Allergic skin disease: investigation of both immediate- and delayed-type hypersensitivity is essential

BACKGROUND: In our clinic we routinely patch test patients referred from occupational health for the investigation of latex contact urticaria. We also undertake both patch and prick testing (where indicated) in patients referred with persistent dermatitis/eczema. If investigation of allergic skin disease is undertaken by a non-dermatologist, it is unlikely that patch testing will be performed. OBJECTIVE: To carry out a retrospective analysis of patients who had been prick tested to establish whether an incomplete diagnosis would have been reached if patch testing had been omitted. METHODS: Details of patients who had attended for patch testing between July 2004 and December 2005 were analysed. Patients who had had prick tests and patch testing were identified. The outcomes of prick tests and patch testing were documented together with the clinical relevance. RESULTS: Three hundred and thirty out of 1060 patients referred to the clinic were prick tested. 54.2% patients were referred from dermatologists. 26.6% were referred from occupational health, 68 patients had positive reactions on prick testing of whom 36 had positive patch tests (52.9%), which were of current relevance in 27 patients (39.7%). Nine out of 106 health workers referred to exclude latex contact urticaria had positive prick tests to latex. Fifty of these patients demonstrated delayed-type hypersensitivity with nickel, cobalt, rubber and its additives being the most common allergens found. Of the 262 patients who had negative prick tests, 121 had positive patch tests (46.1%) of current relevance to patient history in 92 subjects (35.1%). While none of the six patients referred for investigation of reaction to local anaesthetics had a positive prick test, one was allergic to local anaesthetic on patch testing. CONCLUSION: Omission of patch testing from the investigation of allergic skin disease, even when contact urticaria may be the sole suspected diagnosis, would result in the frequent missed diagnosis of contact allergy. We recommend that patients with suspected allergic skin disease are investigated in an environment where investigation of both immediate- and delayed-type hypersensitivity can be undertaken. In particular, patients with atopic eczema, suspected latex rubber allergy, hand dermatitis (particularly occupational) and drug reactions should be targeted to receive both investigations.     

Cow's milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE

BACKGROUND: The objective of the present study was to evaluate the relevance of skin tests and the concentration of cow's milk-specific IgE antibodies in correlation with oral cow's milk challenge in infants with suspected cow's milk allergy. METHODS: The study material comprised 143 infants under the age of 2 years who had undergone a diagnostic elimination challenge because of suspected cow's milk allergy in 1996. Cow's milk-specific IgE was measured, and skin prick and patch tests were performed. RESULTS: Of the 143 oral cow's milk challenges performed, 72 (50%) were positive. Of the positive reactions, 22 involved immediate-type reactions. In 50 patients, delayed-onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge-proven cow's milk allergy, 26% showed elevated IgE concentrations to cow's milk, 14% had a positive skin prick test, and 44% had a positive patch test for cow's milk. Interestingly, in most patch test-positive patients, the prick test for cow's milk was negative. CONCLUSIONS: Our study demonstrated that many patients with a negative prick test result had a positive patch test to cow's milk. The patch test was a more sensitive method than the prick test or RAST to detect cow's milk allergy in this study population. Our results indicate that patch testing will significantly increase the probability of early detection of cow's milk allergy. Confirmation of the diagnosis is essential in patients with negative test results but a clinical suspicion of food allergy, and in patch test-positive patients. For this purpose, the most reliable method is the elimination-challenge procedure.     

Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study

Background:  Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions.
Methods:  Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls.
Results:  Skin test specificity was 96–100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure.
Conclusions:  These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.     

Wheat allergy: diagnostic accuracy of skin prick and patch tests and specific IgE

BACKGROUND: Food allergy makes an important contribution to the pathogenesis of atopic eczema in infants. However, clinical data on cereal allergy are scanty. The objective was to study the relevance of patch testing, skin prick tests, and the concentration of wheat-specific IgE antibodies (CAP RAST) in correlation with oral wheat challenge in infants with suspected wheat allergy. In particular, we aimed to determine whether the patch test could increase the diagnostic accuracy in detecting wheat allergy. METHODS: The study material comprised 39 infants under the age of 2 years. Of these patients, 36 were suffering from atopic eczema and three had only gastrointestinal symptoms. The patients were subjected to a double-blind, placebo-controlled or open wheat challenge. Wheat-specific IgE was measured by CAP RAST, and skin prick and patch tests were performed. RESULTS: Of the total 39 wheat challenges, 22 (56%) were positive. Of the positive reactions, five involved immediate-type skin reactions over a period of 2 h from the commencement of the challenge. In 17 patients, delayed-onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge-proven wheat allergy, 20% showed elevated IgE concentrations to wheat, 23% had a positive skin prick test, and 86% had a positive patch test for wheat. The specificities of CAP RAST, skin prick tests, and patch tests were 0.93, 1.00, and 0.35, respectively. CONCLUSIONS: Our study demonstrated that patch testing with cereals will significantly increase the probability of early detection of cereal allergy in infants with atopic eczema and is helpful in the planning of successful elimination diets before challenge. The specificity of the patch test was lower than that of other tests. Therefore, confirmation of the diagnosis with the elimination-challenge test is essential in patients with positive patch test results.     

Occupational hypersensitivity to metal salts, including platinum, in the secondary industry

BACKGROUND: Exposure to platinum group elements (PGEs) - platinum (Pt), palladium (Pd), rhodium (Rh) and iridium (Ir) - may cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and (less frequently) contact dermatitis. Our aim was to determine the prevalence and the clinical characteristics of hypersensitivity to platinum salts and to other elements of the platinum group. METHODS: A total of 153 subjects working in a catalyst manufacturing and recycling factory were examined. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test for PGEs and other common aeroallergens, and patch tests for PGEs. Skin prick tests and patch tests were performed with H(2)[PtCl(6)], K(2)[PtCl(4)], Na(2)[PtCl(6)], IrCl(3), RhCl(3), PdCl(2), aqueous solutions at different concentrations. RESULTS: Positive prick test reactions to Pt-salts at various concentrations were found in 22 (14.4%) of 153 workers; eight had simultaneous reactions to all Pt-salts tested; seven had positive responses to H(2)[PtCl(6)] only; four had simultaneous positive reactions to both H(2)[PtCl(6)] and K(2)[PtCl(4)]; three had positive reactions to H(2)[PtCl(6)] and Na(2)[PtCl(6)]. Three of 22 had positive reactions to H(2)[PtCl(6)] and IrCl(3) solutions, two of these had positive reactions to H(2)[PtCl(6)], IrCl(3) and RhCl(3) solutions. Positive patch test reactions to platinum salts at day 2 were seen in two of 153 subjects. CONCLUSIONS: The results of this study demonstrate that Pt-salts are important allergens in the catalyst industry and that the clinical manifestations involve both the respiratory system and the skin. Hexachloroplatinic acid should be considered the most important salt to use for skin prick tests.     

Occupational type I allergy to Christmas cactus (Schlumbergera)

The study aimed to determine whether occupational contact urticaria and symptoms of mucous membranes, reported by five workers in a cactus nursery, were due to IgE-mediated allergy to Schlumbergera cacti. The five persons had positive skin prick tests to the plants as is and positive histamine-release tests, and in three of them specific IgE to the cacti could be demonstrated by Maxisorp RAST and immunoblotting. Four of the patients were atopic, and the fifth had a positive skin prick test to cat dander, indicating latent atopy. Skin prick tests with cacti were negative in most atopic volunteers, and all had negative histamine-release tests. The results suggest a true IgE-mediated allergy to the cacti, and both genetic predisposition and close contact with the plants at work seem to be important factors in the emergence of this new occupational allergy.     

Usefulness of intradermal test and patch test in the diagnosis of nonimmediate reactions to metamizol

BACKGROUND: Metamizole is a pyrazolone derivative, and its most common reactions are IgE-mediated reaction and idiosyncratic reactions. Non-immediate reactions are poorly described and there are very few reports on non-immediate reactions to pyrazolones. MATERIALS AND METHODS: We evaluated 12 patients (nine men) who consulted for a non-immediate reaction after metamizol administration. We performed cutaneous tests (skin prick tests and immediate and delayed intradermal tests) and epicutaneous tests, and, if necessary, an oral challenge test. RESULTS: All skin prick and intradermal tests, if necessary, were negative in immediate reading. Delayed intradermal tests were positive in six of 10 patients (60%) and epicutaneous tests were positive in four of 11 patients (36%). Three cases (25%), were diagnosed by a positive oral challenge test. DISCUSSION: Delayed-reading intradermal tests and patch tests are useful tools in the diagnosis of nonimmediate reactions to pyrazolones and should be considered the first step when evaluating these type of reactions. Intradermal test appears to be more sensitive than patch test. The positivity of skin tests suggests an immunological reaction, probably mediated by T lymphocytes, but further studies are required.     

Clinical Features of Immediate Hypersensitivity to Isopropylantipyrine

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.     

Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell-mediated hypersensitivity to β-lactams

Background:  Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to β-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to β-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to β-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to β-lactams.
Methods:  From our database we selected 73 patients with cell-mediated allergy to β-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing.
Results:  Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction.
Conclusions:  Our rate of cross-reactivity between imipenem-cilastatin and other β-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to β-lactams. Patients with cell-mediated allergy to β-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.     

Diagnosis of iodinated contrast media hypersensitivity: results of a 6-year period

Background Iodinated contrast media (ICM) hypersensitivity reactions represent a serious problem. Very few clinical data concerning systematic skin testing to ICM are available. Objective To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity. Material and methods All patients referred over a 6‐year period for ICM hypersensitivity past reactions were skin tested for (a) the implicated ICM, or (b) a set of ICM if they were positive for the implicated ICM or if its name was unknown. Results Forty‐four patients, with a median age of 56 years, were studied (15 males, 29 females). The ICM skin tests were positive in 10 patients (23%): one had a positive skin prick test, seven an immediate positive intradermal test (IDT) and two a delayed positive IDT. Skin tests were more often positive in patients with immediate (9/32) as compared with those with non‐immediate reactions (1/11). The time interval between the reaction and skin testing was shorter for those patients with an immediate ICM reaction and a positive skin test result (3 months [2.5–174.0]) as compared with those with an immediate ICM reaction and a negative skin test (48 months [6.8–159.0]), (P<0.05). Respiratory allergy was more frequent in the positive group (6/10 vs. 7/34, P<0.05). Conclusions Skin tests with ICM are positive in a subgroup of patients with ICM hypersensitivity and may play an important role in the diagnosis of ICM allergy.     

Insect Allergy

One hundred and seventeen persons all stung by yellow jacket (YJ) and/or bee were examined by means of skin prick test with venom of these insects, skin prick test with 10 inhalant allergens and analyses of total IgE. Specific IgE and IgG against honey bee and YJ venom. Eighty-seven persons had had a systemic reaction. Positive correlations ( P < 0.05) were found between results of skin prick tests and specific IgE against venoms and, for YJ, between the severity of symptoms after sting and the size of skin prick test with the venom. That some of the more severe symptoms could have been caused by non-immunological mechanisms could explain why a significant correlation was present only between the results of the prick test and specific IgE and not between these tests and the clinical symptoms. Specific IgE values against YJ and honey bee venom showed convariation, although no correlation could be demonstrated between the clinical symptoms after stings from these insects, or between skin prick test results using the two different extracts. The severity of the sting reactions was not correlated to age, atopic disposition, amount of total IgE, number of stings during life, or positive skin prick test to inhalant allergens. It is concluded that in insect allergy, specific IgE analysis and skin prick tests are supplementary.     

Immunohistological analysis of 'negative' patch test sites in atopic dermatitis

Background Variable results have been obtained when patients with atopic dermatitis (AD)) have been patch tested with allergens known to produce a positive prick lest. The significance of patch test results in our understanding of the pathogenesis of AD therefore remains questionable. Objective This study was designed to determine the relevance of either positive or negative patch test results in relation to the expression of cell mediated immunity to allergens in patients with AD. Methods Thirty-five patients with AD exhibiting patch test positivity to one or more aeroallergens on ‘tape stripped’ areas of the back were retested without prior tape stripping. Nine patients again showed positivity to one or more allergens while 26 failed to show positive reactions. In six of the positive patients both positive and negative patch tests were observed. Skin biopsies were taken from these matched positive and negative patch test sites as well as from an area of uninvolved skin. Samples were frozen and cryostat sections were analysed with immunohistological techniques using monoclonal antibodies to investigate the distribution of immunocompetent cells. Results All positive patch tests exhibited characteristics of a cell mediated immune response. The negative patch test sites were also found to contain evidence of mononuclear cell infiltration. Both negative and positive patch test sites showed significantly greater proportions of T cells compared to uninvolved skin. No increase in numbers of RFD1 positive and RFD7 positive macrophages were observed in either positive or negative patch test sites. Expression of CD23 by CD1 positive Langerhans cells was raised in both negative and positive patch tests compared to uninvolved areas. A significant increase in the population (RFD7+, CD23+) was seen in positive patch test sites compared to uninvolved skin. An increase in the proportion of RFD1 positive cells expressing CD23 was also seen in both negative and positive patch tests compared to uninvolved skin. Conclusions This paper demonstrates that immunological reactions are promoted at ‘non-tape stripped’ patch test sites where no clinical evidence of reactivity is seen. Together the data demonstrate that the presence of systemic cell mediated immunity to specific allergens identified in patients by positive patch test, may also be present when no clinical signs are seen at the patch test site.     

Hypersensitivity to trimethoprim

We present two patients who experienced life-threatening immediate reactions and one patient who developed generalized urticaria following oral administration of trimethoprim (TMP) and sulfamethoxazole (SMX) combination. Skin prick tests with TMP were positive in the three patients. No patients reacted to skin prick tests with SMX. No significant levels of IgE antibodies to TMP were found by RAST in the serum of the patients. Normal subjects used as controls did not react to any of these tests. Single-blind, placebo-controlled oral challenges were positive with TMP and negative with SMX in all patients. These results suggest that the three patients developed type I hypersensitivity reactions to TMP. In our patients skin prick tests with TMP were useful in TMP hypersensitivity diagnosis.     

Skin and radioallergosorbent tests in patients with sensitivity to bee and wasp venom

Intradermal (ID) and prick tests with bee or wasp venom (Pharmalgen) have been performed on 102 subjects with a history of adverse reactions to stings and forty-six control subjects giving no such history. Venom was diluted 100, 10 and 1 μg/ml for prick testing and 10^-2, 10^-2, 10^-3 and 10^-4%mUg/ml for ID injections. In forty-six control subjects all were tested with the highest concentration of prick testing solution (100 μg/ml), eight (17%) had positive reactions, a similar reaction rate to that reported in control subjects using 10^-1μg/ml ID. In our 102 test subjects skin tests were therefore regarded as positive only if the reaction was elicited by 10^-2μg/ml or less by prick test of 10^-2μg/ml or less ID. In general the results with skin prick tests and ID tests were comparable when the prick solution was 1000 times the concentration of that used for ID testing. ID tests were positive in thirteen with negative skin prick, seven of whom had detectable antibodies when tested by RAST. Conversely four with a positive skin prick test (two of whom were RAST positive) were considered negative on ID testing. As judged either by RAST or skin tests it appeared that sensitivity diminished with the time interval from the last sting (P< 0-001).     

Long-term absence of sensitization to mepivacaine as assessed by a diagnostic protocol including patch testing

BACKGROUND: Prospective assessment of non-reactivity to local anaesthetics is a frequent reason for allergy consultation. OBJECTIVES: To investigate the clinical profiles of subjects referred for allergy evaluation; to prospectively reduce the frequency of evaluation by assessing the persistence, during clinical use, of non-reactivity to contaminant/additive-free mepivacaine; and to determine the usefulness of a diagnostic protocol involving patch testing. METHODS: In a prospective study, 198 consecutive patients underwent collection of clinical data, skin prick tests and patch tests using allergens/antigens relevant for the investigation, and an intradermal/subcutaneous challenge procedure using contaminant/additive-free mepivacaine, as appropriate. Patients were followed up for 3 years for assessment of non-reactivity persistence using the same diagnostic protocol. RESULTS: Only one-third of the patients had a history of previous adverse local anaesthetic reactions. Absence of sensitization to contaminant/additive-free mepivacaine persisted in all subjects completing the follow-up. Controlled challenge with mepivacaine was negative in 196 patients with both negative specific skin prick tests and patch tests but it was eventful in two subjects with positive specific patch tests. A few subjects displayed positive skin prick tests and/or patch tests for latex and/or additives. CONCLUSIONS: A few patients had a relevant history for potential local anaesthetic-induced adverse reactions. Upon assessment of absence of sensitization and reactivity, contaminant/additive-free mepivacaine could safely be given for as long as 3 years. The patch testing was shown to be useful and safe for prediction of challenge outcomes. True allergic reactions to contaminant/additive-free mepivacaine were not observed in our patient series.     

A comparison of two RAST methods and skin prick testing in the diagnosis of wasp venom allergy

With the aim of evaluating the correlation between skin prick test and two radioallergosorbent tests (RAST) using paper (P-RAST) and Al(OH)3 (Al-RAST) as sorbent materials, 45 consecutive patients known to have been stung by wasp within 6 months were examined. Four patients had a normal reaction, four a large local reaction and 37 a systemic reaction. We found a good correlation between a systemic reaction and a positive P-RAST. Fifty-one per cent of patients with a systemic reaction had a negative Al-RAST, whereas only 8% had a negative P-RAST. Eight per cent of patients with a systemic reaction had a negative SPT. In the eight patients without a systemic reaction, the same patient reacted positively in Al-RAST and P-RAST.     

Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins

There are some contradicting data about clinical allergic cross-reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins. The purpose of this study was to assess the safety of administering cephalosporins to penicillin-allergic patients. The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction. To assess the clinical tolerance to cephalosporins, 41 well-characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone. Skin prick and intradermal tests with all cephalosporins tested were negative. All penicillin-allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect. These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin-allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.     

Frequency and significance of immediate contact reactions to peanut in peanut-sensitive children

BACKGROUND: Parents of atopic children frequently report, and are alarmed by, contact reactions to foods. Some schools restrict foods due to concerns regarding possible systemic reactions following contact in allergic children. OBJECTIVE: We aimed to determine the frequency with which peanut-sensitive children exhibited contact sensitivity to peanut butter and to assess the significance of such reactions. METHODS: One gram of peanut butter was applied directly to the skin of 281 children who were skin prick test (SPT) positive to peanut (immediate skin application food test; I-SAFT). The test was considered positive if one or more weals were present when the patch was removed after 15 min. A subset of children then underwent an open-label oral challenge with graded amounts of peanut protein. RESULTS: During 3515 clinic visits, 330 I-SAFT tests for peanut contact sensitivity were performed; 136 (41%) were positive. The mean SPT diameter was 10 mm in the I-SAFT-positive children and 8.5 mm in the I-SAFT-negative children (t-test, P<0.0001). No child had a systemic reaction following topical application of peanut butter. Eighty-four children had 85 oral challenges after blinded, placebo-controlled I-SAFT testing. Challenge was positive in 26/32 of those with a positive I-SAFT and negative in only 6/32. Challenge was also positive in 26/53 but negative in 27/53 of those with a negative I-SAFT (sensitivity 50%, specificity 82%, chi2, P=0.003). CONCLUSION: A minority of children sensitized to peanut (positive SPT) develop localized urticaria from prolonged skin contact with peanut butter. No tested subjects, including ones with systemic reactions upon oral challenge, developed a systemic reaction to prolonged skin exposure to peanut. Therefore, systemic reactions resulting from this mode of contact with peanut butter appear highly unlikely.     

T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests

BACKGROUND: In addition to immediate reactions, late adverse reactions to iodinated contrast media (ICM) were reported in 2% to 5% of patients exposed to ICM and, as a consequence, have recently gained more attention. A few well-documented case reports postulate a hypersensitivity mechanism. OBJECTIVE: The aim of this study is to demonstrate a T cell-mediated mechanism to the ICM by using in vitro and ex vivo tests. METHODS: We analyzed 12 patients with 13 adverse ICM reactions, 9 of whom were women. Clinical history suggested an immune reaction to ICM. Skin tests (skin prick, intradermal, and patch tests) were performed with various ICM and read after 15 minutes and 24 and 48 hours. Skin biopsy specimens of positive test sites of 11 patients were evaluated by means of immunohistology. T-cell reactivity to ICM in vitro was analyzed with lymphocyte activation tests. RESULTS: Seven patients showed generalized maculopapular eruptions, one of them with fever; 4 had a so-called drug hypersensitivity syndrome with exanthema, eosinophilia, and fever; 1 had maculopapular eruptions and fever; 1 had late-onset urticaria with loss of consciousness; and 1 had facial edema and respiratory distress. An immune reaction to ICM was inferred from positive skin prick test (2 patients), positive patch test (10 patients), and positive intradermal test (9 patients) at 24 and 48 hours. Skin biopsy specimens revealed a T-cell infiltrate in the dermis with predominantly CD4 + T cells in 8 patients, CD8 + T cells in 1 patient, and equal numbers in 1 patient. Cross-sensitivities to several ICM were observed (9/12). Other drug allergies were noted in 6 of the 12 patients. CONCLUSIONS: Delayed reactions to ICM are most likely caused by immune reactions to these drugs and can elicit different clinical features. The involvement of T cells is suggested by positive skin test, as well as positive proliferative responses, to the drugs in vitro . A high degree of cross-reactivity with other than the eliciting ICM was observed. Moreover, 50% of these patients reported another drug hypersensitivity, suggesting a predisposition to immune reactivity in some patients.     

Diversity of asparagus allergy: clinical and immunological features

BACKGROUND: Asparagus (Asparagus officinalis) is an extensively grown and consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic contact dermatitis (ACD) due to asparagus has been reported. However, only a few case reports of asparagus IgE-mediated allergy have been published. In a previous study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and Aspa o 1.02) were relevant allergens of asparagus. OBJECTIVE: We retrospectively analysed the 27 patients diagnosed with asparagus allergy during the last 5 years. All of them reported adverse symptoms after either asparagus ingestion or handling. We describe their clinical features and evaluate whether they were associated to immunological findings (immunoblot pattern and skin reactivity to LTPs). METHODS: Patients underwent skin prick and patch tests with standard panels of vegetables and aeroallergens. Besides crude asparagus extract, two purified LTPs were prick and patch tested. Total and specific IgE measurements and asparagus extract IgE immunoblotting were performed. Patients reporting asthma symptoms underwent specific inhalation challenge to asparagus. RESULTS: Of the 27 subjects, eight had ACD, 17 had IgE-mediated allergy and two had both ACD- and IgE-mediated allergy. Positive patch tests with the crude asparagus extract but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with IgE-mediated disease, 10 had contact urticaria after asparagus handling. Of them, five subjects and five others without skin allergy showed respiratory symptoms; of them, eight were diagnosed with occupational asthma confirmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Four patients suffered from immediate allergic reactions related to asparagus ingestion (food allergy); three of them reported anaphylaxis whereas the other had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45-70 kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to LTPs, six showed bands at 15 kDa. Either IgE-binding bands or positive prick tests to LTPs were observed in asthma (62%) and anaphylaxis (67%). CONCLUSION: Asparagus is a relevant source of occupational allergy inducing ACD and also IgE-mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs seem to play a major role. The clinical relevance of LTP sensitization among patients with mild disease or symptom-free subjects should be addressed in prospective studies.