Comprehensive analysis of sodium polystyrene sulfonate-induced colitis: A systematic review

Table 1 Baseline features in 59 patients with colitis induced by polystyrene

Variable	Patients, n = 59 (100%)
Mean age (yr) (SD)	60.6 ± 16.6
Sex (male)	35 (60.3)
Signals and symptoms
Abdominal pain	35 (60.3)
Bloating	18 (31)
Hematochezia	18 (31)
Constipation	7 (12)
Diarrhea	7 (12)
Hypotension	6 (10.3)
Melena	4 (6.9)
Fatigue	4 (6.9)
Fever	4 (6.9)
Vomiting	4 (6.9)
Pneumoperitoneum	3 (5.1)
Gastrointestinal involvement
Cecum	18 (31)
Rectum	15 (25.8)
Small intestine	13 (22.4)
Transverse colon	10 (17.2)
Ascendent colon	9 (15.5)
Sigmoid	9 (15.5)
Descendent colon	8 (13.7)
Pancolitis	3 (5.1)
Stomach	2 (3.4)
Mean potassium levels (mmol/L) (SD)	6.5 ± 0.98
Comorbidities
Chronic kidney disease	37 (63.7)
Hypertension	20 (34.4)
Type 2 diabetes	12 (20.6)
Peripheral arterial disease	7 (12)
Coronary artery disease	6 (10.3)
Polystyrene type
Calcium (Kalimate)	11 (18.9)
Sodium (Kayexalte)	47 (81)
Mean polystyrene dose (g) (SD)	83.6 ± 70
Administration route
Per os	38 (65.5)
Retal	5 (8.6)
Per os and retal	3 (5.1)
Mean time of onset symptoms (d) (SD)	5.5 ± 6.9
Biopsy	51 (87.9)
Treatment
Surgery	29 (50)
Outcomes
Recovery	39 (67.2)
Death	12 (20.6)
Mean time to outcome (d) (SD)	36.7 ± 35.5

Table 2 Summary of systematically reviewed clinical cases

Ref.	Country	Age (yr)	Sex	Polystyrene type	Total dose (g)	First symptom (d)	Symptoms	Gastrointestinal compromise	Colonoscopy	Histology	Outcomes
Patel et al[52], 2017	United States	45	M	Kayexalate	30	-	None	Small intestine, cecum, ascending colon, transverse colon	Large ulcers at terminal ileum hepatic flexure and rectum	Small bowel: Acute enteritis and basophilic crystals with “fish-scales”	Recovery
Mizukami et al[53], 2016	Japan	64	M	Kayexalate	NR	30	Hematochezia	Rectum	Multiple ulcers were found in the upper to mid-rectum	Rectum: SPS crystals	Recovery
Rogers et al[33], 2001	United States	55	M	Kayexalate	NR	5	Diarrhea, Melena, Abdominal Pain	Sigmoid colon, descending colon	Large rectal ulcer and surrounding edematous and boggy mucosa	Rectum: Acute transmural necrosis with inflammatory and necrotic debris on the surface. Crystalloid foreign materials that were adherent to the ulcer bed	Recovery
Cervoni et al[54], 2015	United States	58	M	Kayexalate	NR	21	None	Descending colon	Severely friable mucosa with ischemic- appearing ulceration and apparent site of perforation in the proximal descending colon	Descending colon: Basophilic crystals with a mosaic pattern resembling fish scales	Recovery
Singla et al[55], 2016	United States	50	F	Kalimate	15	2	Constipation, Abdominal Pain, Bowel Sounds Were Absent	Cecum	NR	Cecum: Colonic necrosis and presence of SPS crystals in necrotic colonic mucosa	Recovery
Buraphat et al[34], 2019	Thailand	61	M	Kayexalate	210	NR	Constipation, Abdominal Pain	Small intestine	NR	Small intestine: Multiple erosions with ischemic changes and basophilic angulated crystals on the surface, Sigmoid Colon: numerous basophilic angulated crystals with a fish scale appearance were observed adhering to the surface of the mucosa	Death
Buraphat et al[34], 2019	Thailand	74	F	Kayexalate	150	NR	Abdominal Pain	Cecum	NR	NR	Death
Buraphat et al[34], 2019	Thailand	89	F	Kayexalate	180	NR	Constipation, Abdominal Pain	Sigmoid colon	NR	NR	Recovery
Fiel et al[19], 2018	Brazil	56	M	Kayexalate	NR	7	Constipation, Abdominal Pain, Fatigue, Abdominal Distension, Pneumoperitoneum, Hypokalemia CPS Bezoar	Cecum	NR	Serositis and transmural ischemia	Death
Jacob et al[1], 2016	India	75	M	Kalimate	NR	7	Abdominal Pain	Sigmoid colon	Inflamed edematous and ulcerated cecum, small ulcer with slough 4–5 cm from anal verge rectum, Stricture in splenic flexure scope could not be passed beyond, nodularity with superficial ulceration in rectum, ulcers in rectum and sigmoid colon	All biopsies showed similar findings with ulceration and inflammatory granulation tissue in most. Crystals which were basophilic and irregular ranging from 1 to 200 in number, ranging in size from 50 to 150 μ were noted. They had a mosaic or ribbed pattern or both	Recovery
Jacob et al[1], 2016	India	72	M	Kayexalate	NR	7	Abdominal Pain	Rectum	NR	Equal above	Recovery
Jacob et al[1], 2016	India	72	M	Kayexalate	NR	7	Abdominal Pain	Rectum	NR	Equal above	Recovery
Jacob et al[1], 2016	India	64	F	Kayexalate	NR	7	NR	Descending colon	NR	Equal above	Recovery
Jacob et al[1], 2016	India	48	F	Kayexalate	NR	7	NR	Rectum	NR	Equal above	Death
Jacob et al[1], 2016	India	52	M	Kayexalate	NR	7	NR	Sigmoid, Rectum	NR	Equal above	Death
Joo et al[8], 2009	South Korea	34	F	Kayexalate	215	2	Hematochezia	Descending colon	Diffuse active ulceration with mucosal necrosis and hemorrhage from the rectum to beyond the reach of an endoscope	Colitis with mucosal necrosis or ulceration and irregular shaped and sized angulated crystals with a characteristic crystalline mosaic pattern on the mucosa and ulcer bed tissue and within the necroinflammatory debris	Death
Akagun et al[56], 2011	Turkey	78	F	Kayexalate	60	2	Abdominal Pain, Pneumoperitoneum	Sigmoid colon	NR	Necroinflammatory debris and various sized fragments of basophilic crystalloid material with angulated margins on microscopic examination	Recovery
Cheng et al[20], 2021	Australia	53	F	Kayexalate	30	15	Diarrhea, Vomiting, Abdominal Pain, Abdominal Distension, Fever, Pneumoperitoneum	Transverse colon	NR	Multiple discrete areas of deep ulceration with intramural necrosis abscess formation and focal transmural penetration SPS crystals were present in the inflammatory debris	Death
Castillo-Cejas et al[57], 2014	Spain	73	M	Kayexalate	NR	NR	Hypotension	Cecum, ascending colon, transverse colon	Ischemic lesions in cecum, ascending colon and hepatic angle	Ascending colon: Mucosal necrosis and Kalimate crystals with their characteristic mosaic pattern within the granulation tissue from one of the colonic ulcers	Recovery
Thomas et al[23], 2009	United States	64	F	Kayexalate	90	27	Hematochezia, Abdominal Pain, Abdominal Distension, Hypotension	Sigmoid colon, Rectum	Friable area of 15 to 25 cm from the anal verge	Rectum: Ulcerated mucosa and prominent granulation tissue with small eosinophilic angulated crystals embedded in mucosal ulcers	Recovery
Bomback et al[31], 2009	United States	56	F	Kayexalate	15	NR	Abdominal Pain	Transverse colon	Large sessile mass in the midtransverse colon	Transverse colon: Crypt miniaturization with leakage of red blood cells and fibrin into the lamina propria associated with polygonal basophilic crystals	Recovery
Scott et al[37], 1993	United States	48	M	Kayexalate	50	0.5	Abdominal Pain, Abdominal Distension	Descending colon, Sigmoid colon, Rectum	The rectum, sigmoid, and left colonic mucosa were erythematous and friable. The mucosa became frankly necrotic at the splenic flexure	NR	Recovery
Chou et al[58], 2011	Taiwan	30	M	Kayexalate	90	3	Hematochezia	Transverse colon	Colon ulcers included scattered erosion longitudinal ulcerations and sharply defined segment of involvement	Transverse colon and splenic flexure: Necrotic debris adjacent to eroded colonic mucosa. A few basophilic and rhomboid crystals with fish-scale-like mosaic pattern were identified	Recovery
Ribeiro et al[59], 2017	Portugal	72	M	Kalimate	NR	1	Abdominal Pain	Cecum, ascending colon	Congestive and ulcerated mucosa in the right colon and a deep necrotic ulcer in the cecum, with a diameter of 40 mm	Cecum: Necroinflammatory and granulation tissue containing basophilic-stained polystyrene sulfonate crystals	Recovery
Wootton et al[60], 1989	United States	48	M	Keyexalate	200	0.5	Abdominal Pain, Abdominal Distension, Fever	Transverse colon	NR	Transverse colon: Patchy transmural infarction of the colon. Near the necrotic mucosa were large quantities of amorphous Kayexalate material	Recovery
Chelcun et al[61], 2012	United States	51	M	Keyexalate	30	NR	Melena	Small intestine	Large ulcer surrounded by erythema was found at the ileocecal valve	Ileocecal valve: Reactive colonic mucosa with ulceration and prominent acute inflammatory exudate containing basophilic crystals consistent with SPS use	Recovery
Tapia et al[62], 2009	Switzerland	71	F	Kayexalate	80	10	Diarrhea, Abdominal Pain, Vomiting	Cecum, ascending colon	Segmental, circumscribed colitis in the cecum and at the left flexure	Cecum and left flexure: Segmental ulcers lightly distorted crypts with mucus depletion and fibrosis in the lamina propria accompanied by a mixed inflammatory infiltrate with lymphocytes and some neutrophils. Colon fragments with the angular crystals/foreign bodies	Recovery
Trottier et al[63], 2009	Canada	24	M	Kayexalate	110	1	Constipation, Abdominal Pain, Abdominal Distension, Fever, Hypotension	Small intestine	NR	Ileum-multifocal, acute ulceration. Patchy transmural necrosis and SPS crystal deposition within the intestinal mucosa	Recovery
Kao et al[64], 2015	Taiwan	59	M	Kalimate	120	2	Abdominal Pain, Abdominal Distension, Hypotension	Small intestine, Sigmoid colon	NR	Ileum-transmural necrosis and perforation with basophilic angulated crystals extending from the ulcerated luminal surface into the transmural	Death
Singhania et al[25], 2020	United States	30	M	Kayexalate	15	0.16	Hematochezia, Vomiting, Abdominal Pain, Abdominal Distension	All colon	NR	NR	NR
Goutorbe et al[65], 2011	United States	73	M	Kalimate	15	3	Abdominal Pain, Hypotension, Tachycardia	Small intestine, cecum	NR	Transmural abscess massive inflammatory infiltrate, ulceration and inflammation of the ceca mucosa with a fibrinous and purulent coating. Small fray-purple or blue angulated crystals	Death
Gerstman et al[18], 1992	United States	43	NR	Kayexalate	50	2	Abdominal Pain, Abdominal Distension, Confusion, Blood in the Gastric Aspirate	Cecum	NR	NR	Recovery
Gerstman et al[18], 1992	United States	42	NR	Kayexalate	135	NR	Hematochezia, Abdominal Pain	Cecum	NR	NR	Recovery
Aguilera et al[66], 2000	Spain	83	M	Kayexalate	NR	1	Abdominal Pain, Hypotension	Small intestine	NR	Transmural necrosis and in its course and in the peritoneal surface there are numerous basophilic crystals with hematoxylin	Death
Gardiner et al[30], 1997	Canada	66	M	Kayexalate	240	NR	NR	Stomach, small intestine	NR	Coagulative necrosis of the mucosa with overlying purple rhomboid kayexalate crystals, submucosal edema and acute transmural inflammation	Death
Gardiner et al[30], 1997	Canada	71	F	Kayexalate	105	NR	Hematochezia	Small intestine, ascending colon	NR	Hemorrhagic mucosal necrosis associated	Death
Pusztaszeri et al[67], 2007	France	87	M	Kalimate	NR	NR	Abdominal Distension	Small intestine	NR	Kayexalate crystals, submucosal edema and acute transmural inflammation	NR
Islam et al[26], 2015	United States	71	F	Kayexalate	15	0.5	Vomiting, Abdominal Pain, Nausea	Cecum	NR	Diffuse mucosal necrosis with dark purple crystals	Recovery
Kardashian et al[68], 2016	United States	65	F	Kayexalate	NR	2	Hematochezia, Constipation, Abdominal Pain, Fatigue, Abdominal Distension	NR	NR	Dark purple SPS crystals	Recovery
Shahid et al[69], 2019	United States	78	F	Kayexalate	43	1	Abdominal Pain	Cecum, ascending colon	NR	Findings of ischemic colitis with detached purple refractile material	Recovery
Strader et al[70], 2017	United States	60	M	Kayexalate	NR	NR	Nr	Cecum	4cm circumferential, ulcerating mass in the cecum partially obstructing the lumen as well	Biopsies in both areas reveal material morphologically consistent with kayexalate with associated colitis, ulceration and necroinflammatory debris, with no evidence of malignancy	Recovery
Albeldawi et al[71], 2014	United States	61	M	Kayexalate	NR	NR	Hematochezia, Fatigue, Dizziness	Cecum	Evidence of colitis and localized ulcerations in the cecum	Revealed basophilic, non-polarizable, rhomboid-like crystals without evidence of necrosis	NR
Ofori et al[72], 2017	United States	80	F	Kayexalate	NR	7	Hematochezia, Abdominal Pain, Abdominal Distension	Transverse colon	Revealed lumen obstructing clot in the mid transverse colon with adjacent unhealthy mucosa which was bleeding upon contact. Scope could not be advanced safely past the large clot	NR	Recovery
Abramowitz et al[27], 2014	United States	70	F	Kayexalate	NR	NR	Hematochezia	Rectum	Scattered diverticula throughout the colon and a 2 cm × 3 cm semi-circumferential friable rectal ulceration just proximal to the anorectal junction with active oozing of blood	Fragments of granulation tissue and crystalline fragments consistent with Kayexalate that were seen on the surface	NR
Rugolotto et al[73], 2007	Italy	0,01	NR	Kayexalate	6.8	4	Abdominal Distension	Small intestine	NR	Ileum specimen showed multiple areas of trans-mural necrosis, whereas the lumen showed basophilic and Zihel–Neelsen stain positive angulated crystals surrounded by fibrinoid and giant cells exudates	Recovery
Edhi et al[74], 2018	United States	73	M	Kayexalate	30	1	Abdominal Distension	Cecum, ascending colon, transverse colon, descending colon	Highly consistent with ischemic colitis in the descending colon	Inflamed and ulcerated colonic mucosa and basophilic, non-polarizable, angulated, intramucosal crystals, highly consistent with SPS induced ischemic colitis	Recovery
Chatelain et al[75], 2007	France	46	M	Kayexalate	150	NR	Diarrhra, Hematochezia	Descending colon, Sigmoid colon, Rectum	Segmental ulcerations of the sigmoid colon	Ischemic colitis with ulcerations and transmural inflammation. Kayexalate crystals were present in the colonic lumen, adherent to ulcers. Thickened and fibrous submucosa containing numerous basophilic and purple polygonal crystals surrounded by macrophages and giant cells	Recovery
Oliveira et al[7], 2018	Portugal	83	F	Kayexalate	NR	2	Diarrhea, Abdominal Pain	Rectum	Visualization of the rectum, a depressed area in the lower rectum, partially ulcerated, without apparent necrosis was found and biopsied	Presence of basophilic structures with mosaic pattern, 1ilar to fish scales, surrounded by an intense active chronic inflammatory infiltrate, aspects compatible with lesion caused by ion exchange resin deposition (Kayexalate Crystals)	Recovery
Florian et al[76], 2019	United States	69	M	Kayexalate	NR	NR	Hematochezia	Cecum, Ascending colon	Extensive circumferential ulceration and pseudomembrane in the cecum and proximal ascending colon. Persistent ulcerations with erythematous friability in the same area	Revealed acute reactive epithelial atypia with embedded polystyrene sulfonate crystals	NR
Lee et al[77], 2017	United States	66	F	Kayexalate	NR	5	Hematochezia	Rectum	Two relatively isolated ulcers located in the transverse colon and in the rectum	The rectal ulcer demonstrated findings of crystal-like structures suggestive of kayexalate crystals	Recovery
Chang et al[78], 2020	United States	66	M	Kayexalate	30	NR	NR	Small intestine	NR	Acute ischemic enteritis featuring mucosal ulceration associated with crystals morphologically compatible with SPS, submucosal arterial and venous thrombosis and acute organizing serositis	Recovery
Moole et al[79], 2014	United States	80	F	Kayexalate	30	1	Diarrhea, Hematochezia, Abdominal Pain, Abdominal Distension	Sigmoid colon, Rectum	Severe well demarcated colitis in the rectosigmoid junction with a large amount of blood clots at the demarcation	Showed distal rectosigmoid ischemic colitis, with mucosal and focal submucosal necrosis and crystals consistent with Kayexalate	Recovery
Edhi et al[24], 2017	United States	78	M	Kayexalate	NR	NR	NR	Transverse colon, Descending colon	Diffuse moderate inflammation in the descending colon, with severe inflammation in the transverse colon	Ulceration of the colonic mucosa with basophilic crystal consistent with SPS induced injury and no features of ischemia, infectious changes or granulomas	NR
Huang et al[80], 2011	United States	57	M	Kayexalate	160	5	Constipation, Abdominal Pain, Abdominal Distension	NR	NR	Demonstrated crystals characteristic of SPS toxicity and concluded that the patient’s bowel perforation was likely caused by SPS	Recovery
Gürtler et al[81], 2018	Switzerland	56	M	Kayexalate	NR	1	Melena, Abdominal Pain	Small intestine	Gastroscopy demonstrated severe ulcerative duodenitis with no evidence of active bleeding	Revealed a severe erosive duodenitis. Abundant SPS crystals were detectable within the fibrinoleukocytic exudates of the duodenal ulcers and on the surface of the inconspicuous gastric mucosa	Recovery
Hajjar et al[29], 2018	Canada	48	M	Kayexalate	NR	NR	Abdominal Pain, Abdominal Distension	Stomach	NR	Revealed the presence of fibrinoleukocytic debris with rhomboid, birefringent crystals, suggestive of Kayexalate in the gastric wall	Recovery
Almulhim et al[28], 2018	Saudi Arabia	64	M	Kayexalate	30	9	Hematochezia, Melena, Abdominal Pain, Fatigue, Fever, Anemia	Descending colon, transverse colon	Findings were suggestive of right colon colitis with possible etiology of ischemia and necrotic appearing mucosa	Specimen was found to be granulated and contain SPS crystals	Recovery
Dunlap et al[5], 2016	United States	55	F	Kayexalate	30	2	Diarrhea, Hematochezia, Abdominal Pain, Abdominal Distension, Peritonite	All colon	Flexible sigmoidoscopy, which identified several ulcerations that were biopsied, later revealing ischemic necrosis of the bowel	Diffusely hemorrhagic with extensive multifocal ulcerations. Crystalloid particles consistent with kayexalate were identified throughout the bowel wall	Recovery
dos Santos et al[12], 2021	Brazil	77	F	Kayexalate	120	4	Diarrhea	Sigmoid colon	Revealed edema, enanthema, and erosion into the sigmoid colon	Typical fish scale-like SPS crystal	Recovery

NR: not reported; SPS: Sodium polystyrene sulfonate.

Table 3 Sodium polystyrene sulfonate characteristics – adapted from Rahman et al[13]

Indications	Mechanism of action	Administration	Dose (g)	Adverse effects (mild)	Adverse effects (serious)	Contraindications
Hyperkalemia	Resin exchanges sodium with potassium ions from the intestinal cells	Orally or rectally	Usually, 15 to 60 daily	Diarrhea, nausea, vomiting, loss of appetite, bloating	Ischemic colonic necrosis, constipation, seizures, confusion, abdominal pain, irregular heart beat	Hypokalemia, previous hypersensitivity to SPS, bowel obstruction, neonates with reduced gut motility

SPS: Sodium polystyrene sulfonate.