Introduction
Kayexalate, an ion exchange resin used along with sorbitol to treat hyperkalaemia which may crystallize in the gastrointestinal tract leading to ischemia, ulceration and erosions. Colon is the most commonly involved site.1 These crystals are luminal or adherent to intact surface epithelium or mixed with an inflammatory infiltrate at the site of ulcer or erosion.2 Since the associated adverse effects are linked to fatality, this should be treated as a medical emergency. We report 2 such cases with kayexalate-induced mucosal damage in the gastrointestinal tract who responded positively after discontinuation of the causative medication.
Case Report
A 64-year old, male patient presented with non-specific abdominal pain. Lower gastrointestinal endoscopy was performed to evaluate the mucosa. It revealed multiple colonic erosions. These sites were biopsied. Histopathological examination showed microscopic findings of colitis and ulceration with associated crystals having fish scale-like appearance (Figure 1). Later, after detailed review of the history, it was found that the elderly patient had chronic renal failure who was treated with sodium polystyrene sulfonate (Kayexalate) for hyperkalaemia caused due to electrolyte imbalance.
Figure 1
Photomicrographs showing colonic biopsies with features of colitis associated with kayexalate crystals (marked by arrows)
Figure 2
Photomicrographs showing microscopic features of colitis associated with kayexalate crystals in a resected segment of colon (marked by arrows)
In another case, a resected segment of colon from a child with Hirschsprung’s disease was referred for histopathological examination which revealed similar crystals associated with the ulcerated mucosa (Figure 2 A, B, C). This patient had a history of administration of enema for constipation.
Correlating HE, AFB, PAS and alcian blue staining with the history, the mucosal damage in both the cases was found to be associated with sodium polystyrene sulfonate (Kayexalate) due to sorbitol administration and enema.
These patients, on follow up, showed significant improvement and eventually recovered completely after the withdrawal of the causative agent.
Discussion
Resins are nonabsorbable medications that are used to treat conditions such as hyperkalaemia (Kayexalate), hyperphosphatemia (Sevelamer) and elevated bile acids (Cholestyramine) and are commonly referred to as medication crystals. These work via exchange of ions as they course through the gastrointestinal tract.
Sodium polystyrene sulfonate (Kayexalate) is a Food and Drug Administration (FDA) approved medication for management of hyperkalaemia. It is administered orally or via rectal route. This polymer is designed to exchange sodium ions against potassium ions from the intestinal cells which, then is eliminated from the body in stool. After administration, it should be retained within the colon for 30 to 60 minutes and should be followed by irrigation to remove the residual resin.3
In 2009, FDA warned against the use of Kayexalate sorbitol due to its adverse GI side effects.4, 5
These include small bowel and colorectal necrosis, intestinal ulcers, ischaemia, thrombosis and even perforation.6, 7 Many have questioned the association of sodium polystyrene sulfonate and adverse gastrointestinal effects in absence of sorbitol. However, in recent times, reports do mention about the possible toxic effects of kayexalate alone.1
Identification of these resins on histopathological sections is a challenge, more so since there is a morphological overlap between the various types of resins. Kayexalate crystals are rectangular with internal narrow, regular creases or strokes resembling “fish scales”; also termed as “mosaic pattern”.8 These crystals are purple on haematoxylin-eosin staining (Figure 1 A, B and Figure 2 A, B), black on AFB (Figure 1 C) and magenta coloured on PAS staining (Figure 2 C) as seen in our cases. These crystals concentrate around the ulcerated mucosa or are embedded within it with associated inflammation and necrosis.8, 9 Other resin crystals simulating kayexalate crystals are of Sevelamer and bile acid sequestrants which have their own characteristic morphologies.8 The Sevelamer crystals are deep eosinophilic, broad, curved with “irregularly spaced” fish-scales. Also, these stain magenta on AFB and appear two- toned on PAS-D (pink linear accentuations over a rusty yellow background. In contrast to these, the bile acid sequestrants (Cholestyramine) crystals are glassy, smooth, bright orange to pink and lack the fish scale appearance on HE. They are neon green on AFB, grey or sometimes bright pink on PAS-D.10 Bisphosphonates which are used to prevent bone resorption may sometimes lead to crystal deposition in the GI mucosa, where the crystals are non-polarizable and are associated with non-specific histological findings.10
This case report highlights kayexalate as a cause of lower gastrointestinal mucosal injury. The abdominal symptoms are vague in crystal associated colitis and recognition of kayexalate crystals in histologic sections is challenging without a proper medical history. Ancillary staining can come handy along with proper patient history for accurate recognition and timely diagnosis. Finding these crystals on endoscopic biopsies marks the sorbitol induced mucosal damage and thus may aid in establishing the correct diagnosis in scenarios where we encounter clinically and endoscopically misleading signs and symptoms.
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