Report

ACUTE ZINC DEPLETION SYNDROME DURING

PARENTERAL HYPERALIMENTATION

LT. [AMES W. STEGER, MC, USNR AND CAPT. GENE T. IZUNO, MC, USN

From Dermatology Service andCimical Investigation Center,Naval Regional Medical Center,San Diego, California

ABSTRACT: Zinc is an essential trace elementwhose malabsorption in early childhood may re-suli in d skin disorder known as acrodermatitisenteropathica. Cutaneous lesions typical of ac-rodermatitis vnlcropdthicj have been describedduring total parenteral nulrition on zinc-dcliciontiniravenous solutions in both adulls and children.This condition has been namvd the "acute zincdepletion syndrome." A case is described inwhich a patient, despite a zinc intake of doublethe daily requirement, manifested the acute zincdepletion syndrome during therapy with com-bined liquid diet plus parenteral hypcralimenta-tion. Predisposing factors in this individual in-cluded a short bowel syndrome and a large oralload of calcium laciate. Zinc metabolism is re-viewed with attention to alterations in disease andduring hyperalimvntation. The clinical manifesla-tions, predisposing factors, therapy and preven-tion of the ac ute zinc depletion syndrome are dis-cussed.

Supported in part by Bureau of Medicine and SurgeryClinical Investigation Program.

The opinions or assertions expressed herein are thoseof the authors and are not to be construed as official or asreflecting the views of the Navy Department or the n.ivalservice at large.

Familial zinc deficiency disease is wellrecognized when manifested as acroder-matitis enteropathica (AE), a rare disease ofearly childhood first described by Danboltand Closs in 1942.' The distinguishing fea-tures of this condition include alopecia,diarrhea and a peculiar eczematoid to bul-lous or verrucous dermatitis localized to theacral areas. Patients may also manifest glos-sitis, stomatitis, conjunctivitis, photophobia,paronychia, dystrophy of the nails, perleche,irritability and emotional disturbances, andfrequent secondary infections of themucocutaneous surfaces with monilial orbacterial organisms.'' Since 1974 this previ-ously lethal disorder has been considered amalfunction in the absorption of zinc by thegut. --*

Cutaneous manifestations typical of ac-rodermatitis enteropathica have also beendescribed in at least 17 patients undergoingtotal parenteral nutrition with zinc-deficientintravenous regimens.^"" An additional casehas been reported in a chronic beer drinkertollowing subtotal gastrectomy and Billrothtype II anastomosis.'^ The constellation ofclinical manifestations of acrodermatitis en-teropathica with associated zinc deficiencyon an acquired basis is now designated theacute zinc depletion syndrome (AZDS).**

The following case report deals witli a | \ i -tient who manifested the acute /me de[)le-

472

No. b ACUTE ZINC DEPLETION Stoger ,t/id Izuno 473

lion synflrc;nu' during combined licjuid dietand parenleral hyperalimentation therapy,despite a zific intake doLihle the normal dailyrequirement. We wi l l review the clinicallindifigs in this syndrome and pertinent as-l")ects of zinc metabolism, detine those condi-tions under which AZDS occurs, and giveguidelines tor ils tre.itmefil and prevention.

Case Report

A 55-year-ol(l man was initi.illv seen in March I'J75 attlie Na\al Regional Medical Center in San Diego with ahistory ol lower tihdominal pain and decre,isecl stoolcaliber which had [jersisted for several months. Evalua-tion revealed a Dukes stage D |)erfi)ralecl mucinousddenocarcinoma ot the colon tor which a ptiMiotiveabdominal-peritoneal resection with colostomy was per-formed. Despite chemotherapy with 5-FU (5-ikiorouracill and MrCCNLJ | l-i^-chlorethyll -3-para-methyl-cyclohexyl-1 -nitrosourea], metastatic diseaseresulted in small-bowel obstruction in December 1976.Extensive small-bowel resection wilh jc'|unosf(}my wasperformed, lea\inf^ ihe p.itietit 85 centimeters of intes-tine distal lo ihe liganienl of Treit/. His subsequentcourse was m.irred b\ frec|uent hospitali7ations tor de-hydration and malabsor|>tion.

On November i, I 177, fhe patieni was reatlmitfed torsevere dehyclralion and malnutrition alter 1 3-kilograniweight loss in fhe preceding 72 hours. On admission, thepatient appeared nioribLind. Physical exam revealed .iweight ot 49 kilogr.ims, male pattern baldness, poor skinfurgor with rlry mucous membranes, multiple siirgitalscars on the abdomen, a timctioning iejunostomy,gener.ili/ecl mLis( le wasting, and prostration. Lahor.itorvabnormalities included a hemoglobin of 9.9 g/dl, hemato-trit of 30.1%, and a hypochloremic alkalosis with stxfium141 mec]/L, pot.issium .i. t meq/L, chloride 8b meq/L.and total CX).j 4.i meq/L.

Resuscitation began with iniravenous ikiicis and in-tensive oral iee(li[ij5s with Prec ision LR *, J nutritionallycomplete liquid diet containing H.7 mg elemental zinc[ler liter, Parenteral hvperalimenlation was begun on theI nil hc)s|)(lal day, employing Travasol 8..')%*. glucose<intl electrolytes, mulli|)le vitamins, supplemental vita-min C and B complex, dnd trace elements (/inc 21)mtg/L, copper, coball, iodide, manganesel. To preveiif(lt'hydr<ition from [jrofiise diarrhea, daily fluid infakeolten exceeded 15 liters tind inrluded 4 lifers othyperalimenlalion and 1 lifer ot Precision LR*. Addi-tional Iherapv inc_luded pericxlic transfusion .ind claiKsupplemenfafion with CtikiLim lact.ite and mediLimc h.iin triglycerides.

On the 2.trd hospital d.iy, during ,i sLisi.iined ph.ise olanabolic metabolism, the patient develo()e(l a biLiIeralpurulent cc>njunc tivitis. Within three clays, an ery-fliematoiis scaling eru|3tion developed along the \u-tienl's nasolabial folds whuh was iiiilicilly thought forepreseni ,in intectious ec/ematc»id tiermalilis t Uitlerappro|)riate Jntibiollt therapy, the toiiJLincjfivitis

Fig. 1. Acute zinc depletion syndrome with facialdermatitis resembling acrodermatitis enteropdthica.Note the angular cheilitis, blepharitis and the patient'sapathetic appearance.

cle.irecl, liul fhe skin eru|)tio[i cc)[ifinued to expand cir-c Limierenfi.illv, surrounding fhe nose and moulh with ashar|>ly marginated desquamative plaque resemblingseborrheic dermatitis (Fig. 1). The patient respcjncledpoorly Io topical sferoids.

By the 2b\h day, a generan7ed noncicafricial alopeciaof fhe scalp also became apparent, especially in the oc-c ipital region. Some thinning of the eyelashes occurredsimultaneously. Between the 2hth and the 4 ird hospitaldays, the fac iaI dermafitis gradually spread to involve thee\elids, fhe earlobes, posterior nec:k, and scalp margins

Fig. 2. Pronounced alopecia oi the occipital regionwith associafed seborrheic-like dermafifis along thescalp margin.

474 INTERNATIONAL lOURNAL OF DERMATOLOCY [uly-August l')79 VoL 18

Fig, 3. A n i-TMhcuiLilnLj-- i>i,K]Lie c o n f a i i i i n g m u l t i p l e

pustules is present on the buttocks centered about thepatient's former anal area. (Anterior-posterior colon re-section has been performed.).

(Fig. 21. Painful erosions of the lips, oral, and nasal mu-cosa as well as angular cheilitis developeci shortly there-after, ,Most distressing to fhe patient was the markedscrotal intlammalion and erosion associated with can-didiasis which appeared shortly after the tacial eru[itiondeveloped. Additional lesions included an erythematousplaque on the lett elbow, a large erythematous plaqueon the buttocks studded with several 1-3 mm pustules.

i>Fig. 4. Scdllered 1 lu 2 nun pustules and excona-

tions on the feet and toes constitute the patient's acrallesions.

occasionally culturing Staphylocnccu^ 3ureus iFig. 3),an erythematous, scal> plaque on line rit;ht posterior calf,and vesicles and fiustules on the dorsal surfaces ot bofhfeet (Fig. 4). Xerosis was generalised buf spared theflexural areas. Throughout most of his hospitali/ation thepatient was irritable. There was no history of clysgeusia,increase in cliarrhe.il stools, or depression, although thepafienf was often a|xifhetic. At no time were lesionsnoted on the patient's hands.

Because ot the alopecia and xerosis, serum-iree faftyacid levels were drawn on days 2b and 29 with results of0,2 and 0.1 mcg/L (normal range 0.1-0.7 mcg/Ll. In-tra\enous 10% Intralipid''* and cutaneous safflower oilap|)lications were initiated, pending the above results,but failed to curb the progressive skin changes.

By fhe 43rd hospital day, the patient's cutaneous find-ings resembled acrodermafilis enteropathica sufficientlyto arouse suspic ion of an acquired zinc deficiency. Lab-oratory analysis yielded a hair , inc le\el of 180 mcg/ghair (normal range 75-1 5t) mcg/g hairi and a serum nnclevel of 80 mcg/d( (normal range 75-1 50 mcg/dll. Pend-ing these results, an addifionai 8.1 mg of elemenfal nnc(20 mg ^inc sulfate) was given intravenously [ler day.Within three days, the patient's skin showed significantreduction m erythema and oozing of lesions. By day 49,the day of discharge, the patient's skin was essentiallytree of primary lesions. Alopecia, fine desquamafion,linii desiccated vesicles were the only residua. Repeatserum 7inc level was 145 mg/dl. On discharge, the pa-tient weighed 67 kilograms. tJutpatient thera|5y includedone liter ot' Precision LR ' per clay and 52 mg cjf elemen-tal zinc four times per day. Epigastric distress and emesiscaused premature discontinuation of the supplementalzinc, Des|3ite fhis, the pafient remained free of lesions.On follow-uf). Beau's lines failed fo develop. The pafienthas been on home hyperalimentation since fhe place-menf ot a SUIK ufaneoLis mdwelling shunf in lanuary1978.

Discussion

As in the case presented, the clinical fiian-

ifestations of the AZDS usually occur during

the anabolic recovery phase made possible

by [jarefiteral hyperalimentalion,•'•''' Diarrhea,

depression, or dermatitis may be the herald-

ing sign and may appear between 2 and 20

weeks lollowing the institution ot parenteral

feeding. Characteristically, the dermatitis be-

gins on or around the ala nasi or at the angles

ot the moulh where it rapidly s|)reads to in-

volve most of the face. Satellite lesions may

affect the eyelids as a marginal blepharitis

and may also involve the earlobes and the

neck. Although the eruption most commonly

resembles seborrheic dermatitis, it may also

appear as bullae, eczema craquele, or as an

No. 6 AC UTl /INC DEPICTION and Izunn 475

erythematous oozing, crusted dermatitis.Similar changes frequently aflect the ex-tremities and the perianogenital regions. Theacral regions are the common sites of bullaeformation, especially along Ihe linger and toecreases. Paronychial inflammation has beenreported in a lew cases.^'** Erythematousplaques and bulLie have develo|)ed on iheelbows in a couple of cases."'^ Strangely, ourpatient developed such a lesion only on oneelbow. Nail disease is frequent in acroder-matitis enteropathica, but has been describedin only three patients with A7DS: one withbrittle nails^" and two with horizontal ridges(Beau's lines).'^ The latter are generally seenfour lo six weeks alter the institution of zinctherapy when the nail [ilate has grown sulli-ciently to push the line distally. (Beau's linesrepresent growth arrest ol the nail matrix andmay be directly de|)endent on /inc levels oralterations in zinc metabolism.'^1 Early in-volvement of the mucous membranes inAZDS is the rule and may arise as stomatitis,glossitis (associated with dysgeusia in onecase^), angular cheilitis, or fissuring ol the!ips. Conjunctivitis frequently accomiwniesacrodermatitis enteropathica, but is reportedhere associated for the firsl time wilh AZDS.

About one to two weeks after the cip|)ear-ance of the dermati t is, a nonscarringalopecia of the scal|i becomes evident, ottenappearing first on the occipital scalp tormechanical reasons. Allhough mild in somecases, the hair loss may |)roceed to alopeciatotalis, Hairpluck examination has shownbroken-ofi hairs rather than the club hairsexpected wi lh a telogen effluvium.^ Thealopecia is the slowest cutaneous sign to re-solve during zinc therapy but may be com-plete in time." Our patient demonstated somerecovery six weeks following the Initiation otzinc therapy.

The extracutaneous manifestations includediarrhea, fever, and mental changes rangingfrom a|)athy and depression lo irritability andconfusion. In cases where diarrhea was pres-ent prior to [he ini t iat ion of [larenteralhyperal in ientat ion, ..in increase in the

amount of diarrhea over baseline levels isconsistent wilh gut involvement in AZDS.*"

Perhaps the most characteristic and diag-nostic feature of the acute zinc de|iletionsyndrome in patients with suggestive skin le-sions is the rapid and virtually complete re-S|ionse of both cutaneous and extracutane-ous manifestations to exogenous zincsupplementation.^"''^ Initial response is seenwi th in 48 to 71 hours. Except for thealofiecia, complete resolution within twoweeks is usually Ihe rule.

As shown in Table 1, the patient man-ifested most ot the symptoms and signs as-sociated wi th both acrodermatit is en-tero|)athica ..md the acute zinc depletionsyndrome. Allhough he did not have an ab-normally low serum zinc level, serum zinc isnot necessarily reflective of total body storesand tissue levels.''' Consequently, al |)resent,the critical tcsl tor zinc tieficiency at the tis-sue level is a definitive clinical res|)onse tozinc sup|jlementation under controlled con-ditions.'^' Although serum zinc levels may tallal a rate ot b.b mcg/d l /week dur inghyperalimentation"' and the average patientmay become hypozincemic in seven weeks,not all such [patients develo|i the clinicalmanifestations of AZDS in the \c\cc ot overtlylow serum levels, '"'•'^ nor do al! |)<itients withoverl clinical manifestations have depressedserum zinc levels.'"' In contrast lo serum zinclevels, hair zinc content is more reflective oftotal body stores. However, because hair re-growth is slow, tow levels are more indica-tive of long-term deticiencies, while acLitedeficiencies may nol be registered at all.'-'^Thus, the diagnosis of the acute zinc deple-tion syndrome rests on clinical grounds andon a dramatic res|ionse to a thera|)eulic trialof zinc.

The major considerations in therlitterentialdiagnosis of AZDS during hy|)eralimcntationinclude inherited zinc deficiency (acroder-matitis enteropathica), vitamin deficienciesof riboflavin or pyridoxine, essential tattyacid def ic iency, and |)ossibly theglucagononia syndrome. In those |>e(liatric

476 INTERNATIONAL lOURNAL OF DERMATOLOGY luly-AugusI 1979 Vol. 18

Table 1. Clinical Manifestations of Acute ZincDepletion Syndrome Disorders iAZDS)

Manifestation

Periorofacial dermalitisAlopeciaResponse to zinrPerttinogenilal dermatitisAcral dermalitisDecreased serum zincDiarrheaStomatitis/perlecheEmolional disturbanceParonychidStaph infeclionGlossitisCandidiasisBeau's linesDecreased hair ^incConjunctivilisNail dyslrophyPhotophobia

AE*

X

XX

X

X

X

XX

X

X

X

XX

X

X

XX

X

PresentCase

Report

X

XX

X

X_

_

X

X_

X_

X_

_

X_

-

AZDS

X

XX

X

XX

X

X

X

X

X

XX

X

X_

_

-

Number otPositive Cases of 18Comprising AZDS

18161 4 t131211

844433221000

* Acrodermatitis enleropathica.t The tour other palients responded to discontinu,ince ot hyperdlimentatton dnd initiation of a nurmdl diet.

patients whose diarrhea begitis with thechange trom human to bovine milk or for-mula, the diagnosis of inherited acroder-matitis enteropathica must be considered.Thus, the three pediatric |)atients''-'' diag-nosed as having ati AZDS, who develo|)edthe characteristic dermali t is dur inghyperalinientation lor iheir diarrhea, must beregarcJcfl with some sus[)icion. Riboflavinand pyridoxine deliciencies tioth are as-sociated with glossitis and a seborrhea-likef5eriort)la{ iai dermalitis which begins on theala nasi."^ Other manilestations, as well as atherapeulic trial of zinc, \w\\) to cliMerentiatethem from AZDS. Essential fatty acid defi-ciency (linoleic acid deticiency) develo[)s ininfants as erythematous oozing and scaling le-sions beginning in the intertriginous areas.Dry, leatherv thickening ot the skiti, as wellas extoliation, may become generalized."* Inadulls on hyperalimentation, essential faltyacid deficiency has been associated withgeneralized pruritus, dry exfoli.itive skin witha very fine scale, and abnormally fragile hairwhich leads to alopecia, especially in the

occipital region where the head rests on a pil-Icjy , 20.21 Response to linoleic acid replace-ment may be as rapid as 72 hours.^" Diag-nosis may he aided by low serum levels or bythe reduced ratio of essential fatty acids toolher sertim latty acids.•^' The glucagonomasyndrome incltides a necrolytic migrattjry er-ythema similar in a|ipearance and distribu-tion tf) ihe eczomatoid lesions of acute zincde|)letion. Patients wilh this syntfrome ahodemonstrate |)aiu reatic lumors, elevatedblood glucagon levels, derangements of glu-cose metabolism, characteristic hislologicteatures, and a clinical course distinctivetrom thai of AZ[3S.^- It would be unlikely forsuch patients to undergo hyperalinientationtherapy [irior lo the ert/plion of their der-matosis-

In order to better understand those situa-tions in which the acute zinc depletion syn-drome develops, it is necessary to reviewcertain aspects of zinc biochemistry and me-tabolism.

Zinc is an essential trace element serving abroad range ot indispensable biologic func-

No. 6 ACUTE ZINC DEPLETION and l/uno 477

tions in over 70 metalloenzymes and pro-teins.'" In man, the minimum daily require-ment ot elemental zinc necessary lo niainlainthe 1.36 to 2.J2 g of total body stores-^ hasbeen estimated lo be 2.4 to 4.2 mg.'"* Be-cause this is significantly less than the 10 to15 mg ol elemental zinc normally found inthe average western diet, nutritionally ac-quired zinc deficiency disease is corrr-S|)ondingl\ rare.

In reviewing the intestinal absorption otzinc in adult rats, Becker and Hockstra 'concluded Ihat the duodenum appeared tohave the highest rate of zinc absorption (40%per unit length), followed by the ileum andjejunum (15% per unit length), while thecolon and stomach retained less than 2% perunit length after oral -" Zn administration.Using whole body monitoring techniques,Hawkins et al.'-* found an overall 61% meanretention rate after oral « Zn in seven humansubjects. Similarly, Spencer et al.^*' noted76% mean retention following intravenousadministration. Eollowing either mode ofadministration, the excretion is primarily viathe gut by way of biliary and pancreatic se-cretions and usually far exceeds that by theurinary route.'-'-^-' In Hawkins' study,'-* meanfecal loss during the first week was 28.2%,while mean urinary loss totaled 0.5%. Thedaily rate of loss of ^^Zn ranged from 0.14to 0.26% per day after the first week. Basedon normal body stores and a mean daily lossof 0.18%, the minimum daily requirement tomaintain the body stores was calculated tobe 2.4 to 4.2 mg, an amount easily providedby the average western diet. Following oraladministration, peak plasma levels occurwithin two hours.

The molecular mechanism of gastrointes-tinal zinc absorption is poorly understood.However, Evans et a l . " have noted a zinc-binding ligand, probably a peptide, in pan-creatic secretions of the rat which markedlyincreases "^Zn absorption. The significanceof tbe peptide is enhanced by the fact thatzinc does not occur in the uncombined statein nature or in foodstuffs. In biologic systems.

it is complexed to organic ligands rather thanexisting as a metal or free ion. -* Evans' modelshows the zinc-ligand complex as taken upin the intestinal microvilli, broken downintraceltularly, and the zinc adsorbed tobinding sites on tbe basolateral plasmamembranes where it can be transferred tometal-free albumin. Preliminary evidence isavailable suggesting the presence of a humanintestinal and salivary zinc-binding ligand. 'In the plasma, zinc is 98% bound.**

Based on the above model, zinc deficiencymay result from decreased oral or intrave-nous intake, decreased intestinal uptake, in-creased urinary, fecal, or fislula excretion.Theoretically, decreased absorption couldresult from hypoalbuminemia. Zinc depie-tion on a striclly nutritional basis has onlyrecently been recognized in man,'^-''^ al-though long recognized in animals.^^ Thismechanism plays the major role in thepathogenesis of AZDS in most patients un-dergoing total parenteral nutrition withzinc-deficient solutions. Urinary losses mayrise significantly during major operations, asthe result of burns, trauma, and other severestress situations probably due to increasedcatabolism of zinc-rich skeletal muscle.^Zinc deficiency due to disruption of the mi-crovillous brush border secondary to in-flammation is the probable mechanism inCrohn's disease. Fistula secretions may playan additional role in Crohn's disease as wellas in ulcerative colitis. Malabsorption on thebasis of decreased absorptive surface follow-ing ileal or jejunal resection is obvious. Ac-cording to Lombeck et al.,-" the zinc deple-tion in acrodermatitis enteropathica appearsto be on the basis of inadequate absorption,since only 29.3% retention of oral ' Zn oc-curred in AE patients as compared to 66% incontrols, while daily losses of retained zincwere the same.

At the molecular level, zinc absorptionmay be hindered by chelation to nonabsorb-able organic anions such as phytate ' or byoligo|ieptides in acrodermatitis en-teropathica as suggested by Moynahan.^

478 INTERNATiC^NAL lOURNAI OE DERMATOLOGY luly-Au8iiM 197'J Vol. 18

Table 2. Predisposing Factors of the ZincDepletion Syndrome in 18 Patients

No. ofF-actor Patients

Parenterd! hyperalimentation

Gastrointestintil diseaseCrohn's diseaseDiarrhedUkerdtive colitisPeptic ulcer diseaseCl carcinomaMotility disorderAlcoholism with chronic

pancreatic insufficiencyIntrddbdomindl abscesses

following splenectomy

Surgical proceduresPartial or total colectomySmall bowel resectionSubti)t.il gdstrectomy

(Billroth IIIRoux-en-y(idstrojeiunostomy, then

duodenojejudostomyColoslomy wilh tistuta

formation

17

443321

Elhylenediaminotetraacetate (EDTA], one ofthe better known synthetic chelators, appar-ently increases zinc availability from [)lantproteitis by competing with phytate or olhermetal binders. •' It is possible that diiodohy-droxyquin may act similaHy or, as Moynahansuggests, by chelation of the oligopeptides.With the recent evidence of a pancreaticzinc-binding ligand facilitating zinc absorp-tion in the rat and man, competitive inhibi-tion of absorption is theoretically [lossible.Calciutn, atiother divalent ion, is known todecrease zinc absorption by an unknownmechanism.^^ Portney and Molokhia ''" haveshown that cin exacerbation ot acrodermatitisenteropathica occurs when a patient's diet ischanged from human milk to cow's milk, thelatter containing 2 to 3 times greater concen-tration ot calcium. The possibility exists thatcalcium may actively compete for this zinc-binding ligatid and may (precipitate AE in asusceptible individual.

In ihe patient [iresetited, several mecha-nistns affecting zinc intake were [iroljably

o|)erative. First, he had a marked decrease inthe total absor|itive surtace of his gut sec-ondary to stnall-bowel and colonic resec-tions. Secondly, he had a marked oral load ofcalcium lactate—two 325 mg tablets fourtimes per day. Last, he had a chronically lowserum albumin, usually 2,9 gm/dl (normalrange 3.5-5.5 gm/dl). These, in combinationwith his zinc-requiring anabolic growthphase in the face of apparently inadequateintravenous and oral zinc supplementation,were responsible for his acute zinc depletion.Althotigh increased urinary losses prior to theinstitution ot parenteral hyijeralimetitalionmay have contributed to the depletion, nomeasurements wore obtained.

With regard to the predisposing factors ofAZDS in the otber 18 patients reviewed, par-enteral hyperalimentation with zinc-deticientsolutions, preexisting gastrointestinal dis-ease, and maior c^perations were of over-whelming importance (Table 2).

Results obtained in the treatment of theacquired zinc depletion syndrome have beensuccessful with initial responses noted in 48hours and cotnplete resolution within twoweeks.**'"' Children have been successfullytreated with a daily dose of 14 mg of elemen-tal zinc orally^ and 1.11 mg intravenously.^Daily adult doses have ranged from 30 to240 mg orally^"*^-'" and 5 to 32 mg intrave-nously. - Although such doses were said to bewell tolerated, the patient reported here ex-perienced severe epigastric distress andemesis on a daily dose of 144 mg. Intrave-nous zinc toxicity has been reported in onlyone case where the dose approached 3,000mg per day.^' For comparison, Moynahan^reported daily oral maintenance doses of 14mg of elemental zinc in acrodermatitis en-teropathica, with optimum doses of 60 mgduring intercurrent intestitial disease.

Ideally, bowever, preventive therapy isbest. In pediatric patients receiving total par-enteral nutrition, ii appears that 0.01 to 0.04mg/kg/day intravenously is probablyadequate profihylaxis against tbe acute zincdepletion syndrome, while the dose in adults

No. b ACUTE ZINC DEPLETION Steger and Izuno 479

ranges from 2.0 to 4.0 mg zinc intravenouslyper day.'^'^^ Such dosages may have to bealtered when many predisposing factors forzinc depletion are present. Formtilas for thepreparation of trace element solutions arereadily available.^-'' With the wides|5read dis-semination of knowledge on /inc metabo-lism and requirements, il is ho[)ed that iat-rogetiic acute zinc depletion syndrome willbecome a curiosity in medical history.

Acknowledgments

The juthors would like lo ihank LCDR Stephen W,Shevi/ni.ike for hii assistance m the prepardtion ol thisnidnust ript.

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1. Danbolt, N., dnd Closs, K.: Acrodermatitis en-teropdthicd. Ada Derm. Venereol, 23:127, 1942.

2. Wells. B. T., dnd Winkelnidnn, R. K.: Acrodermatilisenteropdthicd: report of six rases. Arth. Dermatol84:90, 19bl.

i. Moynaiian, E. ).: Acrodermatilis enteropalhicd: alethal inherited human /inc-deficiency disorder.Lancet Il:.i99, 1974.

4. Lombeck, 1., Schnippering, H. C. et al.: Absorptionof zinc in dcrodermatitis enteropathica. Ldncet1:855, 1975,

3. Arakawa, T., Tamura, T., Igdrdshi, Y,, et al.: Zincdeticiencv in two infants during total parenterdi nu-trition tordidrrhed. Am. ), Clin. Nutr. 29:197, 1976.

6. Kay, R. C , Tasman-jones, C, Pybus, |., et al.: Asyndrome of acute zinc deficiency during total par-enterdl dlimentation in man. Ann. Surg. 183:331,1976.

7. Tucker, S. B., S* hroeter, A. L,, Brown, P. W., et dl.:Acquired 7inc deticiency: cutdneous manifestationstypical ot acrodermatitis enteropathica. (AMA235:2399, 1976.

8. Weisniann, K., Hjorth, N., and Fischer, A.: Zinc de-pletion syndrome with acrodermatitis during long-term intravenous feeding. Clin. Exp. Dermdtol.1:237, 1976,

4. Okada, A,, Takagi, Y., Itakura, T., et al,: Skin lesionsduring intravenous hyperdHmentdtion: zinc deti-ciency. Surgery 80:629, 1976.

11). Wexler, D., dnd Pace, W.: Acquired zinc delicicncydisease of skin. Br. j . Dermatol. 96:669, 1977.

11. Fleming, C, R., Smith, L. M., and Hodges, R. E.:Essential tatty acid deliciency in ddults receivingtotdl parenteral nutrition. Am. |. Clin. Nutr. 29:976,1976,

12. Weismann, K., Roed-Petersen, ),, Hjorth, N., et al.:Chronic zinc deficiency syndrome in a beer drinkerwitii Billrotii II resection. Int. |, Dermatol. 15:757,197fi.

13. Weismann, K.: Lines ol Beau: possible markers ofzinc deticiencv. Acta Derm. Venereoi. 57:88, 1977.

14, Hawkins, T., Marks, |. M., Pliimnier, V. M., et al.:Whole bofiy monitoring and oilier studios of zinc-65 nietdbolism in |)atients with dermdtolojjical dis-eases. Clin. Exp, Dermatol. 1:243, 1976.

15, Prasad, A. S.: Zinc deficiency in [lian. Am. |. Dis,Child. 130:359, 1976.

16, Fleming, C. R., Hodges, R, E,, and Hurley, L. S.: A[irospective study ol serum copper dnd zinc levelsin patients receiving total pdrenteral luitntiiin. Am.|. Clin. Nutr, 29:70, 1976.

1 7. Messing, B., Poilras, P., and Bernier, ). ),: Zinc defi-ciency in total parenteral nutrition. Lancet 11:97,1977.

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