Aquagenic keratoderma treated with tap water iontophoresis.

Aquagenic keratoderma (AK) is a rare acquired skin condition characterized by recurrent and transient white papules and plaques associated with a burning sensation, pain, pruritus and/or hyperhidrosis on the palms and more rarely, soles triggered by sweat or contact with water. Often AK cause significant discomfort, thus requiring an appropriate therapy. Topical aluminum-based products are the most commonly used medications, but they are not always effective. We report a case of AK unresponsive to topical 20% of aluminum chloride successfully treated with tap water iontophoresis.

What was known?

Aquagenic keratoderma (AK) is a rare acquired condition consisting in recurrent and transient white papules and plaques associated with a burning sensation, pain, pruritus and/or hyperhidrosis on the palms and more rarely, soles triggered by sweat or contact with water.

The pathogenesis of AK is still unknown, despite multiple hypotheses have been proposed including eccrine gland or nerve dysfunction, hyperhidrosis, defective stratum corneum barrier function, increased sweat salt concentration in the stratum corneum, occlusion of the eccrine duct ostia, or weakness of the eccrine duct wall.

Often AK cause significant discomfort, thus requiring an appropriate therapy. Topical aluminum-based products are the most commonly used medications, but they are not always effective. Other anecdotal therapies include salicylic-acid based products, formalin 3% in alcohol, antihistamines, botulinum toxin injections and iontophoresis. Regarding this last therapy, there is only one report describing its use in AK, but the results were not specified.

Introduction

Aquagenic keratoderma (AK), also known as aquagenic palmoplantar keratoderma, aquagenic syringeal keratoderma, aquagenic wrinkling of the palms and aquagenic acrokeratoderma, is a rare condition presenting with recurrent and transient white papules and plaques on the palms and more rarely, soles triggered by sweat or contact with water. AK is predominant in women with a mean age of onset of 21 years. Its etiology is unknown, although about one-third of cases are associated with cystic fibrosis (CF) and some instances are induced by intake of various drugs, including aspirin, indomethacin, salazopyrin, rofecoxib and celecoxib.[123] Often AK cause significant discomfort, thus requiring an appropriate therapy.[1] Topical aluminum-based products are the most commonly used medications, but they are not always effective. Other anecdotal therapies include salicylic-acid based products, formalin 3% in alcohol, antihistamines, topical corticoids, topical erythromycin, barrier agents, botulinum toxin injections and iontophoresis.[34] We report a case of AK unresponsive to topical 20% of aluminum chloride successfully treated with tap water iontophoresis.

Case Report

This was a case report of a 30-year-old male patient presented with a 3-year history of a burning sensation and papular lesions on both palms arising after sweating or immersion in water for a few minutes. The manifestations were transient and resolved within 30-60 min after drying his hands. No other family members presented similar findings. Patient also reported a history of hyperhidrosis, while denied relevant personal pathological antecedents or history of drug intake. Physical examination revealed a normal palmar skin surface. After immersing the hands in water at 15°C for 5 min, small white pebble-like papules with prominent eccrine ostia were evident [Figure 1a and b] and the patient reported a burning sensation. The lesions and symptoms normalized within 40 min after drying. The history and clinical observations led to the diagnosis of AK. Considering the possibility of association between AK and CF,[5] we decided to perform a sweat test, which showed a normal amount of chloride; the patient declined further genetic testing for CF.

Figure 1

(a) Small white pebble-like papules with prominent eccrine ostia after immersing the hands in water at 15°C for 5 min; (b) magnification of the papules after immersion

He was treated with topical 20% of aluminum chloride applied once daily, without any significant results on AK and hyperhidrosis after 6 weeks of therapy. Therefore, we decided to suspend it and start a new treatment with tap water iontophoresis; both hands in the pronated position were immersed in tap water and were exposed to controlled electric current (10-15 mA) for 15 min on Monday, Wednesday and Friday for 4 weeks. No side-effects were observed, except for the onset of some transient white papules on the palms associated with a tolerable fleeting burning sensation; both findings decreased gradually over the therapeutic sessions. At the end of treatment schedule, we performed a new immersion test, which showed a notable clinical improvement with remission of the burning sensation [Figure 2a and b]. Furthermore, the patient reported a significant improvement of hyperhidrosis. During the subsequent 3-month follow-up period, the patient retained the results achieved.

Figure 2

(a) A new immersion test after treatment with tap water iontophoresis for 4 weeks shows a notable clinical improvement; (b) magnification of the prior image

Discussion

AK is a rare acquired condition consisting in translucent whitish papules and plaques of the palms and more seldom, of the soles which occur after sweating or immersion in water, especially when warm and disappear after drying within minutes to an hour. Most of the cases are bilateral, although instances of unilateral palmar AK have rarely been described in the literature. Often patients report a burning sensation, pain, pruritus and/or hyperhidrosis associated with skin lesions. The diagnosis of AK is mainly clinical and the “hand-in-the-bucket” sign, when patients submerge their hands in water for a time ranging from 2 to 10 min in order to demonstrate the lesions, is an important diagnostic clue.[4] Histopathology is nonspecific and may show orthokeratotic hyperkeratosis and dilated eccrine ducts.[14] The main differential diagnosis is hereditary papulotranslucent acrokeratoderma, which appears during puberty with persistent, asymptomatic, yellow-white, translucent palmoplantar papules and plaques that are unrelated to water exposure.[6] The pathogenesis of AK is still unknown; despite multiple hypotheses have been proposed including eccrine gland or nerve dysfunction, hyperhidrosis, defective stratum corneum barrier function, occlusion of the eccrine duct ostia, or weakness of the eccrine duct wall.[47] Furthermore, based on association some cases of AK with CF and intake of aspirin or cyclo-oxygenase-2 inhibitors, some of the authors have suggested that AK could be due to increased sweat salt concentration in the stratum corneum.[1] However, this explicative model is hardly applicable in our case, since the amount of chloride in the sweat was normal.

Although cases of spontaneous remission have been described,[5] in most patients AK tends to persist and cause a significant physical and psychological discomfort, thus requiring an appropriate therapy. Several treatments have been reported including aluminum-based or salicylic-acid based products, formalin 3% in alcohol, antihistamines, botulinum toxin injections and iontophoresis.[4] Regarding this last therapy, there is only one report describing its use in AK, but the results were not specified.[8]

In our case, the patient was found to resistant to topical 20% of aluminum chloride, while he had a significant improvement to tap water iontophoresis.

The latter has long been known to inhibit sweat production and therefore it is often used for the treatment of hyperhidrosis. It has been suggested that tap water iontophoresis selectively targets areas with high levels of electrolytes because of enhanced current flow. A local electro-chemical coagulation of proteins occurs in these areas and subsequently disrupts eccrine gland function. Another theory hypothesizes iontophoresis causes interrupted stimulus-secretion-coupling that leads to a functional disturbance of sweat secretion.[9]

The exactly mechanisms by which this therapy acts upon AK are unknown. Anyhow, on the basis of the foregoing and whereas improving of AK in our case has occurred together with the reduction of sweating, it is possible to speculate that the effects of iontophoresis on AK are attributable to the reduction of sweat production and/or functional changes of eccrine gland.

Conclusion

The clinical improvement observed in this report suggests that a protocol based on tap water iontophoresis, as the one exposed here, followed by post-treatment follow-up could be considered as a possible therapeutic option for AK, especially for cases unresponsive to topical drugs. Moreover, the successful treatment of AK with tap water iontophoresis, which is known to influence the activity of eccrine sweat glands, further supports a possible involvement of these glands in the pathogenesis of this condition, as assumed by some Authors on the basis of the efficacy of other therapies, which act on their function.[410] Anyhow, further studies and reports are needed to confirm these assumptions.

What is new?

The clinical improvement observed in this report suggests that a protocol based on tap water iontophoresis, as the one exposed here, could be considered as a possible therapeutic option for AK, especially for cases unresponsive to topical drugs.

The successful treatment of AK with tap water iontophoresis, which is known to influence the activity of eccrine sweat glands, further supports a possible involvement of these glands in the pathogenesis of this condition.