Aquagenic Palmoplanta keratoderma: Response to Topical Pimecrolimus and Literature Review

Introduction

Aquagenic palmoplantar keratoderma (APK) is a rare skin disease, which is characterized by the rapid appearance of white papules, excessive wrinkling and swelling of the palm after brief contact with water. Under normal circumstances, wrinkles appear on the palms within an average of 12 minutes when soaked in water.^1,2 We described a female patient who was treated with pimecrolimus for affected hands and wrists.

Case Presentation

A 50-year-old woman presented to the outpatient dermatology department with an over 20-years history of rapid appearance of white papules, excessive wrinkling and swelling of the palm after brief exposure to warm water or sweating,but there were no symptoms of itching, burning, or pain. Upon water removal, the symptoms disappeared rapidly. She denies having a history of atopic dermatitis or hyperhidrosis, smoking, or a history of special medications, as well as denying engaging in long-term frequent hand washing work, and no other family members have experienced similar symptoms.

On examination, after soaking both hands in hot water or sweat, diffuse white spots were visible on the dorsal of the hands and wrists, with skin lines remaining. The palmar skin exhibited a pebbly appearance and slight edema, accompanied by excessive swelling (Figure 1A and B). Approximately half an hour after the sweat evaporated, the skin keratinization of the dorsal of the hands and wrists subsided, leaving behind a few white spots, and only a few erythematous spots were visible on the palms (Figure 1C and D). Due to the patient’s clinical symptoms, a biopsy was not taken. Based on her history,the appearance of her hands and an otherwise normal physical examination, we diagnosed aquagenic palmoplanta keratoderma(APK). She applied topical Pimelomos ointment twice a day and was advised to continue her daily routine, including weekly moisturizing and follow-up. Her palm texture and symptoms improved within a week (Figure 2). When she stopped treatment and was exposed to sweat or hot water again after 2 months, the symptoms recurred but also responded to retreatment with pimecrolimus.

Figure 1 Clinical images of aquagenic plamoplantar keratoderma in a 50-year-old woman. (A) Diffuse white spots were visible on the dorsal aspects of the hands and wrists, with skin lines remaining. (B) Visible erythema on the palm, diffuse white spots were visible on the wrists. (C) Upon the removal of water, the skin keratinization on the dorsal aspects of the hands subsided, leaving behind a few white spots. (D) After the palm dries,only a few erythematous spots were visible on the palms.

Figure 2 Substantial improvement noted in skin texture and wrinkling of hand skin 1 week after treatment with pimecrolimus ointment.

Discussion

APK is triggered on the palms and soles after brief immersion in water, and is characterized by the rapid appearance of translucent papules or macerated plaques.¹ The pathogenesis is still unclear; in atopic dermatitis, impaired barrier function leading to increased skin water absorption, and hyperhidrosis, cystic fibrosis, or drug-induced increase in sweat salt concentration may play a role.^1–6 While there has been a strong association between APK and cystic fibrosis(CF), APK has also been shown to be drug-induced independent of CF history. In this case, the patient has no history of medication,we plan to further investigate whether it is related to cystic fibrosis, as APK may be a skin manifestation of CF.

Most treatment strategies aimed at preventing water exposure, reducing any related hyperkeratosis, and alleviating symptoms have proven ineffective and disappointing results in APK.⁷ The experience of using Vaseline and/or the use of gloves is still mostly frustrating, as pointed out in our case. In her case, repeated treatment with urea cream did not yield any benefits, and avoiding contact with water in daily work and life was impractical and could cause serious psychological and social problems.⁷ We observed that the patient’s skin symptoms were relieved in one week of topical pimecrolimus. Mild recurrence occurred after stopping treatment for two months, and the therapeutic effect was good after retreatment that the topical pimecrolimus was perhaps remittive therapy.

As a clinically approved calcineurin inhibitor for atopic dermatitis, the immune mechanism of pimecrolimus is often used for off label therapy, and its efficacy is comparable to that of topical corticosteroids. It is speculated that COX-2 inhibitors induce APK by inhibiting sodium reabsorption in epidermal cells and increasing sodium retention, analogous to renal effects. In a randomized study, calcineurin inhibitors inhibited COX-2 activity, thereby suppressing sodium transport in epidermal cells.⁸ In the experimental model, calcineurin inhibitors selectively regulate the renal cyclooxygenase subtype COX-1 and more selectively regulate COX-2 dependent prostaglandin synthesis, thereby regulating the homeostasis of keratinocytes.^9–11 These mechanisms extending beyond immunomodulation—may elucidate topical pimecrolimus efficacy in APK pathogenesis.

We searched PubMed for eligible articles related to APK from 2015 to 2025 using the following keywords: “Aquagenic palmoplanta keratoderma”; “treatment” and “case report”. After screening, 10 articles meet the eligibility criteria and have been included.^9,12–20 Table 1 shows the characteristics of patients and data on treatment and response. Overall, four patients experienced recurrence symptoms or treatment failure. These patients showed slight improvement in symptoms after local application of urea cream, aluminum chloride, Vaseline and intradermal injections botulinum toxin, but relapsed after discontinuation of the medication. Five patients showed improvement in symptoms after receiving urea, oral oxybutynin, and endoscopic thoracic sympathetic nerve examination, but no long-term treatment observation results were mentioned.

Table 1 Treatment in Reported APK Cases

Although patients usually experience symptoms such as burning, pain, or itching after immersion in water, this patient did not have similar symptoms. As in our case, physical findings typically resolve promptly after water removal. Lesions on the dorsal fingers are rarer than palmar involvement.^4,5 Many APK cases may be overlooked clinically without a water contact test.¹

In conclusion, we report a case of hand involvement in a healthy female APK patient treated with pimecrolimus. It is worth noting that clinicians use water contact testing as a screening test for suspected APK patients; furthermore skin biopsy and cystic fibrosis transmembrane conductance receptor mutation testing are recommended.