Aquagenic Wrinkling of the Palms as a Screening Indicator for Cystic Fibrosis Beyond Infancy

Aquagenic wrinkling of the palms (AWP) has been associated with cystic fibrosis (CF) and may support screening approaches beyond infancy in low-resource settings. We evaluated the diagnostic accuracy and reproducibility of a standardized brief immersion in water (BIW) test in 100 children with genetically confirmed CF, 50 heterozygous CF transmembrane conductance regulator (CFTR) mutation carriers, and 100 age-matched healthy controls. Both hands were immersed in tap water (22-24°C) for 11 minutes and assessed at 3, 7, and 11 minutes. Transepidermal water loss (TEWL) was measured after immersion using a portable VapoMeter. Early AWP at three minutes occurred in 68/100 (68%) CF patients, 4/50 (8%) CFTR heterozygous carriers, and 0/100 (0%) controls (p < 0.01); at the three-year follow-up, 35/50 (70%) CF patients again showed early wrinkling. Wrinkling with papule formation at seven minutes provided optimal discrimination (94% sensitivity, 98.3% specificity). A TEWL threshold ≥ 203 g/m²/h further differentiated CF from non-CF participants (86% sensitivity, 98% specificity). The BIW test is rapid, reproducible, and feasible in resource-limited settings; thus, a positive seven-minute response should prompt confirmatory testing (e.g., sweat chloride and/or CFTR genotyping).