Encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a rare condition characterized by the formation of a fibrocollagenous membrane encasing the small intestine, leading to recurrent bowel obstruction. It can be idiopathic or secondary to various triggers; long-term peritoneal dialysis is the most common cause. Other causes include infections such as tuberculosis, systemic inflammatory disorders, and certain medications. Clinical features are often chronic and include abdominal pain, distention, and vomiting. Diagnosis is based on clinical findings and confirmed with imaging, primarily abdominal CT, which may show peritoneal thickening, calcifications, and tethering of bowel loops. Management focuses on treating the underlying cause, providing nutritional support, and stage-dependent medical therapy with glucocorticoids for inflammation and/or tamoxifen for fibrosis. Surgery is reserved for refractory cases. The prognosis is often poor, with high mortality, particularly in patients on peritoneal dialysis.

• The overall incidence and prevalence of EPS are unknown due to the rarity of the condition.
• Patients on peritoneal dialysis
  • Incidence: 0.14–2.5% annually ^[1][2]
  • Prevalence: 0.4–8.9% ^[3]
  • Incidence increases with longer duration of peritoneal dialysis. ^[2]
• Primary (idiopathic) EPS ^[4][5]
  • Mean age: ∼ 35–40 years
  • ♂ > ♀ (2–3:1 ratio)
  • More commonly reported in tropical and subtropical regions (e.g., China, India, Turkey, and Nigeria)

Epidemiological data refers to the US, unless otherwise specified.

Triggers for secondary EPS include: ^[5]

• Mechanical or chemical irritants
  • Peritoneal dialysis (most common cause of secondary EPS)
  • Intraperitoneal chemotherapy
  • Ventriculoperitoneal or peritoneovenous shunts
  • Abdominal surgery or trauma
  • Foreign bodies (e.g., talcum powder, asbestos)
  • Ruptured dermoid cyst
• Infections
  • Tuberculosis
  • Non-tuberculosis mycobacteria
  • Bacterial peritonitis
  • Fungal infections
  • Parasitic infections
  • Cytomegalovirus
• Systemic inflammatory disorders
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Familial Mediterranean fever
• Medications
  • Beta blockers
  • Methotrexate
  • Antiepileptic drugs
• Other associated conditions
  • Cirrhosis
  • History of organ transplantation (e.g., liver, kidney)
  • Endometriosis
  • Gynecologic neoplasms (e.g., thecoma, granulosa cell tumor)

• EPS is believed to develop in patients with an underlying predisposition (e.g., recurrent peritoneal injury) when a triggering event (e.g., infection, medication) leads to peritoneal inflammation.
• Two-hit hypothesis for EPS in the setting of peritoneal dialysis
  • First hit: noninflammatory peritoneal sclerosis from long-term exposure to dialysis solution
  • Second hit: A proinflammatory trigger (e.g., infection) initiates a cascade of cytokines (e.g., TGF-β1, VEGF).
• Potential genetic predisposition

A staging system for peritoneal dialysis-associated EPS is based on clinical, laboratory, and radiological findings. ^[6]

• Stage 1 (pre-EPS)
  • Mild abdominal symptoms
  • Mild inflammation
  • No encapsulation
• Stage 2 (inflammatory)
  • Symptoms include nausea and diarrhea.
  • Mild to severe inflammation
  • Partial encapsulation
• Stage 3 (encapsulating)
  • Periodic ileus
  • Mild inflammation
  • Encapsulation is present.
• Stage 4 (chronic or ileus stage)
  • Persistent ileus
  • Inflammation is absent or mild.
  • Encapsulation is present.

• Chronic symptoms
  • Abdominal pain
  • Nausea and vomiting
  • Anorexia or early satiety
  • Constipation
  • Diarrhea
• Acute symptoms (e.g., symptoms of bowel obstruction)
• Constitutional symptoms
  • Weight loss
  • Fever
  • Fatigue
• Physical examination findings
  • Abdominal distention
  • Palpable abdominal mass
  • Ascites
  • Cachexia

Encapsulating peritoneal sclerosis is diagnosed based on a compatible clinical presentation, most commonly recurrent or progressive intestinal obstruction, together with characteristic imaging findings showing encapsulation of the bowel. ^[7]

Laboratory studies ^[3][8]

• Findings are nonspecific and may reflect underlying inflammation or malnutrition.
• Possible findings include:
  • ↑ CRP
  • Leukocytosis
  • Anemia
  • ↓ Albumin

Imaging ^[7]

• CT abdomen ^[7][8][9]
  • First-line and primary diagnostic modality
  • Typical findings include:
    • Diffuse, smooth peritoneal thickening
    • Peritoneal calcifications
    • Tethering of small bowel loops with proximal dilation
    • Bowel wall thickening
    • Features of mechanical bowel obstruction
• X-ray abdomen ^[7][10]
  • May show peritoneal calcifications and/or dilated bowel loops with air-fluid levels
  • Contrast studies may show delayed transit and bowel loop crowding (e.g., “cauliflower” appearance).
• Abdominal ultrasound: may show clustered, dilated bowel loops encased by a thick echogenic fibrous layer with associated intraperitoneal stranding ^[6]
• MRI abdomen: may more clearly show peritoneal thickening and bowel encasement ^[10]

Gross pathology ^[6]

Findings on exploratory laparotomy include:

• Diffuse thickening with brown discoloration of the peritoneum
• Fibrous sac-like encapsulation of the bowel
• Small bowel loops stuck together
• Calcified deposits within the peritoneum

Histopathology ^[6]

• Findings are nonspecific and may resemble those of simple peritoneal sclerosis or infectious peritonitis.
• Histology typically shows a thickened fibrocollagenous membrane with:
  • Denudation of the mesothelial cell layer
  • Fibroblast proliferation
  • Fibrin deposition

• Peritoneal carcinomatosis ^[12]
• Congenital peritoneal encapsulation
• Internal hernia
• Sclerosing mesenteritis
• Sclerosing malignant lymphoma
• Mesenteric tumors
• Other causes of bowel obstruction (e.g., postoperative adhesions)

The differential diagnoses listed here are not exhaustive.

General principles ^[7]

• The treatment approach depends on the disease stage.
• All patients: Treat the underlying cause if possible.
  • Discontinue peritoneal dialysis and switch to hemodialysis.
  • Withdraw any potential offending medications.
• Patients with inadequate oral intake or malnutrition: Provide nutritional support (often with total parenteral nutrition).

Pharmacological treatment ^[7][8]

The evidence for pharmacological treatment is of low quality.

• Immunosuppressive agents: for the inflammatory stage
  • Glucocorticoids (e.g., methylprednisolone, prednisolone): best-studied option
  • Alternative options include colchicine, azathioprine, and cyclosporine.
  • Indication: active inflammation (after exclusion of infection)
• Antifibrotic therapy
  • Tamoxifen
  • May be started in early stages to help prevent EPS progression
  • May be used alone or in combination with other therapies

Surgery ^[8]

• Reserved for patients who do not respond to conservative medical therapy
• Should be performed in centers with surgical expertise in EPS
• Procedures with curative intent are preferred, e.g., enterolysis (removal of fibrotic tissue and release of adhesions).

• Recurrent small bowel obstruction
• Bowel ischemia or perforation
• Bowel adhesions or fistulas
• Ascites leading to:
  • Fluid and electrolyte imbalance
  • Respiratory distress
• Malnutrition

We list the most important complications. The selection is not exhaustive.

Mortality in patients on peritoneal dialysis: ∼ 50% within one year of diagnosis ^[3]