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by David Wallace, Medically reviewed by Dr. C.H. Weaver M.D. updated 6/2020

A high percentage of polycythemia vera – MPN patients suffer from Aquagenic Pruritus, a fancy clinical term for itching. Few patients presenting with itching are tested for PV, but it is a classic symptom that tags along with a host of other strange bed fellows including fatigue, headache, dizziness, shortness of breathe, red skin tone, gastro-intestinal issues, body pain, cognitive impairment and the list goes on. There are few treatments for itching that are highly effective and provide consistent relief.

Itching 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.

I have been involved in patients’ discussions on this issue and it is very real. This article will focus on itching and treatment, the driving mechanisms behind itching with discussion of other symptoms as well. It is written from the patient perspective with medical commentary to follow.

A Personal Perspective

I was out of town for a medical procedure and packed my bags (and meds) methodically or so I thought. It was not until shower time that I discovered I had forgotten my Atarax, also known as hydroxyzine, a drug I did not like to take because of the undesirable side effects, but used as a last resort. I shivered in nervous anticipation as I approached the shower the next morning knowing good and well I was helpless. Afterwards, I suffered a frantic bout of itching with no relief in sight. Atarax is not a preventative treatment for itching at all, actually it just knocks you out (it is also prescribed for anxiety and panic attacks….go figure) after an episode has begun, so you don’t feel the itching as much. This was going to be a miserable trip, like the BMB (bone marrow biopsy) wasn’t enough….if I didn’t come up with an alternative.

The Z combo Zyrtec (Cetirizine Hydrochloride) and Zantac, a lifesaver! - Zantac (ranitidine) however is no longer available but another H2 blocker can be substituted: famotidine is approximately 40 times more potent than cimetidine

I was keeping a plan B tucked away to try in a “break the glass emergency.” It was so simple, it was hard to believe it might actually work. During one of our online discussions about furious bouts of itching (2 or 3 weeks prior to the trip), one of my friends, Roy Randall, reported great success using over the over the counter combo. Other patients chimed in, sharing successful results from the combo. I made a mental note, I would have to try this in a bind. The time is now…

That afternoon, I high tailed it to Walgreens, bound and determined to try this mysterious combo, practically unknown to the MPN world. I was already taking (1) 10 mg Zyrtec in the morning for allergies and added an H2 blocker to my routine. It provided itching relief quickly….during the next several days my itching faded away, nearly 100%, I was saved from a pruitis meltdown!! Miraculous relief that I hope will be helpful to many fellow MPN patients. It should be noted that generic versions.

When I was having regular phlebotomies (before Pegasys/Jakafi treatment), I noticed once my HCT rose to 42 or more, I become highly symptomatic and the itching creeps back into the symptom equation (although to a lesser extent) regardless of the Z and Z combo.

The Z 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 finetuning of both dosage levels and drug choice often being very specific to the patient. A very successful choice is the well-known “ZZ” combo of Zyrtec and Zantac since this combination blocks both the H1 and H1 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 in Polycythemia Vera

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.

The light has been shed on one of the key culprits in the complex universe of MPN symptoms. The graphic above provides a visual representation summarizing histamine-mediated symptoms. The discussion on itching just scratches the surface, no pun intended!

About David Wallace

David Wallace won the MPN Hero award in 2016 for Commitment to the Broader MPN Community. Diagnosed with polycythemia vera (PV) in 2009, David created PV Reporter and its sister website, MPN Cancer Connection. The patient-focused myeloproliferative neoplasm (MPN) hubs give members of the MPN community easy online access to resources as they start learning about their MPN.

Early on, David realized how important it is for newly diagnosed patients to have a one-on-one connection with a patient who is farther along in their journey with an MPN. That’s why he reaches out to others in the MPN community. He connects with other patients via email, Facebook groups, and MPN patient meetings. He knows what affects PV patients and addresses those topics in order to share relevant information at the point of need.


(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.