- Email: [email protected]
An improved prick skin-test procedure for young children
An improved prick skin-test procedure for young children Dennis R. Ownby,
M.D., and John A. Anderson,
M.D. Detroit,
Mich.
The prick method of skin testing is advantageous for young children because of the decrea,sed risk of anaphylaxis and less patient discomfort. Some would argue, however, that the necessity of keeping extract drops at the skin-test sites makes prick testing impractical compared with intradermal testing for squirming youngsters. Since the literature is not clear concerning the length of time extract must be present at the prick site, we performed duplicate sets of prick tests with jive concentrations of ragweed extract on 16 ragweed-sensitive adults. For one set of tests, the drops were removed immediately after the skin had been pricked; for the other set, extracts remained at the site for 15 min. After 15 min we recorded the size of the wheal and flare response for each test. On the basis of analysis of these paired observations, we concluded that there is no significant difference between these two methods of administering prick skin tests. (JAUERGYCUNIMMUNOL~~:~~~,1982.)
trations of 1: 20, 1: 50, 1: 100, 1: 1000, and 1: 10,000 w/v. Sixteen adults who were undergoing serial skin-test titrations as part of an immunotherapy study agreed to have the ragweed titrations performed twice. A set of tests with each of the five concentrationswas placed on the volar surfaceof each forearm. The prick tests were performed by placing single drops of extract on previously cleansed sites. A sterile, disposableneedle with the tip bent at 45” to the shaft (Greer Laboratories) was then passedthrough the drop and into the epidermis. The needle was withdrawn with a lifting motion producing a pricking sensation. Care was taken to avoid pricking deeply enough to causebleeding. After the skin had been pricked, the extract drops were immediately removed from one arm chosen randomly after the testshad been placed. The drops of extract were left on the opposite arm until the tests were read after 15 min. The wheal and flare responseswere outlined with different colored pens, and the ink impressionswere transferred to paper tape, which was then transferred to a data sheet. The sheetswere coded, and the results were read without knowledge of the code. The sizesof the reactions were recorded by measuring the greatestdiameter and the largest diameter perpendicular to the greatest diameter in millimeters. The two diameters were multiplied to produce a score. This method of scoring was chosen becauseit had been previously found to correlate well with the actual areas of the reactions. Scoresfor both wheal and flare were recorded. The data were analyzed using the Michigan Interactive Data Analysis System (MIDAS).3 The wheal and flare scoreswere transformed into their natural logarithm equivalents producing approximately normal distributions of the scores.For purposesof analysis, the concentrations of extract were expressedas the natural logarithm of the dilution factor (i.e.. 1: 20 = ln20 = 2.9957).
Many factors must be considered when selecting the best method for skin testing young children. High among these factors are concern for the safety of the patient and the degree of patient discomfort. Prick skin testing is preferable to intradermal testing by both of these criteria, since the prick method produces less discomfort and carries a lower risk of provoking a systemic reaction, l, 2 The chief disadvantage to prick testing is the problem of keeping extract drops at the sites of the tests in an upset child. The desire to allow young children freedom of movement immediately after the prick tests had been applied led us to question the need for the extract to remain at the test site. Allergy textbooks differed on the length of time required before extract drops could be removed from test sites, one stating that they must remain until the test is read,’ another that they could be removed after 1 min.2 This study was designed to resolve this question because we believed that this information would be useful when comparing skintest methods for use with small children. MATERIALS
AND METHODS
We used freshly diluted short ragweed extract (HollisterStier Laboratories, 50% glycerol preservative) at concenFrom the Division of Allergy and Clinical Immunology, Henry Ford Hospital, Detroit, Mich. Received for publication Sept. 30, 198 1. Accepted for publication March 11, 1982. Reprint requests to: Dennis R. Ownby, M.D., Division of Allergy and Clinical Immunology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202. 0091-6748162/060533+03$00.3010
0
1982 The
C. V. Mosby
Co.
Vol.
69, No.
6, pp.
533-535
534
Ownby
TABLE
and
J. ALLERGY CLIN. IMMUNOL. JUNE 1982
Anderson
I. Comparison
of wheal
and
Wheal
flare
scores
scores
(Ln)
Flare
Concentration I:20
Mean SD Number
4.716 0.616 16
Mean Number
4.886 0.596 16
t value p value
0.217 0.83
SD
1:50
(Ln)
Concentration
1:lOO
1:lOOO
1: 10,000
1:20
3.112 0.261 11
7.105 0.525 16
2.981 0.505 11
7.078 0.730 16
-0.101 0.922
-1.696 0.11
Not removed (set 1) 4.589 4.349 3.772 0.711 0.515 0.701 16 16 16 Removed (set 2) 4.542 4.375 3.690 0.565 0.471 0.799 16 16 16 0.351 0.73
scores
0.098 0.92
0.276 0.786
1:50
TABLE II.
I:100
1: 1000
1: 10,000
Not removed (set 3) 6.781 6.281 5.495 0.831 1.145 1.466 16 16 16 Removed (set 4) 6.705 6.259 5.605 0.959 1.279 1.588 16 16 16 0.300 0.77
-0.191 0.85
Comparison
5.535 0.966 11 5.558 0.625 11
0.93 0.37
0.640 0.54
of dose-response
relationships Line
Intercept Set 1 Set 2 Set 3 Set 4
5.774 5.963 8.292 8.269
equations
Slope
by regression Correlation coefficient
-0.314 -0.353 -0.407 -0.417 Comparison
0.929 0.913 0.895 0.896
I
I
1:10.000
Ragweed
I
1:1.000
Extract
I
1:1001:50
1
1:20
Concentration
FIG. 1. Relationship between wheal and flare scores and the concentration of ragweed extract used. Closed circles, Mean wheal scores when extract was not removed; open circles, mean wheal scores when extract was immediately removed; closed squares, mean flare scores when the extract was not removed; open squares, mean flare scores when the extract was removed; solid lines, regression line best fitting the closed squares and circles; dashed lines, regression line fitting the open squares and circles.
RESULTS The logarithmically
transformed
data were divided
into four sets for analysis and discussion. Set 1 contains the wheal scores at tbe five concentrations tested when extract was not removed from the test site. Set 2 contains the wheal scores when extract was immedi-
Set 1 vs set 2 Set 3 vs set 4
Set 1 vs set 3 Set 2 vs set 4
0.641 0.725 0.300 0.814
Significance
of dose-response regressions by analysis of covariance Probability
Slopes
analysis
of equal:
Intercepts
0.894 0.928
Regression8
0.934 0.936
ately removed. Set 3 is the flare scores corresponding to the wheal scores in set 1, and set 4 is the flare scores corresponding to the wheal scores in set 2. All the numbers are presented as natural logarithms (Table I). The wheal and flare scores were compared when extract was removed immediately and not removed at each concentration by a paired Student’s t test. No significant differences were found (Table I). The dose-response relationships between the extract concentration and the wheal and flare scores were evaluated by multivariable regression analysis. The results of the analysis are displayed in Fig. 1 and Table II. There were highly significant relationships between the concentration of extract and both the
VOLUME 69 NUMBER 6
wheal and flare scores (Fig. 1 and Table II, top). The dose-response relationships of the four sets were then compared with each other by analysis of covariance. The results in Table II, bottom, show that there were no significant differences between the dose-response relationship of the wheal scores or the flare scores when the extract was immediately removed or not (set 1 vs set 2 and set 3 vs set 4). As seen in Fig. 1, the regression lines appear to be paralleled (i.e., have equal slopes) when the wheal scores are compared with the flare scores. This hypothesis cannot be rejected, as seen in the lower half of Table II, where the probabilities of the slopes of set 1 vs set 3 and set 2 vs set 4 being equal are 0.30 and 0.8 1, respectively. The intercepts of the regression lines of the wheal scores compared with the flare scores are highly significantly different (p < O.OOOl), as expected.
DISCUSSION This study compared skin reactions produced by prick tests when extract drops were immediately removed with those produced when extracts remained at the test site until the reactions were maximal. We found that after the skin had been pricked, the presence of extract was of no consequence. This is in agreement with the early work of Squire,4 who estimated that a prick introduces 3 ~1 of fluid into the skin so that it becomes a microintradermal test. We also noted that since the relationship between the wheal and flare scores was relatively constant, it made little difference which was measured. Skin testing small children is difficult even when it is strongly indicated on clinical grounds. Although each method of skin testing has its proponents, the prick and intradermal methods are most widely used. A presumed advantage of the intradermal test is that
Prick
test
for
children
535
the child is free to move about immediately after the injections are finished, compared with the fussing encountered when a child is kept still for prick tests. Since the results of this study indicate that there is no difference in the degree of reaction produced when extract drops are immediately removed, we conclude that the prick and intradermal methods are of equal convenience. Prick-test results have been shown to correlate well with the presence of allergic disease, as determined by other methods. 5, 6 This correlation also extends to food allergies,’ which are often a concern in young children. These advantages, the elimination of a presumed disadvantage, and the relative safety’, ’ all suggest that the prick method should be the principal method used for skin testing children.
REFERENCES 1. Vanselow NA: Skin testing and other diagnostic procedures, in Sheldon JM, Love11 RG, Matthews KP, editors: A manual of clinical allergy. Philadelphia, 1967, W. B. Saunders Co., p. 58. 2. Norman PS: In vivo methods of study of allergy, in Middleton E Jr, Reed CE, Ellis EF, editors: Allergy: principles and practice. St. Louis, 1978, The C. V. Mosby Co., p, 259. 3. Fox DJ, Guire KE: Documentation for MIDAS, ed. 3. Statistical Research Laboratory, Ann Arbor, 1976, The University of Michigan. 4. Squire JR: The relationship between horse dandruff and horse serum antigen in asthma. Clin Sci 9: 127, 1950. 5. Erikson NE: Diagnosis of reaginic allergy with house dust, animal dander, and pollen allergens in adult patients. II. A comparison between skin tests and provocation tests. Int Arch Allergy Appl Immunol 53:341, 1977. 6. Cavanaugh MJ, Bronksy EA, Buckley JM: Clinical value of bronchial provocation testing in childhood asthma. J ALLERGY CLIN IMhtuN0~ 59:41, 1977. 7. Bock SA, Lee WY, Reinigir L, Hoist A, May C: Appraisal of skin tests with food extracts for diagnosis of food hypersensitivity. Clin Allergy 8:559, 1978.
M.D., and John A. Anderson,
M.D. Detroit,
Mich.
The prick method of skin testing is advantageous for young children because of the decrea,sed risk of anaphylaxis and less patient discomfort. Some would argue, however, that the necessity of keeping extract drops at the skin-test sites makes prick testing impractical compared with intradermal testing for squirming youngsters. Since the literature is not clear concerning the length of time extract must be present at the prick site, we performed duplicate sets of prick tests with jive concentrations of ragweed extract on 16 ragweed-sensitive adults. For one set of tests, the drops were removed immediately after the skin had been pricked; for the other set, extracts remained at the site for 15 min. After 15 min we recorded the size of the wheal and flare response for each test. On the basis of analysis of these paired observations, we concluded that there is no significant difference between these two methods of administering prick skin tests. (JAUERGYCUNIMMUNOL~~:~~~,1982.)
trations of 1: 20, 1: 50, 1: 100, 1: 1000, and 1: 10,000 w/v. Sixteen adults who were undergoing serial skin-test titrations as part of an immunotherapy study agreed to have the ragweed titrations performed twice. A set of tests with each of the five concentrationswas placed on the volar surfaceof each forearm. The prick tests were performed by placing single drops of extract on previously cleansed sites. A sterile, disposableneedle with the tip bent at 45” to the shaft (Greer Laboratories) was then passedthrough the drop and into the epidermis. The needle was withdrawn with a lifting motion producing a pricking sensation. Care was taken to avoid pricking deeply enough to causebleeding. After the skin had been pricked, the extract drops were immediately removed from one arm chosen randomly after the testshad been placed. The drops of extract were left on the opposite arm until the tests were read after 15 min. The wheal and flare responseswere outlined with different colored pens, and the ink impressionswere transferred to paper tape, which was then transferred to a data sheet. The sheetswere coded, and the results were read without knowledge of the code. The sizesof the reactions were recorded by measuring the greatestdiameter and the largest diameter perpendicular to the greatest diameter in millimeters. The two diameters were multiplied to produce a score. This method of scoring was chosen becauseit had been previously found to correlate well with the actual areas of the reactions. Scoresfor both wheal and flare were recorded. The data were analyzed using the Michigan Interactive Data Analysis System (MIDAS).3 The wheal and flare scoreswere transformed into their natural logarithm equivalents producing approximately normal distributions of the scores.For purposesof analysis, the concentrations of extract were expressedas the natural logarithm of the dilution factor (i.e.. 1: 20 = ln20 = 2.9957).
Many factors must be considered when selecting the best method for skin testing young children. High among these factors are concern for the safety of the patient and the degree of patient discomfort. Prick skin testing is preferable to intradermal testing by both of these criteria, since the prick method produces less discomfort and carries a lower risk of provoking a systemic reaction, l, 2 The chief disadvantage to prick testing is the problem of keeping extract drops at the sites of the tests in an upset child. The desire to allow young children freedom of movement immediately after the prick tests had been applied led us to question the need for the extract to remain at the test site. Allergy textbooks differed on the length of time required before extract drops could be removed from test sites, one stating that they must remain until the test is read,’ another that they could be removed after 1 min.2 This study was designed to resolve this question because we believed that this information would be useful when comparing skintest methods for use with small children. MATERIALS
AND METHODS
We used freshly diluted short ragweed extract (HollisterStier Laboratories, 50% glycerol preservative) at concenFrom the Division of Allergy and Clinical Immunology, Henry Ford Hospital, Detroit, Mich. Received for publication Sept. 30, 198 1. Accepted for publication March 11, 1982. Reprint requests to: Dennis R. Ownby, M.D., Division of Allergy and Clinical Immunology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202. 0091-6748162/060533+03$00.3010
0
1982 The
C. V. Mosby
Co.
Vol.
69, No.
6, pp.
533-535
534
Ownby
TABLE
and
J. ALLERGY CLIN. IMMUNOL. JUNE 1982
Anderson
I. Comparison
of wheal
and
Wheal
flare
scores
scores
(Ln)
Flare
Concentration I:20
Mean SD Number
4.716 0.616 16
Mean Number
4.886 0.596 16
t value p value
0.217 0.83
SD
1:50
(Ln)
Concentration
1:lOO
1:lOOO
1: 10,000
1:20
3.112 0.261 11
7.105 0.525 16
2.981 0.505 11
7.078 0.730 16
-0.101 0.922
-1.696 0.11
Not removed (set 1) 4.589 4.349 3.772 0.711 0.515 0.701 16 16 16 Removed (set 2) 4.542 4.375 3.690 0.565 0.471 0.799 16 16 16 0.351 0.73
scores
0.098 0.92
0.276 0.786
1:50
TABLE II.
I:100
1: 1000
1: 10,000
Not removed (set 3) 6.781 6.281 5.495 0.831 1.145 1.466 16 16 16 Removed (set 4) 6.705 6.259 5.605 0.959 1.279 1.588 16 16 16 0.300 0.77
-0.191 0.85
Comparison
5.535 0.966 11 5.558 0.625 11
0.93 0.37
0.640 0.54
of dose-response
relationships Line
Intercept Set 1 Set 2 Set 3 Set 4
5.774 5.963 8.292 8.269
equations
Slope
by regression Correlation coefficient
-0.314 -0.353 -0.407 -0.417 Comparison
0.929 0.913 0.895 0.896
I
I
1:10.000
Ragweed
I
1:1.000
Extract
I
1:1001:50
1
1:20
Concentration
FIG. 1. Relationship between wheal and flare scores and the concentration of ragweed extract used. Closed circles, Mean wheal scores when extract was not removed; open circles, mean wheal scores when extract was immediately removed; closed squares, mean flare scores when the extract was not removed; open squares, mean flare scores when the extract was removed; solid lines, regression line best fitting the closed squares and circles; dashed lines, regression line fitting the open squares and circles.
RESULTS The logarithmically
transformed
data were divided
into four sets for analysis and discussion. Set 1 contains the wheal scores at tbe five concentrations tested when extract was not removed from the test site. Set 2 contains the wheal scores when extract was immedi-
Set 1 vs set 2 Set 3 vs set 4
Set 1 vs set 3 Set 2 vs set 4
0.641 0.725 0.300 0.814
Significance
of dose-response regressions by analysis of covariance Probability
Slopes
analysis
of equal:
Intercepts
0.894 0.928
Regression8
0.934 0.936
ately removed. Set 3 is the flare scores corresponding to the wheal scores in set 1, and set 4 is the flare scores corresponding to the wheal scores in set 2. All the numbers are presented as natural logarithms (Table I). The wheal and flare scores were compared when extract was removed immediately and not removed at each concentration by a paired Student’s t test. No significant differences were found (Table I). The dose-response relationships between the extract concentration and the wheal and flare scores were evaluated by multivariable regression analysis. The results of the analysis are displayed in Fig. 1 and Table II. There were highly significant relationships between the concentration of extract and both the
VOLUME 69 NUMBER 6
wheal and flare scores (Fig. 1 and Table II, top). The dose-response relationships of the four sets were then compared with each other by analysis of covariance. The results in Table II, bottom, show that there were no significant differences between the dose-response relationship of the wheal scores or the flare scores when the extract was immediately removed or not (set 1 vs set 2 and set 3 vs set 4). As seen in Fig. 1, the regression lines appear to be paralleled (i.e., have equal slopes) when the wheal scores are compared with the flare scores. This hypothesis cannot be rejected, as seen in the lower half of Table II, where the probabilities of the slopes of set 1 vs set 3 and set 2 vs set 4 being equal are 0.30 and 0.8 1, respectively. The intercepts of the regression lines of the wheal scores compared with the flare scores are highly significantly different (p < O.OOOl), as expected.
DISCUSSION This study compared skin reactions produced by prick tests when extract drops were immediately removed with those produced when extracts remained at the test site until the reactions were maximal. We found that after the skin had been pricked, the presence of extract was of no consequence. This is in agreement with the early work of Squire,4 who estimated that a prick introduces 3 ~1 of fluid into the skin so that it becomes a microintradermal test. We also noted that since the relationship between the wheal and flare scores was relatively constant, it made little difference which was measured. Skin testing small children is difficult even when it is strongly indicated on clinical grounds. Although each method of skin testing has its proponents, the prick and intradermal methods are most widely used. A presumed advantage of the intradermal test is that
Prick
test
for
children
535
the child is free to move about immediately after the injections are finished, compared with the fussing encountered when a child is kept still for prick tests. Since the results of this study indicate that there is no difference in the degree of reaction produced when extract drops are immediately removed, we conclude that the prick and intradermal methods are of equal convenience. Prick-test results have been shown to correlate well with the presence of allergic disease, as determined by other methods. 5, 6 This correlation also extends to food allergies,’ which are often a concern in young children. These advantages, the elimination of a presumed disadvantage, and the relative safety’, ’ all suggest that the prick method should be the principal method used for skin testing children.
REFERENCES 1. Vanselow NA: Skin testing and other diagnostic procedures, in Sheldon JM, Love11 RG, Matthews KP, editors: A manual of clinical allergy. Philadelphia, 1967, W. B. Saunders Co., p. 58. 2. Norman PS: In vivo methods of study of allergy, in Middleton E Jr, Reed CE, Ellis EF, editors: Allergy: principles and practice. St. Louis, 1978, The C. V. Mosby Co., p, 259. 3. Fox DJ, Guire KE: Documentation for MIDAS, ed. 3. Statistical Research Laboratory, Ann Arbor, 1976, The University of Michigan. 4. Squire JR: The relationship between horse dandruff and horse serum antigen in asthma. Clin Sci 9: 127, 1950. 5. Erikson NE: Diagnosis of reaginic allergy with house dust, animal dander, and pollen allergens in adult patients. II. A comparison between skin tests and provocation tests. Int Arch Allergy Appl Immunol 53:341, 1977. 6. Cavanaugh MJ, Bronksy EA, Buckley JM: Clinical value of bronchial provocation testing in childhood asthma. J ALLERGY CLIN IMhtuN0~ 59:41, 1977. 7. Bock SA, Lee WY, Reinigir L, Hoist A, May C: Appraisal of skin tests with food extracts for diagnosis of food hypersensitivity. Clin Allergy 8:559, 1978.