Aquagenic Syringeal

Aquagenic syringeal acrokeratoderma (ASA), also known as aquagenic palmoplantar keratoderma and transient reactive papulotranslucent acrokeratoderma, was first described in 1974 by Elliott who observed “skin wrinkling” among children with cystic fibrosis (CF).¹ 

In 1996, Drs. English and McCollough later described 2 sisters who would develop a tightening sensation on the palms 3 to 5 minutes after water exposure.² This condition is rare. In total, at least 20 women and at least 10 men have been described in the literature. Two cases have been described in Worcester, MA, of a 15- and a 19-year-old woman.³ Another group described 2 patients, a 25- and a 33-year-old woman, who would both develop a burning sensation on the palms and a whitish thickening after minutes of water contact. Their physical examination revealed normal palmar skin when not exposed to water.⁴ This disorder occurs most frequently in the early 20s, especially in young women (mean age of onset 21.0 years, range 6-45 years).⁵ 

Clinical Presentation 

ASA presents as a transient and recurrent keratoderma on the palms. It is characterized by symmetric, hypopigmented, flat-topped papules.³ The first case reported of the 2 sisters describes symmetric, flesh-colored to white, smooth papules located on the palms and fingers. These would evolve into translucent, white, punctate papules with water exposure. Patients also present with hyperhidrosis and foot involvement.² Linear streaky papules on the palmar creases have also been reported.⁶ The lesions can trigger symptoms such as burning pain, pruritus and tingling. A water immersion test usually elicits the lesions. Some sources describe the “hand-in-the-bucket” sign, in which patients present with their hands in water to allow the features to be seen.⁷

Pathology

Histologically, ASA presents with focal hyperkeratosis, acanthosis and normal eccrine ducts and basement membranes.³ Some have described dilated eccrine ostia in the epidermis and eccrine glandular hyperplasia. Eosinophilia in the cytoplasm can also be seen.⁸ 

In addition, dermoscopy can be very useful in the diagnosis of ASA, which reveals pinpoint white papules (sweat duct puncta) located between the parallel furrows (intra-epidermal eccrine ducts).⁶ 

Differential Diagnosis

Several skin diseases can occur with water contact, including xerosis, aquagenic urticaria, aquagenic pruritus and aquadynia. Hereditary papulotranslucent acrokeratoderma, which appears soon after puberty and persists throughout life, presents with focal hyperkeratosis, acanthosis and normal eccrine ducts similar to ASA.⁵ 

Pathogenesis

The pathogenesis of ASA remains unclear, but it may be a primary keratoderma or related to an acquired sweat gland abnormality.⁹ ASA may be associated with increased salt content in the skin. This is demonstrated by its common concurrence with CF, in which mutation of the CFTR gene results in decreased salt reabsorption in the eccrine duct.^6,10 

Impaired barrier function in the stratum corneum may result in increased absorption of water, leading to swelling of the corneum and damage of the eccrine sweat glands. To support the hypothesis of decreased barrier function, one case report describes exacerbation of ASA with laundry detergent use (similar to conditions like eczema).⁵ Abnormal regulations of transmembrane channels such as aquaporin 3 and weakness of eccrine duct walls have also been considered. 

Associated Diseases And Syndromes

Disorders and diseases associated with ASA include allergic rhinitis, asthma, CF and malignant melanoma.¹¹ Because ASA is frequently associated with CF, patients who present with lesions characteristic of ASA should also be screened for CF.  Signs and symptoms of this disease include: respiratory (frequent sinusitis, bronchitis, pneumonia, pneumothorax, bronchiectasis), gastrointestinal (pancreatitis, rectal prolapse, liver failure, diabetes, cholelithiasis) and reproductive (absence of vas deferens in males). 

However, it is important to note that patients specifically with CF may develop a rare palmar dermatosis known as aquagenic “wrinkling of the palms.” This disorder is also characterized by development of edema and excessive wrinkling of the palms after submersion in water. While most sources believe this condition is the same as ASA, other researchers regard it as a completely separate entity.¹²  

Treatment

Aluminum chloride, salicylic acid ointment and antihistamines are the current mainstay treatments for ASA. Topical formalin 3% in alcohol applied to the palms once daily may be beneficial.  Luo et al⁵ found that 1 patient could tolerate longer periods of water immersion with fewer symptoms after 4 weeks of use.⁵ Etretinate 30 mg a day for 2 weeks resulted in marked reduction of the hyperkeratosis.⁵ In a separate study, 1 patient showed no improvement with 2 months of 20% topical aluminum chloride.⁹ In refractory cases presenting with concurrent hyperhidrosis, botulinum toxin injection may be another option. 

Our Patient 

The patient was reassured and prescribed aluminum chloride 20% solution to use at night on both palms, initially twice a week at night prior to bedtime, followed by a progressive increase in frequency. Follow-up revealed resolution of her symptoms. 

Conclusion 

ASA is a rare skin condition. It is characterized by transient symmetric, hypopigmented, flat-topped papules on the palms that develop with exposure to water. Histologically, ASA presents as focal hyperkeratosis, acanthosis and normal eccrine ducts and basement membranes. The differential diagnosis includes xerosis, aquagenic urticaria, aquagenic pruritus, aquadynia and hereditary papulotranslucent acrokeratoderma. 

Due to its association with CF, ASA may be linked to increased salt content in the skin, impaired barrier function in the stratum corneum (resulting in increased absorption of water), swelling of the corneum and damage of the eccrine sweat glands. Aluminum chloride, salicylic acid ointment and antihistamines are the current mainstay treatments for ASA. n 

Dr. Kallini is with the Saint Louis University Department of Dermatology, St. Louis, MO.

Dr. Khachemoune, the Section Editor of Derm DX, is with the Department of Dermatology at the State University of New York Downstate in Brooklyn, NY, and Veterans Affairs Medical Center in Brooklyn, NY.

Disclosure: The authors report no relevant financial relationships.

References

1. Elliott RB. Letter: skin wrinkling in cystic fibrosis. Lancet. 1974;2(7893):1383.

2. English JC 3rd, McCollough ML. Transient reactive papulotranslucent acrokeratoderma. J Am Acad Dermatol. 1996;34(4):686-687. 

3.  MacCormack MA, Wiss K, Malhotra R. Aquagenic syringeal acrokeratoderma: report of two teenage cases. J Am Acad Dermatol. 2001;45(1):124-126. 

4.  Itin PH, Lautenschlager S. Aquagenic syringeal acrokeratoderma (transient reactive papulotranslucent acrokeratoderma). Dermatology. 2002;204(1):8-11.

5.  Luo DQ, Li Y, Huang YB, Wu LC, He DY. Aquagenic syringeal acrokeratoderma in an adult man: case report and review of the literature. Clin Exp Dermatol. 2009;34(8):e907-e909.

6.  Sezer E, Erkek E, Duman D, Sahin S, Cetin E. Dermatoscopy as an adjunctive diagnostic tool in aquagenic syringeal acrokeratoderma. Dermatology. 2012;225(2):97-99. 

7.  Yan AC, Aasi SZ, Alms WJ, et al. Aquagenic palmoplantar keratoderma. J Am Acad Dermatol 2001;44(4):696-699.

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(2):486-488. 

9.  Falcón CS, Ortega SS. Aquagenic syringeal acrokeratoderma. J Am Acad Dermatol. 2008;59(5 suppl):S112-S113. 

10. Weil B, Chaillou E, Troussier F, et al. [Aquagenic palmoplantar keratoderma in children with cystic fibrosis]. Arch Pediatr. 2013;20(12):1306-1309. 

11. 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.

12. Kaplan DL. What are those white spots? Consultant. 2013;53(9):671-672.