acrodermatitis enteropathica ( ae ) is an autosomal recessive condition resulting in severe zinc deficiency .
the deficiency is caused by a defect of dietary zinc absorption in the duodenum and jejunum .
zinc is an essential co - enzyme in metal enzymes ( like alkaline phosphatase ) ; it is an important structural component of gene regulatory proteins ( required , for example , for the intracellular binding of tyrosine kinase to t - cell receptors ) and it has also a function in regulation ( has the ability to regulate gene expression ) .
consequently , there are multiple signs and symptoms in severe deficiency : growth retardation , impaired immune function , and multiple skin or gastrointestinal lesions .
signs and symptoms in infancy can include diarrhea , mood changes , anorexia , and neurological disturbance . in schoolchildren and toddlers ,
zinc deficiency is characterized by growth retardation , alopecia , weight loss , and recurrent infections .
laboratory diagnosis is hazardous , zinc levels in serum , urine , or hair are used ( although they are not specific , neither sensitive ) , zinc absorption tests are cumbersome , genetic testing is definite ( defect in 8q24 , gene slc39a4 ) though not routinely available .
most clinicians therefore depend on immediate results of a therapeutic zinc regimen ( 330  mol / kg body weight ) . in denmark
another study reported also an incidence of 1 per 500,000 children without predilection for race or sex .
we present the case of a caucasian 14-month - old boy , admitted for skin lesions that occurred from the first months of life .
the boy was born prematurely , weighing 1800  g , without any perinatal medical history .
he had been breastfed for 1 month and then formula - fed up to 5 months , followed by diversified nourishment .
his family history revealed an apparently healthy 5-year - old sister and another sister who died at the age of 5 months with similar superinfected skin lesions .
his parents stated that the skin lesions started at the age of 2 months , about 1 month after the infant was weaned from breastfeeding ; initially , lesions were discrete and partially ameliorated with local treatment . at the age of 10 months , the boy had bacterial skin superinfections with staphylococcus aureus , including suprapubic and right thigh abscesses , which required surgical incisions followed by antibiotic treatment with clindamycin , intravenous , for 10 days , according to sensitivity testing .
the antibiotic treatment for s aureus determined the disappearance of the pus , but the lesions of ae persisted .
he was born weighing 1800  g , so he had shown no evidence of delay in his growth . at admission to our clinic ,
skin examination revealed erythematous and micro pustular lesions predominantly on the buttocks , thighs , and perioral region ( figure 1 ) .
antibiotic treatment with piperacillin - tazobactam , intravenous , was conducted under sensitivity testing with slight improvement in skin lesions .
the dermatologist suspected napkin psoriasis , and a local treatment with fluticasone propionate was started .
skin biopsy was performed , and then , the patient was discharged to continue local treatment until the arrival of the skin biopsy result .
histopathological examination of left thigh skin biopsy revealed epidermal hyperplasia with acanthosis , clustered necrotic keratinocytes and parakeratosis , crusts , and intraepidermal vacuolization ( figure 2 ) .
skin lesions in the diaper area , thighs ( a ) , and face ( b ) .
epidermal hyperplasia with acanthosis , hyper and parakeratosis , crusts , he 40 ( a ) and intraepidermally vacuolization , he 100 ( b ) .
one month later , he was readmitted with more extensive erythematous , scaly and pustular lesions located in the inguinal and perianal regions , on the thighs , on the scalp , and periorificial on the face .
the hair was thin , with areas of alopecia , the eyebrows and the eyelashes were fallen , perionychia was present ( figure 3 ) .
an abscess was developed on the right thigh , which required surgical incision , followed by antibiotic treatment with clindamycin , according to sensitivity testing for s aureus isolated from pus .
erythematous , scaly , and pustular lesions located in the inguinal and perianal regions , on the thighs ( a ) , periorificial on the face , perionychia ( b ) , and on the scalp with alopecia areas ( c ) .
the patient 's serum and urinary zinc levels were low : 23  g / dl ( normal value  =  65118  g / dl ) , respectively , 11.4  mg in the urine of 24  hours ( normal value  =  1501200  mg/24  h ) , thereby confirming the diagnosis .
serum alkaline phosphatases , a zinc - dependent enzyme , was also to the lower limit of normal ( 50  u / l , normal  =  40600  u / l ) .
his immune function revealed iga and igg deficiency ( iga  =  10.87  mg / dl , igg  =  426.29  mg / dl ) .
other causes of malabsorption were excluded : antitissue transglutaminase antibodies ( iga and igg ) for celiac disease and -lactoglobulin for cow 's milk protein intolerance were negative . also , iontophoresis was negative ( chloride concentration was 34 
zinc therapy was instituted at a dosage of 3  mg / kg daily of elemental zinc , with rapidly favorable evolution : the lesions became smaller and paler after 2 to 3 days of treatment .
the infant was discharged to continue daily zinc treatment ; the doses were to be adapted to the evolution and weight . on 2 months check - up , the skin lesions and alopecia were almost completely remitted ( figure 4 ) , the agitation episodes disappeared , and the child had a normal behavior .
he is currently continuing his zinc treatment , and he will be undergoing regular check - ups .
cutaneous aspects after 2 months of treatment , with remission of periorificial lesions and alopecia .
zinc is an essential trace element required for the proper functioning of all cells , and plays an important role in the metabolism of protein , carbohydrate , and vitamin a. it is a cofactor of numerous metal enzymes such as alkaline phosphatases , alcohol dehydrogenase , rna polymerase , and numerous digestive enzymes .
there are many causes of acquired zinc deficiency : premature infants , low birth weight , zinc deficiency in maternal milk , exclusive parenteral nutrition , malabsorption syndromes such as crohn disease and celiac disease , alcoholism , low calcium and phytate diet , and kwashiorkor .
 it is caused by an autosomal recessive mutation of slc39a4 ( solute carrier family 39 member 4 ) gene on chromosome 8q24.3 , which determines a congenital partial or total deficiency of the zinc transporter protein zinc - ligand binding protein 4 ( zip 4 ) .
the clinical manifestations of acquired zinc deficiency and ae are similar and consist of 3 essential symptoms : periorificial dermatitis , alopecia , and diarrhea .
the disease begins with symmetrical erythematous , squamous or eczematous lesions , sometimes vesiculobullous or pustular lesions , located around perioral , anogenital , and acral areas .
skin damage becomes erosive and spreads to other periorificial areas of the face ( eyes , nose , and ears ) , neck , lower abdomen , back , inguinal area , and thighs . in some instances
other mucous and cutaneous signs consist of diffuse alopecia , loss of eyelashes and eyebrows , glossitis , gingivitis , stomatitis , onychodystrophy , onycholysis , and pachyonychia .
unfortunately , it is also the most variable , and it can be intermittent or totally absent . in children with watery diarrhea , general symptoms and neuropsychological disorders are common ( irritability , lethargy , depression , anorexia ) , and also growth retardation , weight loss , anemia , and ophthalmic involvement ( photophobia , blepharitis , conjunctivitis ) .
secondary bacterial infections ( with gram - positive and sometimes gram - negative ) or candidiasis ( candida albicans ) are common and they can modify the clinical picture .
so , clinical findings in ae described in the literature encompass a broad spectrum , making the diagnosis challenging . in our patient , repetitive bacterial skin superinfections with e coli and s aureus modified the symptomatology , also requiring surgery , which leaded to a diagnosis delay .
the diagnosis is based on clinical symptoms and is confirmed by low plasma zinc levels and rapid clinical response to zinc supplementation . in our case
, in the absence of certainty diagnostic and with periorificial lesions that seemed to be typical for ae , we performed zinc test .
low serum alkaline phosphatase value , a zinc - dependent metal protease , has an indirect role in establishing the diagnosis .
histopathologic findings have a less significant contribution at establishing the diagnosis , because microscopic aspects are not specific , but , in our case , we performed biopsies in the absence of certainty diagnostic .
histopathology of cutaneous lesions reveals a psoriasiform necrolysis , most often pale , by cytoplasmic vacuolization , subsequent focal , or confluent necrosis of keratinocytes in the superficial part of the epidermis and parakeratosis more or less confluent . in resolving or chronic ae lesions ,
acrodermatitis enteropathica has been described in breast - fed infants related to low zinc levels in the mothers . in our case ,
the skin lesions started at the age of 2 months , about 1 month after the infant was weaned from breastfeeding .
serum alkaline phosphatase levels , in our child , were to the lower limit of normal ( 50  u / l ) . in another study also , the authors reported a low value ( 18  u / l ) at the time of diagnosis . the differential diagnoses to consider are psoriasis , atopic dermatitis , seborrheic dermatitis , contact dermatitis , skin infections with candida , langerhans cell histiocytosis , and cystic fibrosis .
once the disease has been diagnosed , the treatment consists of oral zinc supplementation given daily , which leads to a dramatic disappearance of the symptoms within a few days . with treatment , the survival rate is 100% .
the limitation of our case report is the fact that on presentation to a genetic consult , dna samples were taken to carry out specific genetic tests for both the patient and his parents , but we still could not perform them , because these techniques are currently unavailable in romania .
acrodermatitis enteropathica is a rare condition ; early recognition of cutaneous manifestation being necessary , particularly because of immunodeficiency and infection concerns in these patients .
patients with repetitive bacterial skin superinfections may be misdiagnosed for months after initial presentation , as in the case of our patient . in the presented case ,
the diagnosis was delayed because of change in clinical symptoms , through the absence of the diarrhea and through the recurrent bacterial superinfection .
 abstractacrodermatitis enteropathica is a rare genetic autosomal recessive disorder , characterized by periorificial dermatitis , alopecia , and diarrhea . 
 it is caused by mutations in the gene that encodes a membrane protein that binds zinc . 
 we report a 14-month - old boy , admitted for erythematous , scaly and pustular lesions , initially located in the inguinal and perianal regions and on thighs , and very few erythematous lesions on the face . due to the numerous bacterial skin superinfections with staphylococcus aureus , 
 including abscesses that required surgical incision , the clinical picture was modified , leading to a delayed establishment of the diagnosis . 
 later , the symptoms became suggestive for this disease , the diagnostic having been confirmed by low plasma zinc values . under zinc therapy , 
 skin lesions improved significantly in a few days , with favorable outcome . 
 two months later , the skin lesions almost disappeared.abscesses due to bacterial skin superinfections may lead to initially misdiagnosed acrodermatitis enteropathica . 
INTRODUCTION
CASE PRESENTATION
DISCUSSION
CONCLUSIONS