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I just saw a news article about a woman with Aquagenic Urticaria which basically means she produces antibodies against H2O molecules which causes very bad symptoms if she touches or drinks water.

We're told you can't be allergic to oxygen, glucose, salt etc because they're too small and simple. So why is H2O an antigen?

NCBI source - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276800/

Willy A
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The pathogenesis behind Aquagenic Urticaria isn't definitively known - and the extreme rarity of the condition makes studying it difficult (only ~100 cases published!)

It does appear to be an allergic-type response - as shown in the linked article from your question the wheals are formed when histamine is released and AU appears to respond to antihistamine treatment in most cases.

One theory (Czarnetzki et al ) is that the patient isn't having an allergic reaction to the water itself but rather a water-soluble antigen present at the epidermal layer - and that when the antigen is dissolved in the water it then diffuses through the epidermal layer causing the mast cells to release histamine and produce the wheals.

However that is probably not the full story - since there have been reported cases where there was no signs of a histamine response and treating with antihistamines proved ineffective (Luong et al)

So to summarize - no definitive mechanism as been determined, but it's probably not a case of simply being allergic to H2O molecules.

motosubatsu
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    How does the water soluble antigen explain people who also cannot drink water because they have a reaction in their throat? – Willy A Mar 22 '19 at 15:23
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    @WillyA plenty of skin in the mouth and it's vicinity (for example the lips) for that to come from. But it's far from a perfect theory by any means, about all everyone can agree on is that it's not a straight allergic response to water molecules - an IgE mediated allergy to H20 would be far more catastrophic since we have rather a lot of it inside our bodies. – motosubatsu Mar 22 '19 at 15:35
  • Within this soluble antigen theory, is an assumption that the antigen is a not an essential nutrient required? In other words, can allergy occur from an essential nutrient? –  Mar 22 '19 at 15:38
  • Couldn't this theory be tested by examining wheals from saline? Wouldn't injecting a hypertonic solution inhibit dissolving the antigen? –  Mar 22 '19 at 15:40
  • @fredsbend I believe the suggestion was that it was a component of the epidermis itself that acted as the antigen. As to whether it's possible to be allergic to an essential nutrient - no idea, I'd imagine you probably wouldn't live very long were you to have such an allergy though! – motosubatsu Mar 22 '19 at 15:45
  • But how does this explain throat and mouth reactions to drinking water, but less so or not at all to diet cola or orange juice for instance? – Willy A Mar 22 '19 at 15:52
  • @WillyA Most drinks are hypertonic, which means there's more solutes in it than in the body on average. That means passive diffusion tends towards the drink, not the body. That is to say, water will tend to move out of the tissues, rather than in, leaving tissue solutes more likely to remain in tissue. –  Mar 22 '19 at 15:59
  • So it takes pure water to move the antigens in the skin towards the mast cells via osmosis/pressure? That clears things up a lot so thanks – Willy A Mar 22 '19 at 16:04
  • @WillyA Well, sort of. The water moves passively through cell walls (mostly). When confronted with a solution that is not in equilibrium, the cell begins active transport mechanisms to move water and solutes, in and out, whichever helps keep the cell interior at optimum solution. So if confronted with a hypotonic solution (like drinking water), the water passively moves into the cell, changing the interior solution. One route the cell may take to keep optimum solution within itself is to push solutes out, which this theory predicts is the antigen in this condition. –  Mar 22 '19 at 17:00
  • I'm unfamiliar with this theory and condition, but this is how I would make sense of harder reactions to water than to juice or something else. They're are, after all, many other reasons cells actively move molecules. Also there's many molecules between cells, but the principles of solutions still applies. –  Mar 22 '19 at 17:01