Latex, the content of lactifier cells of the rubber tree (Hevea brasiliensis), used as the raw material for natural rubber, induces immediate and delayed hypersensitivity reactions. Symptoms include contact urticaria, rhinitis, conjunctivitis, asthma, urticarial rash, angioedema, and anaphylactic shock (1–9).
The first cases of allergy to natural rubber latex (NRL) were described in 1979–1980 (1,2). Subsequently, allergic reactions to latex proteins have been reported with increasing frequency because of the worldwide use of latex-containing items, such as medical equipment, household and professional gloves, condoms, balls and balloons, footwear, baby pacifiers, carpets, and sport equipment (3). Although anyone may be susceptible to sensitization, children with spina bifida, health care workers, and patients undergoing repeated surgical procedures or internal examinations are at more frequent risk than the general population (4–6).
An allergic cross-reaction between latex and various foods (most often banana, avocado, kiwi, and chestnut) has been observed (7). The main cross-reacting allergens may be represented by specific latex proteins (such as hevamines, heveins, proheveins, patatins, and profilins) contained in several plants and fruits.
Latex may also cross-react with pollens: a history of pollinosis with positive allergological test to ragweed and grass pollens has been often reported in patients clinically allergic to latex (9). Until now, the principal therapeutic approach to latex allergy was to avoid the exposure to latex (which is, however, particularly difficult because of the ubiquity of latex products).
Just two recent reports are available in the literature dealing with the subcutaneous desensitizing treatment with latex extracts in patients with allergy to latex. In the reported cases, the desensitization was partially successful, but during the protocol many patients experienced important anaphylactic reactions requiring medical treatment (10,11). To investigate the possibility of safer alternative methods for desensitization, we present five cases of desensitization to latex, successfully performed by means of an original contact exposure protocol.
The desensitization protocol was approved by our hospital’s ethics review board, and all patients gave fully informed written consent to the treatment. Nine health care workers with proved immunoglobulin (Ig) E-mediated (Type I) latex allergy were consecutively followed up as outpatients of the Department of Allergology of Policlinico A. Gemelli, Rome. The admission criteria included a history of cutaneous reaction, systemic reaction, or both after contact with latex items, with positive prick test and IgE radioallergosorbent test (RAST) with latex extracts.
Complete allergological evaluation tests (including specific prick tests, measurement of total and specific IgE, and contact and mucosal provocation tests) were performed in all patients. Prick tests were performed with a 1-cm2 piece of surgical latex glove material (the prick-by-prick method, in which a puncture device is pushed into the skin through a piece of surgical latex glove; the gloves were manufactured by Triflex Allegiance Health Care Co., McGaw Park, IL) and a standard latex skin test reagent (500 mg/L; ALK Abellò, Madrid, Spain) at increasing concentrations (5, 50, and 500 mg/L). A wheal larger than 4 mm in diameter was considered as a positive response.
Cornstarch may be used as a latex glove powder. Although it has been repeatedly demonstrated to be inert, a prick test with corn was also assessed in all investigated subjects to exclude corn allergy. The patch tests were performed by using the standard latex preparation used for the prick tests and an 1-cm2 piece of surgical glove latex material. Because some patients presented cross-reactions with food allergens, prick tests with the specific food allergens were also performed.
Any reaction was checked 72 h after the patch had been placed, assessing positivity according to the North American Contact Dermatitis Group criteria (12): negative reaction (0); macular erythema (?); erythema, infiltration, and possibly papules (1+); erythematous papules, vesicles, or both (2+); and spreading blisters, crust with ulceration, or both (3+). Total and specific antinatural rubber latex IgE were measured by means of fluorescent enzyme immunoassay (Pharmacia UniCAP System, Uppsala, Sweden). In vitro detection of specific antinatural rubber latex IgG4 antibodies was obtained with a latex-specific fluorescent enzyme immunoassay (Pharmacia CAP FEIA, Uppsala, Sweden).
To confirm the diagnosis of allergy to latex, a specific contact provocation test (asking the patients to wear a latex glove on one hand until any symptoms appeared) and a mucous challenge (asking the patients to hold a latex-gloved finger in their mouth for an hour and recording the occurrence of any symptoms) were performed in all subjects. After the preliminary allergological examination, a desensitization treatment was proposed to all subjects.
Four patients refused to undergo any desensitization treatment; they were four women aged from 24 to 40 yr. Therefore, these subjects were requested merely to avoid contacts with latex-containing items, and they were followed up for at least 1 yr as a control group.
Five patients gave their informed consent to the desensitization and were admitted for treatment. The important clinical data of the five treated patients are summarized in Table 1.
The adopted original protocol for contact latex desensitization, with a duration of 12 mo, is described in detail in Table 2. It consists of a progressively increasing exposure to latex, obtained by wearing latex gloves daily for increasing periods. Allegiance Triflex latex gloves were used. The starting exposure time was 10 s once a day in one hand only (right hand). The scheduled exposure time was incremented every second or third day (Table 2), reaching a 10-min exposure twice a day (right hand only) at the end of the fifth month. Thereafter, a progressively increasing left hand exposure was started (Months 6 to 8), maintaining a 10-min exposure twice a day on the right hand. In such a way, a 10-min exposure in both hands was achieved at the end of the eighth month. During Months 9 to 12, latex exposures (on both hands simultaneously) were increased, reaching a final exposure of 1 h twice a day at the end of the 12-mo treatment (Table 2). After the desensitizing treatment, a maintenance latex exposure of at least 60 min in both hands three times a week was recommended. A complete allergological evaluation was reassessed at the end of the specific latex desensitization treatment (treated patients) or after a 12-mo follow-up period (control subjects).
According to the inclusion criteria, the prick test with latex extract and the anti-NRL IgE radioallergosorbent test were positive in all subjects, whereas the patch tests were negative. The results of contact provocation tests and the mucous challenges were positive in all patients as well (Table 3). These data are consistent with the occurrence of an IgE-mediated (Type I, immediate) allergy to latex.
The prick test with corn was negative in all the investigated subjects. No dermographism was present. The results of prick tests with food allergens (prick-by-prick method) were positive in some patients, both in treated and control subjects (Table 3).
The contact desensitization protocol was successfully completed in all treated patients, with no remarkable side effects. After the 12-mo treatment, all patients could wear latex gloves on both hands for more than 1 h daily, with no side effects. This fact was particularly important for professional health care workers with latex-induced occupational allergy, who are supposed to use latex gloves daily. All the patients, at the end of the treatment, could stay in an environment where they were exposed to latex inhalation. The desensitization treatment also resulted in a clinical improvement of the associated cross-reactions, because Patients 1, 3, and 4 could eat again melon, fresh tomato, or banana and pineapple without any clinical symptoms.
The mucous challenge, performed to better confirm the occurrence of a complete desensitization, had negative results in all treated subjects. Moreover, Patient 3 became pregnant after the desensitizing treatment and successfully delivered a baby. During pregnancy and delivery, the patient was always examined and assisted by latex-glove-wearing medical staff, and she had no allergic reactions.
After the desensitization, the allergological examination showed a marked reduction of the cutaneous response to latex antigens. The mean diameter of the wheal of the prick test with latex standard extracts (dilution 1:100) decreased from 9 to 4 mm in Patient 1, from 10 to 5 mm in Patient 2, and from 10 to 3 mm in Patient 3. Also, the reactions to prick tests to food allergens were markedly decreased after desensitization to latex (from 7 to 3 mm to tomato and from 5 to 2 mm to melon in Patient 1; from 8 to 4 mm to banana in Patient 3; and from 5 to 2 mm to pineapple in Patient 4).
An almost 40% decrease in specific IgE levels was observed after treatment (from 9.48 ± 2.32 to 5.86 ± 2.62 U/mL; mean ± se). However, such a difference did not reach statistical significance (paired Student’s t-test), probably because of the reduced number of subjects investigated. The values of total IgE did not show significant changes after desensitization (from 204.5 ± 68.1 to 190.3 ± 92.5 U/mL).
No significant variation in specific IgG4 levels was observed after treatment. All control subjects still exhibited a positive contact and mucous challenge with latex, as well as positive latex (and specific food) prick tests, at the end of the 1-yr follow-up period. Serum values of total and specific IgE levels did not significantly vary in control subjects after the follow-up period.
Until now, the principal therapeutic approach to latex allergy was to avoid exposure to latex. However, this seems particularly difficult because of the ubiquity of latex-containing products, their similarity to nonallergenic synthetic rubber products, and often inadequate and sometimes misleading product labeling.
Moreover, because the transmission of blood-borne diseases is one of the most pressing public health concerns, the use of (often latex-containing) gloves and condoms is essential to reduce the risk of sexually or blood-transmitted diseases. Current efforts by industry and by the Food and Drug Administration aim at reducing the antigenicity of medical latex products, although it is doubtful that any latex product could be made 100% antigen free.
Sensitized health care workers are encouraged to wear low-protein, powder-free gloves. However, the protective effect of some alternative gloves is controversial (13), and some of them are unacceptable to surgeons (14) because nonlatex gloves generally do not have the same mechanical characteristics as latex ones and therefore do not provide an accurate “touch.”
There are two recent reports dealing with patients experiencing allergy to latex who underwent a subcutaneous specific desensitization (10,11). However, many patients developed important side reactions during the treatment which required the use of epinephrine or steroids.
Our patients are the first to be treated with a contact desensitization. The adopted protocol seems to be very effective, because after treatment, patients with demonstrated allergy to latex could tolerate exposure to latex without any symptoms. The proposed contact desensitization protocol seems absolutely safe (even though we treated only a few patients), and no side effects were reported. Moreover, we reported a slight decrease of serum-specific IgE to latex in treated patients, together with a reduction of prick test results as already observed during conventional subcutaneous hyposensitizing treatment (for instance, in respiratory allergy); instead, contrary to what is observed during conventional immunotherapy, specific IgG4 (blocking antibodies) did not show any modification. We cannot explain this fact, but we think it can be caused by the route of the administration of the allergen, which probably requires more time to produce modifications of the immune system.
The only drawback of the adopted protocol seems to be the relatively long time—12 months—required for desensitization. However, the method is very simple and, because of its complete safety, may be easily performed by the patient at home with just a periodic control by experienced allergological staff.
In the last 15 years, to reduce the frequency and severity of potential side effects of conventional subcutaneous immunotherapy, many alternative desensitization methods have been proposed in allergic patients; these methods are based on the oral, nasal, sublingual, or bronchial introduction of the specific allergen. The effectiveness and the safety of sublingual desensitization have been confirmed in controlled, double-blinded studies (15,16).
There are no data concerning desensitization treatments performed by percutaneous administrations of the allergen (neither latex nor other allergens). However, a satisfactory transcutaneous absorption may be hypothesized for many allergens, because many drugs have a well known transcutaneous absorption.
On the basis of experimental observations on mice, sensitization to protein allergens and even immediate-type allergy may develop transcutaneously. Moreover, a transcutaneous immunization has also been demonstrated in humans (17). A desensitization might be performed by means of the percutaneous administration of a specific antigen. In this way, the adopted contact desensitization may act exactly as the conventional subcutaneous desensitization, the only difference consisting of a different route of the allergen administration.
After a long period of absence of any exposure to a specific allergen, positive allergological tests may spontaneously turn negative (18,19) in the absence of any treatment. However, in our opinion, the occurrence of a complete desensitization to latex cannot be explained by a spontaneous “natural course” of latex allergy in our patients, who had professionally repeated exposure to latex allergens in the months preceding the desensitization, and, of course, during the whole desensitization period. Moreover, such a spontaneous desensitization did not occur in any of our control subjects, who still exhibited allergy to latex at the end of the one-year follow-up period without contact with latex-containing items.
In conclusion, although this study has been completed in only five patients, it provides evidence that a safe therapeutic approach to latex allergy is possible. Contact desensitization seems to be safe even in patients with latex-induced occupational asthma, in which the application of latex to skin can induce asthmatic responses. However, further studies in larger groups of patients are necessary to fully confirm these preliminary results and to assess whether this technique can be successfully applied to treatment of allergic responses to other environmental allergens.
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