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Systemic reaction to papain in a nonoccupational setting
Systemic reaction to papain in a nonoccupational setting Lyndon
E. Mansfield,
El Paso.
Tex.
M.D., Lt.Col.,
M.C., and Charles H. Bowers,
B.S.
A patient experienced a severe systemic allergic reaction after ingesting meut tenderizer. Evaluation revealed that the reaction was mediated by IgE antibody to papain, an ingredient of the tenderizer. Papain hypersensitivity has been reported among pharmacists and,factorq lvorkers exposed to the ugent, but few nonoccupational cases have been described. The present case may be thejrst in which the sensitization appears to have occurred via the gastrointestinal route. Papain-containing products are commonly used throughout our society and papain hypersensitivity may represent an unrecognized cause of allergic symptoms. (J ALLERGY CLIN
I~ht(1~0~71:37/,
1983.)
Papain is a proteolytic enzyme derived from the latex of Carica papaya. Allergic reactions to this protease have been well documented in the workplace.” 2 Papain has many industrial applications, chiefly in the tenderizing of meat products and the clarifying of beer, and is an important reagent in the biochemical, immunochemical, and pharmaceutical laboratory. Clinical sensitivity to papain among exposed workers has been usually expressed as respiratory illness in the form of asthma, rhinitis, or both .3 Development of sensitivity is postulated to be by exposure to airborne particles.” In most cases IgE-specific antibodies to papain can be demonstrated,‘, 2 and antibodies of the IgG class have also been found.2 However, the role of the IgG antibodies in disease is unclear. The general population is exposed to papain in numerous ways. Papain is found in the meat tenderizers for commercial and home use, in natural health foods used as digestive aids, the fresh papaya fruit, and in
From the Allergy-Immunology Service, William Beaumont Army Medical Center, El Paso, Tex. Received for publication June 14, 1982. Accepted for publication Oct. 4, 1982. Reprint requests to: Lt. Cal. Lyndon E. Mansfield, AllergyImmunology Service, William Beaumont Army Medical Center, El Paso, TX 79920. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense. The protocol under which this study was conducted was approved by the Clinical Research and Human Use Committee of William Beaumont Army Medical Center and the Office of the Surgeon General, United States Army.
salves. With the increasing popularity of natural health food and of the use of meat tenderizers, the exposure to papain of the general population is considerable. In spite of this, reports of papain allergy outside of the workplace are few. The following case report is of a patient who experienced a hypersensitivity reaction to papain not related to occupational exposure. Furthermore, this patient appears unusual because the oral route seems to be the likely mode of sensitization. CASE REPORT The patient is a 3 1-yr-old man who ate a beefsteak that he had liberally treated with Adolph’s Seasoned Meat Tenderizer prior to cooking. Within 20 to 30 min after ingestion, the patient experienced generalized itching, followed by swelling of hands, feet, lips, and eyelids. Shortly afterwards he felt tightness in his throat and chest, and began to wheeze He was rushed to the emergency room where treatment with epinephrine, corticosteroids, and antihistamines relieved his respiratory symptoms and itching. His angioedema persisted. The patient was admitted to the hospital for observation and further treatment as required. At no time did the patient have any recorded fall in blood pressure. The next morning the Allergy-Immunology Service was consulted. At the time of this visit, the only residual from the previous evening’s events was angioedema of the lips
and eyelids. The patient had a lifelong history of allergic rhinitis, atopic dermatitis, childhood asthma, and recurrent sporadic urticaria and angioedema. The patient had experienced two similar episodes to the presenting illness while in West Germany. On both of these occasions, he felt that the attacks followed the ingestion of German draft beer in large Vol.
71, No.
4, pp.
371-374
372
Mansfield
J. ALLERGY6LlN. IMMUNOL. APRIl 1983
and Bowers
quantities. The patient recognized that eating fried eggs, corn, or raw cake batter caused urticaria and angioedema. In spite of avoiding these foods, he still experienced five to six sporadic attacks OF mild urticaria or angioedema per year. Most often these episodes of urticaria and angioedema occurred after he had dined at a restaurant. The patient stated that he had used other brands of meat tenderilerx without any problems. During the meal preceding the pre\ent attack. the food and drink other than the tenderized steak had been previously tolerated without any recognized problems. The physical examination revealed a healthy man in no distress. A small amount of angioedema of the lips and eyelids was present. There was mild cobblestoning of the palpebral conjunctiva. The nasal mucosa was pale and edematous without polyps. There were no urticarial lesions on the skin, but lichenified skin was present in the anticubital and popliteal areas. The initial laboratory data were a hematocrit of 489, a white blood cell count of 12,800 with 9% eosinophils. a serum IgE level of 6000 IU/ml, and a nasal smear with sheets of eosinophils. Pulmonary Functions were within normal limits and demonstrated no significant reversibility after an inhaled adrenergic bronchodilator. Routine aeroallergen prick skin testing was positive for all of the local El Paso pollens. Food skin testing was positive for corn, egg white, kidney bean, lima bean. and chocolate. it was negative to baker’s or brewer’s yeast. All skin testing was done by the prick method with I : 20 w/v glycerol saline extracts. Seventy-five common food antigens were tested.
MATERIALS AND METHODS Direct skin testing As mentioned above, the patient had previously used other meat tenderizers without problems. A brand that he claimed to tolerate, Schilling’s Meat Tenderizer, was compared with Adolph’s Seasoned Meat Tenderizer for differing ingredients. The ingredients in both agents were as follows: Adolph‘s natural meat tenderizer seasoned with spice, sodium chloride, spices, sugar, tricalcium phosphate. garlic, papain. partially hydroxygenated vegetable oil; Schilling’s meat tenderizer unseasoned, sodium chloride, dextrose, calcium stearate, bromelain. The difference that appeared most important was in the proteolytic enzymes used for tenderizing. Schilling’s contained bromelain while Adolph’s contained papain. An extract of the papain-containing seasoned meat tenderizer was made. and a second extract was made of a seasoning salt containing the same ingredient> with the exception of papain. Chemically pure preparations of papain and bromelain were obtained for skin testing. All extracts were freshly prepared in normal saline solution just prior to testing. They were cold sterilized by filtration through a 0.22 pm millipore filter. The greatest test concentrations used were 0.1 gmiml for seasoning salt and IO mgiml for papain and bromelain.
Passive transfer
skin testing
The patient’s serum was obtained for passive transfer skin testing. It was tested for hepatitis-associated antigen
and VDRL. An aliquot of the serum was heated at 56” f‘ till 2 hr, and 0. I ml of heated and unheated serum was inject& intracutaneously into skin sites of a nonalierglc ~luntecr. After 48 hr these skin sites were challenged wirh F.hcpapain extract in a concentration previously tlemonsttdted not to IX* an irritant.
Testing
for IgG antibodies
The presence of IgC antibodic, was evaluated h:%cloublc diffusion in gel. with the patient ‘5 xcrum and :hc ptlrc’ p;:pain preparation used in various concentrationc
Oral challenge The patient’s reaction to ingested papain wab ic.stetl m 2~ single-blind fashion according to the following protocol: On the first day he took five white placebo capsLllek. I’hirn:g) minutes later he ate a cooked untreated hamburger. Hc VI:I> closely observed for the next 2 hr. On the second da) the procedure was the same except that each capsule k:ontaincd 20 mg of cromolyn. The third chnllcnge day the capsules were placebo but were followed hy :I hamburgcl ilk whil.-tl ! 10 mp of papain had been added. For the fourth trial. the> rile capsules each contalned 20 mg ot cromolyn and the barit burger contained 10 mg of papain. The patient wa:, advised that six to eight challenge trials might be required tk ~a!~, not aware of the sequence oi’ the triaib.
RESULTS Direct skin testing Direct prick skin testing to the Adolph’s meat fenderizer (0.1 gmiml) and to pure papain (9 I. E.O. and 10 mgiml) was positive (Fig. 1). Similar testing of three nonallergic controls was negative, The patient had small skin whealing reactions to seasoned salt at 1.O mg/ml and to bromelain at 10 mg:‘ml, but these were similar to the response in our nonallergic controls. Passive transfer
testing
The injection of’ 0.02 ml of 0.1 mg/ml papain into the three skin sites of the passive transfer recipient caused a large whealing response at the unheated serum site, with a minimal response at an untreated site, or at the site in which the heated patient’s serum had been previously injected (Fig. 2). Test for IgG antibody There were no visible precipitant lines in the peX between the various concentrations of papain used and the patient’s serum. Oral challenge On the first two oral challenges the patient experienced no adverse reactions. On the third day. 20 to 30 min after ingesting the hamburger containing papain, he experienced palatal itching and tightness in his
VOLUME 71 NUMBER 4
L.
MEAT
TENDERIZER
CONTROLS
PAPAIN
CONTROLS
x 3 NEGATIVE
SEASON
SALT
Q
1
PAPAIN O.lmg/ml
l.Og/ml
CONTROL
(TypeIT)
x 3 NEGATIVE
FIG. 1. Results of direct prick skin testing to meat tenderizer, papain, seasoned salt, and bromelain. The patient’s wheal reactions to meat tenderizer and papain are shown on the left. None of the controls reacted at these concentrations. On the right the patient’s reactions to seasoned salt and bromelain are illustrated. These were no different than in controls. The illustrations are 1.74x enlargements of cellophane tape transfers of the wheal.
throat. He received an injection of epinephrine, which relieved the symptoms. On the fourth trial, when cromolyn was taken 30 min prior to the papain-treated hamburger, no allergic response occurred. The patient stated that he believed this was just another placebo day, and no further challenges with larger doses of papain were undertaken. DISCUSSION This patient appears to have IgE-mediated hypersensitivity to the proteolytic enzyme papain. Although IgG specific antibodies to papain could not be detected by Ouchterlony analysis, a more sensitive assay may have demonstrated their presence. What is unusual about this present patient is that his presumed route of sensitization was by ingestion rather than inhalation, and his exposure was outside of the workplace. There was nothing in the patient’s history to suggest exposure to airborne papain particles. Indeed, he had not used papain-based meat tenderizer until the present episode. We presume, therefore, that sensitization occurred after papain ingestion. It is conceivable that his two previous severe allergic episodes after consuming large quantities of beer may have been due to papain residual in the beer. Papain, even when heating destroys its proteolytic activities, continues to have allergenic activity.l It is also possible that his attacks of sporadic urticaria and agioedema
1
. ........ .:..... : ... ........ ...... : ................... .::. . ... .... ........ .:.x. ....... :>..... ....................... ...~ .......... .................... ..~....................... .:;::. ........I........ .......... .... ..~........... . ............. ..................... ................. 0
423
UNHEATED SERUM
HEATED SERUM
FIG. 2. Patient’s serum transferred reactivity to papain to a nonallergic volunteer. The reaction at the heated serum skin site was no different than that at a site not sensitized by serum. Illustrations are 1.98x enlargements of cellophane tape transfers of the wheal response.
when eating at restaurants resulted from papain treatment of his meat course. The oral challenge was performed with the patient’s consent to establish with surety the role of papain in the reaction. The amount of papain used did not affect the taste of the hamburger as judged by two nonallergic volunteers who ate treated and untreated cooked patties. The procedure was performed with emergency resuscitation equipment available under closely supervised conditions should a severe reaction occur. Furthermore, we believed it valuable to investigate whether the premeditation with an agent such as oral cromolyn could modify the response. It was hoped to offer the patient a means of dealing with his occupational necessity to eat at restaurants and social gatherings. Pretreatment with cromolyn appeared to block the adverse response to papain ingestion. It is unfortunate that our concern for the patient’s well-being when he complained of laryngeal tightness, and our rapid treatment with epinephrine, may have removed the opportunity to demonstrate objective changes such as urticaria or bronchoconstriction. However, it cannot be forgotten that in the other three challenge days, which appeared similar to the patient, he had no subjective complaints.
374
Mansfield
J. ALLERGY CLIN. IMbltl~OL. APHIL 1983
and Bowers
The patient now avoids those foods to which he was skin-test positive, including papain-containing meat tenderizers. He continues to occasionally use bromelain-containing tenderizers without any noted problems. Before dining out he takes 100 mg of oral cromolyn and an H, antihistamine. He carries an antianaphylaxis kit with him on these occasions. This regimen has been instituted for 12 mo, during which the patient has had only one mild attack of angioedema of the lips. Perhaps the most intriguing question raised by this patient’s reaction is whether papain may be a significant unrecognized cause of allergic symptoms in other patients not occupationally exposed to this agent. The previously reported cases of nonoccupational papain hypersensitivity were published many years ago.” 3 At that time papain was added to many products such as tooth powder and was also a popular therapy for wound debridement. At least one patient was reported to develop sensitivity after wound debridement with papain. s In today’s society, the most likely exposures to papain are from meat tenderizers used at home and in restaurants and from natural health food containing papain. With the increasing popularity of natural health food supplements, papain exposures are likely to be increasing. One might speculate that the incidence of sensitization and clinical sensitivity to papain likewise should be increasing. However, there is no evidence at present to support this speculation.
Tar10 et a1.6 reported skin-test sensitivity to papain in seven of 330 allergy clinic patients. in a preliminary evaluation at our clinic, eight of 132 consecutive allergy clinic patients were prick skin-test positive to papain extract 1 mgiml. These findings suggest that IgE antibodies reacting with papain are present in 2% to 6% of allergy patients. The meaning of these positive skin tests to papain needs to be examined by carefully controlled challenge studies. Until such information is available, it is only the dramatic case, such as the present patient”s, for which papain hypersensitivity will be considered. REFERENCES Beecher WL: Hyperesthetic rhinitis and asthma due to ritgcstivc ferments. Illinois Med J 59:343. 1931. 2. Novey HS, Marchioli LE. Sokol WN, Wells 114: Papam induced asthma, physiological and immunological Features 1 I
ALLERGY CLIN IMM~JNOL68:9X. 1979. 3. Baur X, Fruhmann G: Papain-induced asthma: diagnostr by skin test, RAST and bronchial provocation test. Chn ,Atlergy 9:75, 1979. 4. Flindt MLH: Allergy to alphaamylase and papam. (Letter). Lancet 1:1407. 1979. 5. Osgood H: Atopic sensitivity to caroid (papain! J Ar.sr:ex;\ 16:245, 1945. 6. Tar10 S, Shaik W, Bell B. Cwefm C. Davies GM. F~oloGh J. Hargreave FE: Papain induced allergic reactions. Chn Allergy 8:207, 1978.
E. Mansfield,
El Paso.
Tex.
M.D., Lt.Col.,
M.C., and Charles H. Bowers,
B.S.
A patient experienced a severe systemic allergic reaction after ingesting meut tenderizer. Evaluation revealed that the reaction was mediated by IgE antibody to papain, an ingredient of the tenderizer. Papain hypersensitivity has been reported among pharmacists and,factorq lvorkers exposed to the ugent, but few nonoccupational cases have been described. The present case may be thejrst in which the sensitization appears to have occurred via the gastrointestinal route. Papain-containing products are commonly used throughout our society and papain hypersensitivity may represent an unrecognized cause of allergic symptoms. (J ALLERGY CLIN
I~ht(1~0~71:37/,
1983.)
Papain is a proteolytic enzyme derived from the latex of Carica papaya. Allergic reactions to this protease have been well documented in the workplace.” 2 Papain has many industrial applications, chiefly in the tenderizing of meat products and the clarifying of beer, and is an important reagent in the biochemical, immunochemical, and pharmaceutical laboratory. Clinical sensitivity to papain among exposed workers has been usually expressed as respiratory illness in the form of asthma, rhinitis, or both .3 Development of sensitivity is postulated to be by exposure to airborne particles.” In most cases IgE-specific antibodies to papain can be demonstrated,‘, 2 and antibodies of the IgG class have also been found.2 However, the role of the IgG antibodies in disease is unclear. The general population is exposed to papain in numerous ways. Papain is found in the meat tenderizers for commercial and home use, in natural health foods used as digestive aids, the fresh papaya fruit, and in
From the Allergy-Immunology Service, William Beaumont Army Medical Center, El Paso, Tex. Received for publication June 14, 1982. Accepted for publication Oct. 4, 1982. Reprint requests to: Lt. Cal. Lyndon E. Mansfield, AllergyImmunology Service, William Beaumont Army Medical Center, El Paso, TX 79920. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense. The protocol under which this study was conducted was approved by the Clinical Research and Human Use Committee of William Beaumont Army Medical Center and the Office of the Surgeon General, United States Army.
salves. With the increasing popularity of natural health food and of the use of meat tenderizers, the exposure to papain of the general population is considerable. In spite of this, reports of papain allergy outside of the workplace are few. The following case report is of a patient who experienced a hypersensitivity reaction to papain not related to occupational exposure. Furthermore, this patient appears unusual because the oral route seems to be the likely mode of sensitization. CASE REPORT The patient is a 3 1-yr-old man who ate a beefsteak that he had liberally treated with Adolph’s Seasoned Meat Tenderizer prior to cooking. Within 20 to 30 min after ingestion, the patient experienced generalized itching, followed by swelling of hands, feet, lips, and eyelids. Shortly afterwards he felt tightness in his throat and chest, and began to wheeze He was rushed to the emergency room where treatment with epinephrine, corticosteroids, and antihistamines relieved his respiratory symptoms and itching. His angioedema persisted. The patient was admitted to the hospital for observation and further treatment as required. At no time did the patient have any recorded fall in blood pressure. The next morning the Allergy-Immunology Service was consulted. At the time of this visit, the only residual from the previous evening’s events was angioedema of the lips
and eyelids. The patient had a lifelong history of allergic rhinitis, atopic dermatitis, childhood asthma, and recurrent sporadic urticaria and angioedema. The patient had experienced two similar episodes to the presenting illness while in West Germany. On both of these occasions, he felt that the attacks followed the ingestion of German draft beer in large Vol.
71, No.
4, pp.
371-374
372
Mansfield
J. ALLERGY6LlN. IMMUNOL. APRIl 1983
and Bowers
quantities. The patient recognized that eating fried eggs, corn, or raw cake batter caused urticaria and angioedema. In spite of avoiding these foods, he still experienced five to six sporadic attacks OF mild urticaria or angioedema per year. Most often these episodes of urticaria and angioedema occurred after he had dined at a restaurant. The patient stated that he had used other brands of meat tenderilerx without any problems. During the meal preceding the pre\ent attack. the food and drink other than the tenderized steak had been previously tolerated without any recognized problems. The physical examination revealed a healthy man in no distress. A small amount of angioedema of the lips and eyelids was present. There was mild cobblestoning of the palpebral conjunctiva. The nasal mucosa was pale and edematous without polyps. There were no urticarial lesions on the skin, but lichenified skin was present in the anticubital and popliteal areas. The initial laboratory data were a hematocrit of 489, a white blood cell count of 12,800 with 9% eosinophils. a serum IgE level of 6000 IU/ml, and a nasal smear with sheets of eosinophils. Pulmonary Functions were within normal limits and demonstrated no significant reversibility after an inhaled adrenergic bronchodilator. Routine aeroallergen prick skin testing was positive for all of the local El Paso pollens. Food skin testing was positive for corn, egg white, kidney bean, lima bean. and chocolate. it was negative to baker’s or brewer’s yeast. All skin testing was done by the prick method with I : 20 w/v glycerol saline extracts. Seventy-five common food antigens were tested.
MATERIALS AND METHODS Direct skin testing As mentioned above, the patient had previously used other meat tenderizers without problems. A brand that he claimed to tolerate, Schilling’s Meat Tenderizer, was compared with Adolph’s Seasoned Meat Tenderizer for differing ingredients. The ingredients in both agents were as follows: Adolph‘s natural meat tenderizer seasoned with spice, sodium chloride, spices, sugar, tricalcium phosphate. garlic, papain. partially hydroxygenated vegetable oil; Schilling’s meat tenderizer unseasoned, sodium chloride, dextrose, calcium stearate, bromelain. The difference that appeared most important was in the proteolytic enzymes used for tenderizing. Schilling’s contained bromelain while Adolph’s contained papain. An extract of the papain-containing seasoned meat tenderizer was made. and a second extract was made of a seasoning salt containing the same ingredient> with the exception of papain. Chemically pure preparations of papain and bromelain were obtained for skin testing. All extracts were freshly prepared in normal saline solution just prior to testing. They were cold sterilized by filtration through a 0.22 pm millipore filter. The greatest test concentrations used were 0.1 gmiml for seasoning salt and IO mgiml for papain and bromelain.
Passive transfer
skin testing
The patient’s serum was obtained for passive transfer skin testing. It was tested for hepatitis-associated antigen
and VDRL. An aliquot of the serum was heated at 56” f‘ till 2 hr, and 0. I ml of heated and unheated serum was inject& intracutaneously into skin sites of a nonalierglc ~luntecr. After 48 hr these skin sites were challenged wirh F.hcpapain extract in a concentration previously tlemonsttdted not to IX* an irritant.
Testing
for IgG antibodies
The presence of IgC antibodic, was evaluated h:%cloublc diffusion in gel. with the patient ‘5 xcrum and :hc ptlrc’ p;:pain preparation used in various concentrationc
Oral challenge The patient’s reaction to ingested papain wab ic.stetl m 2~ single-blind fashion according to the following protocol: On the first day he took five white placebo capsLllek. I’hirn:g) minutes later he ate a cooked untreated hamburger. Hc VI:I> closely observed for the next 2 hr. On the second da) the procedure was the same except that each capsule k:ontaincd 20 mg of cromolyn. The third chnllcnge day the capsules were placebo but were followed hy :I hamburgcl ilk whil.-tl ! 10 mp of papain had been added. For the fourth trial. the> rile capsules each contalned 20 mg ot cromolyn and the barit burger contained 10 mg of papain. The patient wa:, advised that six to eight challenge trials might be required tk ~a!~, not aware of the sequence oi’ the triaib.
RESULTS Direct skin testing Direct prick skin testing to the Adolph’s meat fenderizer (0.1 gmiml) and to pure papain (9 I. E.O. and 10 mgiml) was positive (Fig. 1). Similar testing of three nonallergic controls was negative, The patient had small skin whealing reactions to seasoned salt at 1.O mg/ml and to bromelain at 10 mg:‘ml, but these were similar to the response in our nonallergic controls. Passive transfer
testing
The injection of’ 0.02 ml of 0.1 mg/ml papain into the three skin sites of the passive transfer recipient caused a large whealing response at the unheated serum site, with a minimal response at an untreated site, or at the site in which the heated patient’s serum had been previously injected (Fig. 2). Test for IgG antibody There were no visible precipitant lines in the peX between the various concentrations of papain used and the patient’s serum. Oral challenge On the first two oral challenges the patient experienced no adverse reactions. On the third day. 20 to 30 min after ingesting the hamburger containing papain, he experienced palatal itching and tightness in his
VOLUME 71 NUMBER 4
L.
MEAT
TENDERIZER
CONTROLS
PAPAIN
CONTROLS
x 3 NEGATIVE
SEASON
SALT
Q
1
PAPAIN O.lmg/ml
l.Og/ml
CONTROL
(TypeIT)
x 3 NEGATIVE
FIG. 1. Results of direct prick skin testing to meat tenderizer, papain, seasoned salt, and bromelain. The patient’s wheal reactions to meat tenderizer and papain are shown on the left. None of the controls reacted at these concentrations. On the right the patient’s reactions to seasoned salt and bromelain are illustrated. These were no different than in controls. The illustrations are 1.74x enlargements of cellophane tape transfers of the wheal.
throat. He received an injection of epinephrine, which relieved the symptoms. On the fourth trial, when cromolyn was taken 30 min prior to the papain-treated hamburger, no allergic response occurred. The patient stated that he believed this was just another placebo day, and no further challenges with larger doses of papain were undertaken. DISCUSSION This patient appears to have IgE-mediated hypersensitivity to the proteolytic enzyme papain. Although IgG specific antibodies to papain could not be detected by Ouchterlony analysis, a more sensitive assay may have demonstrated their presence. What is unusual about this present patient is that his presumed route of sensitization was by ingestion rather than inhalation, and his exposure was outside of the workplace. There was nothing in the patient’s history to suggest exposure to airborne papain particles. Indeed, he had not used papain-based meat tenderizer until the present episode. We presume, therefore, that sensitization occurred after papain ingestion. It is conceivable that his two previous severe allergic episodes after consuming large quantities of beer may have been due to papain residual in the beer. Papain, even when heating destroys its proteolytic activities, continues to have allergenic activity.l It is also possible that his attacks of sporadic urticaria and agioedema
1
. ........ .:..... : ... ........ ...... : ................... .::. . ... .... ........ .:.x. ....... :>..... ....................... ...~ .......... .................... ..~....................... .:;::. ........I........ .......... .... ..~........... . ............. ..................... ................. 0
423
UNHEATED SERUM
HEATED SERUM
FIG. 2. Patient’s serum transferred reactivity to papain to a nonallergic volunteer. The reaction at the heated serum skin site was no different than that at a site not sensitized by serum. Illustrations are 1.98x enlargements of cellophane tape transfers of the wheal response.
when eating at restaurants resulted from papain treatment of his meat course. The oral challenge was performed with the patient’s consent to establish with surety the role of papain in the reaction. The amount of papain used did not affect the taste of the hamburger as judged by two nonallergic volunteers who ate treated and untreated cooked patties. The procedure was performed with emergency resuscitation equipment available under closely supervised conditions should a severe reaction occur. Furthermore, we believed it valuable to investigate whether the premeditation with an agent such as oral cromolyn could modify the response. It was hoped to offer the patient a means of dealing with his occupational necessity to eat at restaurants and social gatherings. Pretreatment with cromolyn appeared to block the adverse response to papain ingestion. It is unfortunate that our concern for the patient’s well-being when he complained of laryngeal tightness, and our rapid treatment with epinephrine, may have removed the opportunity to demonstrate objective changes such as urticaria or bronchoconstriction. However, it cannot be forgotten that in the other three challenge days, which appeared similar to the patient, he had no subjective complaints.
374
Mansfield
J. ALLERGY CLIN. IMbltl~OL. APHIL 1983
and Bowers
The patient now avoids those foods to which he was skin-test positive, including papain-containing meat tenderizers. He continues to occasionally use bromelain-containing tenderizers without any noted problems. Before dining out he takes 100 mg of oral cromolyn and an H, antihistamine. He carries an antianaphylaxis kit with him on these occasions. This regimen has been instituted for 12 mo, during which the patient has had only one mild attack of angioedema of the lips. Perhaps the most intriguing question raised by this patient’s reaction is whether papain may be a significant unrecognized cause of allergic symptoms in other patients not occupationally exposed to this agent. The previously reported cases of nonoccupational papain hypersensitivity were published many years ago.” 3 At that time papain was added to many products such as tooth powder and was also a popular therapy for wound debridement. At least one patient was reported to develop sensitivity after wound debridement with papain. s In today’s society, the most likely exposures to papain are from meat tenderizers used at home and in restaurants and from natural health food containing papain. With the increasing popularity of natural health food supplements, papain exposures are likely to be increasing. One might speculate that the incidence of sensitization and clinical sensitivity to papain likewise should be increasing. However, there is no evidence at present to support this speculation.
Tar10 et a1.6 reported skin-test sensitivity to papain in seven of 330 allergy clinic patients. in a preliminary evaluation at our clinic, eight of 132 consecutive allergy clinic patients were prick skin-test positive to papain extract 1 mgiml. These findings suggest that IgE antibodies reacting with papain are present in 2% to 6% of allergy patients. The meaning of these positive skin tests to papain needs to be examined by carefully controlled challenge studies. Until such information is available, it is only the dramatic case, such as the present patient”s, for which papain hypersensitivity will be considered. REFERENCES Beecher WL: Hyperesthetic rhinitis and asthma due to ritgcstivc ferments. Illinois Med J 59:343. 1931. 2. Novey HS, Marchioli LE. Sokol WN, Wells 114: Papam induced asthma, physiological and immunological Features 1 I
ALLERGY CLIN IMM~JNOL68:9X. 1979. 3. Baur X, Fruhmann G: Papain-induced asthma: diagnostr by skin test, RAST and bronchial provocation test. Chn ,Atlergy 9:75, 1979. 4. Flindt MLH: Allergy to alphaamylase and papam. (Letter). Lancet 1:1407. 1979. 5. Osgood H: Atopic sensitivity to caroid (papain! J Ar.sr:ex;\ 16:245, 1945. 6. Tar10 S, Shaik W, Bell B. Cwefm C. Davies GM. F~oloGh J. Hargreave FE: Papain induced allergic reactions. Chn Allergy 8:207, 1978.