Abstract
Aquagenic wrinkling of the palms (AWP) is a rare dermatological disease characterized by development of rapid and excessive wrinkling and oedema of the palms and transient whitish or yellowish papules without erythema on the palmar surfaces after immersion in water. This phenomenon can be accompanied by pain and/or pruritus. The most common treatment of AWP involves aluminium‐based topicals. This article discusses the associations, pathological mechanisms and treatment options of AWP.
Aquagenic wrinkling of the palms (AWP) is a rare dermatological disease characterized by development of rapid and excessive wrinkling and oedema of the palms, and transient whitish or yellowish papules without erythema on the palmar surfaces after immersion in water. This phenomenon can be accompanied by pain and/or pruritus, and the most common treatment of AWP involves aluminium‐based topicals. This article discusses the associations, physiological mechanisms and treatment options of AWP.
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Introduction
Aquagenic wrinkling of the palms (AWP), also known as aquagenic palmoplantar keratoderma or aquagenic syringeal acrokeratoderma, is a dermatological rare phenomenon characterized by transient oedematous white or translucent papules without erythema on the palmar surfaces after contact with water. AWP affects mostly female patients and the majority of AWP occurs in patients with cystic fibrosis (CF) or CF carriers, although it is also observed in patients with hyperhidrosis, Raynaud disease (RD), marasmus and atopic dermatitis (AD), and in people taking certain medications such as aspirin and rofecoxib. 1 , 2 , 3 In addition, this rare dermatosis can be idiopathic.
Clinical features
AWP is characterized by the excessive wrinkling and the development of oedematous translucent, yellow or whitish plaques and papules on the palms after exposure to water. 4 Normal pathological wrinkling of palmar skin occurs after 11 min of water immersion, whereas AWP usually occurs within 3 min of water immersion 5 and may be accompanied by pain and/or pruritus. 6 An example of the exaggerated wrinkling in both palms in AWP, along with keratotic, pebbly, white plaques and prominent eccrine ostia is shown in Fig. 1a,b. The rapid development of these skin lesions after water exposure is known as the ‘the hand‐in‐bucket’ sign and is pathognomonic for AWP. 1 Symmetrical involvement of the palms is the most common presentation of AWP, with the soles sometimes involved. 1 Other atypical sites for AWP include the forehead, heel and dorsa of the fingers, and unilateral involvement can also be seen. 7 , 8 , 9 , 10 , 11 Most cases resolve within 20 min of terminating water exposure. 12 The possible differential diagnoses of AWP are listed in Table 1.
Figure 1.
(a,b) Exaggerated wrinkling of palm with keratotic, pebbly, white plaques and prominent eccrine ostia. [Colour figure can be viewed at wileyonlinelibrary.com]
Table 1.
Possible differential diagnoses for aquagenic wrinkling of the palms.
| Feature | AWP | Aquagenic pruritis | Aquagenic urticaria | HPA |
|---|---|---|---|---|
| Age of onset | Young adulthood | Adulthood | Adolescence or later | Adolescence |
| Distribution | Symmetrical; palms and soles | Symmetrical; thighs and upper arms | Trunk and upper arms | Symmetrical margins of palms and soles where there is increased pressure and trauma |
| Clinical features | Exaggerated wrinkling and eruption of white or translucent papules and plaques within minutes of water exposure | Itching within seconds to minutes of coming contact with water; no visible changes to skin during itching | Development of folliculocentric weals within 30 min water exposure; weals can appear in areas not exposed to water | Translucent, yellowish‐white plaques and papules and/or wrinkling of palms upon exposure to water |
| Associated findings | Pruritus and/or pain | Excoriations and lichenification of the skin due to scratching | Pruritus and sensations of burning or prickling | Sparse, fine hair and atopic diathesis |
| Inheritance | Sporadic | Sporadic | Sporadic or familial (rare) | Familial |
| Course | Transient | Transient | Transient | Permanent |
AWP, aquagenic wrinkling of the palms; HPA, hereditary papulotranslucent acrokeratoderma.
Histological findings
Histology can show spongiosis of the stratum corneum, eccrine acrosyringia dilation, crenulation of luminal cells of the secretory eccrine coils, acanthosis, orthohyperkeratosis and increased capillary proliferation around eccrine glands. 1 , 13
Associations with other conditions
AWP is associated with several conditions including CF, hyperhidrosis, RD, marasmus and AD. 3 , 5 , 14
Cystic fibrosis
The majority of patients with AWP also have CF, but this is not an invariable finding; AWP is seen in 44–80% of patients with CF 15 and 25% of CF carriers. 16 The development of AWP in patients and carriers is due to homozygous or heterozygous mutation of the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is present in eccrine ducts and regulates electrolyte transport. Defective CFTR proteins result in decreased electrolyte reabsorption, thus producing hypertonic sweat, which increases diffusion of liquids into palmar/plantar skin. 17 In addition, other studies have suggested abnormal expression of aquaporin 5 in the eccrine glands of CF as the cause of the transient oedema in AWP. 18 It is also suggested that dysfunction in transient receptor potential vanilloid (TRPV)4 channels leads to dysregulation of water transport in the epithelial cells of patients with CF. 6 Patient should be screened for CF via sweat test or CF gene mutation panel if they have a family history of CF and/or exhibits symptoms of CF, including but not limited to AWP, abdominal disease, reactive airway disease, nasal polyps, sinus drainage, clubbing, diarrhoea, hyperhidrosis and pancreatic insufficiency. Owing to the strong associations between CF and AWP, other studies have suggested the use of brief immersion in water test of the hands for 7 min as an effective screening tool for patients suspected to have CF. 19 Thorough investigation for CF should be performed in patients with AWP (Table 1).
Neurological conditions
Associated paraesthesias, such as pain and pruritus, suggest an additional neurological component to AWP. Sheskin et al. 20 noted an absence of physiological wrinkling in patients with nerve injuries. Wilder‐Smith and Chow 21 hypothesized that diffusion of water into eccrine ducts disturbs electrolyte homeostasis and affects the membrane stability of surrounding nerve fibres, leading to increased vasomotor firing and subsequent vasoconstriction. The increased vasomotor firing results in small muscle fibre contractions and the vasoconstriction itself results in a loss of volume; both of these result in a downward pull on the skin, which causes palmar wrinkling. 22
Association with medication
AWP has also been observed in patients taking medications that affect sodium retention in cells. Notably, these include common drugs such as aspirin, selective cyclooxygenase (COX) inhibitors, angiotensin‐converting enzyme (ACE) inhibitors and angiotensin‐receptor blockers. Carder and Weston 23 reported a case of rofecoxib‐induced AWP and hypothesized that selective COX‐2 inhibition, known to cause increased sodium reabsorption in the kidneys, may have similar effects on keratinocytes. The increased sodium content of keratinocytes may then increase keratin water‐binding capacity and result in exaggerated wrinkling. Khuu et al. 11 reported a case of aspirin‐induced unilateral AWP and hypothesized a similar mechanism, although they noted that aspirin preferentially inhibits COX‐1 over COX‐2. AWP has also been observed in patients taking aminoglycosides, ACE inhibitors and angiotensin‐receptor blockers, either by potentiating sodium retention or affecting osmotic gradient within keratinocytes. 16
Treatment
The most common treatments for AWP involve aluminium‐based topicals, with 20% aluminium chloride solution shown to dramatically improve symptoms in patients. 24 If the patient cannot tolerate the irritating properties of the alcohol solution, a 15% aluminium chloride gel can be used. 2 Botulinum toxin (BTX)‐A can be used to manage associated hyperhidrosis and autonomic nerve dysfunction and has been recommended as second‐line therapy for patients who do not respond to topical treatments. 1 Measures that create a barrier to water exposure, including gloves, ammonium lactate creams and petrolatum, have been shown to be ineffective in treating AWP. 25 , 26 Other treatment options include 20% salicylic acid, mometasone furoate ointment and 10% urea cream. 27 , 28 There are several reports on the use of topical steroids in patients with AWP; however, the benefits of topical corticosteroids in treating AWP are unclear. 29 , 30 A list of treatment options is shown in Table 2. Aluminium‐based topicals should be considered first in patients with AWP. If a patient cannot tolerate the adverse effects of the aluminium‐based topicals, the dose should be lowered or the patient switched to a different topical. If symptoms of AWP continue to persist despite trying different topicals, BTX‐A injections can be considered.
Table 2.
Tests and treatments for aquagenic wrinkling of the palms.
| Diagnosis of AWP |
| Clinical history and physical findings |
| Brief water immersion test of the palms for 7 min |
| Skin biopsy |
| Associated diagnostic tests (for CF) |
| Genetic test |
| Sweat test |
| Treatment options |
| Aluminium‐based topicals |
| BTX‐A injections |
| Salicylic acid |
| Topical steroids |
| Urea |
AWP, aquagenic wrinkling of the palms; BTX, botulinum toxin; CF, cystic fibrosis.
Conclusion
AWP is an interesting condition with multiple hypothesized mechanisms and a likely multifactorial aetiology. It is strongly associated with CF, and a diagnosis of AWP should prompt thorough investigations for CF. Beyond CF, the literature also reveals an association with common medications that affect sodium transport. Treatment consists primarily of topical aluminium chloride, though many patients are not bothered by their symptoms and defer any treatment.
Learning points.
AWP is a rare phenomenon characterized by transient oedematous white or translucent papules without erythema on the palmar surfaces after contact with water.
Symmetrical involvement of the palms is the most common presentation of AWP, with the soles sometimes involved.
Histological findings include spongiosis of the stratum corneum, eccrine acrosyringia dilation, crenulation of luminal cells of the secretory eccrine coils, acanthosis, orthohyperkeratosis and increased capillary proliferation around eccrine glands.
AWP is strongly associated with CF; 44–80% of patients and 25% of carriers have AWP.
The development of AWP in patients with CF and CF carriers is due to mutations in the CFTR gene, abnormal expression of aquaporin 5 in the eccrine glands, and/or dysfunction in TRPV4 in the epithelial cells of patients with CF.
A diagnosis of AWP should prompt thorough investigation for CF.
Conflict of interest
The authors declare that they have no conflicts of interest.
Funding
None.
Ethics statement
Ethics approval not applicable. The patient provided informed consent for publication of their case details and images.
CPD questions
Learning objective
To gain knowledge on the features of aquagenic wrinkling of the palms, its diagnosis and treatment, and associated conditions.
Question 1
What inherited disorder is commonly associated with aquagenic wrinkling of the palms (AWP)?
(a) Charcot–Marie–Tooth disease.
(b) Cystic fibrosis.
(c) DiGeorge syndrome.
(d) Huntington disease.
(e) Prader–Willi syndrome.
Question 2
Which body part does aquagenic wrinkling of the palms (AWP) affect?
(a) Axilla.
(b) Buttocks.
(c) Gums.
(d) Palms.
(e) Sclera.
Question 3
How long after water immersion does wrinkling of palmar skin occur in patients with aquagenic wrinkling of the palms (AWP)?
(a) 1 minute.
(b) 3 minutes.
(c) 8 minutes.
(d) 9 minutes.
(e) 10 minutes.
Question 4
If a patient is diagnosed with aquagenic wrinkling of the palms (AWP), thorough investigation should be ordered for which disorder?
(a) Bowel cancer.
(b) Crohn disease (CD).
(c) Cystic fibrosis (CF).
(d) Diabetes.
(e) Haemophilia.
Question 5
Dysfunction of a particular protein results in decreased electrolyte reabsorption and resultant hypertonic sweat, which increases diffusion of liquids into palmar/plantar skin in patients with cystic fibrosis who have aquagenic wrinkling of the palms (AWP); which protein is this?
(a) Cystic fibrosis conductance regulator protein.
(b) Filaggrin.
(c) Insulin receptor.
(d) Rhodopsin.
(e) Sodium glucose cotransporter.
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References
- 1. Wollina U, Tchernev G, Semkova K et al. Aquagenic keratoderma. Two new case reports and a new hypothesis. Indian Dermatol Online J 2014; 5: 30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Syed Z, Wanner M, Ibrahimi OA. Aquagenic wrinkling of the palms: a case report and literature review. Dermatol Online J 2010; 16: 7. [PubMed] [Google Scholar]
- 3. Chinazzo C, De Alessandri A, Menoni S et al. Aquagenic wrinkling of the palms and cystic fibrosis: an Italian study with controls and genotype‐phenotype correlations. Dermatology 2014; 228: 60–5. [DOI] [PubMed] [Google Scholar]
- 4. Choi H, Bae IH, Kim MS et al. Two cases of aquagenic wrinkling of the palms in Korean healthy women: easily overlooked disease. Ann Dermatol 2020; 32: 151–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Gild R, Clay CD, Morey S. Aquagenic wrinkling of the palms in cystic fibrosis and the cystic fibrosis carrier state: a case‐control study: AWP in CF and the CF carrier state. Br J Dermatol 2010; 163: 1082–4. [DOI] [PubMed] [Google Scholar]
- 6. Park L, Khani C, Tamburro J. Aquagenic wrinkling of the palms and the potential role for genetic testing: aquagenic wrinkling of the palms. Pediatr Dermatol 2012; 29: 237–42. [DOI] [PubMed] [Google Scholar]
- 7. Neri I, Bianchi F, Patrizi A. Transient aquagenic palmar hyperwrinkling: the first instance reported in a young boy. Pediatr Dermatol 2006; 23: 39–42. [DOI] [PubMed] [Google Scholar]
- 8. Yoon TY, Kim KR, Lee JY, Kim MK. Aquagenic syringeal acrokeratoderma: unusual prominence on the dorsal aspect of fingers? Br J Dermatol 2008; 159: 486–8. [DOI] [PubMed] [Google Scholar]
- 9. Xia Q. Aquagenic acrokeratoderma: case report with no involvement of the palms: correspondence. Int J Dermatol 2012; 51: 1391–3. [DOI] [PubMed] [Google Scholar]
- 10. Bajaj S, Sardana K. Aquagenic wrinkling syndrome involving forehead: an unusual presentation. Indian J Med Res 2018; 147: 521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Khuu PT, Duncan KO, Kwan A et al. Unilateral aquagenic wrinkling of the palms associated with aspirin intake. Arch Dermatol 2006; 142: 1661–2. [DOI] [PubMed] [Google Scholar]
- 12. Luo DQ, Zhao YK, Zhang WJ, Wu LC. Aquagenic acrokeratoderma: aquagenic acrokeratoderma. Int J Dermatol 2010; 49: 526–31. [DOI] [PubMed] [Google Scholar]
- 13. Rongioletti F, Tomasini C, Crovato F, Marchesi L. Aquagenic (pseudo) keratoderma: a clinical series with new pathological insights: aquagenic (pseudo) keratoderma. Br J Dermatol 2012; 167: 575–82. [DOI] [PubMed] [Google Scholar]
- 14. Schmutz J, Barbaud A, Trechot P. Rofecoxib‐induced aquagenic edema with puckering of the palms of the hands: the first case. Ann Dermatol Venereol 2003; 130: 813. [PubMed] [Google Scholar]
- 15. Garçon‐Michel N, Roguedas‐Contios A‐M, Rault G et al. Frequency of aquagenic palmoplantar keratoderma in cystic fibrosis: a new sign of cystic fibrosis? Br J Dermatol 2010; 163: 162–6. [DOI] [PubMed] [Google Scholar]
- 16. Torres‐Laboy PM, Melendez‐Montañez JM, De Jesús‐Rojas W. Aquagenic wrinkling of the palm: a rare diagnostic clue of cystic fibrosis and the response to CFTR‐modulating therapy. Cureus 2021; 13: e14425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Mishra A, Greaves R, Massie J. The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era. Clin Biochem Rev 2005; 26: 135–53. [PMC free article] [PubMed] [Google Scholar]
- 18. Kabashima K, Shimauchi T, Kobayashi M et al. Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the palms. J Am Acad Dermatol 2008; 59(Suppl): S28–32. [DOI] [PubMed] [Google Scholar]
- 19. Alexopoulos A, Chouliaras G, Kakourou T et al. Aquagenic wrinkling of the palms after brief immersion to water test as a screening tool for cystic fibrosis diagnosis. J Eur Acad Dermatol Venereol 2021; 35: 1717–24. [DOI] [PubMed] [Google Scholar]
- 20. Sheskin J, Sabatto S, Yosipovitz Z, Ilukevich A. Lack of wrinkle formation in the fingertips of patients with Hansen's disease. Confirmation of previous observations. Hansenol Int 1983; 8: 54–60. [PubMed] [Google Scholar]
- 21. Wilder‐Smith EPV, Chow A. Water‐immersion wrinkling is due to vasoconstriction. Muscle Nerve 2003; 27: 307–11. [DOI] [PubMed] [Google Scholar]
- 22. Wilder‐Smith EPV. Water immersion wrinkling. Clin Auton Res 2004; 14: 125–31. [DOI] [PubMed] [Google Scholar]
- 23. Carder KR, Weston WL. Rofecoxib‐induced instant aquagenic wrinkling of the palms. Pediatr Dermatol 2002; 19: 353–5. [DOI] [PubMed] [Google Scholar]
- 24. Yan AC, Aasi SZ, Alms WJ et al. Aquagenic palmoplantar keratoderma. J Am Acad Dermatol 2001; 44: 696–9. [DOI] [PubMed] [Google Scholar]
- 25. MacCormack MA, Wiss K, Malhotra R. Aquagenic syringeal acrokeratoderma: report of two teenage cases. J Am Acad Dermatol 2001; 45: 124–6. [DOI] [PubMed] [Google Scholar]
- 26. Rizzo C, Bragg J, Soldano AC et al. Hereditary papulotranslucent acrokeratoderma. Dermatol Online J 2008; 14: 3. [PubMed] [Google Scholar]
- 27. Saray Y, Seckin D. Familial aquagenic acrokeratoderma: case reports and review of the literature. Int J Dermatol 2005; 44: 906–9. [DOI] [PubMed] [Google Scholar]
- 28. Erkek E. Unilateral transient reactive papulotranslucent acrokeratoderma in a child. Pediatr Dermatol 2007; 24: 564–6. [DOI] [PubMed] [Google Scholar]
- 29. Wang F, Zhao Y‐K, Luo Z‐Y et al. Aquagenic cutaneous disorders. J Dtsch Dermatol Ges 2017; 15: 602–8. [DOI] [PubMed] [Google Scholar]
- 30. Houle M‐C, Al Dhaybi R, Benohanian A. Unilateral aquagenic keratoderma treated with botulinum toxin A. J Dermatol Case Rep 2010; 4: 1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
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