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safety record, minimal skin trauma inflicted,low cost results, simple to perform, high sen-sitivity and thus reliable and reproducible11,because largely experimented, as a conse-

quence SPTs are the more used method for adiagnosis of I gE-mediated allergic diseasewhere are present skin sensitizing antibodies.When skin mast cells have surface IgEs forintruding allergens, mast cells degranulate re-leasing their mediators, so producing a cuta-neous wheal-and-flare reaction, a type I im-mune reaction2.

A lthough SPTs are more sensible and spe-cific in respiratory allergies, representing thefirst choice investigation when an IgE-medi-ated allergic disease elicited by aeroallergens

is suspected and in asthma epidemiologicstudies3, in food allergy (FA ) diagnosis, SPTsmight be less reliable, due to different fac-tors. These include the lability of some aller-gens, crossreactivity between allergens be-longing to different plant species or to thesame species, antigenicity loss during extrac-tion and inadequacy of allergenic extracts.

Untoward reactions to SPTs

In a recent paper4, we read that 6 infantsaged less than 6 months suffered from gener-alized allergic reactions after prick tests with

fresh foods. This kind of skin testing is usual-ly referred to as prick by prick (P+P) tests5,and we use it for labile allergens. P+P testswere first performed at our Division in 1989-1990, and never elicited severe reactions. Thetechnique is very simple. One pricks a normallancet into the fresh or frozen fruit or veg-etable, and immediately thereafter into theskin6-8. Otherwise8 the skin can be prickedfirst, and a piece of fruit/vegetable is firmlytaped to this place, or rubbed on this place,or viceversa: the skin is rubbed first and

pricked immediately thereafter.

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A bstract. Background. Studies have re-ported adverse reactions during skin prick tests(SPTs), however such reactions are almost nonexistent in children. On the contrary, there arecontroversial data on the effectiveness and reli-ability of diagnostic tools. SPTs are consideredas the more rapid and effective tool for the diag-nosis of pediatric allergies. SPTs, when em-ployed either correctly or with standardized ex-tracts, are rapid, safe, sensitive, inexpensive ona per test basis and the results are reliable,since they are largely experimented.

Observations. SPT is the more employedmethod for the diagnosis of atopic diseaseelicited by type I immune reactions, where sen-sitizing antibodies are present. However, we dis-cuss a study surprisingly reporting six general-ized allergic reactions after prick tests with freshfoods in infants less than 6 months of age out of

1,152 tested during three years (0.17% for eachyear).

Conclusions. In this study, all reactions weretreated with epinephrine and/or antihistamines,plus steroids in three cases. Purpose of the pre-sent study was to assess whether the practiceof performing SPTs, either in the usual manner,or in duplicate could be a risk factor in infantswith extensive eczema. Moreover, excludingyoung babies from STPs or even applying onlyone SPT each visit delays an early diagnosis. Inthe same period of three years, we have doneSPTs in at least 10,000 children, without seeingany generalized allergic reaction.

Key Words:

Skin prick tests, Rapidity, Safety, Sensitivity, Prick +prick tests, Adverse reactions, Duplicate tests, Infants,Extensive eczema, Early diagnosis.

Introduction

SPTs consist in allergen percutaneous ad-ministration. I f correctly done and with stan-

dardized extracts the pros are: an excellent

Can skin prick tests provokesevere allergic reactions?

A. CANTANI, M. MICERA

Division of Allergy and Immunology, Department of Pediatrics, La Sapienza University - Rome (Italy)

2000; 4: 145-148

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We have prospectively P+P tested 118 chil-dren, using cow milk (CM), emulsionedwhole raw egg, and a mixture of flour andboiled water, registering only mild reactions.Our D ivision started to work in 1969-1970,since then we have performed countless SPTsin children, according to fixed rules9,10 buthave never seen severe reactions. Several ad-verse reactions occurred, but only in intrader-mally tested children5, never practiced orseen by us.

Instead, in a retrospective study, the au-thors4 have found during three years (1996-1998) six infants aged less than six months,with active eczema and positive reactions tofood items, who were positive to P+P tests to

fresh food specimen, and suffered from gen-eralized reactions. Each infant was testedwith several foods (from 2 to 4 foods) (Tables1 and 2)4, without performing the negativecontrols. Not only the infants were testedwith numerous foods (Table 1), but the samefood was tested in duplicate in the same baby(Table 2): accordingly, we do not know whichparticular food elicited the reactions. Wehave documented that CM is so a potent al-lergen that one drop posed on the lower lipof an infant during a CM challenge may trig-

ger anaphylaxis11

. Personal data show that inthe first year of life CM allergy (CMA) startsin 72%, and egg allergy in 68% of cases12. Inaddition, the babies were tested with fish(No. 2) and hydrolysates (HFs) (No. 4), how-ever there are no details regarding such foodsin the pertinent section. We use a mixture of5 grams of fish and for HFs the recommend-ed ready to eat concentration which is furtherdiluted with water to one part per hundred.

A s regards the reactions, there were fourcases of generalized erythema, in one case

with crepitations, and two cases of general-ized urticaria, in one case accompanied withrhonchi, and in the other with hoarseness andcough. A ll babies received immediate treat-ment with epinephrine (three cases) and/orantihistamines (three cases) administered bythe nurse. Without delay, a pediatricianadded steroids to the treatment in three cas-es. Since in our Division SPTs are always per-formed by physicians, in case of whateverproblem they immediately visit the child, andprescribe medications if necessary.

In our Division, SPTs are done by a quali-fied and trained doctor assisted by a qualifiednurse, and with epinephrine and antihista-mines at hand with appropriate emergency

equipment available on site. We propose toincrease the current recommendations5

adding a detailed family and personal history,and in children with convincing history ofmore or less severe clinical manifestations,P+Ps should be performed with diluted dosesof the allergen. In addition to possible breastmilk allergens4,5, we mention that SPTs forCM could act as a booster dose in babies fedCM in Maternity hospitals11. Unfortunately,we cannot explore this matter further, since itwas not elucidated whether eczema exacerba-

tions in the four breast babies might corre-spond with the maternal diet, or if the motherwas on a definite elimination diet.

Discussion

One limitation of the study4 is the practicalimpossibility of recognizing which food elicit-ed the reported reactions. We have discussedthe practical repercussions, and we do not

A. Cantani, M. Micera

Child Sex Age at test Heredity

1 Female 5 months 2 siblings2 Male 2.5 months Mother + Father3 Male 3 months Mother4 Male 3 months Mother + Father + Sister5 Male 5 months Sister6 Male 5 months Father

Table I. Summarized informations about the 6 children with eczema.

Modified from reference 4.A ll babies had active eczema of varied severity when the tests were performed. Five out of six babies were breastfed,

one was given also formula.

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know whether the babies were already sensi-tized to any of the food items (in four breast-

fed children no sensitivity to foods had beenidentified previously), otherwise it were inap-propriate to test the babies. A mong the em-ployed foods, CM and egg are highly aller-genic in the first year of life12, and fish hastriggered a 9% of reactions in children aged0.1-15 years12. HFs have provoked a numberof severe, also generalized until to shock andanaphylaxis in a number of infants and youngchildren13,14. However, it is impractical to ex-pand the findings of this article to other freshor commercial foods5.

During three years, the authors tested 1152children, which gives a figure of 0.52%. In 30years we have SPT-tested thousands of chil-dren each year, but both the nurse and oneof us (A C) are regularly present in theDivision since 1988 and have never seen se-vere reactions, therefore it is unachievable apertinent comparison.

A more crucial limitation, when not a riskfactor, is the practice of performing tests induplicate in young infants with extensiveeczema: this was the case of 4/6 infants, whichcertainly caused an extra allergenic load on

the surface of the small arm4, which is greatlylimited in babies with extensive eczema. Theauthors correctly recognize that duplicatetests may increase the risk of summation ofthe reactions, and consequently the risk ofgeneralized reaction4. Hence it would be bet-ter to recur to the determination of specificIgE3. A lthough the parallel use of SPT, CM-specific IgE, patch test and serum eosinophilcationic protein detected 85% of infants withCM allergy, the specificity was as low as 0.2313.

Finally, we would stress that severe adverse

reactions to skin testing were provoked by the

intradermal method, nowadays largely re-placed by SPTs. There were cases of death af-

ter injection of several proteins, including a 5-month-old baby (ovomucoid)14, a 4-year oldgirl (foreign proteins)15, two asthmatic boysaged 10 and 11 years (food extracts)16, and a9-year-old child with asymptomatic asthma(penicillin)17. No lethal reaction has been re-ported after SPTs in three large series16-19.

In conclusion it is largely known that chil-dren tolerate epinephrine better than adults.Retrospective studies deprive doctors of theirdecision making. In comparable cases, a doc-tor considering the extensive eczema, the

young age, and the possible risk of generalizedreactions would have preferred an in vitro test.In our Division, we test several children

each day, and have never excluded childrenaged less than six months4 or recognized thatSPTs are less reliable in infants less than oneear of age5. Application of only one allergenat each visit4, is a time-consuming methodolo-gy for physicians, nurses, and families. This isalso a procedure procrastinating both the in-vestigation and an early diagnosis, thus sub-

jecting the child to unnecessary suffering fromhis allergic disease.

In conclusion, SPTs, when correctly em-ployed or with standardized extracts, arerapid, safe, sensitive, inexpensive on a per testbasis and the results are reliable, since theyare largely experimented: consequently SPT isthe more employed method for the diagnosisof atopic disease elicited by type I immune re-actions, where sensitizing antibodies are pre-sent. SPTs are defined as fairly reliable inFA 20, but Sampson has demonstrated thatSPTs elicit a greater number of positivities incomparison with double-blind, placebo-con-

trolled food challenges21

.

147

Can skin prick tests provoke severe allergic reactions?

Child SPT applied Positive SPT results

1 Egg, CM, Fish, Casein hydrolysate Egg 2, CM 2, Fish 22 Egg, CM Not readable3 Egg, CM Egg 2, CM 24 Egg, CM, Fish, Casein hydrolysate CM5 Egg, CM Egg 2, CM 26 Egg, CM, Casein hydrolysate Egg, CM

Whey hydrolysate

Table II. Summarized informations about SPT applied and SPT results.

A ll SPTs were done in duplicate. Results (5 babies) histamine wheal between 5 and 20 mm (mean = 9 mm), SPTs be-tween 3 and 10 mm (mean = 6.7 mm).

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A. Cantani, M. Micera