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The toxic fraction in certain eczema serums
THE TOXIC
FRACTION FRANCIS
IT\’ CERTATN SCOTT
SAN
SMYTFI,
ECZEMA
SER’T!JIS*
M.D.
FRAK~~90
A
LTHOUGII a brief report of t,his st,ndy has already appeared,] I feel that it will bear repetit,ion and enlargement in relation to the passive transfer of the allergic skin test.
Toxicity as measured by an immediate response to serum injected intracutaneously has been reported by Gay and Chant.? These invest,igators found that heating blood serum at 56” (1. for thirty minutes or more caused a definite and immediate reaction on intracnt,aneous injection. Similar positive reactions were obtained with serum kept at ice-chest temperature for twelve days or more. Our attention was called to this phenomenon by the occurrence of immediate reactions while studyin<).h passive transfer phenomena of infantile eczema serum. Certain of these were of such noticeable intensity that steps were taken to cont,rol the observation. Methocl.-Blood was drawn aseptically before a feeding from infants with eczema. It was allowed to clot at room temperature and the serum was separated by centrifugalization. The serlim was then removed by st,erile pipette and transferred to a small sterile bottle with rubber cap. After being tested for sterility, small amounts were removed for injection as needed. Besides controlling the factor of bacterial contaminat,ion the method safeguarded against the factors previously known to effect the reaction. Serum was not used immediately after elot,ting. It was not heated, nor kept on ice for longer than twent,y-folrr to forty-eight hours. In spit,e of these precautions, certain of the serums gave irnmediate reactions. We then considered the following possibilities : 1. Circnlat,ing antigen in t,he blood of the recipient. This was t,o be considered since the serum was from infants sensitive to foods in the common dietary and since it was possible that sufficient ant,igen might be present at the time of injection t,o give an immediate response. 2. A difference of blood group of donor and recipient. Nothing definite w,as known about the effect of blood groups on t,he reaction to intracutaneous serum injection, but, in view of their effect in transfusions, etc., it was considered possible that. an ineompatibilit,y would produce some variat)ion in response. and
*From the
the Department St. Louis Children’s
of
Pediatrics, Hospital,
St.
Washington I:nivwsity Louis, Missouri.
173
School
of
Medicine
3. The ef%ct of extensive skin injury. In view of Lewis and Harmer ‘9 work on a toxic ‘ ‘ histamine-like ’ ’ snbstanctr released from injured skin cells, a nonspecific toxin arising from various types of skin injury was t,hought. possible. Accordingly, experiments were designed to test these three possible fact,ors. Recipients for the passive t,ransfcr wt~re selected, represent,ing the four blood groups. Tests were made after the recipients had fasted and also on infants whose dirts had never included the foods to which the tlonor was wnsitivr.
S = reaction from the patient’s serum. C = reaction from the control serum. 0 = a heightened response of the recipients IGpinephr’in injected because of the intensive reaction subsided in all instances in twenty-four influenced the successful passive transfer test jection at that timr.
skin to trauma, i. 1’.. dermatograDhia. edema was without effect. This initial to forty-eight hours and in no way with intracutaneous egg albumen in-
Fig. 1 illustrates the results of iyjection of 0.1 c1.c.of serum from an infant with eczema ancl with a positive skin test to egg white. The donor belonged t,o Group 0 (4 “Moss”), while recipients were chosen representing all four blood groups. h control serum from Group 0 was injected simultaneously. After the night.‘s fast the recipients were injected on t,he flexor surface of the forearms. To test the effect of extensive skin injury, blood was obtained from 2 patients with lichen urticatus, 3 patients with extensive burns of
SMTTN
:
TFTE
TOXIC’
FRACTION
IN
(‘ERTAIN
ECZICMA
SERlJMS
17.5
the skin, 1 patient with extensive exfoliative dermatitis, and from 1 child with marked dermatographia. In the last case the blood was taken when extensive reactions had appeared after voluntary scratching. While perhaps this group was rather small, the negative results obtained point to the fact that extensive skin injury is not necessarily accompanied by the production of toxic properties in t,he blood serum, at least so far as can be .jndged by intracntaneous injection. DISCUSSION
While Gay and Chant4 have described the effects of heat and prolonged exposure t,o cold which renders even normal serum toxic for intracutaneous inject,ion, we have found t,hat specimens of serum from infant,s with extensive eczema and sensitive t,o certain allergens by skin and passive transfer tests, show a similar immediate toxic react,ion. Walzer,” in a series of studies, demonstrated wheal formation at the sit,e of serum injection when the recipient was fed foods to which the donor was sensitive. Our experiments using infants who had never been given the offending foods, as well as adults on fasting, excluded this phenomenon. Theoretically, the skin cells might contain toxic substances which Lewis and IIarmer” have elaborated wonld be liberated after cell injury. this explanation for the react,ion of the skin to trauma. especially pronounced in factitious urticaria. According to his theory, trauma releases this “histamine-like” substance which is then free to act on the adjacent tissue with result,ant) capillary permeability, local edema, and erythema. The wheal fluid and blood do not give constant results due, it would seem, to the dilution of the “histamine-like” toxin. In fact,it,ious urticaria there may be a general react,ion (manifestetl by lowering of blood pressure, etc.) while the normal shows only- the local reaction. Since our initial observat,ions on the phenomenon reported here, Alexander7 has studied the effects of skin extracts injected intraHe finds an augnient~ation of the reaction to histamine cut,aneously. injection when a mater-soluble skin ext,ract is added to the histamine. Our experiment,s using serum from patients with extensive skin injury ot,her than eczema? failed to shorn any such toxin. That there may be a question of dilution of t,he substance must, also be borne in mind, though at present, we cannot conclude t,hat the subst,ance result,s from nonspecific skin injury. SUMMARY
On intracutaneous injection, the serums from certain infants vvith In about 30 patients with eczema give an immediate wheal formation. eczema, studied by passive t’ransfer, 10, or over 30 per cent, showed this phenomenon. This toxicity is not related to enteral absorption
Ii6
‘I’III~:
.JOl-f?S.\l.
Ob’
.\l,l~l~:l~(;\
FRACTION FRANCIS
IT\’ CERTATN SCOTT
SAN
SMYTFI,
ECZEMA
SER’T!JIS*
M.D.
FRAK~~90
A
LTHOUGII a brief report of t,his st,ndy has already appeared,] I feel that it will bear repetit,ion and enlargement in relation to the passive transfer of the allergic skin test.
Toxicity as measured by an immediate response to serum injected intracutaneously has been reported by Gay and Chant.? These invest,igators found that heating blood serum at 56” (1. for thirty minutes or more caused a definite and immediate reaction on intracnt,aneous injection. Similar positive reactions were obtained with serum kept at ice-chest temperature for twelve days or more. Our attention was called to this phenomenon by the occurrence of immediate reactions while studyin<).h passive transfer phenomena of infantile eczema serum. Certain of these were of such noticeable intensity that steps were taken to cont,rol the observation. Methocl.-Blood was drawn aseptically before a feeding from infants with eczema. It was allowed to clot at room temperature and the serum was separated by centrifugalization. The serlim was then removed by st,erile pipette and transferred to a small sterile bottle with rubber cap. After being tested for sterility, small amounts were removed for injection as needed. Besides controlling the factor of bacterial contaminat,ion the method safeguarded against the factors previously known to effect the reaction. Serum was not used immediately after elot,ting. It was not heated, nor kept on ice for longer than twent,y-folrr to forty-eight hours. In spit,e of these precautions, certain of the serums gave irnmediate reactions. We then considered the following possibilities : 1. Circnlat,ing antigen in t,he blood of the recipient. This was t,o be considered since the serum was from infants sensitive to foods in the common dietary and since it was possible that sufficient ant,igen might be present at the time of injection t,o give an immediate response. 2. A difference of blood group of donor and recipient. Nothing definite w,as known about the effect of blood groups on t,he reaction to intracutaneous serum injection, but, in view of their effect in transfusions, etc., it was considered possible that. an ineompatibilit,y would produce some variat)ion in response. and
*From the
the Department St. Louis Children’s
of
Pediatrics, Hospital,
St.
Washington I:nivwsity Louis, Missouri.
173
School
of
Medicine
3. The ef%ct of extensive skin injury. In view of Lewis and Harmer ‘9 work on a toxic ‘ ‘ histamine-like ’ ’ snbstanctr released from injured skin cells, a nonspecific toxin arising from various types of skin injury was t,hought. possible. Accordingly, experiments were designed to test these three possible fact,ors. Recipients for the passive t,ransfcr wt~re selected, represent,ing the four blood groups. Tests were made after the recipients had fasted and also on infants whose dirts had never included the foods to which the tlonor was wnsitivr.
S = reaction from the patient’s serum. C = reaction from the control serum. 0 = a heightened response of the recipients IGpinephr’in injected because of the intensive reaction subsided in all instances in twenty-four influenced the successful passive transfer test jection at that timr.
skin to trauma, i. 1’.. dermatograDhia. edema was without effect. This initial to forty-eight hours and in no way with intracutaneous egg albumen in-
Fig. 1 illustrates the results of iyjection of 0.1 c1.c.of serum from an infant with eczema ancl with a positive skin test to egg white. The donor belonged t,o Group 0 (4 “Moss”), while recipients were chosen representing all four blood groups. h control serum from Group 0 was injected simultaneously. After the night.‘s fast the recipients were injected on t,he flexor surface of the forearms. To test the effect of extensive skin injury, blood was obtained from 2 patients with lichen urticatus, 3 patients with extensive burns of
SMTTN
:
TFTE
TOXIC’
FRACTION
IN
(‘ERTAIN
ECZICMA
SERlJMS
17.5
the skin, 1 patient with extensive exfoliative dermatitis, and from 1 child with marked dermatographia. In the last case the blood was taken when extensive reactions had appeared after voluntary scratching. While perhaps this group was rather small, the negative results obtained point to the fact that extensive skin injury is not necessarily accompanied by the production of toxic properties in t,he blood serum, at least so far as can be .jndged by intracntaneous injection. DISCUSSION
While Gay and Chant4 have described the effects of heat and prolonged exposure t,o cold which renders even normal serum toxic for intracutaneous inject,ion, we have found t,hat specimens of serum from infant,s with extensive eczema and sensitive t,o certain allergens by skin and passive transfer tests, show a similar immediate toxic react,ion. Walzer,” in a series of studies, demonstrated wheal formation at the sit,e of serum injection when the recipient was fed foods to which the donor was sensitive. Our experiments using infants who had never been given the offending foods, as well as adults on fasting, excluded this phenomenon. Theoretically, the skin cells might contain toxic substances which Lewis and IIarmer” have elaborated wonld be liberated after cell injury. this explanation for the react,ion of the skin to trauma. especially pronounced in factitious urticaria. According to his theory, trauma releases this “histamine-like” substance which is then free to act on the adjacent tissue with result,ant) capillary permeability, local edema, and erythema. The wheal fluid and blood do not give constant results due, it would seem, to the dilution of the “histamine-like” toxin. In fact,it,ious urticaria there may be a general react,ion (manifestetl by lowering of blood pressure, etc.) while the normal shows only- the local reaction. Since our initial observat,ions on the phenomenon reported here, Alexander7 has studied the effects of skin extracts injected intraHe finds an augnient~ation of the reaction to histamine cut,aneously. injection when a mater-soluble skin ext,ract is added to the histamine. Our experiment,s using serum from patients with extensive skin injury ot,her than eczema? failed to shorn any such toxin. That there may be a question of dilution of t,he substance must, also be borne in mind, though at present, we cannot conclude t,hat the subst,ance result,s from nonspecific skin injury. SUMMARY
On intracutaneous injection, the serums from certain infants vvith In about 30 patients with eczema give an immediate wheal formation. eczema, studied by passive t’ransfer, 10, or over 30 per cent, showed this phenomenon. This toxicity is not related to enteral absorption
Ii6
‘I’III~:
.JOl-f?S.\l.
Ob’
.\l,l~l~:l~(;\