Occupational hand dermatitis web survey in a university hospital during COVID-19 pandemic: the SHIELD study.

BACKGROUND: Occupational hand dermatitis (OHD) is a skin disease occurring on employees' hands in certain jobs. Little is known about prevalence, incidence and characteristics of this adverse skin reaction and its associated risk factors during COVID-19 pandemic. To evaluate both prevalence and incidence of OHD and associated risk factors in Italian clinicians. METHODS: A cross-sectional study was performed using a self-report questionnaire. RESULTS: Two hundred and thirty clinicians responded to the survey and 82% of responders did not report previous OHD history before the COVID-19 pandemic. Daily use of gloves was reported by 80% of responders. OHD prevalence was 18%, while incidence was 80%. We found a protective effect on symptom occurrence for vinyl/nitrile gloves if the time with gloves was ≥ 6 hours per day. CONCLUSIONS: This survey reveals a high OHD incidence in an Italian population of clinicians. Furthermore, wearing vinyl/nitrile gloves for at least 6 hours a day had a protective effect on symptom onset.

Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillins.

BACKGROUND: Although clinicians avoid giving meropenem to patients with penicillin allergy because of potential cross-reactivity, the rate of cross-reactivity between penicillins and meropenem has not been prospectively determined. OBJECTIVE: To assess the tolerability of meropenem in patients with documented penicillin allergy. DESIGN: Prospective skin testing and antibiotic challenge. SETTING: Allergy units of 2 Italian medical centers. PATIENTS: 104 consecutive participants with immediate hypersensitivity reactions to penicillins and positive skin test results to at least 1 penicillin reagent. MEASUREMENTS: Skin tests to meropenem and, if results were negative, challenges with escalating doses of meropenem. RESULTS: One participant (0.9% [95% CI, 0.02% to 5.2%]) had a positive intradermal test result to meropenem. The remaining 103 participants with negative skin test results to meropenem tolerated escalating dose challenges. LIMITATION: Challenges were not followed by therapeutic courses. CONCLUSIONS: These data indicate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem therapy in penicillin-allergic patients should be reconsidered. In patients who especially require meropenem treatment, the authors recommend pretreatment skin tests because negative results indicate tolerability.

Patch testing in non-immediate drug eruptions.

: The present review addresses the literature regarding the sensitivity and specificity of the various diagnostic methods for evaluating non-immediate (ie, occurring more than 1 hour after drug administration) hypersensitivity reactions associated with beta-lactams and other antibiotics, anticonvulsants, heparins, iodinated contrast media, etc. Such reactions include several clinical entities, which range from mild reactions, such as maculopapular rash and delayed-appearing urticaria, to severe ones, such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). Clinical and laboratory studies indicate that a cell-mediated pathogenic mechanism is often involved in maculopapular rashes. However, this mechanism has also been demonstrated in other non-immediate reactions, such as urticarial and/or angioedematous manifestations, TEN, bullous exanthems, and AGEP. Patch tests, together with delayed-reading intradermal tests, lymphocyte transformation tests, and challenges, are useful tools for evaluating non-immediate drug eruptions. Patch tests can be performed with any form of commercial drugs and are safer than intradermal tests. However, patch tests are less sensitive than intradermal tests, and their sensitivity may vary, depending on the vehicle used.

Gene-gene interactions of IL13 and IL4RA variants in immediate allergic reactions to betalactam antibiotics.

OBJECTIVES: Immediate reactions - particularly anaphylactic ones - to betalactams are the most common adverse reactions to antibiotics mediated by a specific immunologic mechanism. The genetic risk factors influencing these mechanisms are poorly known. We aimed to evaluate the association between immediate allergic reactions to betalactams and the polymorphisms of IL13 (R130Q and -1055C>T variants) and IL4RA (I50V, S478P, and Q551R variants). METHODS: We determined these gene variants in 210 patients and 265 age-paired and gender-paired control subjects from Italy. RESULTS: The combination of the less frequent allele of the IL13 R130Q polymorphism with any of the predominant homozygous genotypes of the three polymorphisms of IL4RA was more significantly associated with the risk of betalactam allergy (P=0.0006, 0.0077, and 0.0041, respectively) than any polymorphism considered alone (P=0.1745, 0.0268, 0.1812, 0.0152, respectively). The same associations were observed with serum IgE levels (IL13/IL4RA variant combinations: P=0.0009, 0.0007, 0.0020, respectively and each variant: P=0.0201, 0.0021, 0.0531, and 0.0417, respectively). The combination of IL4RA variants with -1055 C>T polymorphism produced similar associations. CONCLUSION: Our data suggest that these combinations of IL13 and IL4RA variants are predictors of immediate allergic reactions to betalactams through a mechanism related to IgE production.

Cross-reactivity among drugs: clinical problems.

Cross-reactivity among drugs is either mediated by immunologic mechanisms or not. The former kind is usually explained by the presence of common antigenic determinants in the cross-reacting drugs. In the case of compounds provoking non-allergic hypersensitivity reactions, cross-reactivity is explained by a common pharmacological characteristic, such as the inhibitory effect of non-steroidal anti-inflammatory drugs on cyclooxygenase-1 and the capability of muscle relaxants or contrast media to release histamine through a non-immunologic mechanism. The main clinical problem deriving from cross-reactivity among drugs is the compelling need to choose a potentially cross-reactive compound and, therefore, to assess cross-reactivity by diagnostic tests. In choosing alternative compounds, skin testing has been used in evaluating IgE-mediated cross-reactivity between penicillins and cephalosporins, as well as among muscle relaxants. In assessing T cell-mediated cross-reactivity among contrast media, corticosteroids, anticonvulsants and heparins, delayed-reading intradermal tests and patch tests, together with lymphocyte transformation tests, can be performed. Because of the limited sensitivity of in vivo and in vitro testing, the most prudent way of establishing the tolerability of a compound of the same group in patients who especially require one is a graded challenge when other allergologic tests are negative.

Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins.

BACKGROUND: In patients with documented IgE-mediated hypersensitivity to penicillins, data on sensitization to cephalosporins vary. Administering cephalosporins to such patients is often deferred because of the risk for cross-reactivity. OBJECTIVE: To assess the cross-reactivity with cephalosporins and its potential determinants in patients with documented penicillin allergy. DESIGN: Prospective study in patients without clinical indications for cephalosporin treatment. SETTING: Italy. PATIENTS: 128 consecutive patients who sustained anaphylactic shock (n = 81) or urticaria (n = 47) and had positive results on skin tests for at least 1 of the penicillin reagents tested. MEASUREMENTS: All patients were skin tested with cephalothin, cefamandole, cefuroxime, ceftazidime, ceftriaxone, and cefotaxime. Patients with negative results for the last 4 cephalosporins were challenged with cefuroxime axetil and ceftriaxone. RESULTS: 14 patients (10.9% [95% CI, 6.1% to 17.7%]) had positive results on skin tests for cephalosporins, mostly for cephalothin or cefamandole. Skin test results for the minor determinant mixture were positive in 10 of 14 patients (71.4%) with cross-reactivity and 44 of 114 patients (38.6%) without cross-reactivity (odds ratio, 3.90 [CI, 1.17 to 13.40]; P = 0.0189). All 101 patients with negative results on skin tests for cefuroxime, ceftazidime, ceftriaxone, and cefotaxime tolerated cefuroxime axetil and ceftriaxone (tolerability rate, 100% [CI, 96.4% to 100%]). LIMITATIONS: Challenges were not followed by full therapeutic courses. Twenty-two patients declined challenges; positive responses in those patients would have decreased the tolerability rate to 82.1% (CI, 74.2% to 88.4%). CONCLUSIONS: These data confirm the advisability of avoiding cephalosporin treatment in patients with positive results on skin tests for penicillin. In patients who especially require cephalosporin treatment, we recommend skin tests with cephalosporins before assessing the tolerability of the cephalosporin with a graded challenge.

Cross-reactive reactions to nonsteroidal anti-inflammatory drugs.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequent causes of adverse drug reactions, particularly in patients with asthma and chronic idiophatic urticaria. Many subjects report cutaneous and/or respiratory symptoms and, less frequently, anaphylactic shock after the administration of one (single-reactors) or different (cross-reactors) drugs of this class. DIAGNOSIS: There are no reliable cutaneous or in vitro tests which allow NSAID hypersensitivity to be identified in patients with cross-reactive reactions; therefore, the challenge test is considered the "gold standard" for establishing or excluding a diagnosis of NSAID hypersensitivity in such patients. MANAGEMENT: Culprit drugs should always be avoided by patients with suspected or well-established multiple hypersensitivity to NSAIDs. The therapeutic options range from the administration of alternative drugs - such as weak cyclooxygenase (COX)-1 inhibitors and/or preferential or highly selective COX-2 inhibitors to desensitization to the culprit ones. CONCLUSION: In patients with different NSAID-induced reactions, the challenge test with both culprit drugs and alternative ones is the only method to establish a reliable diagnosis of NSAID hypersensitivity and to find some alternative therapeutic options, respectively. In specific cases, drug desensitization can also be performed. However, further studies are required to improve management of such patients.

Hypersensitivity to lamotrigine and nonaromatic anticonvulsant drugs: a review.

Lamotrigine and nonaromatic antiepileptic drugs (valproate, gabapentin, and topiramate) are associated with hypersensitivity reactions, mainly cutaneous eruptions. The underlying mechanisms of these manifestations are not yet completely understood. A cell-mediated pathogenic mechanism has been demonstrated in some cases on the basis of positive patch tests and/or lymphocyte transformation tests. Moreover, an in vitro lymphocyte toxicity assay, which exposes the patient's lymphocytes to arene oxides, has detected lymphocyte susceptibility to toxic metabolites in patients with hypersensitivity reactions to lamotrigine. Subjects with a history of mild hypersensitivity reactions and negative allergologic tests can be challenged with the suspected drugs. Challenge tests can also be useful to identify safe alternatives. Our study reports hypersensitivity reactions to lamotrigine and to nonaromatic antiepileptic drugs, especially those assessed by allergologic tests.

Diagnosing hypersensitivity reactions to cephalosporins in children.

OBJECTIVES: The goals were to evaluate the usefulness of skin tests, patch tests, serum specific IgE assays, and challenges in diagnosing hypersensitivity reactions to cephalosporins and to clarify the pathogenic mechanism of such reactions. METHODS: Children with immediate manifestations (within 1 hour) underwent immediate-reading skin tests with penicillin reagents and any suspect cephalosporins, serum specific IgE assays, and challenges; some children underwent reevaluations. Children with nonimmediate manifestations (after >1 hour) were assessed with patch tests, delayed-reading skin tests, and challenges. RESULTS: We evaluated 148 children with hypersensitivity reactions to cephalosporins, mainly cefaclor and ceftriaxone; 105 had experienced nonimmediate manifestations (mostly urticarial eruptions and maculopapular rashes) and 43 immediate manifestations (anaphylactic shock, urticaria and/or angioedema, and erythema). None of the nonimmediate reactors demonstrated positive results in patch tests and/or delayed skin tests; only 1 subject displayed immediate positive responses to penicillin skin-test reagents. Among the 104 patients with negative results, 96 underwent challenges; 95 tolerated the challenges, and 1 reacted to the cefaclor pediatric suspension and tolerated the challenge with a cefaclor capsule. In the first allergologic evaluation, 33 of the 43 children with immediate reactions displayed skin-test positivity. Of the 10 patients with negative results, 7 underwent challenges, followed by therapeutic courses and reevaluations for 4. All challenges and therapeutic courses were tolerated; in the reevaluation, 1 girl demonstrated positive skin-test results for both the responsible cephalosporin and penicillin reagents. Overall, IgE-mediated hypersensitivity was diagnosed for 34 (79%) of 43 subjects. CONCLUSIONS: Extremely few nonimmediate manifestations associated with cephalosporin therapy are actually hypersensitivity reactions, whereas most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating such reactions.

Etoricoxib tolerability in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem in clinical practice. Our aim was to investigate the clinical tolerability of etoricoxib, a new selective cyclooxygenase-2 inhibitor, in a group of patients with well-established NSAID hypersensitivity. METHODS: We assessed 31 adults (21 women and 10 men) who reported one or more adverse reactions to NSAIDs, manifested as cutaneous, respiratory or anaphylactic symptoms. Sixteen of them reported reactions to a single NSAID (single reactors) and 15 to more than one NSAID (multiple reactors); the most frequently involved drug was acetylsalicylic acid. First, each patient underwent allergologic tests (skin and/or oral challenge tests) with culprit NSAIDs and then tolerability tests with increasing doses of etoricoxib up to 120 mg. All challenges were performed under single-blind, placebo-controlled conditions. RESULTS: NSAID hypersensitivity was diagnosed in all 31 patients: 3 displayed positive results to pyrazolone skin tests and the other 28 to challenges with culprit NSAIDs. None reacted to either placebos or etoricoxib. CONCLUSIONS: Etoricoxib seems to be a safe alternative for patients with well-demonstrated NSAID hypersensitivity.

IgE-mediated hypersensitivity to cephalosporins.

Like penicillins, cephalosporins may cause IgE-mediated reactions such as urticaria, angioedema, and anaphylactic shock, which occur because of sensitization to determinants shared with penicillins or to unique cephalosporin haptens. In particular, side-chain structures may be responsible for selective sensitization or cross-reactivity. For this reason, individual free cephalosporins are usually employed in skin testing, in addition to the classic penicillin reagents. Cephalosporin skin tests are sensitive in diagnosing immediate hypersensitivity to these betalactams. As far as in vitro tests are concerned, IgE assays for cephalosporins, specifically sepharose-radioimmunoassays, are a potentially useful tool in evaluating immediate reactions and could be used as complementary tests. In selected cases displaying negative results in both skin tests and IgE assays, a graded challenge with the implicated cephalosporin can be performed. Cephalosporin IgE-mediated hypersensitivity may be a transient condition; therefore, allergologic exams should be repeated in patients with negative initial allergologic work-ups, including challenges. Performing allergologic tests with cephalosporins other than the culprit, as well as with penicillin reagents, allows the identification of cross-reactivity with penicillins, selective responses, or cross-reactivity among cephalosporins. In the latter group, cross-reactivity is more frequently related to R1 than to R2 side-chain recognition. In assessing the selectivity of the response, negative results in skin testing with cephalosporins other than the responsible one appear to be a reliable indicator of tolerability.

Hypersensitivity reactions to complementary and alternative medicine products.

Complementary and alternative medicine (CAM) is becoming increasingly popular, and is often used for treating hypersensitivity diseases. Virtually all alternative remedies can cause hypersensitivity reactions, but the most frequently involved ones are tea tree oil, members of the Compositae family, propolis, oils used in aromatherapy, substances responsible for photosensitization, and metal-containing compounds. The main target organ is skin, with manifestations ranging from contact dermatitis (the most common) to urticaria-angioedema, maculopapular eruptions, photosensitivity reactions, and the Stevens-Johnson syndrome. Other types of reactions are possible, including respiratory and anaphylactic ones. Different pathogenic mechanisms have been suggested for CAM product reactions, including immunologic ones. Basophils and mast cells participate in IgE-mediated reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most delayed reactions, particularly contact dermatitis and maculopapular eruptions. Skin tests and serum specific IgE assays are carried out to diagnose immediate hypersensitivity reactions, while patch tests and lymphocyte transformation tests are usually performed to evaluate delayed hypersensitivity reactions. Thus clinicians should know about the potential of CAM products for causing adverse reactions. Our study is aimed at highlighting the risk of hypersensitive reactions to CAM remedies on the basis of the numerous cases reported in the literature. Because little is known about adverse reactions to CAM products, further systematic studies and an appropriate regulation by heath authorities are necessary.

Hypersensitivity to aromatic anticonvulsants: in vivo and in vitro cross-reactivity studies.

Aromatic antiepileptic drugs (phenytoin, carbamazepine, oxcarbazepine, and phenobarbital) are frequently associated with cutaneous eruptions. A cell-mediated pathogenic mechanism has been demonstrated in most of such reactions on the basis of positive responses to patch tests and/or lymphocyte transformation tests. Therefore, such tests are useful tools for evaluating anticonvulsant hypersensitivity reactions. Moreover, an in vitro lymphocyte toxicity assay, which exposes the patient's lymphocytes to arene oxides, has detected lymphocyte susceptibility to toxic metabolites in a large percentage of patients with hypersensitivity reactions to aromatic anticonvulsants. Although several hypersensitivity reactions to sequential exposure to more than one aromatic anticonvulsant (i.e., clinical cross-reactivity) have been reported, there are few studies performed with patch tests and/or lymphocyte transformation tests assessing immunologic cross-reactivity, and their data are contradictory. In any case, considering studies performed in samples of at least 10 patients, the immunologic cross-reactivity rate among aromatic anticonvulsants appears to be low. On the other hand, the reported rate of the toxic cross-reactivity (i.e., assessed by lymphocyte toxicity assays) is high. Further in vivo and in vitro studies in large samples of subjects are needed to evaluate cross-reactivity among aromatic anticonvulsants.

Celecoxib tolerability in patients with hypersensitivity (mainly cutaneous reactions) to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed in clinical practice, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem for both general practitioners and allergists. METHODS: We assessed 120 patients (83 women and 37 men) who had experienced adverse reactions to one or more NSAIDs; 64 (53.3%) of them had reacted to only one NSAID (single reactors) and 56 (46.7%) to multiple NSAIDs (multiple reactors). Among our subjects, 76.7% reported cutaneous reactions, 8.3% respiratory symptoms, 10.8% both cutaneous and respiratory symptoms, and 4.2% anaphylaxis. All patients were subjected to a single-blind, placebo-controlled oral challenge with two different doses of celecoxib (50 + 150 mg 1 h later = cumulative dose of 200 mg). RESULTS: None of the patients reacted to the placebo and only one (0.8%) suffered a reaction (urticaria) after the second dose of celecoxib. CONCLUSIONS: Celecoxib showed a 98.9% rate of tolerability in the 92 patients with exclusively cutaneous reactions and was well tolerated by all 28 subjects with NSAID-related respiratory or anaphylactic symptoms.

Effective prophylactic protocol in delayed hypersensitivity to contrast media: report of a case involving lymphocyte transformation studies with different compounds.

A patient with maculopapular reactions to iopamidol needed to undergo angiography for a cerebral arteriovenous malformation. In vivo and in vitro tests were performed with ionic and nonionic contrast media, including iopamidol and iobitridol. All results were positive, demonstrating delayed hypersensitivity. The patient received 6-alpha-methylprednisolone and cyclosporine 1 week before and 2 weeks after four angiograms were obtained with the use of iobitridol, which was well tolerated.

Tolerability of rofecoxib in patients with adverse reactions to nonsteroidal anti-inflammatory drugs: a study of 216 patients and literature review.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, particularly among patients with chronic urticaria or asthma. The identification of an alternative safe and reliable drug is a common problem in clinical practice. OBJECTIVE: To assess the tolerability of rofecoxib, a new NSAID that selectively inhibits the inducible isoform of cyclooxygenase, in a large group of NSAID-sensitive patients. METHODS: We studied 216 patients (164 females and 52 males) who had suffered adverse reactions to one or more NSAIDs; 98 subjects (45.4%) had experienced reactions to only one NSAID (single hypersensitivity) and 118 subjects (54.6%) had reacted to multiple NSAIDs (multiple hypersensitivity). Cutaneous reactions were reported by 79.6% of the subjects, respiratory symptoms by 10.7%, cutaneous and respiratory symptoms by 8.3%, anaphylaxis by 1.4%. All the subjects underwent a single-blind, placebo-controlled oral challenge with divided therapeutic doses of rofecoxib (6.25 mg +18.75 mg 1 h later = cumulative dose of 25 mg). RESULTS: No reactions to the placebo were observed; only 1 subject (0.46%) experienced an urticarial reaction, after the second dose of rofecoxib. CONCLUSIONS: Considering previous studies and our own data, rofecoxib was well tolerated by all of the 174 patients with exclusively NSAID-related respiratory symptoms. Rofecoxib also had a very low rate (1.6%) of cross-reactivity in the 600 patients with exclusively cutaneous reactions to NSAIDs.

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.