From the Guidelines
Aquagenic wrinkling in cystic fibrosis patients is primarily caused by the abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which disrupts normal skin electrolyte balance, as supported by the underlying genetic mutation affecting ion transport across epithelial and other cell membranes 1. When CF patients' skin is exposed to water, excessive salt retention occurs in the epidermis due to defective CFTR channels that would normally regulate chloride transport. This increased salt concentration draws water into the skin through osmosis, causing the outer layer (stratum corneum) to swell disproportionately compared to deeper layers. The result is the characteristic white, wrinkled appearance of the skin, particularly on the palms and fingers, after just a few minutes of water exposure. Some key factors contributing to this condition include:
- Increased skin sodium content
- Elevated sweat electrolyte levels typical in CF patients
- Abnormal keratin expression in the skin of CF patients, which may contribute to this hypersensitivity to water
- The CF phenotype resulting from mutations in the gene encoding the CFTR protein, leading to CFTR deficiency or dysfunction, and changes that disable the transport of sodium and chloride ions across epithelial and other cell membranes 1. Aquagenic wrinkling can actually serve as a clinical marker for CF, as it occurs in approximately 80% of CF patients but is rare in the general population. The association between cystic fibrosis and poor nutritional status, linked directly by factors related to the underlying genetic mutation, as well as indirectly by factors such as higher energy needs, energy losses, greater essential fatty acid (EFA) turnover, and decreased nutrient intake and absorption, is also relevant in this context 1. Patients with CF may have higher than normal requirements for salt, calcium, iron, zinc, and selenium as a consequence of the increased sweating, intestinal malabsorption, and chronic inflammation that are common in CF 1.
From the Research
Causes of Aquagenic Wrinkling in Cystic Fibrosis
- Aquagenic wrinkling of the palms (AWP) is characterized by the rapid and transient oedematous wrinkling of the palms after brief immersion in water, and has been associated with cystic fibrosis (CF) 2, 3, 4, 5, 6.
- The exact cause of AWP in CF is not fully understood, but it is thought to be related to the abnormal function of the cystic fibrosis transmembrane regulator (CFTR) protein, which leads to an imbalance of salt and water in the skin 3, 4.
- Studies have shown that AWP is more common in patients with CF who have a higher concentration of salt in their sweat, supporting the "hyperconcentrated sweat" theory of AWP 4.
- The prevalence of AWP in patients with CF has been reported to be around 50-60%, and it is more common in patients who are homozygous for the DeltaF508 mutation 3, 5.
- AWP has also been reported in CF carriers, although at a lower frequency than in patients with CF, suggesting that it may be a sign of CF gene dysfunction 3.
Key Findings
- AWP is a significant feature of CF, and its presence should prompt investigation of CF gene dysfunction 2, 3, 4, 5, 6.
- The diagnosis of AWP should lead to a genetic or sweat test for CF 4, 6.
- AWP is often associated with hyperhidrosis and pruritus, and symptoms may decrease in adulthood 4, 6.
- The water exposure test is a useful diagnostic tool for AWP, and patients with a positive test result should be referred for further investigation and genetic testing for CF 6.