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Dermatopathology: Practical & Conceptual

October – December 2010 | Volume 16, No. 4

Aquagenic keratoderma: An entity more peculiar than it looks

Patsatsi, Aikaterini; Sotiriadis, Dimitrios

Report of a patient

A 19-year-old girl presented herself in tears complaining of the sudden presentation of edema and whitish flesh-colored papules on her palms every time she immersed her hands in water (Figs. 1A-C). All papules had markedly dilated puncta in their center. She reported a burning sensation and mild pruritus. Lesions gradually disappeared in 30-60 minutes. She did not suffer from hyperhidrosis and did not take any systemic drugs. Her parents and sister had no history of a similar situation.

Figs. 1A-C

Edema with whitish flesh-colored papules on the palms, soon after the patient immersed her hands in water.

After inducement of lesions by immersion of hands in water at room temperature, we took a biopsy of a whitish papule.

Histopathology

Histopathologic changes were very subtle (Figs. 2A-I). Some alteration of the cornified layer with columns of compact orthokeratotic eosinophilic keratin and occasional parakeratotic lamella were seen. Underneath those columns the granular layer was thinned. In the dermis, a sparse perivascular infiltrate of lymphocytes was present. Eccrine glands and ducts were normal.

Figs. 2A-I

Columns of compact orthokeratotic eosinophilic keratin with occasional parakeratotic lamella, thinned granular layer and a sparse perivascular infiltrate of lymphocytes. Eccrine glands and ducts are normal.

Comment

In 1973, a hereditary condition called papulotranslucent acrokeratoderma was first described. [1] It is characterized by symmetric, translucent, yellowish-white, smooth papules and plaques occurring primarily along the margins of the hands and feet usually after trauma or pressure. No specific histopathology has been described. The condition is inherited by an autosomal dominant trait.

Twenty-two years later, English and McCollough first described a similar but acquired condition as transient reactive papulotranslucent acrokeratoderma, [2] involving mainly young females. This entity is characterized by papules with prominent pores that present on the palms and rarely on the soles [3] after exposure to water, and they disappear after drying. The clinical lesions are similar with those observed in normal individuals after prolonged immersion of the hands and feet in water; the difference is that in aquagenic keratoderma they appear 2-3 minutes after the exposure. The “hand-in-the-bucket sign,” a term given by Yan et al., defines wonderfully the major clinical sign of this condition. [4]

Histopathologically, orthohyperkeratosis, hypergranulosis, acanthosis, prominent or dilated eccrine ducts, dilated eccrine ostia or spongiosis around eccrine ducts have been described in a number of cases. [5] In the patient presented here, the biopsy taken directly after lesions had developed on exposure to water revealed only subtle changes in the cornified layer and a mild perivascular infiltrate. No changes of the eccrine glands and ducts were seen.

Since 1996, there have been 40 cases reported in the literature, most of them in females, and many new names given to the same condition: aquagenic palmoplantar keratoderma, aquagenic syringeal acrokeratoderma, acrosyringial acrokeratoderma, instant aquagenic wrinkling of the palms, transient aquagenic palmar, hyperwrinkling, or acquired aquagenic keratoderma. [6]

The origin of the problem remains unclarified. There are two old theories. According to the first one, an aberration of the eccrine sweet glands is the major causative agent, [7] while according to the second, structural modifications (a possible mutation in transglutaminase or involucrine) of the stratum corneum could impair the integrity of the cutaneous barrier and allow an increased water absorbance and a pebbly appearance. [5,6] The histopathologic changes seen in the case presented here seem to be supportive of the latter theory.

Occasional hyperhidrosis is associated with aguagenic keratoderma (AK), with no proved etiological correlation. Recently, an aberrant aquaporin 5 expression in the sweat glands of patients with this disease has been described. [8] The literature is also enriched continuously with information on a possible carrier status for a cystic fibrosis gene (delta F508 CFTR mutation) for patients with AK. [9,10]

Treatment options are limited. Aluminium chloride creams, 12% ammonium lactate cream, 20% acid salicylic in Vaseline®, 10% urea cream, botulinum toxin injections or just avoidance of frequent contact with water. [3] The condition, although very frustrating, is limited in duration. In the patient presented here, creams with aluminum chloride did not help and the patient tried to avoid water as much as possible. Eight months later, a spontaneous remission was observed.

Many questions arose during the 14 years since the first description of AK. Is it really not inherited, and why is it transient? If there is a stratum corneum defect, how is it repaired all of a sudden? New clinical and molecular data regarding the initial presentation and the course of this condition are awaited with great interest. Undoubtedly, aquagenic keratoderma remains more peculiar than it looks.

Summary

A patient with typical clinical findings of aquagenic keratoderma is presented. Histopathologic findings showed subtle alteration of the cornified layer and a mild perivascular infiltrate, while eccrine glands and ducts were normal. The literature on the condition is reviewed and cause and pathogenesis are discussed.

Aikaterini Patsatsi, M.D., is a Lecturer in Dermatology at the Faculty of Medicine at Aristotle University of Thessaloniki in Greece, where Dimitrios Sotiriadis, M.D., is Professor of Dermatology. This article was reviewed by Almut Böer, M.D. Contact corresponding author via email: kaptz@med.auth.gr .

References

1. Onwukwe MF, Mihm MC, Toda K. Hereditary papulotranslucent acrokeratoderma. Arch Dermatol. 1973; 108: 108-110.

2. English JC, McCollough ML. Transient reactive papulotranslucent acrokeratoderma. J Am Acad Dermatol. 1996; 34: 686-687.

3. Bardazzi F, Savoia F, Dika E, Tabanelli M, Giacomini F. Acquired aquagenic keratoderma. Pediatric Dermatol. 2007; 24(2): 197-198.

4. Yan AC, Aasi SZ, James WD, et al. Aquagenic palmoplantar keratoderma. J Am Acad Dermatol. 2001; 44: 696-699.

5. Betlloch I, Vergara G, Albares MP, et al. Aquagenic keratoderma. J Eur Acad Dermatol. Venereol 2003;17:306-307.

6. Pastor MA, González L, Kilmurray L, Bautista P, López A, Puig AM. Aquagenic keratoderma: 3 new cases and a review of the literature. Actas Dermosifiliogr. 2008;99(5):399-406.

7. MacCormack MA, Wiss K, Malhotra R. Aquagenic syringeal acrokeratoderma. Report of two teenage cases. J Am Acad Dermatol. 2001; 45: 124-126.

8. Kabashima K, Shimauchi T, Kobayashi M, Fukamachi S, et al. Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the palms. J Am Acad Dermatol. 2008;59(2 Suppl 1):S28-32.

9. Katz KA, Yan AC, Turner ML. Aquagenic wrinkling of the palms in patients with cystic fibrosis homozygous for the delta F508 CFTR mutation. Arch Dermatol. 2005;141(5): 621-4.

10. Stewart LC, Doe SJ, Bourke SJ, Leech S.Aquagenic palmar wrinkling as a presenting feature of cystic fibrosis gene dysfunction. Clin Exp Dermatol. 2009;34(8):e647-9.