http://www.iponline.net/content/36/1/5 !"#I"$ %pen &ccess Cow's (il) protein aller*+ in children: a practical *uide Carlo Caffarelli 1, , -rancesco .aldi 2 , .ar/ara .endandi 3 , 0ui*i Cal1one 2 , 3iris 3arani 5 , Pa(ela Pas4uinelli 6 , on /ehalf of "$5P&5 &/stract & oint stud+ *roup on cow's (il) aller*+ was con6ened /+ the "(ilia7!o(a*na $or)in* 5roup for Paediatric &ller*+ and /+ the "(ilia7!o(a*na $or)in* 5roup for Paediatric 5astroenterolo*+ to focus /est practice for dia*7nosis, (ana*e(ent and follow7up of cow's (il) aller*+ in children and to offer a co((on approach for aller*olo7*ists, *astroenterolo*ists, *eneral paediatricians and pri(ar+ care ph+sicians. 8he report prepared /+ the stud+ *roup was discussed /+ (e(/ers of $or)in* 5roups who (et three ti(es in Ital+. 8his *uide is the result of a consensus reached in the followin* areas. Cow's (il) aller*+ should /e suspected in children who ha6e i((ediate s+(pto(s such as acute urticaria/an*ioede(a, whee1in*, rhinitis, dr+ cou*h, 6o(itin*, lar+n*eal ede(a, acute asth(a with se6ere respirator+ distress, anaph+la9is. 0ate reactions due to cow's (il) aller*+ are atopic der(atitis, chronic diarrhoea, /lood in the stools, iron deficienc+ anae(ia, *astroesopha*eal reflu9 disease, constipation, chronic 6o(itin*, colic, poor *rowth :food refusal;, enterocolitis s+ndro(e, protein7los7in* enteropath+ with h+poal/u(ine(ia, eosinophilic oesopha*o*astroenteropath+. &n o6er6iew of accepta/le (eans for dia*nosis is included. &ccordin* to s+(pto(s and infant diet, three different al*orith(s for dia*nosis and follow7up ha6e /een su**ested. Introduction Cow's milk protein allergy (CMPA) affects from 2 to 6% of children, with the highest prevalence dring the first year of age !"#$ A%ot &'% of children have %een shown to resolve CMPA within the first year of age, (')*'% within their fifth year !2,+#$ ,he rate of parent)reported CMPA is a%ot - times higher than the real one in chil) dren !-#$ .o, many children are referred for sspected CMPA %ased on parent perception, symptoms sch as ctaneos erption, insomnia, persistent nasal o%strc) tion, se%horreic dermatitis or positive reslts to northodo/ investigations$ Moreover, parents often pt their children on nnecessary diet withot an ade0ate medical and dietary spervision$ ,hese inappropriate dietary restrictions may provoke ntritional n%alances, especially in the first year of age$ ,herefore, an accrate diagnosis of CMPA is important in order to avoid not only the risk of rickets, decreased %one minerali1ation !&#, anaemia, poor growth and hypoal%minemia, %t , Correspondence: carlo.caffarelli<unipr.it 1 =iparti(ento dell'"t> "6oluti6a, Clinica Pediatrica ?ni6ersit> di Par(a, Par(a, Ital+ also that of immediate clinical reactions or severe chronic gastroenteropathy leading to mala%sorption$ 2ecently, three gidelines !6) (# reporting different approaches to the infant with CMPA have %een p%lished$ 3n view of these considerations, a stdy grop with e/pert representatives of 4milia)2omagna 5orking 6rop for Paediatric Allergy and of that for Paediatric 6astroenterology (456P6A), was constitted$ As mmem%ers of the e/pert panel, the athors were assigned to review practice with regard to diagnosis, management and follow)p of CMPA for %oth comm)nity and hospital paediatrician in order to share the same approach towards the child$ ,he docment pre)pared %y the stdy grop was %ased on e/isting recom)mendations, clinical e/perience and evidence from the literatre$ ,he report was discssed and received inpt %y the mem%ers (see participant list in acknowledg)ments) of 456P6A which inclded clinicians e/peri)enced in paediatric allergy, paediatric gastroenterology and general paediatricians, in three meetings held in 7ovem%er 2''(, 8e%rary 2''* and March 2''* and a consenss was reached$ According to the symptoms and @ 2010 Caffarelli et alA licensee .io3ed Central 0td. 8his is an %pen &ccess article distri/uted under the ter(s of the Creati6e Co((ons &ttri/ution 0icense :http://creati6eco((ons.or*/licenses//+/2.0;, which per(its unrestricted use, distri/ution, and reproduction in an+ (ediu(, pro6ided the ori*inal wor) is properl+ cited. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 Pa*e 2 of B http://www.iponline.net/content/36/1/5 the type of infant diet, three different algorithms for diagnosis and follow)p have %een sggested$ ,hese approaches refer to the child in the first year of age$ 2ecommendations for older children have %een %riefly reported$ Cow's (il) protein aller*+: when should we dou/tC A positive atopic familiar history is common in children with sspected CMPA !*#$ ,he diagnosis of CMPA is %ased on a detailed history of symptoms (8ig$ "), skin prick test and serm specific 3g4 to cow's milk protein, elimination diet and oral food challenge$ Clinical mani) festations de to CMPA !6) "-# can %e divided into 3g4) mediated immediate clinical reactions (onset of the symptoms within the +' mintes after the ingestion of cow's milk) and non 3g4)mediated delayed reactions (hors)days after food ingestion), most affecting the skin and the gastrointestinal system$ 9owever, immediate and delayed reactions can %e associated in atopic ec1ema and in eosinophilic oesophageal gastroenteritis (8ig$ ")$ ,he negative predictive vale of skin prick test:specific 3g4 for immediate reaction is e/cellent (;*&%) !"&#, however a small nm%er of these patients can have clin) ical reaction$ ,herefore, despite negative 3g4 tests if there is a strong sspicion of CMPA, an oral food challenge is necessary to confirm the a%sence of clinical allergy$ <n the other hand, a%ot 6'% of children with positive 3g4 tests have CMPA !"&,"6#$ Prick %y prick test with cow's milk s%stittes may %e considered$ <ral food challenge, open or %lind, remains the Dgold standardE to definitely ascertain children with food allergy when the diagnosis is nclear !"=#$ <8C shold %e performed nder medical spervision in a setting with emergency facilities, especially in case of positive skin prick test or serm specific 3g4 to cow's milk and in infants at risk of an immediate reaction$ Cow's (il) su/stitutes A%ot "'% of children with CMPA react to e/tensively hydroly1ed formla (e98) !=#$ 3n comparison with e98, soy formla (.8) provokes more fre0ently reactions in children with CMPA aged less than 6 months !"(# %t not in older children$ .8 mainly indces gastrointestinal symptoms$ Amino acid formla (AA8) is non allergenic !"*#$ 3ts se is limited %y the high cost and %ad taste$ 2ice is allergenic and is often involved in the onset of enterocolitis syndrome in Astralian infants !2'#$ Con) trasting data have %een reported on the effect of protein content on growth !2"#$ 3n 3talian children, rice formla has %een shown to %e tolerated %y children with CMPA !22#$ >arger long)term stdies are warranted to clarify -i*ure 1 I((ediate and late onset reactions in children with cow's (il) protein aller*+. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 Pa*e 3 of B http://www.iponline.net/content/36/1/5 the se of rice formla in infants with CMPA$ 2ice for) mla may %e a choice in selected cases taking into con) sideration the taste and the cost$ 9ome)made meals may %e a dietary option after - months of age$ Mammalian milks are not ntritionally ade0ate$ 6oat's milk commonly provokes clinical reactions in more than *'% of children with CMPA !2+#, donkey's milk in a%ot "&% !2-,2&# and has a high cost$ & child fed with cow's (il) for(ula with (ild7 (oderate s+(pto(s :-i*. 2; 3n infants with immediate symptoms (vomiting, acte hives, angioedema, whee1ing, rhinitis, dry cogh) or late symptoms (moderate:severe atopic dermatitis, diarrhoea, %lood in the stools, iron deficiency anaemia, gastroeso) phageal refl/ disease (6<2?), constipation) a CMPA can %e sspected !6) (,"') "-#$ <ther cases are to %e considered for patients nresponsive to treatment$ 3nfant colic (more than + hors of crying a day, + days for more than + weeks) is not nanimosly considered as a conse0ence of CMPA$ ,he paediatrician has to consider the opportnity of a cow's milk free diet in the most tro%lesome cases !26,2=#$ Mild immediate reactions may %e of difficlt interpretation %ecase they can %e the reslt of cases different from CMPA$ 9ow) ever, if these symptoms are strongly related to cow's milk ingestion, we recommend to eliminate cow's milk and follow the algorithm for severe reactions (8ig$ 2)$ 2egarding delayed onset gastrointestinal symptoms, other pathologies (i$e$ infections) shold %e e/clded %efore investigating allergic sensiti1ation$ 3n mild atopic dermatitis, investigations for CMPA are not necessary in the a%sence of a clear relation %etween cow's milk intake and onset of symptoms$ 5hen a CMPA is sspected, infants shold go on a 2)- week diet withot cow's milk protein$ 8or weeks shold %e considered for chronic gastrointestinal symp)toms$ 3nfants shold %e fed with e98 or .8 in children aged more than 6 months and withot gastrointestinal symptoms$ 3f the symptoms improve on a restrict diet, an <8C to cow's milk is necessary to definitely ascertain the diag) nosis$ 3f the oral food challenge is positive, the child mst follow the elimination diet and can %e re)chal)lenged after 6 months (a shorter period for 6<2?) and in any case, after *)"2 months of age$ 3f the oral food challenge is negative, a free)diet can %e followed$ Children less than 1 year fed with regular cows milk formula with suspected mild-moderate CMPA Immediate reactions with unclear history*: Late reactions Test: Vomiting Atopic dermatitis (moderate/severe)* SPT, Acute orticaria, angioedema Diarrhoea, stool blood, iron defciency anaemia, specifc IgE Wheezing, rhinitis, dry cough GORD, constipation (with exclusion of other causes) *If history is clear, exclusion diet is requested, Infantile colic challenge is not necessary (see severe *mild atopic dermatitis: no restrict diet is requested if symptoms) there is negative history of reactions to cows milk. Elimination diet for 2-4 week (4 weeks for gastrointestinal symptoms): Extensively hydrolyzed formula Soy formula if >6 months of age (without gastrointestinal symptoms) Test: SPT, specifc IgE, stool eosinophils or stool blood Positive IgE test with history of strongly related clinical reaction Yes Improves ? No Oral food challenge (consider to perform Positive Negative IgE test challenge test in a clinical setting in case IgE test Atopic dermatitis of positive specifc IgE and/or SPT) Positive Avoid cows milk for at least 6 months and until 9-12 months of age (assess a shorter period in GORD). Amino acid Negative formula Not better Regular cows Oral food challenge Regular milk should be considered if it cows milk formula is successful formula -i*ure 2 &l*orith( for children F 1 +ear fed with cow's (il) for(ula and (ild7(oderate s+(pto(s. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 Pa*e 2 of B http://www.iponline.net/content/36/1/5 5hen there is strong sspicion of 3g4)mediated reac)tions, in infants who do not respond to a diet with e98 or .8 an attempt may %e made with a "-)days diet with AA8$ Cow's milk s%stittes are sed in children aged less than "2 months$ 3n older children with CMPA, e98 or AA8 are not sally necessary %ecase an ade0ate diet is easily accessi%le$ & child fed with cow's (il) for(ula with se6ere s+(pto(s :-i*. 3; 3mmediate severe symptoms are considered laryngeal edema, acte asthma with severe respiratory difficlty, anaphyla/is$ ,he following are delayed onset severe symptoms@ chronic diarrhoea or chronic vomiting with poor growth, intestinal %leeding with iron deficiency anaemia, protein losing enteropathy with hypoal%mine) mia, eosinophilic gastroenteropathy confirmed %y %iopsy !=,(,"') "-#$ 3f any of these immediate symptoms are o%served as a conse0ence of sspected CMPA, infants shold follow a cow's milk free diet$ As s%stittes, .8 (if older than 6 months of age) or e98 or AA8 can %e sed$ e98 and .8 shold %e started nder medical spervision %ecase of possi%le clinical reactions$ 3f an AA8 is adopted, it may %e administered for 2 weeks and then the infant may %e switched to .8 or e98$ 3n children with late severe gastrointestinal symptoms with poor growth, anaemia or hypoal%minemia or eosi) nophilic oesophagogastroenteropathy, it is recom)mended to start an elimination diet with AA8 and then switched with e98$ ,he effect of the diet shold check ot within "' days for enterocolitis syndrome, ")+ weeks for enteropathy and 6 weeks for eosinophilic oesophagogastroenteropathy$ 3n children with anaphyla/is and concordant positive 3g4 tests or severe gastrointestinal reactions, oral food challenge is not necessary for diagnosis$ ,he oral food challenge for tolerance ac0isition shold %e performed not %efore 6)"2 months after the last reaction$ Children have to eliminate cow's milk ntil "2 months of age, %t in those with enterocolitis syndrome ntil 2)+ years of age !2(#$ Children with any severe symptoms shold %e referred to a speciali1ed centre$ e98 or AA8 is sed in children aged less than "2 months and in older children with severe gastrointestinal -i*ure 3 &l*orith( for children F1 +ear fed with cow's (il) for(ula and se6ere s+(pto(s. In child less than1 +ear of a*e, infant for(ula is not co(pulsor+. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 Pa*e 5 of B http://www.iponline.net/content/36/1/5 symptoms$ 3n children ; "2 months with anaphyla/is, cow' s milk s%stittes are not always ntritionally re0ired$ & /reast7fed infant with a suspected C3P& :-i*. 2; 3n e/clsively %reast)fed infants, sspected symptoms to the cow's milk proteins are almost always non 3g4) mediated as atopic dermatitis, vomiting, diarrhoea, %lood in the stools, 6<2?, colic !2*#$ A maternal diet withot cow's milk is not recom) mended for mild symptoms$ ,here is no evidence that a maternal diet withot egg and cow's milk in infants with %loody stools (proctocoli) tis) is of vale !+',+"#$ 3n infants with moderate)severe symptoms, cow's milk protein, eggs and other foods shold %e eliminated %y the mother's diet only if history sggests an ne0ivocal reaction$ Moreover, the infant shold %e referred to a speciali1ed centre$ ,he maternal elimination diet has to %e followed for - weeks$ 3f there is no improvement the diet shold %e stopped$ 3f symptoms improved, it's recommended that the mother ingested large amonts of cow's milk for one week$ 3f symptoms occrred, the mother will contine the diet with spplemental intake of calcim$ ,he infant can %e weaned as recommended for healthy children, %t cow's milk shold %e avoided ntil *)"2 months of age and for at least 6 months from the %eginning of the diet$ 3f the volme of %reast milk is insfficient, e98 or .8 formla (if ; 6 months) shold %e administered$ 3f after the reintrodction of cow's milk in mother's diet symptoms do not occr, the e/clded foods can %e introdced one %y one in the diet$ Conclusions ,he diagnosis of CMPA is %ased on oral food challenge that follows a 2)- week elimination diet$ A diagnostic oral food challenge is nnecessary in immediate reactions or late gastrointestinal reactions with anaemia, poor growth or hypoal%minemia if the casative role of cow's milk is clear$ Children can %e challenged after 6)"2 months from the reaction and Breast-fed infants with suspected reactions to cows milk: atopic dermatitis, vomiting, diarrhoea, stool blood, GORD, poor growth, infantile colic. Clinicalevaluation, family history Mild symptoms Moderate-severe smptoms SPT/specifc IgE, No Maternal diet without stool eosinophils or stool diet cows milk for 2-4 weeks. blood. Improves ? No Yes Free Give cows maternal milk to the diet mother for 1 week. Symptoms ? No When it is necessary, breastfeeding should Yes be supplemented with extensively Exclusion Free hydrolyzed formula or soy formula (if > 6 diet maternal months). diet Food challenge test after 6-12 months of avoidance. -i*ure 2 &l*orith( for /reast7fed infants with suspected non7I*" (ediated reactions to cow's (il) protein. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 http://www.iponline.net/content/36/1/5 not %efore "2)2- months of age according to the symptoms$ ?iets mst %e ntritionally %alanced$ 3n children with CMPA, a spplementation with calcim mst %e evalated$ ?iet is not re0ested in children with mild atopic der) matitis and negative history for cow's milk reactions$ .8 shold not %e sed in infants A 6 months of age with allergic symptoms and in those with late gastroin)testinal symptoms$ Children with gastrointestinal reactions and anaemia, poor growth or hypoal%minemia shold %e given AA8 and then switched to e98$ e98 or AA8 is sed in children aged less than "2 months and in older children with severe gastrointest)inal symptoms$ 3n children ; "2 months with anaphy)la/is, cow's milk s%stittes are not always ntritionally re0ired$ 0ist of a//re6iations CMPA@ cow's milk protein allergyB 456PA6@ 4milia) 2omagna 5orking 6rop for Paediatric Allergy and of that for Paediatric 6astroenterologyB e98@ e/tensively hydroly1ed formlaB .8@ soyB AA8@ amino acid formlaB 6<2?@ gastroesophageal refl/ disease$ &c)nowled*e(ents Ph+sicians and specialists of "(ilia7!o(a*na "(ilia7!o(a*na $or)in* 5roup for Paediatric &ller*+ and for Paediatric 5astroenterolo*+ :"$5P5&; who contri/uted to this *uide. Paediatric *astroenterolo*+: Patri1ia &l6isi :?.%. di Pediatria %spedale 3a**iore, .olo*na, Ital+;, Ger*io &(arri :?.%. di Pediatria, !e**io "(ilia, Ital+;, Paolo .aldassarri :?.%. di Pediatria, -orlH,;, Gandra .rusa :?.%. di Pediatria, I(ola, Ital+;, 3arisa Calacoci :Pediatra 0i/ero Professionista, -errara, Ital+;, Iliana Cecchini :?.%. di Pediatria, Cesena, Ital+;, Gara =enti :?.%. di Pediatria, Carpi, Ital+;, &nnarita =i .iase :?.%. di Pediatria, 3odena, Ital+;, Cristina Iost :?.%. di Pediatria, -errara, Ital+;, &ndrea 0a(/ertini :?.%. di Pediatria %spedale 3a**iore, .olo*na, Ital+;, &n*elo 3iano :Pediatra 0i/ero Professionista, Cesena, Ital+;, &nna(aria 3etri :?.%. di Pediatria, -aen1a, Ital+;, 3arco %ccari :?.%. di Pediatria, 3anto6a, Ital+;, !en1o Pini :?.%. di Pediatria, !i(ini, Ital+;, 3arina !ossidoria :Pediatra 0i/ero Professionista, .olo*na, Ital+;. Paediatric aller*+: &ndrea #alenti :?.%. di Pediatria, 0u*o, Ital+;, 3onica #allini :Pediatra 0i/era scelta, .olo*na, Ital+, Ital+;, Iole #enturi :?.%. di Pediatria, !a6enna, Ital+;, 0aura #iola :?.%. di Pediatria, !i(ini, Ital+;. "r(anno .aldo :?. %.di Pediatria, !o6ereto, Ital+;, 3auro .andini :?.%. di Pediatria, !a6enna, Ital+;, -ilippo .ernardi :Clinica Pediatrica %spedale G. %rsola, .olo*na, Ital+;, &driana .or*hi :?.%. Pediatria, Carpi, Ital+;, Paolo .ottau :?.%. di Pediatria, I(ola, Ital+;, 0ucetta Capra :?.%. di Pediatria &1ienda %spedaliera7?ni6ersitaria G. &nna, -errara, Ital+;, 5io6anni Ca6a*ni :%spedale Pediatrico .a(/in 5esJ, !o(a, Ital+;, 3atteo Corchia :Clinica Pediatrica, Par(a, Ital+;, =anilo =alpo11o :?.%.di Pediatria, I(ola, Ital+;, 0eonardo 0oroni :?.%. di Pediatria, !a6enna, Ital+;, 0aura 5io6annini :Pediatra 0i/ero Professionista, 0u*o, Ital+;, 3assi(o 3asi :=iparti(ento KGalute della donna, del /a(/ino e dell'adolescente, Policlinico G. %rsola73alpi*hi, .olo*na, Ital+;, 5iuseppe 3enna :IGG Istituto Gicure11a Gociale, ?.%.C.Pediatria7%spedale della !epu//lica di Gan 3arino, Ital+;, Patri1ia Preti :?.%. di Pediatria %spedale 3a**iore, .olo*na, Ital+;, 5ia(paolo !icci :=iparti(ento KGalute della donna, del /a(/ino e dell'adolescente, Policlinico G. %rsola73alpi*hi, .olo*na, Ital+;, 5iuseppe 8i(oncini :?.%. di Pediatria, -orlH, Ital+;, 0oretta .iserna :?.%. di Pediatria, !a6enna, Ital+;, "lena La(uner :?.%. di Pediatria, !a6enna, Ital+;. Pa*e 6 of B &uthor details 1 =iparti(ento dell'"t> "6oluti6a, Clinica Pediatrica ?ni6ersit> di Par(a, Par(a, Ital+. 2 ?% di Pediatria, &?G0 I(ola, I(ola, Ital+. 3 =iparti(ento KGalute della donna, del /a(/ino e dell'adolescenteE Policlinico G %rsola7 3alpi*hi, Clinica Pediatrica, .olo*na, Ital+. 2 =iparti(ento "(er*en1a ed &ccetta1ione dia*nostica, ?% di Pediatria, -iden1a, Ital+. 5 Pediatria, &?G0 di !a6enna, Ital+. 6 ?% Pediatria, &?G0 di Cesena, Ital+. &uthors' contri/utions CC, -., .., 0C, 33, PP concei6ed the desi*n of the stud+ and participated in its coordination. 8he+ prepared the draft of the (anuscript and re6ised it. &ll authors read and appro6ed the final (anuscript. Co(petin* interests 8he authors declare that the+ ha6e no co(petin* interests. !ecei6ed: 11 =ece(/er 200M &ccepted: 15 Januar+ 2010 Pu/lished: 15 Januar+ 2010 !eferences Iost &: -re4uenc+ of cow's (il) aller*+ in childhood. &nn &ller*+ &sth(a I((unol 2002, NM:6 Guppl 1;:337B. $ood !&: 8he natural histor+ of food aller*+. Pediatrics 2003, 111:16317163B. 1. Iost &, Ial)en G, Jaco/sen IP, Christensen &", Iers)ind &3, Plesner O: Clinical course of cow's (il) protein aller*+/intolerance and atopic diseases in childhood. Pediatr &ller*+ I((unol 2002, 13:Guppl 15;:2372N. 2. !ona !J, Oeil 8, Gu((ers C, 5islason =, Luid(eer 0, Goder*ren G, Gi*urdardottir 8, 0indner 8, 5oldhahn O, =ahlstro( J: 8he pre6alence of food aller*+. & (eta7anal+sis J &ller*+ Clin I((unol 200B, 120:63N726. .lac) !", $illia(s G3, Jones I", 5ouldin* &: Children who a6oid drin)in* cow (il) ha6e low dietar+ calciu( inta)es and poor /one health. &( J Clin Putr 2002, B6:6B576N0. .hatia J, 5reer -, the Co((ittee on Putrition: ?se of Go+ Protein7.ased -or(ulas in Infant -eedin*. Pediatrics 200N, 121:10627106N. #andenplas Q, .rueton 3, =upont C, Iill =, Isolauri ", Oolet1)o G, %rane &P, Gtaiano &: 5uidelines for the dia*nosis and (ana*e(ent of cow's (il) protein aller*+ in infants. &rch =is Child 200B, M2:M027M0N. Oe(p &G, Iill =J, &llen OJ, &nderson O, =a6idson 5P, =a+ &G, Ieine !5, Pea)e J", Prescott G0, Ghu** &$, Ginn J: 5uidelines for the use of infant for(ulas to treat cows (il) protein aller*+: an &ustralian consensus panel opinion. 3J& 200N, 1NN:10M7112. 5reer -!, Gicherer GI, $esle+ .ur)s &, the Co((ittee on Putrition and Gection on &ller*+ and I((unolo*+: "ffects of earl+ nutritional inter6entions on the de6elop(ent of atopic disease in infants and children: the role of (aternal dietar+ restriction, /reastfeedin*, ti(in* of introduction of co(ple(entar+ foods and h+drol+1ed for(ulas. Pediatrics 200N, 121:1N371M1. Iost &: Cow's (il) protein aller*+ and intolerance in infanc+. Go(e clinical, epide(iolo*ical and i((unolo*ical aspects. Pediatr &ller*+ I((unol 1MM2, 5:5 Guppl;:1736. Ieine !5, "lsa+ed G, Ios)in* CG, Iill =J: Cow's (il) aller*+ in infanc+. Curr %pin &ller*+ Clin I((unol 2002, 2:21B725. Gal6atore G, #andenplas Q: 5astroesopha*eal reflu9 and cow (il) aller*+: is there a lin)C. Pediatrics 2002, 110:MB27N2. 3. Iacono 5, Ca6ataio -, 3ontalto 5, et al: Intolerance of cow's (il) and chronic constipation in children. P "n*l J 3ed 1MMN, 3MM:110071102. 2. Gi(eone =, 3iele ", .occia 5, 3arino &, 8roncone !, Gtaiano &: Pre6alence of atop+ in children with chronic constipation. &rch =id Child 200N, M3:10227102B. Celi)7.il*ili G, 3ehl &, #erste*e &, et al: 8he predicti6e 6alue of specific i((uno*lo/ulin " le6els in seru( for the outco(e of oral food challen*es. Clin "9p &ller*+ 2005, 35:26N7B3. #erste*e &, 3ehl &, !olinc)7$ernin*haus C, Gtaden ?, Poconw 3, .e+er O, Pi**e(ann .: 8he predicti6e 6alue of the s)in pric) test weal si1e for the outco(e of oral food challen*es. Clin "9p &ller*+ 2005, 35:122071226. .oc) G&, Ga(pson I&, &t)ins -3, Lei*er !G, 0ehrer G, Gachs 3, .ush !O, 3etcalfe ==: =ou/le7/lind place/o7controlled food challen*e :=.PC-C; as an office procedure: a (anual. J &ller*+ Clin I((unol 1MNN, N2:MN67MB. Caffarelli et al. Italian Journal of Pediatrics 2010, 36:5 Pa*e B of B http://www.iponline.net/content/36/1/5 1N. Ole(ola 8, #anto 8, Juntunen7.ac)(an O, Oali(o O, Oorpela !, #aronen ": &ller*+ to so+ for(ula and to e9tensi6el+ h+drol+1ed whe+ for(ula in infants with cow's (il) aller*+: & prospecti6e, rando(i1ed stud+ with a follow7up to the a*e of 2 +ears. J Ped 2002, 120:21M722. 1M. Iill =J, 3urch GI, !affert+ O, $allis P, 5reen JC: 8he efficac+ of a(ino acid7/ased for(ulas in relie6in* the s+(pto(s of cow's (il) aller*+: a s+ste(atic re6iew. Cl "9p &ller*+ 200B, 3B:N0N7N22. 3ehr GG, Oa)a)ios &3, Oe(p &G: !ice: a co((on and se6ere cause of food protein7induced enterocolitis s+ndro(e. &rch =is Child 200M, M2:2207223. 20. 0ase)an J., Ooo $O$, $alters J, Pe+lan 3, 0ue//ers G: 5rowth, tolerance and /ioche(ical (easures in health+ infants fed a partiall+ h+drol+1ed rice protein7/ased for(ula: a rando(i1ed, /linded, prospecti6e trial. Journ &( Coll Putr 2006, 25:1271M. 21. -iocchi &, !estani P, .ernardini !, 0ucarelli G, 0o(/ardi 5, 3a*a11u 5, 3arse*lia 50, Pittschieler O, 8ripodi G, 8roncone !, !an1ini C: I+drol+sed rice7/ased for(ula is tolerated /+ children with cow's (il)aller*+: a (ulti7centre stud+. Cl "9p &ll 2006, 36:3117316. .ellioni7.usinco ., Pa*anelli !, 0ucenti P, 5ia(pietro P5, Per/orn I, .usinco 0: &ller*enicit+ of *oat's (il) in children with cow's (il) aller*+. J &ller*+ Clin I((unol 1MMM, 103:11M1711M2. 3onti 5, .ertino ", 3uratore 3C, Coscia &, Cresi -, Gil6estro 0, -a/ris C, -ortunato =, 5iuffrida 35, Conti &: "fficac+ of don)e+'s (il) in treatin* hi*hl+ pro/le(atic cow's (il) aller*ic children: an in 6i6o and in 6itro stud+. Pediatr &ller*+ I((unol 200B, 1N:25N7262. 8esse !, Pa*lialun*a C, .raccio G, &r(enio 0: &de4uac+ and tolerance to ass's (il) in an Italian cohort of children with cow's (il) aller*+. Ital J Pediatr 200M, 35:1M. Ieine !5: &ller*ic *astrointestinal (otilit+ disorders in infanc+ and earl+ childhood. Pediatr &ller*+ I((unol 200N, 1M:3N373M1. Ga6ino -: -ocus on infantile colic. &cta Paediatr 200B, M6:125M71262. Powa)7$e*r1+n &, Ga(pson I&, $ood !&, Gicherer GI: -ood protein7 induced enterocolitis s+ndro(e caused /+ solid food proteins. Pediatrics 2003, 111:N2M735. Iill =J, !o+ P, Ieine !5, Ios)in* CG, -rancis =", .rown J, Gpeirs ., Gadows)+ J, Carlin J.: "ffect of a low7aller*en (aternal diet on colic a(on* /reastfed infants: a rando(i1ed, controlled trial. Pediatrics 2005, 116:eB0M7eB15. Rantha)os G&, Gchwi((we J., 3elin7&ldana I, !othe(/er* 3", $itte =P, Cohen 3.: Pre6alence and outco(e of aller*ic colitis in health+ infants with rectal /leedin*: & prospecti6e cohort stud+. J Pediatr 5astroenterol Putr 2005, 21:16722. &r6ola 8, !uus)a 8, Oeranen J, I+ot+ I, Gal(inen G, Isolauri ": !ectal /leedin* in infanc+: clinical, aller*olo*ical and (icro/iolo*ical e9a(ination. Pediatrics 2006, 11B:eB607eB6N. doi:10.11N6/1N227B2NN73675 Cite this article as: Caffarelli et al.: Cow's (il) protein aller*+ in children: a practical *uide. Italian Journal of Pediatrics 2010 36:5. Pu/lish with BioMed Central and e6er+ scientist can read +our wor) free of char*e "BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime." Gir Paul Purse, Cancer !esearch ?O Qour research papers will /e: a6aila/le free of char*e to the entire /io(edical co((unit+ peer re6iewed and pu/lished i((ediatel+ upon acceptance cited in Pu/3ed and archi6ed on Pu/3ed Central +ours S +ou )eep the cop+ri*ht Gu/(it +our (anuscript here: Bio Med central http://www./io(edcentral.co(/info/pu/lishin*Tad6.asp