nutritional deficiency states result in a diverse group of diseases with many distinctive cutaneous manifestations . these nutritional diseases are seen in a wide variety of clinical settings , and they result from inadequate diet , impaired absorption or the defective metabolism of specific nutrients . until now , however , the exact pathophysiologic mechanisms for many of the skin changes associated with nutritional deficiency are unclear . acrodermatitis enteropathica ( ae ) is the clinical phenotype of zinc ( zn ) deficiency characterized by pustular and bullous dermatitis with an acral and periorificial distribution ( 1 ) . pustular paronychia , angular stomatitis , glossitis and generalized alopecia are also usually present ( 2 ) . it can be associated with the acquired form of zinc deficiency resulting from crohn 's disease ( 3 ) , chronic pancreatitis ( 4 ) , and chemotherapy ( 5 ) . cutaneous eruption is a rare complication of whipple 's operation . from the literature review , a few cases have been reported including necrolytic migratory erythema ( 6 ) , protein energy malnutrition ( 7 ) and pseudoglucagonoma ( 8) . we herein present a case of ae - like eruptions that were associated with essential free fatty acid ( efa ) and protein deficiencies as well as a borderline zn deficiency following whipple 's operation in a 31-yr - old woman . a 31-yr - old woman was referred to our hospital for the evaluation of a refractory dermatitis and a diffuse alopecia for 1 yr . after that , her stool became loose and her weight had decreased by 10 kg over the last 6 yr . her medical history also revealed the onset of amenorrhea for 4 months . on physical examination , her height and weight were 161 cm and 41 kg , respectively , and body mass index was 15.1 , and this was well below the normal average value 22 . the cutaneous manifestations were characterized by interconnected , erythematous , scaly , erosive patches , papules and tiny vesicles on her arms , abdomen , lower back and buttocks , and these lesions were especially severe in the flexural areas ( fig . . microscopic examination of the skin lesions showed scattered parakeratosis and upper epidermal clear cell changes with a mild dermal infiltration of lymphocytes . irregular acanthosis , mild parakeratosis and dermal perivascular infiltration were also observed on another skin section ( fig . 2 ) . the transepidermal water loss ( tewl ) measurement in the lesions was shown to be 7.4 times higher , on average , than in normal skin . there were mild angular cheilitis and oral mucosal erosions as well as her having a beefy red tongue accompanied by papillary atropy . her fingers showed the erosion of the finger tips , but there was no paronychia involvement ( fig . the scalp hair was diffusely sparse and light brown but it was not brittle or otherwise abnormal ( fig . abnormal laboratory results were as follows ; hemoglobin , 9.4 g / dl ( 12 - 16 g / dl ) ; post prandial 2 hr glucose test , 255 mg / dl ( < 200 mg / dl ) ; alkaline serine transaminase , 60 iu / l ( 5 - 38 iu / l ) ; serum protein and albumin , 3.7 g / dl ( 6.4 - 8.3 g / dl ) and 1.6 g / dl ( 3.3 - 5.2 g / dl ) , respectively ; stool fat , positive ( negative ) ; beta carotene , 3.41 g / dl ( 50 - 250 g / dl ) ; total cholesterol , 80 mg / dl ( 128 - 250 mg / dl ) ; transferrin , 76.5 mg / dl ( 200 - 360 mg / dl ) ; retinal binding protein , 1.05 mg / dl ( 3 - 6 mg / dl ) ; calcium and magnesium , 6.4 mg / dl ( 8.2 - 10.2 mg / dl ) and 1.8 mg / dl ( 1.9 - 3.1 mg / dl ) respectively ; and serum zinc , 67 g / dl ( 70 - 121 g / dl ) . normal or negative values were obtained for the followings : urinalysis , serum glucagons and blood gas analysis . based on the clinical , histophathological and initial laboratory findings , we diagnosed this woman as a case of zinc deficiency . however , in spite of a 1-week treatment with an oral zinc sulfate supplement , 50 mg a day , her skin lesions did not improve and her serum zinc level did not increase either . with the aid of additional laboratory results , we inferred that her dermatitis came from a combined malnutrition disorder resulting from protein deficiency , efa deficiency and a borderline zn deficiency due to whipple 's operation . the patient was given total parenteral nutrition containing amino acids , albumin , lipids and electrolytes and oral zn supplements , 50 mg a day , and topical linolenic acid . the patient 's dermatitis improved markedly after 1 month of treatment , except for her postinflammatory hyperpigmentation ( fig . the pitting edema also cleared up earlier than the dermatitis , and the tewl returned to that of normal skin . thereafter , she has been maintained on the regular infusion of albumin and lipids together with an oral zinc supplement , and she is without recurrence of her disease . we inferred that it was because of exocrine pancreatic insufficiency resulting from the whipple 's operation . it is likely that the borderline zn , low efa and protein deficiency or perhaps all three in concert , was responsible for this patient 's clinical manifestations , although we could not precisely decide which nutrient was the most important . therefore , we will discuss here the possible contributions and relationship of each of three nutritional deficiencies . it is a congenital autosomal recessive condition characterized by pustular and bullous dermatitis with an acral and periorificial distribution ( 1 ) . pustular paronychia , angular stomatitis , glossitis and generalized alopecia are also usually present ( 2 ) . although the term ae was initially used to describe the congenital form , it is also associated nowadays with the acquired form of zinc deficiency resulting from crohn 's disease ( 3 ) , chronic pancreatitis ( 4 ) and chemotherapy ( 5 ) . the clinical presentations of erythematous , scaly , crusting and erosive patches with alopecia and mucosal involvement and the histological findings in our patient were consistent with ae . however , it is unusual that the lesions were distributed not only on the periorificial and acral area , but also on the buttocks , thigh and both arms , and that there was no paronychia . the diagnostic value of zn in ae is usually below 70 g / dl in comparison with 67 g / dl in our case . some authors have reported ae without hypozincemia ( 9 ) , explaining that accumulation of zinc bound in an immobile chemical form in the tissue could make the element unavailable for metabolic processes . however , the patient with classic ae often has lower zn levels and neldner and hambidge ( 10 ) have reported a patient showing the recurrence of symptoms even at a plasma zn level of 36 g / dl . moreover , ae usually responds to zn supplement therapy within a few days ( 11 ) , as compared with 1 month in our case . from these atypical findings , we have to consider another possible cause other than the zn deficiency in our patient . kwashiorkor , chronic protein deficiency , is characterized by hypopigmentation with fine , branlike desquamation in the circumoral and edematous locations ( 2 , 12 ) animal - derived proteins from our diet are the major source of zinc in humans . conversely , poor protein absorption resulting from exocrine pancreatic insufficiency , as was shown in our patient , may cause a zinc deficiency . in addition , because albumin is the major carrier protein for zinc in human , hypoalbuminemia is associated with a low plasma zinc level . ( 13 ) have shown that pancreatic proteolytic enzyme deficiency leaded to ae without zinc deficiency , and golden et al . ( 14 ) have reported a patient with kwashiorkor who responded to zinc sulfate ointment : they concluded that the skin lesions of kwashiorkor seem to be caused by a deficiency of zinc . structurally , efas elevate the degree of cell membrane lipoprotein unsaturation and influence membrane fluidity ( 2 , 15 ) . efa deficiency can lead to chronic epidermal hyperproliferation causing the thickening , scaling and loss of elasticity in the skin , and to impaired eisocsanoid production resulting in eczematous changes in the skin ( 16 , 17 ) . in addition , tewl measurement in the skin lesions of efa deficiency , as shown in our patient , reveals a marked increase as compared with normal skin ( 2 ) . the association of ae and efa deficiency has been previously noted ( 18 ) , although this link has not been consistently seen . zinc is thought to be the element required in more than 24 metalloenzymes including -6-desaturase and -5-desaturase , and zinc is also required in the mobilization of dihomo--linolenic acid ( 19 ) . from the therapeutic points of view , the clinical manifestations of zinc deficient patients were greatly improved by efa supplement ( 9 ) , pancreatic enzyme preparation ( 20 ) and diiodohydroxyquinoline ( 17 ) , and so some authors have recommended that both efa and zinc determinations be made for the patient with ae - like eruption . liver cirrhosis , crohn 's disease , malabsorption and chronic pancreatitis can cause necrolytic migratory erythema , the prototype of pseudoglucagonoma ( 21 ) . although the pathogenesis is unclear , deficiencies of zinc , amino acids , or essential fatty acids can be associated with this disease ( 22 ) . however , in some cases , there can be an intermingling of features from more than two nutritional dermatoses . in those cases , our patient clearly showed protein , essential fatty acid and borderline zinc deficiency on the physical and laboratory examinations . we inferred that her malnutrition states and symptoms were attributable to pancreatic insufficiency caused by whipple 's operation and , perhaps , all three elements in concert , caused our patient 's clinical manifestations .
we present here a case of acrodermatitis enteropathica - like eruption associated with essential free fatty acid and protein deficiencies as well as borderline zinc deficiency that occurred after whipple 's operation in a 31-yr - old woman . 
 her eruptions were improved not by zinc supplements alone , but her condition was improved by total parenteral nutrition including amino acids , albumin , lipid and zinc . although we could not exactly decide which of the nutrients contributed the most to her manifestations , we inferred that all three elements in concert caused her dermatoses . 
 this case shows that even though the patient 's skin manifestations and laboratory results are suggestive of acrodermatitis enteropathica , the physicians should keep in mind the possibility that this disease can be associated with other nutritional deficiencies such as free fatty acid or protein deficiency .