruding kidney, a pancreatic m ...

are linked to the late stages of encapsulating peritoneal sclerosis. The

intestines The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

become gradually covered with a fibrous cocoon, which causes

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...

malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...

, bowel obstruction, ischemia and strangulation, infection, and death.

Causes

Encapsulating peritoneal sclerosis is typically observed in patients with end-stage renal disease (ESRD) receiving long-term

therapy. Dialysis fluid's high

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

content and acidic pH cause harm to the

. High

concentrations promote

osmosis Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region o ...

and diffusion gradients across the

, while low pH inhibits the production of harmful

degradation products (GDPs). GDPs are created when

fluid is heated to sterilize it and these result in the production of advanced

glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...

end products (AGEs) when

is present. Less GDP-containing biocompatible solutions are now more frequently used, which lessens peritoneal damage. Encapsulating peritoneal sclerosis can also occur in patients who are not on

but are suffering from other illnesses like endometriosis,

sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly a ...

, peritoneal and intra- abdominal cancers, chronic peritoneal

, intraperitoneal

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

, intraperitoneal exposure to particulate matter or disinfectant, abdominal surgery, intraperitoneal infections (

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...

), and

beta-blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...

administration.

Risk factors

The length of

treatment appears to be the primary risk factor for encapsulating peritoneal sclerosis development. The incidence of encapsulating peritoneal sclerosis rose with the length of

(PD) in an Australian survey; for patients on PD for more than 2, 5, 6, and 8 years, the rates were 1.9, 6.4, 10.8, and 19.4%, respectively. Given that there is a high incidence of encapsulating peritoneal sclerosis shortly after

renal transplantation Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantat ...

organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpor ...

seems to increase the risk of developing this condition. A frequent side effect of

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part o ...

is intricately linked to the development of encapsulating peritoneal sclerosis, with the frequency of episodes being correlated with the occurrence of encapsulating peritoneal sclerosis. Encapsulating peritoneal sclerosis has been specifically linked to recurrent peritonitis caused by bacterial contamination, specifically from

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able t ...

spp., Staphylococcus aureus, and specific fungal organisms.

Triggers

Implicated triggers include systemic

rheumatologic Rheumatology (Greek ''ῥεῦμα'', ''rheûma'', flowing current) is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatolog ...

and

inflammatory disorders Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

dermoid cyst A dermoid cyst is a teratoma of a cystic nature that contains an array of developmentally mature, solid tissues. It frequently consists of skin, hair follicles, and sweat glands, while other commonly found components include clumps of long hair ...

rupture, gynecologic neoplasms, endometriosis,

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

, mechanical or chemical intraperitoneal irritants, infection, and medications.

Mechanism

Encapsulating peritoneal sclerosis is believed to happen in patients who have a predisposing condition if a peritoneal inflammatory process (inciting factor) takes place. This is known as the "two-hit" theory in the literature on

, according to which the non-inflammatory peritoneal sclerosis brought on by repeated dialysis treatments is the "first hit" or predisposing factor. This is corroborated by the fact that during

, the cumulative incidence of encapsulating peritoneal sclerosis rises significantly over time. A proinflammatory "second hit" initiates a series of proangiogenic nowiki/>vascular_endothelial_growth_factor_(VEGF).html" ;"title="vascular_endothelial_growth_factor.html" ;"title="nowiki/> nowiki/>vascular_endothelial_growth_factor_(VEGF)">vascular_endothelial_growth_factor.html"_;"title="nowiki/>vascular_endothelial_growth_factor">nowiki/>vascular_endothelial_growth_factor_(VEGF)_proinflammatory_[Transforming_growth_factor-β1.html" ;"title="vascular endothelial growth factor">nowiki/>

vascular_endothelial_growth_factor.html"_;"title="nowiki/>vascular_endothelial_growth_factor">nowiki/>vascular_endothelial_growth_factor_(VEGF)_proinflammatory_[Transforming_growth_factor-β1">transforming_growth_factor_β1_(TGFβ1),_Interleukin_6.html" "title="vascular endothelial growth factor (VEGF)">vascular_endothelial_growth_factor.html" ;"title="nowiki/>vascular endothelial growth factor">nowiki/>vascular endothelial growth factor (VEGF) proinflammatory [Transforming growth factor-β1">transforming growth factor β1 (TGFβ1), Interleukin 6">interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

(IL-6), CCN2]

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s. TGFβ1 stimulates peritoneal

mesothelial cell The mesothelium is a membrane composed of simple squamous epithelial cells of mesodermal origin, which forms the lining of several body cavities: the pleura (pleural cavity around the lungs), peritoneum (abdominopelvic cavity including the mesent ...

s to transdifferentiate into mesenchymal cells, which leads to the depletion of

s, increased extracellular matrix component production collagen_type_1,_alpha_1_(COL1A1).html" ;"title="Collagen, type I, alpha 1">collagen type 1, alpha 1 (COL1A1)">Collagen, type I, alpha 1">collagen type 1, alpha 1 (COL1A1) and

fibrogenesis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

, which forms a fibrocollagenous cocoon.

Diagnosis

Encapsulating peritoneal sclerosis is diagnosed clinically, supported by

radiography Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeu ...

laparotomy A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy. Origins and history The first successful laparotomy was performed without ane ...

, and based on a constellation of clinical findings. The non-specific laboratory results associated with encapsulating peritoneal sclerosis are linked to underlying infections,

malnourishment Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...

, and inflammation. It has been demonstrated that

dialysate In chemistry, dialysis is the process of separating molecules in solution by the difference in their rates of diffusion through a semipermeable membrane, such as dialysis tubing. Dialysis is a common laboratory technique that operates on the ...

from patients with encapsulating peritoneal sclerosis had higher levels of inflammatory

s than did

controls, sometimes up to years before the condition's clinical manifestation. Nevertheless, no biomarker has been discovered to help anticipate the onset of encapsulating peritoneal sclerosis. When distinguishing encapsulating peritoneal sclerosis from other causes of

intestinal obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs a ...

, imaging is frequently useful. Advanced encapsulating peritoneal sclerosis may be suggested by abdominal plain films with peritoneal calcification and dilated bowel loops with air-fluid levels. The small bowel follow-through may be characterized by delayed transit, distension near

small bowel The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...

adhesions, and a "cauliflower" appearance due to peritoneal sclerosis-encapsulated bowel loop compression. Dilated loops of bowel may appear encased in a dense fibrous membrane or matted together and tethered posteriorly on

ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

. The appearance of a trilaminar colon wall may be due to intraperitoneal echogenic strands. As of right now, the most extensively researched and widely used imaging method for encapsulating peritoneal sclerosis diagnosis is the CT scan.

Small bowel The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...

loops are frequently connected by a thickened, encircling

, which is usually accompanied by proximal bowel dilatation. Increased mesenteric fat density, loculated

, and localized or diffuse peritoneal calcification are additional radiographic features. Complex loculations may indicate intra-abdominal hemorrhage, but if they contain gas, there is reason to suspect sepsis or a

perforation A perforation is a small hole in a thin material or web. There is usually more than one perforation in an organized fashion, where all of the holes collectively are called a ''perforation''. The process of creating perforations is called perfor ...

. Elevated thickening or enhancement of the colon wall suggests transmural fibrosis or persistent inflammation. Although it hasn't been used as much for diagnosis, magnetic resonance imaging probably produces similar results. Benefits include better bowel encasement and peritoneal thickening delineation, as well as the avoidance of ionizing radiation. The histologic results for encapsulating peritoneal sclerosis are not specific and can be confused with those for infectious

or simple peritoneal sclerosis. The

mesothelial The mesothelium is a membrane composed of simple squamous epithelial cells of mesodermal origin, which forms the lining of several body cavities: the pleura ( pleural cavity around the lungs), peritoneum ( abdominopelvic cavity including the ...

cell layer is microscopically denuded by fibrin deposition, fibroblast proliferation, and fibrocollagenous deposition. When inflammation is active, there may be an infiltration of inflammatory mononuclear cells. Encapsulating peritoneal sclerosis is distinguished from peritoneal sclerosis and peritonitis by the transmembrane glycoprotein

podoplanin Podoplanin is a protein that in humans is encoded by the ''PDPN'' gene. Structure and function Podoplanin is a mucin-type protein with a mass of 36- to 43-kDa. It is relatively well conserved between species, with homologues in humans, mice, rat ...

, which is present on peritoneal

s and binds inflammatory

Classification

Based on the clinical presentation, encapsulating peritoneal sclerosis is classified into four stages: # Pre-encapsulating peritoneal sclerosis stage: Mild

, no inflammation, and no symptoms. # Inflammatory stage: The patient's symptoms, which include intestinal swelling and partial encapsulation of the bowel,

and

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

. There is an exudation of fibrin and mild inflammation. # Encapsulation: Signs of

intestinal blockage Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs ...

brought on by the encapsulation-causing fibrous cocoon. It may be linked to inflammation, ranging from mild to severe. # Chronic stage of ileus: The thickening of the encapsulating fibrous cocoon causes patients to experience complete bowel obstruction. At this point, there's not much, if any, inflammation.

Prevention

There is currently no known way to stop encapsulating peritoneal sclerosis from developing, despite numerous studies pointing to potential causes. There has been much discussion regarding the "expiry date" for patients receiving

because the risk of developing encapsulating peritoneal sclerosis rises with the length of the treatment. Research from Japan has indicated that patients should switch to hemodialysis after the recommended 8-year safe period for continuing

. Setting an expiration date, however, is not advised since it may worsen quality of life and raise the risk of complications for patients receiving

hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...

via tunneled lines in cases where they had no symptoms while receiving

Treatment

Treating the underlying cause of encapsulating peritoneal sclerosis is recommended whenever it is feasible. This entails switching from peritoneal dialysis to

in the case of

. The nutritional status should be evaluated upon encapsulating peritoneal sclerosis diagnosis. Encapsulating peritoneal sclerosis cannot be effectively treated with bowel rest or

total parenteral nutrition Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding companies. The person receives a nutritional mix ...

(TPN) alone; however, making sure the patient receives enough nutrition is crucial.

Enteral feeding Enteral administration is food or drug administration via the human gastrointestinal tract. This contrasts with parenteral nutrition or drug administration (Greek ''para'', "besides" + ''enteros''), which occurs from routes outside the GI tract ...

is frequently not tolerated due to obstruction, necessitating TPN. Many medications have been used to target the inflammatory component of encapsulating peritoneal sclerosis such as mammalian target of rapamycin (mTOR) inhibitors,

cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

mycophenolate mofetil Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liv ...

colchicine Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken b ...

, corticosteroids, and

azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...

. For patients who have already experienced significant

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...

might not be enough. A potent anti-fibrotic agent,

tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...

is a selective estrogen receptor modulator (SERM) that inhibits

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...

, a crucial

in the fibrosis process. Because encapsulating peritoneal sclerosis surgery is a time-consuming, dangerous, and technical procedure, it should only be performed on patients who have not responded to conservative medical therapy and, if at all possible, in facilities with prior experience performing such procedures.

Outlook

Patients with encapsulating peritoneal sclerosis have a very high death rate, which ranges from 26% to 58%, and rises with the length of peritoneal dialysis.

Malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...

and

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

are the most common causes of death among those with encapsulating peritoneal sclerosis.

Epidemiology

Encapsulating peritoneal sclerosis occurs between 0.5% and 7.3% of the time worldwide, but in patients receiving peritoneal dialysis for 15 years or longer, the frequency can reach 17.2%. After nine years of

, the encapsulating peritoneal sclerosis risk rose to 8% in one study involving over 17,300 patients from Australia, New Zealand, and Scotland; however, when the competing risk of death was considered, the risk dropped to just 1.5%.

References

External links

StatPearls

Peritoneal dialysis
-

American Kidney Fund The American Kidney Fund (AKF) is a publicly supported non-profit organization founded in 1971. The AKF provides comprehensive programs of kidney health awareness, education, and prevention. It provides financial assistance that helps 1 out of ...

{{Kidney disease, state=collapsed Renal dialysis Kidney diseases Rare diseases