Is it appropriate to add famotidine to the treatment regimen of a patient with Ehlers-Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS) who experiences itching unrelieved by antihistamines such as Zyrtec (cetirizine) and Xyzal (levocetirizine)?

Adding Famotidine for Itching in a Patient with EDS and POTS

Yes, adding famotidine is appropriate for treating persistent itching in a patient with Ehlers-Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS) who has failed trials of cetirizine (Zyrtec) and levocetirizine (Xyzal). 1

Rationale for Adding Famotidine

• H2 receptor antagonists like famotidine are specifically recommended in treatment guidelines for patients with EDS and POTS who experience symptoms suggestive of mast cell activation 1
• The combination of H1 antagonists (like Xyzal) with H2 antagonists (like famotidine) provides more complete histamine receptor blockade, which can be more effective for controlling pruritus than H1 antagonists alone 1
• Famotidine is particularly useful in patients with EDS/POTS as these conditions are frequently associated with mast cell activation syndrome (MCAS), which can manifest as itching and other histamine-mediated symptoms 1

Dosing and Administration Considerations

• Standard dosing of famotidine for pruritus is typically 20-40 mg once or twice daily 2
• Start at the lower dose and titrate as needed based on symptom response 1
• Monitor for common side effects including headache, dizziness, and constipation 2

Benefits of Combined H1 and H2 Blockade

• H1 antagonists primarily address dermatologic manifestations like pruritus and flushing 1
• H2 antagonists help with abdominal and vascular symptoms that may be contributing to the patient's overall symptom complex 1
• The combination provides more comprehensive control of histamine-mediated symptoms 1

Important Considerations for EDS/POTS Patients

• Patients with EDS and POTS frequently have comorbid MCAS which may require multi-receptor blockade for symptom control 1
• Itching in these patients may be related to mast cell activation rather than traditional allergic pathways, making the addition of an H2 blocker particularly beneficial 1
• Famotidine has fewer anticholinergic effects compared to some other H2 blockers, making it preferable in patients with dysautonomia like POTS 1

Contraindications and Precautions

• Avoid famotidine in patients with a history of serious hypersensitivity reactions to H2 receptor antagonists 2
• Use with caution in patients with renal impairment as dosage adjustment may be needed 2
• Monitor for less common adverse effects including arrhythmia, confusion, and hypersensitivity reactions 2

Additional Management Strategies

• Consider trigger avoidance (certain foods, alcohol, temperature changes, mechanical stimuli) 1
• If symptoms persist despite combined H1 and H2 blockade, consider adding mast cell stabilizers like cromolyn sodium 1
• For severe cases unresponsive to standard therapy, referral to an allergy specialist or mast cell disease research center may be warranted 1