What alternatives can be used to support bowel motility in a patient with Mast Cell Activation Syndrome (MCAS) and psoriatic arthritis who cannot tolerate MiraLAX (polyethylene glycol) due to MCAS reactions, Linzess (linaclotide) due to migraines, or osmotic laxatives due to exacerbation of psoriatic arthritis?

Alternative Motility Support for MCAS and Psoriatic Arthritis with Multiple Laxative Intolerances

Start with fiber supplementation (psyllium or methylcellulose) combined with stimulant laxatives (bisacodyl or senna), as these are the safest first-line alternatives when osmotic agents trigger inflammatory conditions. 1

First-Line Approach: Fiber Plus Stimulant Laxatives

• Begin psyllium 15g daily or methylcellulose as bulk-forming agents that are generally well-tolerated and have minimal adverse effects except rare allergic reactions to psyllium 1, 2
• Add bisacodyl 10-15mg orally or senna as stimulant laxatives to enhance intestinal motility 1, 3
• Stimulant laxatives work by stimulating the myenteric plexus and can be used long-term safely despite historical concerns about intestinal damage, which have not been supported by clinical evidence 1
• Bisacodyl suppositories 10mg rectally can be added if oral therapy is insufficient, administered 30 minutes after meals to synergize with the gastrocolonic response 1, 3

Second-Line Option: Lubiprostone

• Lubiprostone 24 mcg twice daily is a chloride channel activator that increases intestinal fluid secretion without the osmotic mechanism that triggers your patient's psoriatic arthritis 1, 4
• This agent works through a different mechanism than polyethylene glycol or other osmotic laxatives, making it potentially tolerable despite osmotic laxative intolerance 4
• FDA-approved for chronic idiopathic constipation with demonstrated efficacy in increasing spontaneous bowel movements within 24 hours 4
• Common side effects include nausea (which may be manageable with antiemetics like ondansetron) but does not typically trigger MCAS or inflammatory arthritis 1, 4

Third-Line Prokinetic: Prucalopride

• Prucalopride (5HT4 receptor agonist) is a selective serotonin receptor agonist with prokinetic properties that can be used when other laxatives fail 1
• Headache and gastrointestinal symptoms are the most common side effects, typically transient and occurring at treatment initiation 1
• This agent works through a completely different mechanism than linaclotide (which your patient cannot tolerate), making it a viable alternative 1

Alternative Prokinetic Options

• Erythromycin 250-900mg daily acts as a motilin agonist and may improve small bowel dysmotility, though subject to tachyphylaxis with prolonged use 1, 5
• Azithromycin may be more effective for small bowel dysmotility than erythromycin 1
• Pyridostigmine (parasympathomimetic) has shown benefit in refractory constipation including diabetic patients, using a stepped dosing regimen to minimize cardiovascular side effects 1

MCAS-Specific Considerations

• Ensure adequate H1 and H2 antihistamine coverage (cetirizine, fexofenadine with famotidine) plus mast cell stabilizers (cromolyn sodium) to reduce baseline MCAS activity that may be contributing to dysmotility 1
• Consider montelukast as a leukotriene receptor antagonist for additional MCAS control 1
• In refractory MCAS cases with multiple drug intolerances, tofacitinib has shown benefit for MCAS symptoms and could theoretically help both the MCAS and psoriatic arthritis, though this is off-label 6

Critical Pitfalls to Avoid

• Discontinue docusate immediately as it is ineffective for established constipation 3
• Avoid magnesium-based osmotic laxatives given the patient's documented intolerance to osmotic agents and risk of exacerbating psoriatic arthritis 1
• Do not use IL-17 inhibitors for psoriatic arthritis management if inflammatory bowel symptoms develop, as these can worsen GI inflammation 1, 7
• Avoid lactulose as it is an osmotic agent that may trigger the same inflammatory response as other osmotic laxatives 1

Practical Algorithm

1. Start fiber (psyllium 15g daily) + bisacodyl 10mg daily 1
2. If inadequate response within 1 week, add bisacodyl suppositories 10mg rectally 1, 3
3. If still inadequate after 2 weeks, switch to lubiprostone 24 mcg twice daily while continuing fiber 4
4. If lubiprostone fails or is not tolerated, trial prucalopride 1
5. Consider erythromycin or azithromycin as adjunctive prokinetic therapy if above measures insufficient 1, 5