Diagnosing nonimmediate reactions to penicillins by in vivo tests

BACKGROUND: Maculopapular and urticarial rashes are nonimmediate manifestations common during penicillin treatment; the former often represent cell-mediated hypersensitivity. Our objectives were to assess the incidence of allergy in adults reporting nonimmediate manifestations during penicillin therapy and to evaluate the diagnostic potential of patch tests, delayed-reading skin tests and challenges in such cases. METHODS: We used prick and intradermal tests as well as patch tests with penicillin determinants, ampicillin, amoxicillin and any other suspect penicillins. We also performed challenges with the suspect antibiotics. RESULTS: Such antibiotics were aminopenicillins in 93.1% of 259 patients, most of whom had suffered from maculopapular rashes followed by piperacillin (4.2%). Three subjects displayed immediate skin test positivity. Ninety-four subjects showed patch test and delayed intradermal test positivity to the culprit penicillin (90 to aminopenicillins and 4 to piperacillin) and were considered as having had delayed hypersensitivity reactions. Five of the 8 subjects who displayed delayed intradermal test positivity and patch test negativity to the suspect penicillin underwent challenges, 2 reacted positively to the responsible aminopenicillin. Among the remaining 154 with negative results in allergologic tests, 125 agreed to undergo challenges; only 3 reacted. In all, 98 patients -- 93 of whom had experienced maculopapular rashes -- displayed delayed hypersensitivity (94 to aminopenicillins and 4 to piperacillin). CONCLUSIONS: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to penicillins, particularly maculopapular rashes. Patch test and delayed intradermal positivity together indicate delayed hypersensitivity. Intradermal testing appears to be slightly more sensitive than patch testing.     

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.     

Diagnosis of nonimmediate reactions to beta-lactam antibiotics

Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during beta-lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug. Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to beta-lactams.     

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.     

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.     

Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children

Background:  Nonimmediate allergic reactions (NIR) to aminopenicillin include several entities, the most common of which are urticaria-like and maculopapular exanthemas.
Aims of the study:  To evaluate a group of children who developed one or more episodes of skin reactions suggestive of NIR after aminopenicillin administration.
Methods:  The inclusion criteria required negative immediate skin tests and absence of specific IgE antibodies to different penicillins. Intradermal and patch tests were carried out with delayed readings and, if negative, a drug-provocation test including a full therapeutic course of the drug was given. Two different groups were compared: A) children with positive skin testing or a positive drug-provocation test and B) children with negative skin testing and good tolerance after a drug-provocation test.
Results:  Group A was composed of 20 patients. Positive intradermal/patch tests were found in one patient and in the remaining 19, a positive response to a drug-provocation test confirmed the diagnosis. Group B (the control group) consisted of 19 patients with similar symptoms after aminopenicillin intake but good tolerance. No differences in age, dose or number of previous treatments were observed between the groups. The clinical entities were also similar in both groups.
Conclusions:  Reproducible nonimmediate skin reactions to aminopenicillins may occur in children in spite of negative skin testing. The value of this diagnostic procedure seems to be limited in this type of reaction, with drug-provocation tests (DPT) being a reasonable and safe alternative if the diagnosis has to be confirmed.     

In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions.

BACKGROUND: beta-Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. METHODS: Fifty patients with a well-documented history of allergic reactions to beta-lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. RESULTS: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. CONCLUSION: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.     

Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes

We assessed 195 subjects with histories of adverse reactions to aminopenicillins, using 1) skin tests with penicilloyl polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), amoxicillin, and ampicillin (read after 20 min and 48 h); 2) patch tests with PG, amoxicillin, and ampicillin; and 3) RAST for penicilloyls G and V. Oral challenges with ampicillin, amoxicillin, and penicillin V were administered to 34/60 patients reporting maculopapular reactions. Immediate hypersensitivity (IH), in most cases for both penicillin and aminopenicillins, was diagnosed (based on skin tests, RAST, or both) in 35 subjects who had suffered anaphylactic shock, or urticaria, angioedema, or both urticaria and angioedema. Thirty-three of the 60 subjects reporting maculopapular reactions presented delayed intradermal and patch-test positivity, indicating delayed hypersensitivity (DH), for ampicillin and amoxicillin, and three were also positive for PG. Diagnoses were confirmed with oral challenges in 18/33. The remaining 27/60 were negative in all allergologic tests, with oral-challenge confirmation in 16. Our findings highlight the importance of the amino group in DH to aminopenicillins. Moreover, the mean time interval between the last reaction and our tests was significantly (P < 0.01) longer in DH subjects (54.96 months) than in those with IH (18.62 months), suggesting that the time of testing is less important in cases of DH.     

Recent advances in the diagnosis of drug allergy

PURPOSE OF REVIEW: The present review addresses the most recent literature regarding the diagnosis of drug hypersensitivity reactions, which can be classified as immediate or nonimmediate according to the time interval between the last drug administration and the onset. Immediate reactions occur within 1 h; nonimmediate ones occur after more than 1 h. RECENT FINDINGS: Clinical and immunological studies suggest that type-I (IgE-mediated) and type-IV (cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. New diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation. SUMMARY: In diagnosis, the patient's history is fundamental; the allergologic examination includes in-vivo and in-vitro tests selected on the basis of the clinical features. Prick, patch, and intradermal tests are the most readily available forms of allergy testing. Determination of specific IgE levels is still the most common in-vitro method for diagnosing immediate reactions. The sensitivity of allergologic tests is not 100%; in selected cases, therefore, provocation tests are necessary. The routine use of the basophil activation test and the lymphocyte activation test could increase the sensitivity of diagnostic work-ups, thus reducing the need for drug provocation tests.     

*Nonimmediate reactions to betalactams: prevalence and role of the different penicillins

In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6%, of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93 Q of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions. The high percentage (65%) of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte-mediated reaction occurred. However, the possibility that other mechanisms may also have been involved cannot be ruled out     

Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins

Background:  Administration of meropenem to penicillin-allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross-reactivity to imipenem, the prototype of the carbapenem class of β-lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross-reactivity between penicillins and both meropenem and imipenem in adults.
Objective:  To assess cross-reactivity and tolerability of meropenem in children with documented penicillin allergy.
Methods:  One hundred and eight consecutive children who had suffered a total of 129 immediate reactions (120 urticarial and/or angioedematous manifestations and 9 anaphylactic shocks) to penicillins and had positive results to skin tests for at least one of the penicillin reagents tested underwent skin tests with meropenem and negative subjects were challenged with it.
Results:  One subject (0.9%) displayed a positive intradermal test to meropenem. The remaining 107 subjects with negative skin tests to meropenem tolerated challenges. Challenges were not followed by full therapeutic courses.
Conclusions:  Our results demonstrate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem in children with immunoglobulin E-mediated hypersensitivity could be abandoned; in those who especially require meropenem treatment, prophylactic skin tests are advisable, because negative results indicate tolerability.     

Recent advances in the diagnosis of drug allergy

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.     

T-cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application — patch testing and LTT in patients with adverse reaction to local anaesthetics

BACKGROUND: Local anaesthetics are known to elicit T-cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side-effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E-mediated, since immediate skin tests are mostly negative. OBJECTIVES: We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T-cell sensitization to local anaesthetics, which might be responsible for the symptoms. METHODS: Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed. RESULTS: Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive. CONCLUSIONS: Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell- mediated sensitization, which might be detected by patch testing or LTT.     

Management of hypersensitivity reactions to iodinated contrast media

All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.     

Nonimmediate reactions to systemic corticosteroids suggest an immunological mechanism

BACKGROUND: Administration of corticosteroids (CS) by different routes may cause varying types of allergic reactions, thereby hampering their further use in affected patients. In order to verify an immunological involvement we evaluated a group of patients with symptoms compatible with nonimmediate allergic reactions to CS. METHODS: Studies included patch and intradermal tests, immunohistochemical studies and controlled administration to reproduce the response. The cytokines interleukin (IL)-4, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were quantified in peripheral blood during the response. RESULTS: Of 32 subjects evaluated presenting nonimmediate urticaria or exanthema, 21 were finally considered positive after re-exposure. The drugs most frequently involved were betamethasone and dexamethasone. Fewer than half the patients responded to prednisolone whilst some responded to three or more CS. Hydrocortisone and deflazacort were well tolerated by all the patients. Subjects with a positive intradermal or patch test had a perivascular mononuclear cell infiltrate with the presence of CD4 and CD8 lymphocytes positive for CD45RO+ (memory) and CD69 (activation marker) cells. Monitoring peripheral blood during the acute response showed expression of IFN-gamma and TNF-alpha, with downregulation of IL-4. CONCLUSION: Adverse systemic responses to different CS are suggestive of a nonimmediate reaction. The symptoms elicited together with the immunlogical studies suggest a T-cell mediated response. The response to closely related CS was especially marked between betamethasone and dexamethasone, whereas hydrocortisone and deflazacort were well tolerated.     

Skin and laboratory tests in amoxicillin- and penicillin-induced morbilliform skin eruption

BACKGROUND: Cutaneous amoxicillin- and penicillin-mediated reactions can be classified as immediate and delayed-type reactions. Immediate reactions are thought to involve IgE antibodies and have been studied extensively. In contrast only few data exist about delayed reactions such as morbilliform or maculopapular rash. OBJECTIVE: To assess the predictive value of immediate skin tests, skin-patch tests, specific IgE and lymphocyte transformation tests with regard to the diagnosis of delayed skin eruptions. METHODS: Skin and in vitro tests were performed in 18 subjects. Twelve subjects had penicillin- or amoxicillin-induced morbilliform exanthema and six were controls without hypersensitivity reaction, tested before and after exposure. RESULTS: Specific IgE to penicillin and immediate penicillin skin tests were negative in amoxicillin- or penicillin-induced delayed skin eruptions. In contrast, skin-patch testing and LTT were positive in 9/12 or 10/12, respectively, but negative in all six controls. CONCLUSION: These findings substantiate a T-cell-mediated immune pathomechanism in the majority of penicillin-induced delayed skin reaction. Moreover, they underline the necessity to adapt the test procedures to underlying pathomechanisms and support the diagnostic value of skin-patch testing and LTT in delayed cutaneous reactions to penicillins.     

The value of acoustic rhinometry in assessing nasal responses to cat exposure

Background: Acoustic rhinometry (AR) uses sonar principles to map the anatomy of the nasal cavity and has been used in other studies to assess acute airway responses to allergen exposure. Objective: The purpose of this study was to evaluate the utility of AR in assessing acute airway responses to cat allergen exposure by using a well-characterized cat exposure model. Methods: Thirty subjects with a history of cat-induced rhinitis and a positive skin prick test response to cat allergen underwent an environmental cat challenge. Of these 30 subjects, 10 also had repeat challenges at lower levels of antigen to determine whether there was a dose response. Five subjects with negative skin test responses to cat were recruited as control subjects. During the 1-hour cat exposure, upper and lower respiratory symptoms were scored every 5 minutes, and spirometry and AR were obtained every 15 minutes. Results: Although 29 of 30 subjects had changes in AR measurements, no correlations were detected between upper respiratory symptom scores and any of the changes observed in AR. In comparing the baseline challenges with lower antigen level challenges, upper respiratory symptom scores differed significantly (P = .002), whereas AR responses were nearly identical. Subjects without cat allergy did exhibit less response by AR (P = .05 to .13), but the greatest differences remained in the upper respiratory symptoms scores (P < .0001). Conclusion: We conclude that although AR does provide an objective measure of nasal response to allergen exposure, it has significant limitations. These are evidenced by the lack of correlation with symptoms, the inability to measure a dose response, and the changes noted even among the control subjects. (J Allergy Clin Immunol 1998;102:896-901).     

The patch test, skin prick test, and serum milk‐specific IgE as diagnostic tools in cow's milk allergy in infants

We evaluated the value of the patch test, skin prick test, and milk‐specific IgE by CAP RAST in 301 infants with suspected hypersensitivity to cow's milk. The patch test was carried out with milk powder, and the skin prick test with cow's milk‐based formula. Hypersensitivity to cow's milk was determined with double‐blind, placebo‐controlled challenge. An immediate reaction to cow's milk challenge was observed in 100 infants (33%), a delayed reaction in 76 (25%), and a negative result in 125 (42%). Skin prick test wheals were significantly greater in infants with immediate reactions than in infants with delayed or negative reactions. Milk‐specific IgE was correlated with the skin prick test ( r =0.78, P <0.001, n =268) but did not contribute to further discrimination of immediate reactions from delayed or negative reactions compared to skin prick test alone. In our study population, the skin prick test (diameter ≥3 mm) showed a specificity and sensitivity of 91% and 69%; the results for milk‐specific IgE (≥0.7 kU/l) were 88% and 58%, respectively. The patch test did not distinguish subjects with immediate or delayed reactions from those with negative reactions.     

Atopic dermatitis and aeroallergen contact sensitivity

Atopic dermatitis (AD) may be worsened by ingested foods or contact with irritants. We have identified 10 patients (six male and four female subjects, aged 1 to 54 years) with AD and contact sensitivity to a variety of aeroallergens. Marked improvement in skin symptomatology was noted when these patients were removed from their usual environment. The patients had markedly positive immediate wheal-and-flare reactions to a variety of aeroallergen extracts in response to prick tests and were subsequently patch tested on uninvolved skin with aeroallergen extracts (1:20 wt/vol, 50% glycerine) that elicited positive prick tests. Patch tests were applied for 48 hours, removed, and then were interpreted 24 hours later. Fifty percent glycerine was used as a negative control. Significant delayed cutaneous responses to a variety of aeroallergens were noted: house dust mite, tree, grass and weed pollens, animal danders, and various molds. Positive delayed cutaneous responses correlated strongly with aeroallergens identified in the patient's environment and/or suspected by the patients as provocateurs of their AD. Delayed cutaneous reactions were negative to aeroallergens not historically relevant to their AD. We conclude that aeroallergen contact may play an important role in selected patients with AD. The demonstration of immediate and delayed cutaneous responses in AD suggests both IgE and cell-mediated hypersensitivity as contributory mechanisms.     

Clinical presentation and time course in hypersensitivity reactions to beta-lactams

Background:  β-lactam hypersensitivity reactions are classified as immediate or nonimmediate. Diagnosis is usually based upon skin tests and provocation challenges.
Objective:  The time course of the reactions in proven β-lactam hypersensitivities was studied and then correlated with the symptoms to determine the relationship between the clinical presentations and the time course.
Method:  All of the patients who consulted between 1996 and 2004 for a suspected β-lactam hypersensitivity reaction were studied. Two hundred and ten patients with a proven hypersensitivity reaction diagnosed according to the European Network on Drug Allergy were included in the present study.
Results:  Of the patients, 36.7% had urticaria as a single symptom, 19.1% anaphylaxis without shock, 17.6% anaphylactic shock and 19.1% maculopapular exanthema. Anaphylactic shock and anaphylaxis mostly occurred within 1 h after drug administration. Exanthema mainly occurred after 24 h. Urticaria as a single symptom occurred at any time. A firm diagnosis was determined using immediate-reading skin prick (10.0%) and intradermal tests (38.1%), late-reading skin tests (19.1%) or provocation tests (32.9%).
Conclusion and clinical implication:  Depending on the time course of the reaction, three clinical groups were identified: anaphylaxis and anaphylactic shock (immediate reaction); maculopapular exanthema (late reaction) as well as urticaria (immediate and late reaction).