Medical Mysteries: Aquagenic Urticaria, the “Water Allergy”

Figure 1. Water being poured into a cup. Image from Getty Images.

Water is undoubtedly crucial to survival. Approximately 60 percent of the human body is composed of water, and some internal organs like the lungs contain even higher concentrations (U.S. Geological Survey, n.d.). The same holds true for the rest of the world, with the five major ocean basins accounting for nearly three quarters of the Earth’s surface (U.S. National Oceanic and Atmospheric Administration, 2013). As such, it would be impractical—and virtually impossible—to avoid water, whether it be rain from thunderstorms, sweat from exercise, or merely using faucet water for drinking, bathing, and cleaning.

Despite this, aquagenic urticaria (AU), also known as “water allergy,” has been observed in humans. Following skin-to-skin contact with water of any temperature and purity, individuals with AU develop cutaneous hives (physical urticaria) in exposed areas (Sibbald et al., 1981). Typically, symptoms include blisters, lesions, pruritus (itching), and general inflammation of the skin; however, more severe cases have also been linked to respiratory hyperreactivity and resistance, as well as other comorbidities like cancer (Genetic and Rare Diseases Information Center [GARD], n.d.; Luong & Ngyuen, 1998; Park et al., 2011).

Figure 2. Patient suffering from aquagenic urticaria having an allergic attack. Image from Casale & Olsen 2013.

Contrary to popular beliefs surrounding the more ubiquitous “water allergy” term, AU doesn’t prevent individuals from ingesting water—urticaria only appears when the most superficial skin layer (epidermis) comes into contact with water, not the internal organs. Drinking water still causes discomfort since the oral cavity and esophagus are lined with the same squamous epithelial cells that comprise the body’s external skin (Biga et al., n.d.; Esposito, 2016; Gorvett, 2016; Tsoulis-Reay, 2015).

Much of this information is based on known cases: the first verified instance of AU dates back to 1963, when a 15-year-old girl went water-skiing and broke out in sores afterward (Shelley & Rawnsley, 1964). Others have been diagnosed since then, with some even publicizing their experiences through prominent media outlets (Esposito, 2016; Gorvett, 2016; Luong & Ngyuen, 1998; Selway, 2019; Tsoulis-Reay, 2015). AU remains relatively rare, though—across the globe, only about 100 additional cases have been officially reported within the last fifty-odd years (Park et al., 2011). Such a small sample population with large variances in symptoms and sensitivity has limited experimentation and understanding of the causes of AU. However, that’s not to say that progress hasn’t been made; in fact, scientists have proposed two major theories about the possible bodily mechanisms behind this immune response.

Causal Theory 1 — Histaminergic & Antigen-based Mechanism

Shelley and Rawnsley initially suggested that the interaction between water and a substance on the stratum corneum—a sub-layer of squamous epithelial cells in the stratified epidermis—produced a toxin that stimulated histamine production, and eventually urticaria (1964). Subsequent research by Chalamidas and Charles yielded more supporting evidence: When an AU-diagnosed male was patch tested with a mixture of his own sweat and stratum corneum sebum, significant urtication occurred, along with a marked increase in histamine (1971). Czarnetzki et al. then tested this theory again by injecting two female AU carriers with aqueous extracts of human callus, ultimately producing a prolonged burning, itchy sensation and heightened histamine levels. Since this reaction couldn’t be replicated in non-AU patients, they hypothesized that AU was caused by a water-soluble antigen that penetrated the epidermis to increase histamine production, which would then trigger urticaria (1986).

Causal Theory 2 — Histaminergic Mechanism

In a separate series of tests, Sibbald et al. reaffirmed that histamine plays an important role in the pathogenesis of AU. However, they also discovered that removal of the stratum corneum in two AU patients didn’t change the severity or quantity of manifested urticaria—if anything, it worsened the reaction. As a result, they argued that Shelley and Rawnsley’s hypothesis was implausible. Other epidermal components might play a causal role, just not the stratum corneum and its related substances (1981).

Scholars have yet to come to a consensus on the most “correct” causal theory, and there have been additional reports of anomalies that seem to violate both proposed theories (Gallo et al., 2013; Luong & Ngyuen, 1998; Sibbald et al., 1981). But regardless of this lingering uncertainty, these studies have certainly helped doctors refine AU remedies. 

These days, AU is typically treated with antihistamines, topical agents and skin barriers, or ultraviolet therapy. Of these, antihistamines are generally the most effective and thus prescribed first (GARD, n.d.; Kim et al., 2014; Park et al., 2011). In particular, Cetirizine and other H1 antihistamines that block H1 receptors are preferred; H2 antihistamines such as Cimetidine can be used if the prior fails, or if the sedative effects of H1antihistamines are too difficult to manage. The other methods can be pursued as secondary measures to help manage symptoms, but only antihistamines have successfully “cured” some cases of AU (GARD, n.d.; Park et al., 2011; Rothbaum & McGee, 2016; Sibbald et al., 1981). 

Fortunately, Omalizumab—a severe asthma medication—seems to be a promising new treatment, with recent research suggesting that it may be just as effective as antihistamines. In one study, an AU-diagnosed patient unresponsive to traditional antihistamine treatments was injected with 300mg of Omalizumab every 28 days. After just two doses, the patient reported that they no longer developed urticaria when exposed to water (Rorie & Gierer, 2016). 

Clearly, scientific experimentation and analysis of individual case studies has produced new, significant insights on AU. For the most part, however, it remains a medical mystery—one that will hopefully be resolved in the future.

Edited by Nathan Jacob & Daisy Li

References

Biga, L. M., Dawson, S., Harwell, A., Hopkins, R., Kaufmann, J., LeMaster, M., … Runyeon, J. 5.1 Layers of the Skin. Anatomy Physiology. https://open.oregonstate.education/aandp/chapter/5-1-layers-of-the-skin/

Chalamidas, S. L., Charles, C. R. (1971). Aquagenic Urticaria. Arch Dermatol, 104(5), 541–546. doi:10.1001/archderm.1971.04000230083015. 

Czarnetzki, B. M., Breetholt, K.-H., & Traupe, H. (1986). Evidence That Water Acts as a Carrier for an Epidermal Antigen in Aquagenic Urticaria. Journal of the American Academy of Dermatology, 15(4), 623–627. https://doi.org/https://doi.org/10.1016/S0190-9622(86)70215-6

Esposito, L. (2016, November 4). What It’s Like Being Allergic to Water. U.S. News & World Report. https://health.usnews.com/wellness/articles/2016-11-04/what-its-like-being-allergic-to-water.

Gallo, R., Gonçalo, M., Cinotti, E., Cecchi, F., Parodi, A. (2013, January). Localized Salt-Dependent Aquagenic Urticaria: A Subtype of Aquagenic Urticaria. Clinical and Experimental Dermatology, 38, 754–757. doi:10.1111/ced.12147. 

Gorvett, Z. (2016, September 15). The Woman Who Is Allergic To Water. BBC Future. https://www.bbc.com/future/article/20160915-the-woman-who-is-allergic-to-water.

Kim, J. E., Eun, Y. S., Park, Y. M., Park, H. J., Yu, D. S., Kang, H., … Lee, J. Y. (2014, April). Clinical Characteristics of Cholinergic Urticaria in Korea. Annals of Dermatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037671/

Luong K. V., Nguyen L. T. (1998, June). Aquagenic Urticaria: Report of a Case and Review of the Literature. Ann Allergy Asthma Immunol, 80(6), 483-485. doi:10.1016/S1081-1206(10)63071-2. 

Park, H., Kim, H. S., Yoo, D. S., Kim, J. W., Kim, C. W., Kim, S. S., … Choi, Y. J. (2011, December). Aquagenic Urticaria: A Report of Two Cases. Annals of Dermatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276800/

Rorie, A., & Gierer, S. (2016). A Case of Aquagenic Urticaria Successfully Treated with Omalizumab. The Journal of Allergy and Clinical Immunology: In Practice, 4(3), 547–548. https://doi.org/10.1016/j.jaip.2015.12.017

Rothbaum, R., & McGee, J. S. (2016). Aquagenic Urticaria: Diagnostic and Management Challenges. Journal of Asthma and Allergy, 9, 209–213. https://doi.org/10.2147/JAA.S91505

Selway, N. (2019, July 12). My ‘Allergic to Water’ Skin After a Bath (Microscope Footage). Youtubehttps://www.youtube.com/watch?v=VAZ1sIDIJGA.

Shelley, W. B., Rawnsley, H. M. (1964). Aquagenic Urticaria: Contact Sensitivity Reaction to Water. Journal of the American Medical Association, 189(12), 895–898. doi:10.1001/jama.1964.03070120017003.

Sibbald, R. G., Black, A. K., Eady, R. A., James, M., & Greaves, M. W. (1981). Aquagenic Urticaria: Evidence of Cholinergic and Histaminergic Basis. The British Journal of Dermatology, 105(3), 297–302. https://doi.org/10.1111/j.1365-2133.1981.tb01289.x 

Tsoulis-Reay, A. (2015, October 27). What It’s Like to Be Allergic to Water. The Cut. https://www.thecut.com/2015/10/what-its-like-to-be-allergic-to-water.html.

U.S. Department of Commerce, National Oceanic and Atmospheric Administration (NOAA) (2013, June 1). How Much Water is in the Ocean? NOAA. https://oceanservice.noaa.gov/facts/oceanwater.html

U.S. Department of Health and Human Services, Genetic and Rare Diseases Information Center (GARD). Aquagenic Urticaria. National Center for Advancing Translational Health Studies (NIH). https://rarediseases.info.nih.gov/diseases/10901/aquagenic-urticaria

U.S. Department of the Interior, U.S. Geological Survey (USGS). The Water in You: Water in the Human Body. United States Geological Survey: Water Science School. https://www.usgs.gov/special-topic/water-science-school/science/water-you-water-and-human-body?qt-science_center_objects=0.

Image References

Casale, T. & Olsen, J. (2013). Aquagenic Urticaria. The Journal of Allergy and Clinical Immunology, 1(3): 295–296. https://doi.org/10.1016/j.jaip.2013.02.003

HR NewsWire. (2020, January 15). Yes, drinking more water may help you lose weight. https://hub.jhu.edu/at-work/2020/01/15/focus-on-wellness-drinking-more-water/

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