Aquagenic Urticaria – When Water Becomes Lethal

Priasha Dutta, Amity University Kolkata

INTRODUCTION

Water, one of the fundamental sources of life, is capable of being an annoyance for some individuals. Aquagenic urticaria (AU) or “water allergy” is a unique form of physical or chronic inducible urticaria caused by water exposure. Urticaria (also called hives) is a skin reaction in response to an allergen or stress where the skin is characterized by itching, burning, swelling, redness, and bumps. These bumps or welts usually continue to appear and fade anywhere on the body. The disease has received a negligible amount of attention from the scientific community, with less than 100 reported cases only. However, the pathogenesis of this condition remains unknown. Because trigger avoidance is nearly impossible, treatment is based on symptomatic control.

EPIDEMIOLOGY

Several cases of AU seem to occur occasionally in people with no family history of this disorder. However, familial cases have been reported on many occasions, with one of them describing the disease in three generations of the same family. Some familial cases have been stated concerning other conditions, some of which can be ancestral. The family members who were diagnosed with AU also had another medical condition that was potentially inherited. However, to our knowledge, no specific inheritance pattern has been definitively associated with AU. The first case of sporadic AU was found in Mexico. The patient showed a sufficient therapeutic response to a skin barrier–repairing cream and second‐generation antihistamine.

From the research and observation of these cases so far, the net inference states that a female prevalence has been shown over males. The condition usually develops during puberty and shows chronic behavior. For many individuals, disease occurs sporadically, without any comorbidities. Numerous isolated reports have documented familial occurrence and coexistence with familial lactose intolerance, papillary carcinoma of the thyroid, Bernard‐Soulier syndrome, and polymorphic light eruption. Due to the scarcity of AU cases, it is unknown whether these conditions share a common background or whether there are predisposing environmental or genetic factors.

PATHOGENESIS

Three hypotheses have been formulated to explain the pathogenesis. The first proposal was that water reaction with the sebaceous glands or sebum forms a toxic substance resulting in mast cell degranulation. It was also assumed that some unknown epidermal antigens that are water soluble in nature may diffuse across the dermis, thus leading to histamine release. Thirdly, histamine‐independent mechanisms were proposed after observing unaffected serum histamine levels in a patient. Salt‐dependent AU (SDAU; when the allergy is triggered by saltwater) has been defined in less than 10 cases.

Since the exact pathogenesis of AU is not understood well, here is a rough idea of the causes and symptoms. Water reacts with the unknown components within the skin, leading to the release of histamine from mast cells and the formation of an urticarial rash. Triggers may include freshwater, sweat, tears, and seawater. AU is independent of the water temperature, pH, and other psychogenic factors.

SYMPTOMS

Symptoms begin to show 20–30 minutes after the skin is in contact with water. The most common allergic response is 1–3 mm folliculocentric wheals (an area of the skin surrounding a central follicle that is swollen and itchy (or pruritic)). Such wheals may also surround 1–3 cm erythematous flares, i.e.; flashes of inflammation and redness that keep appearing and disappearing anywhere on the body. The rash mainly targets the trunk and upper arms, sparing the palms and soles. It may also spread to areas that are not in contact with water.

Other symptoms include burning, pruritus, and prickling. In extreme cases, systemic symptoms of shortness of breath and wheezing can be seen. There are, however, some uncommon clinical presentations of AU as well. Some reports of patients implied that the reactions depend on the salinity of the water. For instance, a patient reacted to sweat, snow, and tap water, but could still swim in the ocean without urticaria. There can be an aggravated urticarial response to water in patients who have had cutaneous exposure to organic solvents decreased thickness of the stratum corneum following epilation.

DIAGNOSIS AND TREATMENT

The method of diagnosing someone with this disease is bound to be easy. The “water provocation test” simply consists of applying water at room temperature to a cloth and putting it on the patient’s skin for 30 minutes, after which the skin is checked for appropriate symptoms of an urticarial reaction. But the treatment of the overlooked disease is equally difficult. Avoidance of one of the fundamental sources of life is an impractical feat for patients.

The urticarial symptoms such as wheal formation can be partially mediated by the effects of histamine on the H₁ receptor. Thus, the first-line treatment consists of oral H₁ antihistamines. First-generation H₁ antihistamines have substantial sedative side effects. These undesirable effects can continue much longer than the therapeutic effect, which lasts for 4 to 6 hours only. Because of this reason, the newer, second-generation H₁ antihistamines causing lesser central nervous system depression, but a greater extent of action is preferred. Anecdotal reports infer that several patients with AU cannot attain symptomatic control solely with oral antihistamines.

In one study, H₂ antihistamines in combination with H₁ antihistamines have shown some effect at reducing the wheal response in patients even further. Therefore, combination therapy using H₁ and H₂ antihistamines can be considered for the H₁ antihistamine-resistant cases. Anticholinergics like scopolamine can also be considered as an accessory therapy with H₁ antihistamines to curb the urticarial response. Psoralens are compounds extracted from plants that are activated by light. They can photosensitize the skin and are well known for such treatments when used in combination with UV radiation.

In a few cases the role of phototherapy, including Psoralens UV radiation A and UV radiation B, has been reported to inhibit symptoms of AU. Psoralens ultraviolet radiation A has also been used in combination with antihistamine therapy, producing a good response. The suggested mechanisms of phototherapy for treating AU include the reactive thickening of the epidermis and decreasing the mast cell activity – leading to reduced water penetration. There have also been many case reports that recommend the use of drugs like stanozolol and selective serotonin reuptake inhibitors. Stanozolol is an anabolic steroid having no significant androgenic side effects. It has been shown to raise the levels of normal C1 esterase inhibitors in managing hereditary angioedema. This proposes an interesting possibility of serotonin involvement in the pathogenesis of AU.

CONCLUSION

There is still room for improvement in understanding the mechanism of this rare and difficult disease. More attention and research could lead to more efficacious, evidence-based treatment strategies for patients. However, the cornerstone therapy for these patients to date revolves around phototherapy, second-generation H₁ antihistamines, H1 and H2 antihistamines, or a suitable combination of the aforementioned therapies. There are numerous therapeutic options currently available such as oral and topical agents, but there is a lack of strong evidence of their effectiveness. Some patients may be refractory to these forms of treatment and still need to depend on minimizing water exposure by avoiding certain water-based activities or even limiting their bathing time.

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REFERENCES –

1. Robles-Tenorio, A., Tarango-Martinez, V. M., & Sierra-Silva, G. (2020). Aquagenic urticaria: Water, friend, or foe?. Clinical Case Reports, 8(11), 2121-2124. https://doi.org/10.1002/ccr3.2880
2. 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
3. Chen, Y. C., Hsu, W. H., Sun, C. M., Liu, C. H. (2018). A case of aquagenic urticaria with a brief review of the literature. Dermatologica Sinica, 36 (3), 146-148. https://doi.org/10.1016/j.dsi.2017.12.003
4. (2021). Aquagenic urticarial. Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Rarediseases.info.nih.gov. https://rarediseases.info.nih.gov/diseases/10901/aquagenic-urticaria#:~:text=Aquagenic%20urticaria%20is%20a%20rare,a%20form%20of%20physical%20urticaria

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