Aquagenic Wrinkling of the Palms and Cystic Fibrosis: An Italian Study with Controls and Genotype-Phenotype Correlations

Abstract

Aims: The primary aim was to determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared to controls, and secondarily to evaluate genotype-phenotype correlations among CF subjects found to have AWP. Methods: Fifty-eight patients with CF underwent a hand immersion test in tap water. Twenty-three of their CF carrier relatives and 7 subjects with a negative genetic test for CF were recruited as controls. Secondary analyses explored associations with genotype, pulmonary function, and sweat electrolyte levels in all subjects with and without AWP. Additional information about atopic diathesis, hyperhidrosis of the palms and drug intake were also collected. Results: Thirty-one of the patients with CF (53.4%) exhibited AWP, in contrast to only 2 carriers (8.7%) and none in the control group. No correlation was found between CF genotype and AWP score severity. Twenty-three (39.7%) CF patients reported a history of hyperhidrosis, and in 17 of them (74%) AWP had been provoked. No correlation with history of atopy and lung function was noted. The difference between CF patients with hyperhidrosis and those without was highly significant (p = 0.016). Salt concentrations were significantly higher in patients with AWP. Conclusions: AWP is linked to CF and its diagnosis should lead the patients to a genetic or sweat test for CF. We found a significant association with hyperhidrosis and sweat electrolytes which supports the ‘hyperconcentrated sweat' pathogenetic theory of AWP.

Water‐related dermatoses

“…It is reported to occur in 40–80% of CF patients and in 25% of CF carriers. Usually, it takes more water exposure time in carriers to manifest the palmar wrinkling as compared to CF homozygous patients . In brief, CF is an autosomal recessive disease, characterized by a malfunctioning cyclic adenosine monophosphate epithelial chloride channel which is needed in sweat glands for the augmentation of sodium reabsorption.…”

“…This triggers vasoconstriction which in turn causes skin wrinkling. Second, the increased sodium content of sweat causes an increase in water‐binding ability of palmar proteins such as keratins, hence resulting in false hyperkeratosis and wrinkling …”

“…Usually, it takes more water exposure time in carriers to manifest the palmar wrinkling as compared to CF homozygous patients. 32 In brief, CF is an autosomal recessive disease, characterized by a malfunctioning cyclic adenosine monophosphate epithelial chloride channel which is needed in sweat glands for the augmentation of sodium reabsorption. Hence in CF, sweat sodium concentration is higher, resulting in a hypertonic solution similar to hypersweating.…”

“…wrinkling. 30,32 In addition to the increase-salt hypothesis, a decrease in skin barrier function has been noted to play a role in the ability of the skin to absorb more water than usual. This was deduced from the association of AWP with atopy.…”

Atypical familial aquagenic syringeal acrokeratoderma

“…Several diseases have also been reported to be associated with the development of ASA, including cystic fibrosis, marasmus, nephrotic syndrome, and atopy. 1,7,14,16,17,25,26,28,42,46,48,49,55,[60][61][62]65,68,69,95 Interestingly, tobramycin (employed therapeutically for a patient with cystic fibrosis), may be linked to the development of ASA. Notwithstanding, some of the drug-induced ASA reports should be viewed lightly; several of the reported cases are for drugs used to treat conditions theoretically linked to ASA such as atopy and cystic fibrosis.…”