Aquagenic Wrinkling of the Palm: A Rare Diagnostic Clue of Cystic Fibrosis and the Response to CFTR-Modulating Therapy

Abstract

Aquagenic wrinkling of the palms (AWP), also known as aquagenic palmoplantar keratoderma, is an uncommon dermatosis characterized by transient translucent whitish papules, edema, and hyper-wrinkling of the palms and soles shortly after water immersion. Approximately up to 80% of cases reported are associated with cystic fibrosis (CF) patients and up to 25% with CF carriers. We present the case of a 16-yearold male who complains of new-onset symmetrical edematous wrinkling on his palms associated with brief water exposure. After evaluation and genetic testing, the patient was diagnosed with CF and AWP. While there are numerous theories regarding the pathogenesis of AWP, no consensus has been reached regarding its etiology or relationship with CF. However, given the high prevalence of AWP associated with the genetic disease, physicians should have a high index of suspicion of CF or cystic fibrosis transmembrane regulator (CFTR)-related disease in pediatric patients with this presentation. The presence of AWP as part of the physical examination may help recognize challenging CF cases with uncommon genetic variants. Prompt recognition of CF disease leads to timely initiation of CFTR-modulating therapy, improving the patient's health outcomes and quality of life. In this case, we also present the patient's response to CFTR-modulating therapy and compare with baseline status.

Aquagenic wrinkling of the palms: review of the literature

“…reported a case of aspirin‐induced unilateral AWP and hypothesized a similar mechanism, although they noted that aspirin preferentially inhibits COX‐1 over COX‐2. AWP has also been observed in patients taking aminoglycosides, ACE inhibitors and angiotensin‐receptor blockers, either by potentiating sodium retention or affecting osmotic gradient within keratinocytes 16 …”

“…The majority of patients with AWP also have CF, but this is not an invariable finding; AWP is seen in 44–80% of patients with CF 15 and 25% of CF carriers. 16 The development of AWP in patients and carriers is due to homozygous or heterozygous mutation of the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is present in eccrine ducts and regulates electrolyte transport. Defective CFTR proteins result in decreased electrolyte reabsorption, thus producing hypertonic sweat, which increases diffusion of liquids into palmar/plantar skin.…”

“…AWP has also been observed in patients taking aminoglycosides, ACE inhibitors and angiotensin‐receptor blockers, either by potentiating sodium retention or affecting osmotic gradient within keratinocytes. 16 …”