aquagenic keratoderma ( k ) is a rare skin disorder also known as acquired aquagenic palmoplantar keratoderma , transient reactive papulotranslucent acrokeratoderma , aquagenic wrinkling of the palms or aquagenic syringeal acrokeratoderma . its main characteristic is skin wrinkling with edema of palms / soles , whitish papules , pruritus , burning , and pain after contact with water . prolongation of water exposure and temperature of the water affect the rate and intensity of lesion development . however , pathogenesis of ak is poorly understood . we report two new cases and provide an overview about clinical presentation , histopathology and genetics , and therapy . a 12-year old girl presented with three months history of burning of palms and loss of skin dermatoglyphics after exposure to water [ figure 1 ] . clinical examination revealed hyper - wrinkling of the palms after immersion in water without any other skin and/or mucous changes . aquagenic keratoderma of the palms after water immersion in a 12 year - old girl therapy was initiated with 20% alcohol solution of aluminum chloride hexahydrate once daily at night . the treatment resulted in significant clinical improvement with reduction of the frequency and duration of ak episodes . the second patient was a 27-year - old male suffering from cystic fibrosis ( cf ) and focal palmar hyperhidrosis . he was tested positive for homozygosity for the f508 mutation of the cf transmembrane conductance regulator ( cftr ) gene . his medication consisted of macrolide antibiotic prophylaxis and inhaled corticosteroids . without immersion in the water , he showed whitish translucent papules and increased wrinkling of the palms [ figure 2 ] . aquagenic keratoderma of the palms in a 27 year - old male with palmar hyperhidrosis and cystic fibrosis . in the presentation without water immersion a milder clinical appearance of whitish translucent papules is obvious we treated him twice daily with a topical aluminum chlorohydrate emulsion ( ansudor n , galderma ) . a 12-year old girl presented with three months history of burning of palms and loss of skin dermatoglyphics after exposure to water [ figure 1 ] . clinical examination revealed hyper - wrinkling of the palms after immersion in water without any other skin and/or mucous changes . aquagenic keratoderma of the palms after water immersion in a 12 year - old girl therapy was initiated with 20% alcohol solution of aluminum chloride hexahydrate once daily at night . the treatment resulted in significant clinical improvement with reduction of the frequency and duration of ak episodes . the second patient was a 27-year - old male suffering from cystic fibrosis ( cf ) and focal palmar hyperhidrosis . he was tested positive for homozygosity for the f508 mutation of the cf transmembrane conductance regulator ( cftr ) gene . his medication consisted of macrolide antibiotic prophylaxis and inhaled corticosteroids . without immersion in the water , he showed whitish translucent papules and increased wrinkling of the palms [ figure 2 ] . aquagenic keratoderma of the palms in a 27 year - old male with palmar hyperhidrosis and cystic fibrosis . in the presentation without water immersion a milder clinical appearance of whitish translucent papules is obvious we treated him twice daily with a topical aluminum chlorohydrate emulsion ( ansudor n , galderma ) . most cases are sporadic , but familial involvement has also been reported in the literature . clinically , it is characterized by whitish papules , edema and hyper - wrinkling with or without desquamation of the palms and/or soles . the morphological changes develop after contact with water , with gradual improvement within 2 - 20 min . this accentuation of skin lesions after water immersion is known as the  hand - in - the - bucket  sign and is considered diagnostic . several unusual presentations have been reported in the literature , including a localized form on the heel and involvement of the dorsum of fingers , sparing of the palms , and a unilateral type . in histopathology , most characteristic findings are spongiotic changes in the stratum corneum , orthohyperkeratosis with acanthosis , and , in the majority of cases , dilation of eccrine acrosyringia , and crenulated appearance of the luminal cells of the secretory eccrine coils . increased capillary proliferation adjacent to the former could also be found . the biopsy should be taken after exposure to water as no abnormalities are seen in tissue specimens after drying the skin . ak continues to be also a focus of research as to its genetic predisposition and association with other diseases including cf , focal hyperhidrosis , and raynaud phenomenon . regarding cf , it is estimated that between 44% and 80% of patients with cf have ak . that is why , this disease served as a model to study the genetic association and the underlying pathogenic mechanisms of ak . in fact , the cause of development of these associated disorders is a homo - or heterozygous mutation for f508 , which was first discovered in the cftr gene in cf . cftr is involved in the regulation of electrolyte transport , and the mutation leads to the reduction of electrolyte reabsorption in eccrine ducts ; thus , increasing the levels of salt in the sweat . the latter explains the pathogenic formulation and development of ak as the increased electrolyte composition results in increased diffusion of liquids in palmar skin . higher concentrations of salts in the sweat increase the specific thermal capacity what might contribute to subjective sensory symptoms . similar pathogenic mechanism has been proposed for the development of ak associated with various medications such as celecoxib and rofecoxib . these drugs lead to inhibition of the enzyme cyclooxygenase-2 , contributing to the concentration of electrolytes in sweat . ak is limited to those areas , which are positive in minor 's iodine starch test for focal hyperhidrosis . the high sweat salt concentrations as in cf - associated ak contributes to an increased water holding capacity of the horny layer . an increase of natural moisturizing factor ( nmf ) would result in higher water holding capacity of human epidermis , but would require time for synthesis and transport . concerning the rapid , but temporary effect of water immersion , we suggest an overactivity of certain aquaporins ( aqps ) . indeed , an aberrant expression of aqp5 was detected in secretory clear cells of eccrine sweat glands in the involved palmar area in contrast to healthy skin where only dark cells express aqp5 . on the other hand , furthermore , swelling of the stratum corneum could lead to sweat retention in the whole epidermis . its sensitivity is further enhanced by temperature and protons . from clinical experience higher temperature during water immersion exerts a stronger ak response . hyperosmolarity of sweat and increased water temperature leads to increased ca2 influx and swelling of cells . aqp3 is expressed by keratinocytes from the basal epidermal layer up to the spinous layer in human skin . because of its capability to open water channels rapidly in addition to carrier - mediated transport , aqp 10 more than aqp3 would be a possible candidate for the abnormal reaction of palmar skin to water immersion . when expression of aqp3 is increased by all - trans retinoic acid , none of the features of ak develop . ak therefore seems to represent the product of sympathetic over - activity and rapid changes of water holding capacity by aqps . ak can be associated with cf and it is extremely important to exclude pauci - symptomatic or heterozygous cf with the use of the appropriate ancillary studies . a variety of topical treatments have been published . based upon available data , pathogenesis and own experience , we suggest avoidance of water immersion , the use of aluminum salts or iontophoresis . botulinum toxin a ( bont - a ) is effective in hyperhidrosis and it affects preganglionic sympathetic and parasympathetic nerves and postganglionic parasympathetic nerves . we recommend bont - a for cases not responding to topical treatment , as second line therapy . in conclusion , ak is an exogenous skin disease based upon increased sympathetic activity , possible involvement of tvrt-1 , and increased expression of selected aqps in involved skin [ figure 3 ] . the secretory coil in ak shows an increased expression of aquaporin ( aqp ) 5 . water immersions and secretion of hyperosmotic sweat activates osmosensitive transient vanilloid receptor type-1 , increasing the ca2-influx , and aqp 10 .
aquagenic keratoderma has been described as a transient condition affecting predominantly young females and defined clinically by the appearance of palmar hyper - wrinkling accentuated after immersion in water . 
 we present two new cases with aquagenic palmoplantar acrokeratoderma  a child and a young male . 
 a significant clinical improvement was achieved after topical treatment with aluminum salts . 
 aquagenic palmar keratoderma may be a clue to cystic fibrosis in adolescents and young adults . 
 we developed a new hypothesis on its pathogenesis .