15 Jan New Itch Pathway Helps Explain Why Antihistamines Don’t Always Work
MedicalResearch.com Interview with:
Brian Kim, MD
Associate Professor of Dermatology
Co-Director, Center for the Study of Itch & Sensory Disorders
John T. Milliken Department of Internal Medicine
Washington University in St. Louis
MedicalResearch.com: What is the background for this study?
Response: Patients with eczema suffer from chronic itch due to the rashes they have on their body. However, as a physician, I have always noticed that patients with eczema will have sudden flares of their itching all over there body that is often triggered by what appear to be allergens – being around a cat, pollen, mold in a house, etc. Eczema is in the family of allergic diseases such as food allergy, asthma, and hay fever. All of these conditions are noted for patients being reactive to allergens by way of an antibody called IgE that coats a cell called the mast cell. Upon IgE binding an allergen, mast cells produce tons of histamine which can cause symptoms like itching. So we speculated that perhaps because patients with eczema have such misbehaving IgE, that exposure to allergen is what triggers this kind of severe itch flare that we see in patients.
MedicalResearch.com: What are the main findings?
Response:Indeed, this is what we found. However, surprisingly, IgE was acting on another very rare cell called the basophil and causing the release of another non-histamine molecule, which causes even more severe itching than even histamine. Strikingly, this molecule stimulates a very specific populations of sensory nerves that are specialized to cause itch. Interestingly, something about having eczema causes this unique basophil-itch nerve circuit to open up and override the histamine pathway. This explains now why such acute itch flares are triggered by allergens and why this is not responsive to antihistamines like Benadryl or Zyrtec. Importantly, this opens up new targets for itch in eczema and possibly other forms of itch.
MedicalResearch.com: What should readers take away from your report?
Response: There is more than one form of itch in eczema. Also, many patients complain of this kind of itch but I think we as providers have often disregarded it because we do not really know what’s causing it. This gives us new tools to diagnose, avoid triggers, and develop new therapeutics to alleviate this form of itch.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: A fundamental question in the field of allergy is, “Why do some people harbor IgE that is reactive to an allergen (like peanut) and develop severe symptoms (anaphylaxis), while others who have similar IgE do not develop any symptoms?” Our findings suggest that this may be because how IgE reacts to allergens may differ from person to person depending on their “inflammatory state”. In other words, although the allergen is getting on what appears to be the same train, depending on whether it’s the local or express line, it may end up at very different destinations! Also, why do some allergens cause food allergy, while others just cause itch? How these differences arise is a major question for the future.
Disclosures: Brian S. Kim has served as a consultant for AbbVie, ABRAX Japan, Almirall, AstraZeneca, Cara Therapeutics, Daewoong Pharmaceutical, Incyte, LEO Pharma, Lilly, Maruho, Menlo Therapeutics, OM Pharma, Pfizer, and Third Rock Ventures. He has also participated on the advisory board for Almirall, Boehringer Ingelheim, Cara Therapeutics, Kiniksa Pharmaceuticals, Menlo Therapeutics, Regeneron Pharmaceuticals, Sanofi Genzyme, and Trevi Therapeutics. He is stockholder of Locus Biosciences. He has also filed a patent application for the target the basophil/lipoxygenase pathway in itch.
A basophil-neuronal axis promotes itch
Wang, Fang et al.
Cell, Volume 0, Issue 0
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