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by MedMaven, Medically Reviewed by Dr. C.H. Weaver M.D. Updated 4/2022

Many individuals with autoimmune and rheumatoid conditions suffer from Aquagenic Pruritus, a fancy clinical term for itching. There are few treatments for itching that are highly effective and provide consistent relief but the Z and P or T combination appears to work well for many individuals.

Itching occurs in many autoimmune, rheumatologic, and even blood disorders and may be caused or worsened by exposure to water without observable skin lesions. The symptoms may be felt immediately after contact with water and may last an hour or longer. It generally occurs in the trunk and nearby extremities. Most patients describe itching, but others report a tingling, burning or stinging sensation.

The Z and P or T combo (Zyrtec and Pepcid (famotidine) or Tagamet (cimetidine) is a simple solution for itching that is widely used by individuals with polycythemia vera and is reported to provide great success. It should be noted that generic versions Cetirizine Hydrochloride (Zyrtec) and Pepcid (famotidine) or Tagamet (cimetidine)  can be purchased from Costco or Walmart for a considerable discount from the branded versions.

The Z and P or T combo’s effectiveness in Mast Cell disorders is confirmed in William Alford’s article:

“Patients with urticaria (hives) and mast cell disease are typically treated with various combinations of antihistamines which block histamine receptor sites on cells, with a fine tuning of both dosage levels and drug choice often being very specific to the patient. A very successful choice is the well-known combo of Zyrtec and Pepcid (famotidine) or Tagamet (cimetidine) since this combination blocks both the H1 and H2 histamine receptors. Other antihistamines include ChlorTrimeton, Benadryl, Dramamine, Claritin, and Tavist.”

Note: Before taking any medications, even OTC, be sure to check with your doctor or pharmacist.

More Strategies to Beat Itching

Mast Cell Disease and the Release of Histamines

Mast cells have long been known to contribute to the discomforts of mankind by releasing histamine and producing the miseries of allergies. However, patients with mast cell disease may also present with a multitude of disparate symptoms such as arthritis, GERD, constipation, malabsorption, cramping, severe abdominal bloating, short term memory problems, headache, nausea, bone pain, heart palpitations, changes in cognitive function and mood and more. Sound familiar?….nearly identical to the symptoms we experience as MPN patients. Mastocytosis, one of the myriad of mast cell diseases are classified as an MPN, so no surprise there!

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Mast cell diseases are histamine disorders (be sure to click on the preceding link and scroll down midway for the excellent graphic, Histamine Intolerance & Mast Cell Activation) that come in many flavors – mast cell activation syndrome (MCAS), mast cell activation disorder (MCAD) and mastocytosis (numerous types) among others. Other conditions with a link to histamine/mast cell include: Fibromyalgia, Cancer, Multiple Sclerosis, Narcolepsy, IBS, Crohn’s, Parkinson’s, Alzheimer’s and heart disease.

Mast cell activation syndrome is a fancy way of saying the immune system is freaking out and dumping inflammation into the body, sometimes chronically.

While mast cells present throughout the body, all body tissues that come in direct contact with the outside world have mast cells and they are concentrated in the skin, gut, nasal passages, lung, urinary tract and other mucus membranes.

With MPNs, we suffer with excess histamine due to basophil breakdown (a type of white blood cell). Histamine is one of the inflammatory players released by mast cells, along with heparin and serotonin. They also contain cytokines, interleukin, leukotrienes, prostaglandins and other inflammatory agents. The release of these proinflammatory agents results in the classic allergy symptoms which most of us are familiar with.

However, the principle chemical mediator of mast cells is histamine which can cause tissue swelling, itching, flushing and other noxious skin responses. It is what causes the itching and swelling of the mosquito bite and the itch of healing wounds with the rapid growth of new tissue. But it can also cause systemic responses such as headache, nausea, dizziness, diarrhea and can be involved in other GI disease such as gastric ulcer and IBS.


  1. William Alford, “Mast Cells and GI Motility Disease, 2005” – Permission is granted by the author for anyone to copy and distribute this document to any other part so long as the author’s name and the copyright notice is retained on all copies or sections of the document.
  2. Wikipedia, mast cell.
  3. Indian Journal of Dermatology, Aquagenic Pruritis: Beneath Water “Lies,” 2011
  4. The Low Histamine Chef, Yasmina Ykelenstam, “Natural Mast Cell Stabilizers for Histamine,” 2016.