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Anesth Analg 2002;95:956-960 © 2002 International Anesthesia Research Society
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Abstract |
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The prevalence of latex allergy has rapidly increased. Clinical manifestations range from contact urticaria-angioedema and rhinoconjunctivitis to more severe bronchial asthma and anaphylactic shock. The only effective therapy is desensitization. We studied 24 patients allergic to latex: 12 of them underwent a rush (4-day) sublingual desensitization to latex, performed by putting increasing doses of latex extract under the patients’ tongues for 3 min every 20 min, followed by a maintenance therapy. The other 12 patients were considered controls. The sublingual rush desensitization protocol was successfully completed in all patients with no side effects. After 3 mo, all patients underwent an allergological evaluation, which showed a significant improvement of symptoms scores after challenges in the treated group as compared with the controls. All the desensitized patients can now wear latex gloves and undergo medical procedures without any symptoms.
IMPLICATIONS: We present 12 cases of latex allergy in patients who underwent desensitization by a sublingual exposure protocol. This study provides evidence that a safe therapeutic approach to latex allergy is possible.
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Introduction |
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Allergy to natural rubber latex (NRL) proteins is a problem whose prevalence has rapidly increased (1). Even though contact with latex products is also frequent in the general population, there are some groups at increased risk for latex allergy: patients undergoing multiple operations (children with neural tube defects) or requiring long-term hospitalization, health care and rubber industry workers, and patients with atopy. Exposure to the antigen mainly occurs through the respiratory mucous and the skin. Clinical manifestations range from contact urticaria-angioedema and rhinoconjunctivitis to more severe bronchial asthma and anaphylactic shock.
Latex cross-reacts with various foods (such as banana, avocado, kiwi, and chestnut) because of the presence of specific latex proteins in several plants and fruits, and allergens common to both latex and foods have been identified (2–4). To reduce the risk of sensitization and to avoid the exposure to latex in sensitized people, some measures, such as the use of latex-free condoms and gloves (which are more expensive and are not accepted by some surgeons) have been suggested, but they are quite difficult to apply because of the large presence of latex in many products. Two clinical reports describing subcutaneous desensitization to latex are available in the literature and suggest desensitizing treatments, which resulted in severe side effects (hypotension, urticaria, wheezing, pharyngeal edema, and anaphylactic reactions requiring the use of epinephrine) (5,6).
We have already successfully used two alternative methods of desensitization (sublingual and percutaneous routes) (7–9). Therefore, we decided to perform a clinical trial evaluating the efficacy and safety of sublingual rush desensitization in 24 patients with allergy to latex. The sublingual rush desensitization is a desensitizing therapy performed by administering increasing doses of latex by the sublingual route. It is "rush" because it requires just 4 days to be performed. The primary efficacy criterion was whether patients could be exposed (by contact and/or inhalation) to latex without symptoms after the 3-mo follow-up period.
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Methods |
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The clinical trial was conducted in the Department of Allergology of the Policlinico A. Gemelli of Rome in accordance with good clinical practice after being approved by our hospital’s ethics review board. Twenty-four patients with allergy to latex proteins were studied; 10 of them were health care workers. The diagnosis of latex allergy was made on the basis of the medical history and a complete allergological evaluation.
All patients had a history of adverse reactions when wearing latex gloves. Twenty of them had cutaneous symptoms. In 17 patients, the respiratory tract was involved (Table 1). Twelve of the patients had symptoms (oral itching, generalized pruritus, laryngospasm, urticaria, nausea, pyrosis, and dyspnea) after eating foods that cross-react with latex (banana, melon, tomato, kiwi, chestnut, walnut, lettuce, fig, and spinach). Eight patients had allergy (rhinoconjunctivitis, asthma, or both) to pollens (Gramineae) that cross-react with latex (10). Prick and patch tests were performed with a standard latex extract (500 µg/mL; ALK Abellò, Madrid, Spain) and an 1-cm2 piece of surgical glove latex material (prick-by-prick method: a puncture device is pushed into the skin through a piece of surgical latex glove manufactured by Triflex Allegiance Health Care Co., McGaw Park, IL).
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Prick tests (prick-by-prick method) with specific foods were also performed in the patients with referred food intolerance. Because cornstarch may be used as latex glove powder, a prick test with corn was performed to exclude corn allergy. Prick tests were performed with a Morrow-Brown needle (Alk Abellò) on the volar surface of the forearm. Negative (glycerin solution) and positive (10 mg/mL of histamine) controls were also performed. Tests, read after 20 min, were considered positive for wheal diameters larger than 4 mm.
Patch tests were performed to find out a type IV delayed cell-mediated hypersensitivity to latex proteins. The patch tests results were checked 72 h after the patch had been placed, assessing positivity according to the North American Contact Dermatitis group criteria: negative reaction (0); macular erythema (?); erythema, infiltration, and possibly papules (1+); erythematous papules and/or vesicles (2+); and spreading blisters and/or crust with ulceration (3+) (11).
Total and specific anti-NRL immunoglobulin (Ig) E and eosinophilic cationic protein (ECP) were mea-sured by means of fluorescent enzyme immunoassay (UniCAP System; Pharmacia, Uppsala, Sweden). In vitro detection of specific anti-NRL IgG4 antibodies was obtained with a latex-specific fluorescent enzyme immunoassay (CAP-FEIA; Pharmacia).
To confirm the diagnosis of allergy to latex, some specific challenge tests were performed. The contact-glove challenge test (12,13) was performed by asking the patients to wear a latex glove until symptoms appeared. The mucous challenge test was performed by asking the patients to hold a latex-gloved finger in their mouths until symptoms appeared. The maximum exposure time for both the challenges was 1 h.
The sublingual challenge test and the conjunctival challenge test were performed with increasing doses of latex extract: extemporaneous dilutions of the standard extract (500 µg/mL; Alk Abellò) were used. The threshold dose was defined as the smallest allergen concentration able to induce the appearance of symptoms. The sublingual challenge test was performed by putting one drop of the extract under the tongue, starting with the smallest concentration of 500 x 10-8 µg/mL. When the test result remained negative after 20 min, the larger concentration was used, until the largest concentration of 500 µg/mL was reached.
The conjunctival challenge test was performed by instilling one drop of the extract into the lower conjunctival fornix, alternating the eye exposed, starting with the smallest concentration of 500 x 10-8 µg/mL, up to a concentration of 50 µg/mL, which was considered the largest threshold dose, because the larger (500 µg/mL) dose caused symptoms in 20 non-latex-allergic subjects, perhaps because of a nonspecific irritant action. In addition, a negative control test was also performed in all the investigated patients by using physiologic saline.
During cutaneous, mucous, and sublingual challenges, ocular (tearing, itching, erythema, and conjunctival edema), respiratory (rhinorrhea, nasal itching, nasal blockage, sneezing, wheezing, cough, dyspnea, and laryngospasm), and mucocutaneous symptoms (generalized pruritus, erythematous-papular rash, urticaria-angioedema, and oral and pharyngeal itching) were recorded by the same physician, who observed the patient until the end of each challenge and scored symptoms on a four-point scale: 0 (absent), 1 (mild), 2 (moderate), or 3 (severe).
For the conjunctival challenge test, the smallest allergen concentration able to induce symptoms (tearing, itching, erythema, or conjunctival edema) was recorded. Patients were randomly allocated into two groups (treated and control groups) by using tables of random numbers; the 12 patients (9 women and 3 men, aged 8 to 64 yr) assigned to the treated group gave informed consent to undergo the desensitizing treatment. Parental consent was obtained for the children included in the study. The remaining 12 patients were assigned to the control group: 6 of them had a history of adverse reactions after eating foods that cross-react with latex. These subjects were merely asked to avoid contact with latex-containing items and cross-reacting foods: they were followed up for 3 mo.
Rush (4-day hospitalization) sublingual desensitization to NRL was performed with increasing doses of latex extract (ALK Abellò) under the patient’s tongue for 3 min every 20 min, starting with an initial dose of a drop of solution containing 500 µg/mL of latex diluted 1:1018. On the first day, the patients received a cumulative dose of 28 x 10-10 µg; on the second day, they received 2.8 µg; on the third day, they reached the cumulative dose of 500 µg of latex; and on the fourth day, the desensitization protocol was successfully completed with the dose of 500 µg of latex (1 mL of the pure solution) in one administration with no side effects (Table 2). All the patients were hospitalized during such procedures, and resuscitative equipment and personnel were available.
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During the allergological evaluation and during the rush phase of desensitization, auscultation and measurement of expiratory peak flow, pulse rate, and blood pressure were recorded. When the desensitization was completed, a maintenance latex exposure, with five drops (sublingual administration) of a solution containing 500 µg/mL of latex three times a week, was recommended.
Three months after the specific latex desensitizing treatment, an allergological evaluation was performed again: serum levels of ECP and total and specific anti-NRL IgE were measured both in the treated group and in the control group. Challenge tests were performed again. The efficacy of treatment was evaluated by calculating the total score in terms of respiratory, conjunctival, and mucocutaneous symptoms recorded during the cutaneous, mucous, and sublingual challenges. Specific challenge tests were also repeated in the controls.
The conjunctival challenge test was performed again in all patients. Student’s t-test was performed to evaluate the differences, in terms of threshold dilution, between T0 (before) and T1 (after desensitization) in the treated and control groups.
The Shapiro-Francia test for normality was performed to evaluate the normal distribution of the score for every symptom recorded during challenges. Score differences between treated and control groups were tested by performing unpaired Student’s t-tests. The paired Student’s t-test was performed to compare the mean score before (T0) and after (T1) desensitization in the treated group. Two-tailed P values of <0.05 were considered statistically significant. With this sample size, we expected to find a mean score difference between groups that was more than two points, with a power of 0.8. Statistical analysis was performed with STATATM 6.0 software (College Station, TX).
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Results |
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Prick tests and the specific anti-NRL IgE immunoassay were positive, whereas the patch tests were negative, in all 24 patients. These findings are consistent with the occurrence of an IgE-mediated allergy to latex. The prick tests with food allergens were positive (banana, melon, tomato, kiwi, chestnut, walnut, lettuce, fig, and spinach) in patients with a history of adverse reactions to food.
The contact-glove challenge test was positive in all patients: after 10–45 min, they presented cutaneous itching, urticaria, and rhinoconjunctivitis (total score in 12 patients in the treatment group, 29; total score in 12 control patients, 32). The mucous challenge test was positive in 22 patients: after 20–48 min, they presented cutaneous and oral itching, cough, and rhinitis (total score in the treatment group, 30; total score of control patients, 34). The sublingual challenge test was positive in 21 patients: after 12–20 min, they presented oral itching, conjunctival erythema, cough, dyspnea, and rhinitis (total score in the treatment group, 25; total score of control patients, 27). There was no significant difference between the two groups.
The sublingual rush desensitization protocol was successfully completed in all patients, with no side effects. In fact, 1 mL of pure latex solution put under patients’ tongues did not provoke any symptoms. During the treatment, no changes of expiratory peak flow, pulse rate, or blood pressure were recorded.
During the maintenance therapy, only two patients manifested symptoms (one patient had perioral wheals in two episodes, and another patient had light labial and ocular angioedema), some minutes after the sublingual administration of latex, and did not require therapy.
Serum levels of specific IgE were lower than before desensitization in seven patients: from class 4 to 3 in one patient, from class 3 to 2 in four patients, and from class 2 to 1 in two patients (<0.35 kU/L, class 0; 0.35 to <0.7 kU/L, class 1; 0.7 to <3.5 kU/L, class 2; 3.5 to <17.5 kU/L, class 3; 17. 5 to <50 kU/L, class 4; 50 to <100 kU/L, class 5; >100 kU/L, class 6). In the remaining five patients, there was an initial decrease, but after desensitization, serum levels of specific IgE remained high. The values of total IgE, ECP, specific IgG4 did not show significant changes after desensitization. There was no significant variation of the total or specific anti-NRL IgE, IgG4, or ECP in the control group during the follow-up.
After the rush desensitization, the sublingual, cutaneous, and mucous challenges became negative in the 12 patients desensitized: they were able to wear latex gloves for 6 h and hold a latex-gloved finger in their mouth for 1 h without symptoms (Table 3). Also, the 12 control patients who were not desensitized underwent challenge tests after a 3-mo follow-up: they did not manifest any significant variation in symptom scores (data not shown) compared with basal tests.
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Analysis of symptoms scores after challenges showed a significant improvement in the treated group compared with the control group in terms of respiratory, conjunctival, and mucocutaneous symptoms. In the treated group, mean score differences before (T0) and after (T1) desensitization are statistically significant for sublingual (t = 6.2; P < 0.001), mucous (t = 4.0; P = 0.002), and cutaneous (t = 5.2; P < 0.001) challenges. Differences in symptom scores were statistically significant for sublingual (t = -5.15; P < 0.001), mucous (t = -3.36; P = 0.003), and cutaneous (t = -4.12; P < 0.001) tests, also if compared with controls (Table 4).
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The difference in threshold dilutions in the conjunctival challenge test before and after desensitization was statistically significant (t = -2.93; P < 0.01) in the treated group. It became negative in 50% of treated patients. No differences were recorded in the control group (Table 3).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The main therapeutic approach in latex-sensitized people is to avoid latex exposure. However, the use of condoms and latex gloves is essential to reduce the risk of sexually or blood-transmitted diseases. Removing the antigenicity of latex products is very difficult. The use of alternative products is controversial because other materials are more expensive and may have different mechanical characteristics (e.g., some surgeons may consider latex-free gloves not acceptable because they do not provide an accurate "feel").
Two clinical reports available in the literature suggest subcutaneous desensitizing treatments, which can result in serious side effects—even anaphylactic reaction, which requires the administration of epinephrine. The effectiveness and safety of sublingual desensitization in respiratory allergy has been confirmed in controlled, double-blinded studies (14,15). For these reasons, we decided to attempt desensitization by using an alternative route. We have already succeeded in performing sublingual desensitization in a latex-allergic medical student (7).
To confirm these results, we successfully performed the same protocol of desensitization in a group of 12 patients. Our protocol seems to be safe: none of our patients experienced side effects. Moreover, we reported a decrease of serum specific IgE to latex in 7 of 12 treated patients. These results are similar to those obtained in conventional subcutaneous hyposensitizing treatment in respiratory allergy. Furthermore, our protocol lasted just four days. After desensitization, a maintenance latex exposure is required, which can be easily performed by the patients themselves at home. A complete spontaneous desensitization to latex, because of the natural course of latex allergy, is not likely to have occurred in our patients. In fact, it requires a long period without any exposure to a specific allergen, whereas our patients were exposed to latex daily. Furthermore, the untreated patients maintained their hypersensitivity to latex. In conclusion, our study provides evidence that a safe therapeutic approach to latex allergy is possible.
Our treatment was safe even in patients with occupational latex-induced asthma. In fact, during the treatment, they did not experience any change of expiratory peak flow, pulse rate, or blood pressure. All these patients now are able to stay in an environment where they are exposed to latex items—particularly important for professional health care workers with latex-induced occupational allergy—and undergo medical procedures without any symptoms. They can also eat some foods that they did not tolerate before desensitization. It is possible that food-induced anaphylaxis in latex-sensitive patients is due to cross-reactivity among food and latex antigens. Chitinase enzymes related to plant defense are believed to be involved in this cross-reaction. A strong connection between food allergy and NRL allergy is recognized (16) and is demonstrated by the fact that patients who undergo desensitization to latex also become tolerant to foods that they could not previously eat.
We believe that our protocol of sublingual rush desensitization provides a new important therapeutic approach to latex allergy, without clinically detectable side effects, in our study population. The success of our new method of desensitization makes us optimistic about the future of patients with latex allergy, even though further prospective, randomized, double-blinded, placebo-controlled trials would need to be performed on a larger group of patients.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Poley GE Jr, Slater JE. Latex allergy. J Allergy Clin Immunol 2000; 105: 1054–62.[Web of Science][Medline]
- Lauvaud F, Prevost A, Cossart C, et al. Allergy to latex, avocado, pear and banana: evidence for a 30KD antigen in immunoblotting. J Allergy Clin Immunol 1995; 95: 557–64.[Web of Science][Medline]
- Lauvaud F, Cossart C, Reiter V, et al. Latex allergy in a patient with allergy to fruit. Lancet 1992; 339: 492–3.
- Breiteneder H. The allergens of Hevea brasiliensis. ACI Int 1998; 10: 101–8.
- Pereira C, Rico P, Lourenço M, et al. Specific immunotherapy for occupational latex allergy. Allergy 1999; 54: 291–3.[Web of Science][Medline]
- Leynadier F, Herman D, Vervloet D, Andre C. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. J Allergy Clin Immunol 2000; 106: 585–90.[Web of Science][Medline]
- Nucera E, Schiavino D, Buonomo A, et al. Latex rush desensitization. Allergy 2001; 56: 86–7.
- Patriarca G, Nucera E, Buonomo A, et al. Latex allergy desensitization by exposure protocol: five case reports. Anesth Analg 2002; 94: 754–8.
[Abstract/Free Full Text] - Nucera E, Schiavino D, Pollastrini E, et al. Desensitization to latex by percutaneous route. J Investig Allergol Immunol 2002; 12: 134–5.
- Fuchs T, Spitzauer S, Vente C, et al. Natural latex, grass pollen, and weed pollen share IgE epitopes. J Allergy Clin Immunol 1997; 100: 356–64.[Web of Science][Medline]
- Marks JG, Belsito DV, De Leo VA, et al. North American Contact Dermatitis Group patch results for the detection of delayed-type hypersensitivity to topical allergens. J Am Acad Dermatol 1998; 38: 911–8.[Web of Science][Medline]
- Czuppon AB, Allmers H, Baur X. Evaluation of diagnostic procedures in type I latex allergy. ACI Int 2000; 12: 98–104.
- Kurtz KM, Hamilton RG, Adkinson NF Jr. Role and application of provocation in the diagnosis of occupational latex allergy. Ann Allergy Asthma Immunol 1999; 83: 634–9.[Medline]
- Pradalier A, Basset D, Claudel A, et al. Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy 1999; 54: 819–28.[Web of Science][Medline]
- Bousquet J, Scheinmann P, Guinnepain MT, et al. Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study. Allergy 1999; 54: 249–60.[Web of Science][Medline]
- Perkin JE. The latex and food allergy connection. J Am Diet Assoc 2000; 100: 1381–4.[Web of Science][Medline]
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