- Email: [email protected]
Evaluation of the histamine intradermal test as a general indicator of allergy
EVALUATION
OF THE A GENER,AL
HISTAMINE INDICATOR
IN’J’RADERMAL OF ALLERGY”
LAURENCE FARMER, M.D., NEW YORK,
TEST
AS
N. Y.
I
N A paper on the etiology and treatment of M&i&e’s syndrome, Atkinson’ suggested the use of histamine intradermally as a general indicator of the presence of an allergic disturbance. He bases this suggestion on the fact that “there is considerable evidence t,o show that the manifestations of allergy are possibly due to the release of histamine or of a histamine-like substance into the affected tissues.” \\iith the help of the histamine intradermal test, he feels that it is possible to “satisfactorily separate the (histamine) sensitive from the insensitive,” t.he inference being that by this method one can establish whether an individual is allergic or not. On the basis of this reasoning allergy would consist of increased histamine sensitivit,y. We believe this assumption t,o be incorrect. Uhough we strongly subscribe to the assumption that the manifestations of allergy are due to the release of histamine, we do not, believe t,hat allergy is enhanced hist,amine sensitivity, i.e., that allergic individuals arc simply more sensitive to histamine than a.re normal individuals. We, therefore, also feel that it is not possible t,o determine whether or not an individual is suffering from an allergy on the basis of whether he shows a stronger or less strong skin reaction to histamine. In the course of earlier work, we had examined the histamine sensit,ivity of normal and allergic individuals by puncturing histamine into the skin. We did not find any difference in the skin reactivit,y of the two groups: i.e., the allergic individuals did not react more strongly to histamine than did the normal individuals. In the present investigation we repeat,ed these tests intradermally. We used 0.01 mg. of histamine phosphate as suggested by Atkinson. This amount of histamine was contained in 0.05 C.C. of physiologic saline. The control consisted of 0.05 C.C. of physiologic saline. All tested individuals reaetcd to the histarnine with a distinct, wheal which in no instance measured less than 10 to 13 millimeters. However, this is not, a positive reaction according to Atkinson’s terminology. His criteria for a positive reaction are “a wide area of erythema 11/z to 2 inches (3.8 to 5 cm.), a la,rgc wheal Q’? to :y4 inch (1.3 to 1.9 cm.) and the pre.sence of long trailing pscudopodia an inch or rnore in length which appear in t,hree to five minutes, begin to fade only after twenty minutes, and arc still apparent al. t,he end of thirty minutes. Small buds at the edge of the main wheal which fade in ten t,o twenty minutes arc not assessed as positive. ” According to these criteria none of the *From
the
Allergy
Clinic,
Lenox
Hill
Hospital,
44
New
York,
N.
Y.
TABLE SIZES
0~
1
TTISTAMINE
WmAr.s -REACTION
HISTAMINE
PATIENT
WHEAL (MM.)
A.
1. J. I.
PSEUDOPOD (ml.)
FLARE (MM.) Nonallergic
IGrasses
27 45
14 by 14 11 hy 14
55 hv 65 INone 45 hy 55 Small
buds
3. K. D. 4. E. B.
47 25
13 by 15 15 by 15 12 by 14 12 hy 15
50 by 60 55 hy 60
huds
5. J. P. 7. 8. 9. 10. 11.
E. .I. E. L. M. L. B.Z. S.R.
12.
I.C.
;"s
40 hy 45
None Small None Small Small Small Small Small None Small
45hy50
44 60 41 40 48 29
12by14 14hylS llhy15 12 by 14
35 45 50 55 50 65
13. H. C. 14. C.E. 15. J. E. 16. R. K. 17. W.H.
43 37 33 37
15 hy 15
60 by60
lihyl5
18. A. TV.
2:
14hyl5
60 by 55 by 70 by 50 by 45 hy
19. A. L. E. Z. 21. 0.1-I. 22. DeW. Y.
31 39 39 42
13 by 14 17hylT 14 hy 15 15 by 15
35 37 11 39 E
13 by 13 17hy20 14 by 16 11 by12 13 by 13 16 by’18
27 34 55
16hyl6 12by13 15 by 15
J. McK. 24. L. J.
25. 26. 27. 28.
0. Y.
$ i
0 0
w.
$
31.
P. A. S. H.
32. 33.
H. K. M. F.
35. 34. 36.
G.R. E. R. R. K.
30.
3
H. C. J. McC. c.
15 by 15 13hy 15 15 by 15
20.
23.
14hy 15 16 by16
-
60 60 70 50 50
bud hud bud buds buds
18 None None None None None
50 hy 65
Buds None None 75 by 75 Buds
None None 10 80 by 100 None 60 by60 10 60 hy 70 Several small pseudopodia 50 by 55 Small bud 60 by 60 None 60 by 60 Several 10 mm. long 55 by 60 None 55 by 55 None 60 hy 70 50 by 60 55 by60
13 by 15 15by17 22 by 23
: 0
by 40 by 50 hy55 by 55 by 50 by 65
huds
60 by 70 60 by 70
13 by 15 15 by 18
65 by 65
60by65 70 by70
i
EXTRACT
individuals
2. H. L.
6. J. S.
ALLERGEN
Buds 11 10
Ragweed House Ragweed Ragweed Ragweed Ragweed
+ + + +
+ + + + Dust + + + + + + Ash -t t t t + + + +
Grasses
+ + +
Timothy + + + + Plantain + t IIouse Dust
Raic-eed + + + House Dust + + Ragweed + + + Ragweed t t Grasses t + Ragweed + + + + Many false positive reactions Ragweed + + (+) Grasses + + + House Dust + + Ragweed + + + + Ragweed + + + Grasses + t + Ragweed + + + + House Dust + Tree pollens -t + + Grasses + + + Ragweed + + House Dust + Ragweed +++ HouseDust ++ Ragweed + + + Timothy + Ragweed + + + House Dust + Ragweed t t t House Dust t t Rabbit Dander + + Feathers + + Tree Pollen + t Grasses + + + Grasses + + + Ragweed + + + Ragweed + + House Dust + + Ragweed + + + House Dust + + Rabbit Dander + + Cat Dander + + Horse Dander + + Grasses + + + Ragweed + + + Ragweed + + + House Dust Ragweed + + + Ragweed +++ House Dust Ragweed + + + Ragweed + + + Ragweed + + + Plaintain t
Grasses + +
+ + +
Timothy + +
++
Grasses + +
+ +
TABLE
I-CONT
'D REACTION
AGE (YE.)
PATIENT
WHEAL
HISTAMINE FLARE
IPSEUDOPOD
ALLERGENEXTRACT
(MM.)
37. 38. 39. 40. 41.
E.R. W. M. M. K. M. B. J.R.
10 by 15 llbyl3 12by14 13 by 13 14 by 15
50 by 55 50 by 70
Buds Buds
42.
E. R.
0
17byl7
55 by 55
None
43.
G. M.
0
13 by 15
55 by 55
ii
44.
0. F.
$
30
14by16
50 by 50
None
45. R. B.
$
14
15by16
55 by 65
1. A.B. 2. M.V.
T
c
3. M. P. 4. P. P.
None I
5.6. 7. 8. 9. 10. 11. 12.
M.B.F. A. A. S. A.M. E.D. R.N. A.M. R.K.
13. F. G. 14. F. J.
i? : :
p”
16by17 18 by 20
75 by 90 45by55
Small 15
buds
49 24 43 48 34 47
50 50 65 50 50 60 80 40 50 50
Small 6 Small None
bud
ii 56 15
15 15 13 13 12 13 15 15 13 12
69 46
13 by 20 15 by 21
15 15 12 14 15 15 18 15 20 12
by by by by by by by by by by
50 5.0 65 55 50 60 85 50 50 70
60 by 70 70 by80 3. Vasomotov
1. 2. 3. 4.
J. K. M. G.
L. T. P. McG.
5. 6. 7. 8. 9. 10.
C. L. R. I. R. A.
K. P. G. L. C. T.
Qo 0 9
z
bud
5
9 None
+ + + + House
Dust
Ra&eed
+ + + + House
Dust
Wasses
+ + +
+ +
Orris Root + + House Dust + Cat Dander + + + House Dust + Negative Kapok + + House Dust + Negative Cat Dander + + House Dust + House Dust + + Milk + Ragweed + + Cat Dander + Ragweed + House Dust + Feathers + Plaintain + House Dust + + Horse Dander + + Rabbit Dander + + Cat Dander + + Ragweed
+++ i I
t
rhinitis
13by17 13 by 21 14 by 15 11 by 13
55by70 65 by 70 50 by 50 45 by 45
Buds Small Small None
buds bud
54
14 by 19 14 by14 12 by 15 15 by 15 llby12 11 by15
45 by50 65by65 40 by 40 65 by 75, 50by55 60 by60
None None Small Small None None
bud bud
4.
Grasses + + + Cat Dander + House Dust + + + Grasses
Wheat + Orris Root + Rice + Rye Wool + Wheat, +
None lo
27 47 21 44
~~ 51 42 18
+ + + + +
asthma
42 37
by by by by by by by by by by
+ + + + +
Rai:\eed + + + Grasses + + Cat Dander + + Ragweed + + + House Dust + +
I 8. Rronchia7
Ragweed Ragweed Ragweed Ragweed R.agweed ++++ Ragweed
Urticaria
House Dust + + House Dust -I Negative Orris Root + + House Dust + Sweet Vernal Grass + + Goat Dander + Negative Negative Negative Negative Ragweed + + Feathers + + House Dust + +
FARMER
:
EVALUATION
OF
HISTAMINE
TABLE TOTALS
DIAGNOSIS
inaiviads
FROM
INTRADERMAL
47
TEST
II TABLE
1
NUMBER OF PATIENTS WITH POSITIVE SPECIFIC SKIh- TESTS
IXJMBER OF PATIEXTS
9
0
NUMBER OF PATIENTS ---~~-WIT” POSITIVE I NTRADERMAT, EIISTA51lNE TECSTS
A.
Nonallergic
R.
Allergic individtds Hay fever
45
45
7
Vasomotor Bronchial Urticaria Migraine Angioneurotic Total
14 10 3 1 4 $7
125 2 1 0 65
i 0 0 0 12
asthma rhinitis edema
2
individuals examined by us gave a positive histamine reaction. However, in order to afford Atkinson’s conception every possibility of confirmation we designated as positive a, rea.ction in which there appeared a pseudopod of at least 5 mm. in length. Eighty-six individuals were examined. Seventy-seven presented the clinical picture of allergy and in sixty-five of these cases specific skin tests were positive. Only twelve of these latter patients showed a positive histamine reaction according to the above definition. Nine individuals were suffering from nonallergic diseases; none of them had a positive specific skin reaction; two had positive reactions to histamine. Table I summarizes the results of our skin tests. CONCLUSIONS
It is not possible to differentiate ones by the use of an intradermal
allergic individuals histamine test.
from nonallergic
RFIWRENCE Observations 1. Atkinson, M.: J. A. M. A. 116: 1753,
on Etiology 1941.
and
Treatment
of
MBni&re’s Syndrome,
OF THE A GENER,AL
HISTAMINE INDICATOR
IN’J’RADERMAL OF ALLERGY”
LAURENCE FARMER, M.D., NEW YORK,
TEST
AS
N. Y.
I
N A paper on the etiology and treatment of M&i&e’s syndrome, Atkinson’ suggested the use of histamine intradermally as a general indicator of the presence of an allergic disturbance. He bases this suggestion on the fact that “there is considerable evidence t,o show that the manifestations of allergy are possibly due to the release of histamine or of a histamine-like substance into the affected tissues.” \\iith the help of the histamine intradermal test, he feels that it is possible to “satisfactorily separate the (histamine) sensitive from the insensitive,” t.he inference being that by this method one can establish whether an individual is allergic or not. On the basis of this reasoning allergy would consist of increased histamine sensitivit,y. We believe this assumption t,o be incorrect. Uhough we strongly subscribe to the assumption that the manifestations of allergy are due to the release of histamine, we do not, believe t,hat allergy is enhanced hist,amine sensitivity, i.e., that allergic individuals arc simply more sensitive to histamine than a.re normal individuals. We, therefore, also feel that it is not possible t,o determine whether or not an individual is suffering from an allergy on the basis of whether he shows a stronger or less strong skin reaction to histamine. In the course of earlier work, we had examined the histamine sensit,ivity of normal and allergic individuals by puncturing histamine into the skin. We did not find any difference in the skin reactivit,y of the two groups: i.e., the allergic individuals did not react more strongly to histamine than did the normal individuals. In the present investigation we repeat,ed these tests intradermally. We used 0.01 mg. of histamine phosphate as suggested by Atkinson. This amount of histamine was contained in 0.05 C.C. of physiologic saline. The control consisted of 0.05 C.C. of physiologic saline. All tested individuals reaetcd to the histarnine with a distinct, wheal which in no instance measured less than 10 to 13 millimeters. However, this is not, a positive reaction according to Atkinson’s terminology. His criteria for a positive reaction are “a wide area of erythema 11/z to 2 inches (3.8 to 5 cm.), a la,rgc wheal Q’? to :y4 inch (1.3 to 1.9 cm.) and the pre.sence of long trailing pscudopodia an inch or rnore in length which appear in t,hree to five minutes, begin to fade only after twenty minutes, and arc still apparent al. t,he end of thirty minutes. Small buds at the edge of the main wheal which fade in ten t,o twenty minutes arc not assessed as positive. ” According to these criteria none of the *From
the
Allergy
Clinic,
Lenox
Hill
Hospital,
44
New
York,
N.
Y.
TABLE SIZES
0~
1
TTISTAMINE
WmAr.s -REACTION
HISTAMINE
PATIENT
WHEAL (MM.)
A.
1. J. I.
PSEUDOPOD (ml.)
FLARE (MM.) Nonallergic
IGrasses
27 45
14 by 14 11 hy 14
55 hv 65 INone 45 hy 55 Small
buds
3. K. D. 4. E. B.
47 25
13 by 15 15 by 15 12 by 14 12 hy 15
50 by 60 55 hy 60
huds
5. J. P. 7. 8. 9. 10. 11.
E. .I. E. L. M. L. B.Z. S.R.
12.
I.C.
;"s
40 hy 45
None Small None Small Small Small Small Small None Small
45hy50
44 60 41 40 48 29
12by14 14hylS llhy15 12 by 14
35 45 50 55 50 65
13. H. C. 14. C.E. 15. J. E. 16. R. K. 17. W.H.
43 37 33 37
15 hy 15
60 by60
lihyl5
18. A. TV.
2:
14hyl5
60 by 55 by 70 by 50 by 45 hy
19. A. L. E. Z. 21. 0.1-I. 22. DeW. Y.
31 39 39 42
13 by 14 17hylT 14 hy 15 15 by 15
35 37 11 39 E
13 by 13 17hy20 14 by 16 11 by12 13 by 13 16 by’18
27 34 55
16hyl6 12by13 15 by 15
J. McK. 24. L. J.
25. 26. 27. 28.
0. Y.
$ i
0 0
w.
$
31.
P. A. S. H.
32. 33.
H. K. M. F.
35. 34. 36.
G.R. E. R. R. K.
30.
3
H. C. J. McC. c.
15 by 15 13hy 15 15 by 15
20.
23.
14hy 15 16 by16
-
60 60 70 50 50
bud hud bud buds buds
18 None None None None None
50 hy 65
Buds None None 75 by 75 Buds
None None 10 80 by 100 None 60 by60 10 60 hy 70 Several small pseudopodia 50 by 55 Small bud 60 by 60 None 60 by 60 Several 10 mm. long 55 by 60 None 55 by 55 None 60 hy 70 50 by 60 55 by60
13 by 15 15by17 22 by 23
: 0
by 40 by 50 hy55 by 55 by 50 by 65
huds
60 by 70 60 by 70
13 by 15 15 by 18
65 by 65
60by65 70 by70
i
EXTRACT
individuals
2. H. L.
6. J. S.
ALLERGEN
Buds 11 10
Ragweed House Ragweed Ragweed Ragweed Ragweed
+ + + +
+ + + + Dust + + + + + + Ash -t t t t + + + +
Grasses
+ + +
Timothy + + + + Plantain + t IIouse Dust
Raic-eed + + + House Dust + + Ragweed + + + Ragweed t t Grasses t + Ragweed + + + + Many false positive reactions Ragweed + + (+) Grasses + + + House Dust + + Ragweed + + + + Ragweed + + + Grasses + t + Ragweed + + + + House Dust + Tree pollens -t + + Grasses + + + Ragweed + + House Dust + Ragweed +++ HouseDust ++ Ragweed + + + Timothy + Ragweed + + + House Dust + Ragweed t t t House Dust t t Rabbit Dander + + Feathers + + Tree Pollen + t Grasses + + + Grasses + + + Ragweed + + + Ragweed + + House Dust + + Ragweed + + + House Dust + + Rabbit Dander + + Cat Dander + + Horse Dander + + Grasses + + + Ragweed + + + Ragweed + + + House Dust Ragweed + + + Ragweed +++ House Dust Ragweed + + + Ragweed + + + Ragweed + + + Plaintain t
Grasses + +
+ + +
Timothy + +
++
Grasses + +
+ +
TABLE
I-CONT
'D REACTION
AGE (YE.)
PATIENT
WHEAL
HISTAMINE FLARE
IPSEUDOPOD
ALLERGENEXTRACT
(MM.)
37. 38. 39. 40. 41.
E.R. W. M. M. K. M. B. J.R.
10 by 15 llbyl3 12by14 13 by 13 14 by 15
50 by 55 50 by 70
Buds Buds
42.
E. R.
0
17byl7
55 by 55
None
43.
G. M.
0
13 by 15
55 by 55
ii
44.
0. F.
$
30
14by16
50 by 50
None
45. R. B.
$
14
15by16
55 by 65
1. A.B. 2. M.V.
T
c
3. M. P. 4. P. P.
None I
5.6. 7. 8. 9. 10. 11. 12.
M.B.F. A. A. S. A.M. E.D. R.N. A.M. R.K.
13. F. G. 14. F. J.
i? : :
p”
16by17 18 by 20
75 by 90 45by55
Small 15
buds
49 24 43 48 34 47
50 50 65 50 50 60 80 40 50 50
Small 6 Small None
bud
ii 56 15
15 15 13 13 12 13 15 15 13 12
69 46
13 by 20 15 by 21
15 15 12 14 15 15 18 15 20 12
by by by by by by by by by by
50 5.0 65 55 50 60 85 50 50 70
60 by 70 70 by80 3. Vasomotov
1. 2. 3. 4.
J. K. M. G.
L. T. P. McG.
5. 6. 7. 8. 9. 10.
C. L. R. I. R. A.
K. P. G. L. C. T.
Qo 0 9
z
bud
5
9 None
+ + + + House
Dust
Ra&eed
+ + + + House
Dust
Wasses
+ + +
+ +
Orris Root + + House Dust + Cat Dander + + + House Dust + Negative Kapok + + House Dust + Negative Cat Dander + + House Dust + House Dust + + Milk + Ragweed + + Cat Dander + Ragweed + House Dust + Feathers + Plaintain + House Dust + + Horse Dander + + Rabbit Dander + + Cat Dander + + Ragweed
+++ i I
t
rhinitis
13by17 13 by 21 14 by 15 11 by 13
55by70 65 by 70 50 by 50 45 by 45
Buds Small Small None
buds bud
54
14 by 19 14 by14 12 by 15 15 by 15 llby12 11 by15
45 by50 65by65 40 by 40 65 by 75, 50by55 60 by60
None None Small Small None None
bud bud
4.
Grasses + + + Cat Dander + House Dust + + + Grasses
Wheat + Orris Root + Rice + Rye Wool + Wheat, +
None lo
27 47 21 44
~~ 51 42 18
+ + + + +
asthma
42 37
by by by by by by by by by by
+ + + + +
Rai:\eed + + + Grasses + + Cat Dander + + Ragweed + + + House Dust + +
I 8. Rronchia7
Ragweed Ragweed Ragweed Ragweed R.agweed ++++ Ragweed
Urticaria
House Dust + + House Dust -I Negative Orris Root + + House Dust + Sweet Vernal Grass + + Goat Dander + Negative Negative Negative Negative Ragweed + + Feathers + + House Dust + +
FARMER
:
EVALUATION
OF
HISTAMINE
TABLE TOTALS
DIAGNOSIS
inaiviads
FROM
INTRADERMAL
47
TEST
II TABLE
1
NUMBER OF PATIENTS WITH POSITIVE SPECIFIC SKIh- TESTS
IXJMBER OF PATIEXTS
9
0
NUMBER OF PATIENTS ---~~-WIT” POSITIVE I NTRADERMAT, EIISTA51lNE TECSTS
A.
Nonallergic
R.
Allergic individtds Hay fever
45
45
7
Vasomotor Bronchial Urticaria Migraine Angioneurotic Total
14 10 3 1 4 $7
125 2 1 0 65
i 0 0 0 12
asthma rhinitis edema
2
individuals examined by us gave a positive histamine reaction. However, in order to afford Atkinson’s conception every possibility of confirmation we designated as positive a, rea.ction in which there appeared a pseudopod of at least 5 mm. in length. Eighty-six individuals were examined. Seventy-seven presented the clinical picture of allergy and in sixty-five of these cases specific skin tests were positive. Only twelve of these latter patients showed a positive histamine reaction according to the above definition. Nine individuals were suffering from nonallergic diseases; none of them had a positive specific skin reaction; two had positive reactions to histamine. Table I summarizes the results of our skin tests. CONCLUSIONS
It is not possible to differentiate ones by the use of an intradermal
allergic individuals histamine test.
from nonallergic
RFIWRENCE Observations 1. Atkinson, M.: J. A. M. A. 116: 1753,
on Etiology 1941.
and
Treatment
of
MBni&re’s Syndrome,