Rofecoxib-induced instant aquagenic wrinkling of the palms

An 18-year-old woman presented with a 3-week complaint of exaggerated palmar wrinkling and swelling following brief exposure (1-2 minutes) of her hands to water. She had a history of mixed connective tissue disease and had been started on rofecoxib therapy 1 month prior to the onset of her skin symptoms. Discontinuation of rofecoxib was followed by resolution of symptoms within a period of 3 weeks. Similar palmar skin changes following water exposure have been reported to occur in cystic fibrosis and are thought to be due to increased salt content of the skin and secondary increased water-binding capacity. Rofecoxib is a selective COX-2 inhibitor that has been shown to increase sodium reabsorption in the kidney via effects on prostaglandin E₂ and the renal vasculature. The COX-2 protein is also expressed in keratinocytes and plays a role in keratinocyte differentiation. Prostaglandin E₂ also plays a role in keratinocyte proliferation and differentiation. Thus rofecoxib may cause increased sodium reabsorption in the skin, as it does in the kidney. The rofecoxib-associated elevation in skin sodium may increase keratin water-binding capacity and cause exaggerated aquagenic wrinkling of the skin, as occurs in cystic fibrosis.