A Case of Peritoneal Dialysis-associated Encapsulated Peritoneal Sclerosis Treated with a Combination of Chinese and Western Medicine

INTRODUCTION Encapsulating peritoneal sclerosis (EPS) is a severe life-threatening complication that can arise in patients undergoing long-term peritoneal dialysis (PD), and it may even occur after a patient switches to hemodialysis (HD) or receives a kidney transplant. The global incidence of EPS varies, and it tends to increase with the duration of PD, often leading to poor prognoses and high morbidity and mortality rates, with approximately 50% of patients succumbing within 12 months of diagnosis.1 The pathogenic factors contributing to EPS include prolonged exposure to biologically incompatible PD solutions, resulting in long-term peritoneal changes; peritoneal transporter status (including high glucose concentrations); episodes of peritonitis; and peritoneal inflammation. Genetic susceptibility and certain medications may be other potential etiological factors. Many cases of EPS remain idiopathic. The pathogenesis of EPS is currently not well understood, and in the early stages, patients often present with nonspecific symptoms, leading to delayed diagnosis. As the disease progresses, the peritoneum undergoes progressive fibrosis and calcification, encasing the intestines, which can lead to complete or partial intestinal obstruction. This can manifest as abdominal pain, diarrhea, nausea, vomiting, and other symptoms, posing a risk of mortality in severe cases. EPS is relatively rare, and there are currently no established treatment options or relevant clinical trials. However, in August 2023, a patient with EPS was treated in our nephrology department using a combination of Chinese and Western medicine. CASE INFORMATION A 40-year-old male was admitted to hospital with a history of 15 years of regular PD followed by 3 months of hemodialysis. He had suffered abdominal pain and vomiting for one day. He had been diagnosed with chronic renal failure (stage 5 chronic kidney disease CKD) 15 years previously and had undergone regular PD treatment with 2.5% dialysate solution (4 bags) in the abdomen for 24 h. Over the last 3 months, the patient had experienced poor ultrafiltration during PD, accompanied by peripheral swelling and heart failure, leading to the initiation of combined hemodialysis treatment. One month prior to admission, the patient was hospitalized due to an intestinal obstruction. On the day preceding admission, he had visited the emergency room with abdominal pain and vomiting after eating a large meal. Upon admission, the patient's blood tests revealed hemoglobin (HGB) 128 g/L, neutrophil (N) 83.6%, and C-reactive protein (CRP) 25.7 mg/L, and the biochemistry results showed creatinine (CR) 683 µmol/L, glucose (GLU) 8.4 mmol/L, blood urea nitrogen (BUN) 18.6 mmol/L, K (kalium) 4.0 mmol/L, and albumin (ALB) 46 g/L. An ultrasound scan of the abdomen showed no obvious abnormalities in the liver or spleen; plain abdominal radiographs show a fluid flat abdomen with intestinal obstruction not excluded. The initial diagnosis based on the abdominal pain and vomiting was a suspected intestinal obstruction or cholecystitis. The patient received treatment with 0.5 g of sodium chloride, a levonidazole injection, rehydration, acid suppression, and other symptomatic treatments, and he was subsequently admitted to hospital. Upon admission, the patient had right upper abdominal pain, abdominal distension with vomiting, weakness, fever (a temperature of 37.3 ℃), poor appetite, and no urination. The patient's tongue appeared dark with a white, greasy coating, and the pulse was sunken and tense. Upon reviewing the patient's past medical history, it was noted that he had been hospitalized for intestinal obstruction 2 years previously and 1 month previously. The patient was a young male who had experienced repeated intestinal obstructions and long-term calcium and phosphorus metabolism disordersl computed tomography (CT) scans indicated serious calcification of the intestinal wall and thickening of the peritoneum. Considering the clinical symptoms, repeated intestinal obstructions, and the relevant literature, the patient was considered to have a high probability of encapsulated peritoneal sclerosis. Treatment included gastrointestinal decompression, anti-infective therapy, rehydration, acid suppression, protection of the gastric mucosa, PD suspension with a switch to hemodialysis. Combined with the tongue, pulse and clinical manifestations, the TCM diagnosis is dampness and cold in the middle earth and stasis and containment in the etheric wood. The method of treatment is to warm the middle earth, and to relieve the ethereal wood. The specific composition of the TCM was as follows: Astragalus (Huangqi) 10 g, Amomum villosum (Sharen) 6 g, vinegar-processed Curcuma zedoaria (Cujinaijin) 6 g, Salvia miltiorrhiza (Danshen) 15 g, Persica (Taoren) 6 g, Atractylodes macrocephala (Baizhu) 10 g, dried ginger (Ganjiang) 6 g, Citrus reticulata Blanco (Chenpi) 6 g, Codonopsis pilosula (Dangshen) 10 g, and Radix (Zhigancao) 6 g. After two weeks of treatment, the patient's abdominal pain and distension significantly improved, and he was able to consume light food. He requested discharge from the hospital, continuing hemodialysis treatment, and long-term oral Chinese herbal treatment. A two-month follow-up indicated that the patient's condition was stable. DISCUSSION EPS is a rare clinical syndrome characterized by an acquired inflammatory fibrous collagenous membrane encasing the small intestine, leading to intestinal obstruction. The International Society for Peritoneal Dialysis defines EPS as "a syndrome of persistent, intermittent, or recurrent symptoms of intestinal obstruction caused by diffusely thickened peritoneal adhesions".2 The term "chronic fibrosclerotic encapsulated peritonitis" was first coined by Owtschinnikow in 1907.3 EPS is also known as abdominal sclerosis and sclerotic encapsulated peritonitis. The pathogenesis of EPS is multifactorial, with various initiating and accelerating factors at different stages of the disease. Prolonged PD is a recognized risk factor for EPS, and there is a strong linear correlation between the duration of PD and the frequency of EPS. Another important risk factor is peritonitis attacks. Several studies4,5 have shown that the incidence of EPS increases in younger patients and further increases with the duration of PD. According to the "double-strike hypothesis", chronic noninflammatory structural changes in the peritoneum caused by glucose stimulation and degradation in the PD fluid during prolonged and repeated PD are considered the "first strike". On this basis, the sudden interruption of PD, peritonitis, ultrafiltration failure, and other risk factors cause a series of pro-inflammatory factors, cytokines on the peritoneum "second blow", leading to further development of peritoneal fibrosis, adhesions, etc. and ultimately causing EPS.1,6 The patient had been on PD for 15 years and had a history of recurrent intestinal obstructions, placing him at high risk of EPS. Upon admission, he presented with abdominal pain and vomiting. An abdominal plain film suggested an intestinal obstruction, and an abdominal CT scan indicated severe calcification of the intestinal wall and thickening of the peritoneum, leading to a clinical diagnosis of EPS based on the patient's symptoms. The patient's clinical manifestations were relieved slightly by gastrointestinal decompression, and the pain and distension were aggravated by food. Based on the patient's clinical manifestations and a tongue–pulse examination, TCM differentiation indicated a damp, cold central region and blood stasis obstructing the liver channel. The treatment involved warming the middle earth, and to relieving the ethereal wood. A modified TCM formulation of Si Jun Zi Tang was proposed. For abdominal pain, an imbalance of the earth element and antagonism of the wood element may lead to an obstruction in the large intestine, where the regulatory function depends on the wood element. If the wood element is not functioning properly due to blood stasis and dampness and coldness in the central region, it may result in blockage and an increased risk of intestinal obstruction. The formula used was a combination of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), and peach kernel (Taoren) to soothe and enhance the wood element. pericarpium citri reticulatae (Chenpi), Amomum villosum (Sharen), Vinegar chicken inner gold (Cujinaijin), Atractylodes macrocephala (Baizhu), dried ginger (Ganjiang), Codonopsis pilosula (Dangshen), andprepared licorice (Zhi Gancao) were included to warm the central region, and Jiang Houpu (Jianghoupo) was added to regulate and decrease Qi in the intestines. In the formulation, Codonopsis pilosula (Dangshen) was included for its sweet, warm properties, contributing to the augmentation of Qi, invigoration of the spleen, and nourishment of the stomach. Atractylodes macrocephala (Baizhu), characterized by its bitter taste and warm nature, served to fortify the spleen, eliminate dampness, and reinforce Qi while facilitating its movement. Astragalus membranaceus (Huangqi) —a key Qi-tonifying herb with a sweet and mildly warm nature—was belongd to the spleen and lung meridians to supplement spleen Qi. When combined with Codonopsis pilosula, it had a synergistically enhancing and toning effect on Qi. Amomum villosum (Sharen), which is pungent, was used to disperse coldness, warm the body, promote the movement of Qi, and thus awaken the spleen and stomach. Dried ginger (Ganjiang), characterized by its pungency and heat, aligned with the spleen and stomach meridians, contributing to warming the middle region, invigorating the spleen, and promoting the Yang Qi of the spleen and stomach. Vinegar chicken inner gold (Cujinaijin), belonged to the spleen, stomach, small intestine, and bladder meridians, was incorporated to facilitate the transportation capacity of the spleen and aid digestion, thereby strengthening the spleen and stomach functions. Magnolia officinalis (Houpo), characterized by its bitter and pungent properties, warmth, and association with the spleen, stomach, lungs, and large intestine meridians, was indispensable for eliminating distension and swelling, promoting Qi circulation, and resolving dampness. Simultaneously, considering the severe calcification of the patient's intestinal wall, additional herbs, such as Persica (Taoren), Salvia miltiorrhiza (Danshen), and a wood-regulating herb, were included to invigorate blood circulation, resolve stasis, and soothe the wood element, with the aim of improving blood circulation within the intestinal wall. The patient was discharged from the hospital after his condition stabilized, and he continued with oral TCM treatment. A two-month follow-up indicated that the patient's condition was stable. EPS is diagnosed based on a constellation of symptoms, but there is no definitive diagnostic test. Clinical manifestations of EPS include irregular, persistent, or frequent gastrointestinal obstructions accompanied by severe abdominal pain, nausea, and vomiting. Inadequate nutrition may lead to weight loss, and some patients may require parenteral nutrition.7 Ultrafiltration is often severely compromised and eventually lost. Radiological studies typically reveal peritoneal sclerosis, thickened peritoneal calcification, and encapsulation of the intestines.8 CT scans show a thickened peritoneum extending from the viscera to the parietal peritoneal surface, mesenteric bands, localized or diffuse peritoneal calcification, and encapsulation of the small bowel, which lead to impaired peristalsis (often referred to as an abdominal "callus knot"). The thickened fibrous membranes often form cystic effusions. As EPS progresses, patients may develop subclinical intestinal ischemia, bacterial passage through the intestinal wall into the abdominal cavity, and increased inflammation, fibrosis, and sclerosis.9–11 Nakamoto et al.11,12 categorized EPS into four stages based on patients' abdominal symptoms and inflammatory encapsulation and intestinal findings: stage 1 (pre-EPS), stage 2 (inflammatory), stage 3 (encapsulated), and stage 4 (chronic). Specifically, clinical manifestations in stage 1 are mainly declining ultrafiltration as evidenced by an increased transit rate, low protein levels, ascites, bloody dialysate, and peritoneal calcification. In stage 2, inflammatory markers (white blood cell count and C-reactive protein level) increase, accompanied by fever, ascites, bloody dialysate, loss of appetite, and weight loss. In stage 3, the inflammation subsides with signs of ileal obstruction. In stage 4, complete ileal obstruction occurs, accompanied by an abdominal mass and anorexia. Unfortunately, there are currently no clinical guidelines or standard treatments for EPS. The evidence regarding treatment is limited to observational evidence, and prospective trials with adequate patient numbers are difficult to conduct. However, there is some empirical knowledge to guide treatment strategies. Early treatment of EPS should be based on glucocorticoids, tamoxifen, and nutritional support because immunosuppressive therapy alone may be ineffective. All pharmacological treatments for EPS should be complemented by clinical symptom treatment, such as pain management and parenteral nutrition at the site of the intestinal obstruction. For most patients who develop EPS during PD, PD is discontinued, but irrigation of the peritoneal cavity may be beneficial. Glucocorticoids act by inhibiting inflammation, tissue fibrin deposition, and collagen synthesis and maturation.13 Jung et al.14 and Lafrance et al.15 reported successful treatment of EPS with glucocorticoids alone and in combination, but in the largest retrospective study involving glucocorticoids to date,16 no improvement in median survival was found in EPS patients. Tamoxifen is a selective estrogen receptor modulator, and clinical studies have shown that tamoxifen is antifibrotic and that EPS patients treated with it survive longer.17 Tamoxifen is relatively well tolerated clinically, so it can be administered when EPS is imminent or in its early stages to prevent the clinical manifestations of life-threatening EPS. It is worth noting that tamoxifen is mostly used in combination with steroids.18 In the severe stages of EPS surgery may be more effective in treating intestinal obstructions and removing inflammatory tissue that has the potential to gradually transform into fibrotic and sclerotic tissue. The presence or absence of peritoneal calcification may be an important factor in determining the need for surgical treatment.19 However, extensive adhesiolysis may cause further trauma and inflammation, exacerbating EPS and leading to more extensive adhesions.20 Surgery can reverse an intestinal obstruction, but it may recur. Surgery is therefore more suitable for patients with EPS who have symptoms of severe intestinal obstruction.21 Since there are no relevant guidelines and medication instructions for the treatment of EPS, the combination of Chinese and Western medicine provides a new therapeutic treatment strategy, especially for alleviating intestinal obstructions and related gastrointestinal symptoms caused by EPS. The efficacy of TCM is remarkable, and it can improve the quality of life of patients with EPS, but this needs to be verified by large-scale experimental studies. There are some regrets regarding the treatment of this patient. As previously explained, EPS is divided into four stages. This patient had an intestinal obstruction 1 year previously and was hospitalized for symptomatic treatment. Due to the patient's lack of knowledge about EPS, EPS was not considered when the patient experienced this first intestinal obstruction, which could have been an early symptom of EPS. Patients with PD must be followed up regularly and undergo peritoneal homeostasis tests. Patients at high risk of EPS, especially those who have maintained PD for more than 7 years, should be seen promptly to assess the development of gastrointestinal symptoms. If possible, regular follow-ups and early CT screening should be performed to monitor EPS, ensure early detection and intervention, and improve patients' prognoses. The mortality rate of EPS is extremely high. Despite increasing awareness of EPS, it remains a serious complication of long-term PD, and there are currently no relevant diagnosis and treatment guidelines. Treating EPS with a combination of TCM and Western medicine can improve patients' clinical symptoms, and we intend to conduct further research to discriminate between the two EPS treatments in the future.