Excessive Wrinkles and a Burning Sensation in a Girl’s Hands After Bathing

Carlos A. Arango, MD, and Matthew Tayon

An 8-year-old girl presented with a protracted history of a burning sensation and excessive wrinkling of her hands for the past few months. The irritation and wrinkling had occurred predominantly after exposure to water. Removal of the hands from water and then drying them with a hair dryer on a low/cool setting after water exposure provided her great relief.

The girl’s past medical history included vesicoureteral reflux, chronic constipation, and viral warts on her left hand. 

Her family history was positive for viral warts in both her mother and father, and her aunt is a gene mutation carrier for cystic fibrosis (CF).

The results of a sweat chloride test were negative for CF in the patient.

wrinkled hands

What is the cause of this girl’s after-bath symptoms?

Answer, discussion, and podcast on the next page

Carlos A. Arango, MD, is an assistant professor in the Department of Family Health and Community Medicine at the University of Florida in Jacksonville.

Matthew Tayon is a second-year medical student at the West Virginia School of Osteopathic Medicine in Lewisburg.


Aquagenic Palmoplantar Keratoderma

Answer: Aquagenic Palmoplantar Keratoderma

Based on her symptoms, the girl received a diagnosis of aquagenic palmoplantar keratoderma (APK).


Aquagenic palmoplantar keratoderma (APK) was first termed and described by Onwukwe in 1973 as a hereditary papulotranslucent acrokeratoderma that presented as “persistent, asymptomatic, yellowish-white, translucent papules and plaques that appear on the hands and feet,” with the lesions being “associated with fine-textured scalp hair and an atopic diathesis.”1 These symptoms seemed to occur near puberty and were exacerbated by immersion in water. The condition was considered hereditary, with an autosomal dominant mode of transmission.

In 1996, English and McCollough2 described a disorder affecting 2 sisters that had all of the characteristic features of hereditary papulotranslucent acrokeratoderma but without the defining presence of sparse hair and atopic diathesis. This led to the description of an independent disorder, transient reactive papulotranslucent keratoderma, which was determined to have an autosomal recessive penetrance.

In order to dispel the notion of the disorder being strictly inherited, Yan and colleagues3 in 2001 renamed the condition aquagenic palmoplantar keratoderma while studying 3 female patients who presented with the defining onset of disease in adolescence or during young adulthood, with burning and discomfort in the hands after water exposure.

APK is now described as an acquired disorder that occurs predominantly in the female population and features bilateral, symmetric, white or translucent papules, and excessive wrinkling on the palms and soles, along with pain or a burning sensation in the affected areas. These lesions can be seen in the hands without contact to water but primarily appear within minutes of exposure to water and progressively worsen with prolonged contact, particularly with warm water.4 The symptoms gradually improve and disappear without treatment, usually within 20 to 50 minutes after removal of the exposed area from water. Drying of the affected area can accelerate the alleviation process.


The pathogenesis of APK still is unclear. Aquagenic wrinkling has been reported with the use of celecoxib, rofecoxib, and aspirin; the mechanism might be excessive retention of sodium in the skin of the palms or soles related to the medications’ inhibition of cyclooxygenase 2 in the epidermal cells, leading to increased sodium retention and water diffusion into the palmoplantar regions.5-8

Because of the rapid absorption of water into the affected areas, the overactivity of aquaporin 10 (AQP10) also has been considered as a possible source of the condition. Increased sympathetic activity along with increased water retention capabilities occurring in persons with AQP10 in the palmar dermal layer could lead to the symptoms seen in APK.9-11

Nerve innervation involved with fingertip wrinkling has a relationship with digit pulp vasoconstriction. The involvement of nerve innervation in the pathogenesis of APK is strengthened by reports of the successful treatment of APK with botulinum toxin, owing to its effect on preganglionic sympathetic and parasympathetic nerves and postganglionic parasympathetic nerves.4,12

The development of APK also appears to correlate with the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR. Several studies have shown that persons with CF also can present with several of the symptoms of APK. In a study of 27 patients with CF in France, Garçon-Michel and colleagues13 found that 41% showed the hallmark signs of APK after exposure to water—hyperwrinkling, white pustule formation, and a burning sensation or pain on the palms.

Results of genetic testing of persons with CF has shown an increase in APK symptom severity between patients who were heterozygous for the ΔF508 sequence variation compared with those with the more severe homozygous presence.14,15 In a study by Rongioletti and colleagues,16 histologic test results of patients who tested positive for this mutation showed dilation of eccrine ducts and thickening of the stratum corneum. The histologic results, along with electrolyte reabsorption dysfunction seen in CF, provide a strong case for the involvement of CF in the hyperwrinkling and pustule formation seen in APK.

Diagnosis and Treatment

The diagnosis of APK generally is made with the use of a water-immersion test, which is used to assess sympathetic nerve function by monitoring for the presence of the characteristic symptoms after prolonged exposure of the hands or feet to water.

Topical aluminum hydroxide, 20%; topical salicylic acid ointment, 5%; topical ammonium lactate, 12%; topical petroleum jelly; and oral antihistamines have been shown to relieve the symptoms of APK.3,17-19 Botulinum toxin injections also have been reported as effective.12

In our patient, empiric treatment with oral antihistamines and topical corticosteroids was initiated to help with the burning sensation in her hands, and topical aluminum hydroxide was used for the hyperhidrosis and excessive wrinkling, with great success.



The author discusses the case in this podcast:




Carlos A. Arango, MD, is an assistant professor in the Department of Family Health and Community Medicine at the University of Florida in Jacksonville.

Matthew Tayon is a second-year medical student at the West Virginia School of Osteopathic Medicine in Lewisburg.


  1. Onwukwe MF, Mihm MC Jr, Toda K. Hereditary papulotranslucent acrokeratoderma: a new variant of familial punctate keratoderma? Arch Dermatol. 1973;108(1):108-110.
  2. English JC III, McCollough ML. Transient reactive papulotranslucent acrokeratoderma. J Am Acad Dermatol. 1996;34(4):686-687.
  3. Yan AC, Aasi SZ, Alms WJ, et al. Aquagenic palmoplantar keratoderma. J Am Acad Dermatol. 2001;44(4):696-699.
  4. Luo D-Q, Zhao Y-K, Zhang W-J, Wu L-C. Aquagenic acrokeratoderma. Int J Dermatol. 2010;49(5):526-531.
  5. Khuu PT, Duncan KO, Kwan A, Hoyme HE, Bruckner AL. Unilateral aquagenic wrinkling of the palms associated with aspirin intake. Arch Dermatol. 2006;142(12):1661-1662.
  6. Schmutz J-L, Barbaud A, Trechot P. Rofecoxib-induced aquagenic edema with puckering of the palms of the hands: the first case [in French]. Ann Dermatol Venereol. 2003;130(8-9 pt 1):813.
  7. Syed Z, Wanner M, Ibrahimi OA. Aquagenic wrinkling of the palms: a case report and literature review. Dermatol Online J. 2010;16(7):7.
  8. Vildósola S, Ugalde A. Celecoxib-induced aquagenic keratoderma [in Spanish]. Actas Dermosifiliogr. 2005;96(8):537-539.
  9. Öberg F, Sjöhamn J, Fischer G, et al. Glycosylation increases the thermostability of human aquaporin 10 protein. J Biol Chem. 2011;286(36):31915-31923.
  10. Boury-Jamot M, Sougrat R, Tailhardat M, et al. Expression and function of aquaporins in human skin: is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta. 2006;1758(8):1034-1042.
  11. Bellemère G, Von Stetten O, Oddos T. Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol. 2008;128(3):542-548.
  12. Bagazgoitia L, Pérez-Carmona L, Salgüero I, Harto A, Jaén P. Letter: aquagenic keratoderma: successful treatment with botulinum toxin. Dermatol Surg. 2010;36(3):434-436.
  13. Garçon-Michel N, Roguedas-Contios AM, Rault G, et al. Frequency of aquagenic palmoplantar keratoderma in cystic fibrosis: a new sign of cystic fibrosis? Br J Dermatol. 2010;163(1):162-166.
  14. Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. Cystic fibrosis: a worldwide analysis of CFTR mutations—correlation with incidence data and application to screening. Hum Mutat. 2002;19(6):575-606.
  15. Park L, Khani C, Tamburro J. Aquagenic wrinkling of the palms and the potential role for genetic testing. Pediatr Dermatol. 2011;29(3):237-242.
  16. Rongioletti F, Tomasini C, Crovato F, Marchesi L. Aquagenic (pseudo) keratoderma: a clinical series with new pathological insights. Br J Dermatol. 2012;167(3):575-582.
  17. Polat M, Gür G, Pelitli A, et al. Acquired aquagenic papulotranslucent acrokeratoderma: report of two cases. Am J Clin Dermatol. 2008;9(4):263-265.
  18. Itin PH, Lautenschlager S. Aquagenic syringeal acrokeratoderma (transient reactive papulotranslucent acrokeratoderma). Dermatology. 2002;204(1):8-11.
  19. Diba VC, Cormack GC, Burrows NP. Botulinum toxin is helpful in aquagenic palmoplantar keratoderma. Br J Dermatol. 2005;152(2):394-395.