Kayexalate-induced colitis and rectal stricture

Abstract

A 57-year-old man underwent emergency laparoscopic loop colostomy for acute recto-sigmoid obstruction. He was hospitalised 2 months previously, at another facility for diabetic ketoacidosis (DKA) and hyperkalaemia. He had no gastrointestinal symptoms prior to the hospitalisation. Both surgical exploration and intraoperative sigmoidoscopy showed ulcerations of sigmoid colon and proximal rectum with a pinhole stricture in mid-rectum. After ruling out all aetiologies, and due to persistence of the colonic ulcerations on a follow-up colonoscopy, a diagnosis of Crohn’s colitis was made, and the patient was started on infliximab and 6-mercaptopurine (6-MP). Six months later, on rereview of all the biopsies, it was noted that a key element of presence of crystals suggestive of Kayexalate on the initial colorectal biopsies was missed. It was later found out that the patient had received rectal Kayexalate for treatment of DKA at the other facility. Hence, infliximab and 6-MP were both discontinued. All the colonoscopies, following the discontinuation of the medications, showed complete resolution of colitis but persistence of the mid-rectum stricture. This was treated with a fully covered metal stent for 12 weeks with only partial improvement of the stricture. He was hence referred for ultra-low anterior resection of rectum and take down of colostomy.

Background

There are several pharmacological agents that cause colitis with presentations mimicking inflammatory bowel disease, ischaemic colitis, focal active colitis, microscopic colitis and necrotising colitis.¹ A temporal relationship between the use of the medication and clinical presentation is imperative to make diagnosis of drug-induced colitis. Medications that are associated with colitis include non-steroidal anti-inflammatory drugs, methotrexate, oral contraceptives, ergotamine alkaloids, sumatriptan, Kayexalate also known as sodium polystyrene sulfonate (SPS), bile acid-binding resins and alosetron among several others. We present a case of Kayexalate-induced severe left-sided colitis resulting in rectal stricture which was treated partially with endoscopic placement of a rectal stent and subsequently referred for surgical ultra-low anterior resection of the rectum with take down of colostomy and re-anastomosis.

Case presentation

A 57-year-old African-American man with diabetes, hypertension and chronic marijuana use presented to our centre for acute partial large bowel obstruction. He was admitted at another facility approximately 2 months prior, for diabetic ketoacidosis (DKA) and severe hyperkalaemia. Prior to his hospitalisation for DKA, the patient had no gastrointestinal (GI) symptoms. On examination, he was tachycardic with a heart rate of 107 beats/minute, and a markedly distended abdomen with hypoactive bowel sounds. His abdominal CT scan showed distended loops of large bowel with point of transition at recto-sigmoid junction. He underwent a laparoscopic loop colostomy and an intraoperative sigmoidoscopy which showed severe sigmoid and proximal rectal ulcerations with a pinhole stricture in the mid-rectum.

Postoperative management

The patient underwent a colonoscopy through the ostomy and via the rectum at 2 weeks and again 3 months after surgery which showed persistent severe ulcerations of sigmoid colon and proximal rectum and the rectal stricture without any improvement (figure 1). Rest of the colon and terminal ileum were normal. Biopsies obtained at time of surgery and colonoscopy showed smooth muscle proliferation and infiltration with a mixture of acute and chronic inflammation (figure 2). Biopsies were negative for viral, mycobacterial and fungal stains. Urine drug screen was negative for amphetamines or cocaine and stool studies were negative for infectious pathogens. Thus, a diagnosis of Crohn’s colitis was made by exclusion of other aetiologies and the patient was started on intravenous infliximab with oral 6-mercaptopurine (6-MP).

Figure 1.

Sigmoid colon with deep ulcerations.

Figure 2.

Proliferation of smooth muscle cells with acute and chronic inflammatory cells. Arrow shows Kayexalate pill fragments.

Six months later, during a routine GI clinic follow-up visit, on rereview of all the biopsies, it was noted that a key element of crystals suggestive of either Kayexalate or sevelamer pill fragments, reported on one of the biopsies was overlooked (arrow in figure 2). Since the use of Kayexalate was not mentioned in the discharge records from the other hospital, all the medication records for that hospitalisation were obtained which revealed the use of Kayexalate enema for hyperkalaemia. Thus, both infliximab and 6-MP were discontinued after just 6 months of use. A colonoscopy was repeated 6 months after discontinuing infliximab and 6-MP, which revealed no recurrence of ulcerations, but persistent mid-rectal stricture. The stricture was treated by endoscopic placement of a 6 cm × 20 mm fully covered oesophageal metal stent (figure 3) for 12 weeks and subsequently removed. This resulted only in partial improvement of the stricture (figure 4) and the patient was eventually referred for surgical ultra-low anterior resection of the rectum with take down of colostomy and re-anastomosis.

Figure 3.

Fully covered metal stent for rectal stricture.

Figure 4.

Residual stricture after removal of stent.

Outcome and follow-up

At the time of the last colonoscopy, the patient was doing well without any GI symptoms and was scheduled for a surgical take down of colostomy, ultra-low anterior resection of the rectum and a colorectal versus a coloanal anastomosis.

Discussion

Kayexalate, also known as SPS, is a cation-binding resin, used for treatment of hyperkalaemia. It acts by exchanging sodium ions for potassium ions in the colon, from where the potassium ions are excreted in the stool. Kayexalate-induced colitis can result in severe complications such as perforation, necrosis and strictures. Other binding resins that can cause intestinal injury include calcium polystyrene sulfonate, cholestyramine, colesevelam, colestipol and sevelamer.

Kayexalate is administered in the form of suspension either by oral or rectal route. In the past, Kayexalate was mixed with 70% sorbitol to counteract its constipating effect and help in catharsis of potassium ions. Animal models have showed intestinal transmural necrosis with both sorbitol and Kayexalate.² In 2009, Food and Drug Association issued a warning to avoid mixing Kayexalate with 70% sorbitol, but the warning did not extend to a premixed oral suspension of Kayexalate in 33% sorbitol. The lack of toxicity with 33% sorbitol was further demonstrated in rat models.³ In a large-scale study of patients with chronic kidney disease, out of Sweden, a dose-dependent increased incidence of serious GI adverse effects was seen with Kayexalate even without concurrent sorbitol.⁴ Thus, it is likely that both Kayexalate and 70% sorbitol can cause intestinal damage.

Intestinal injury resulting in ischaemia, ulcerations, necrosis, perforation and even mortality occurs in about 0.27%–1.8% of patients receiving Kayexalate.^5–7 Risk factors for developing these adverse events include ileus, concurrent use of opiates, large or small bowel obstruction and underlying infectious or inflammatory colitis.^{3 6} Biopsies of affected areas often show basophilic or violet crystals entrapped in the mucosal surface on H&E staining, admixed with superficial inflammatory exudate.¹ Other binding resins such as calcium polystyrene sulfonate, an analogue of SPS, cholestyramine, colesevelam, colestipol and sevelamer show their individual characteristics of crystals on biopsies.¹

As both Crohn’s and Kayexalate-induced colitis are diagnosis of exclusion and show similar non-specific findings on biopsy, unless a careful drug history is obtained, an accurate diagnosis can be missed, and patients may be treated inappropriately. We believe we overlooked the key biopsy finding due to the sheer number of biopsies performed in this patient which further emphasises the need to review each biopsy before a diagnosis of Crohn’s disease is made. Although our patient responded well to infliximab and 6-MP, he may have improved spontaneously over time without any treatment. Our case also brings to attention refractory nature of benign rectal strictures which usually require multi-modal management including endoscopic dilation using through the scope or bougie dilators, rectal stent placement and in some cases surgical management.

Learning points.

• Drug-induced colitis, although rare, should be considered an aetiology of colitis.

• Kayexalate or sodium polystyrene sulfonate is a well-known cause of intestinal injury.

• Awareness of drug-induced colitis can avoid the use of inappropriate treatment of colitis.