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Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. In this retrospective chart review at Memorial Sloan Kettering Cancer Center, we assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. 12,274 patients were treated with paclitaxel. 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction. Age (p < 0.001), race (p < 0.001), and prior history of allergy (p = 0.05) were associated with immediate hypersensitivity reactions. 147 patients (4.0%) had a rash of interest. The most common phenotypes were maculopapular (52%) and urticaria (36%). Race (p < 0.001) and history of allergy (p < 0.001) were associated with development of a cutaneous reaction. Patients with an immediate hypersensitivity reaction were more likely to have developed a delayed cutaneous reaction (OR = 1.80). Risk factors for development of immediate hypersensitivity reactions in this study were younger age, race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Identification of risk factors is critical to guide care coordination. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel. If the cutaneous reactions are bothersome to the patient, the transition of treatment from paclitaxel to nab-paclitaxel may be warranted, or a consideration of re-challenge or desensitization may be discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate and delayed hypersensitivity reactions. Although these reactions are not common, due to the wide usage of corticosteroid medications, corticosteroid hypersensitivity reactions are clinically important., Objective: In this review, we summarise the prevalence, pathogenetic mechanism, clinical manifestations, risk factors, diagnostic and therapeutic approach for corticosteroid-induced hypersensitivity reactions., Methods: An integrative review of the literature was conducted using PubMed searches (mainly large cohort-based studies) regarding the different aspects of corticosteroid hypersensitivity., Results: Hypersensitivity reactions to corticosteroids can be immediate or delayed and can follow all modes of corticosteroid administration. Prick and intradermal skin tests are useful diagnostic tools for immediate hypersensitivity reactions, patch tests are useful for delayed hypersensitivity reactions. According to the diagnostic tests an alternative (safe) corticosteroid agent should be administered., Conclusion: Physicians of all medical disciplines should be aware that corticosteroids can cause (paradoxically) immediate or delayed allergic hypersensitivity reactions. The diagnosis of such allergic reactions is challenging since it is often difficult to distinguish between hypersensitivity reactions and deterioration of the basic inflammatory disease (e.g., worsening of asthma or dermatitis). Thus, a high index of suspicion is needed in order to identify the culprit corticosteroid.

Background: As a result of the COVID-19 outbreak, hygiene regulations have been revised and hand sanitation has been intensified., Objective: To investigate the onset of hand eczema during the COVID-19 pandemic in healthcare workers (HCWs) directly involved in intensive care of COVID-19 patients and HCWs without direct contact with COVID-19 patients. Hereby, we aim at increasing awareness about occupational hand eczema and preventive measures that can be adopted., Method: A survey was distributed amongst 114 HCWs at a single surgical centre and at a COVID-19 intensive care unit of the university hospital Ludwig Maximilian University Munich, Germany. Participants were questioned about the daily frequency of hand hygiene prior to and during the pandemic. Participants self-reported the onset of hand eczema and associated symptoms., Results: Our study revealed a significant increase in hand washing, disinfection, and use of hand cream across all participants (P-value <.001), regardless of having direct contact with COVID-19 patients. A high prevalence of symptoms associated with acute hand dermatitis of 90.4% was found across all HCWs, whereas hand eczema itself was underreported (14.9%)., Conclusion: The increase in hand sanitation during the COVID-19 pandemic impairs the skin of the hands across all HCWs, independent of direct intensive care of affected patients., (© 2020 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Background: Hyaluronic acid (HA) dermal filler injection is believed to be a safe procedure. However, with the increase in the number of performed procedures and indications, the number of product-related complications, especially delayed inflammatory reactions, has also increased. Delayed-type hypersensitivity (DTH) reaction is one of these delayed inflammatory reactions, which is preventable by performing a pretreatment skin test., Objectives: The authors sought to find the incidence of delayed inflammatory reactions and DTH reaction after HA injection and to determine whether a pretreatment skin test is worthwhile to be performed., Methods: The authors conducted a systematic literature review of all the relevant prospective studies, retrospective studies, and case reports on delayed inflammatory reactions and DTH reaction after HA filler injection., Results: The incidence of delayed inflammatory reactions calculated from the prospective studies was 1.1% per year, and that of possible DTH reaction was 0.06% per year. Most retrospective studies estimated a percentage of delayed inflammatory reactions of less than 1% in 1 to 5.5 years. The incidence of DTH reaction would be lower than that. Among all the DTH cases reported, only about 5% of them were proven to be genuine DTH reactions., Conclusions: The incidence of both delayed inflammatory reactions and DTH reaction is low. There is evidence that genuine DTH reactions caused by HA fillers approved by the Food and Drug Administration do exist. This adverse event can be prevented by performing a pretreatment skin test. However, the incidence of DTH reaction is so low that the pretreatment skin test is not mandatory if Food and Drug Administration-approved HA fillers are used., (© 2019 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Delayed-type, T cell-mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug-peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Essure is an effective method for hysteroscopic sterilization. Reports of adverse effects, the underlying mechanisms of which are unknown, have increased in recent years., Objective: The aim of the study was to determine whether there is a relationship between adverse events attributed to Essure and nickel sensitization., Methods: Patients presenting alleged adverse reactions to Essure were referred for nickel patch testing before removal. Data regarding medical history of nickel sensitization and symptoms attributed to Essure were collected. Dimethylglyoxime spot tests were performed on the explanted Essure. There was a follow-up at 3 months to evaluate whether there is improvement of the symptoms after Essure removal., Conclusions: Nickel sensitization via the classic delayed hypersensitivity pathway did not seem to be responsible for adverse events attributed to Essure. Among systemic symptoms reported, extracutaneous symptoms had the highest prevalence. Systemic contact dermatitis to nickel could not be ruled out in one case.

Background: The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients., Objectives: To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation., Method: We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium - the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents., Results: Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC., Conclusions: This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis., (© 2020 S. Karger AG, Basel.)

Background: The various adverse drug reactions (ADRs) arise from different types of iodinated contrast media (ICM)., Objective: Thus, we investigated the occurrence rate and types of ADRs according to the total usage cases of the 7 most common ICM., Methods: We retrospectively reviewed 74,242 causal ADRs caused by ICM from the Korea Adverse Event Reporting System database between January 2014 and December 2016. The 11,712,796 total usage cases that represent all administrations of ICM reported from individual medical institutions were received from the Health Insurance Review and Assessment Service. A proportionality test was used to examine the differences in the frequency ratio of causal ADRs to total usage cases., Results: Immediate hypersensitivity (44,467 cases, 88.56%) occurred more frequently than delayed hypersensitivity (5,725 cases, 11.4%; P < .001). The overall occurrence rate of causal ADRs and serious ADRs considering total usage cases was 0.37% and 0.02%, respectively (P < .001). The ICM most commonly resulting in ADRs were iomeprol (0.7%) and iopromide (0.59%). The serious ADRs were most common for iomeprol (0.05%). When ADRs were classified according to the system organ class, "skin and appendages disorders" (47,065 cases, 63.4%) occurred most common. Iodixanol resulted in the highest frequency of "urinary system disorders.", Conclusions: By comparison of the ADRs considering total usage cases, the incidence and classification of ADRs were different for each contrast medium. A prospective study is needed because the differences in these 7 major contrast media may assist in the selection of ICM tailored for each patient., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Animal and human studies show that exposure to solar-simulated UVR is immunomodulatory. Human studies that used natural sun exposure and controlled for confounding are rare. We immunized 217 healthy adults (age range = 18-40 years) with a T-cell-dependent antigen, keyhole limpet hemocyanin, and measured personal clothing-adjusted UVR exposure (for 5 days before and after immunization), lifetime cumulative UVR exposure, serum 25-hydroxyvitamin D concentration at immunization, and potential confounding factors. We tested cellular and humoral immune responses in relation to UVR exposure. The delayed-type hypersensitivity response to keyhole limpet hemocyanin recall challenge was lower in individuals with higher personal clothing-adjusted UVR exposure on the day before immunization (P = 0.015) and during intervals spanning the day before to 2-3 days after immunization. There was an incremental increase in T helper type 17 cells (as a proportion of CD4 + T cells) from preimmunization to postimmunization in the high, compared with the low, personal clothing-adjusted UVR exposure group (0.31% vs. -0.39%, P = 0.004). Keyhole limpet hemocyanin-specific antibody titers were not associated with acute or cumulative UVR exposure or serum 25-hydroxyvitamin D levels. Higher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics. This has implications for the effectiveness of vaccinations and susceptibility to infections that rely on cell-mediated immune responses., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This French multicenter, cross-sectional, observational study aimed to describe the family history of atopy in infants with cow's milk protein allergy (CMPA), and the related diagnostic approaches used by specialists in a real-life ambulatory setting., Patients and Methods: In total, 1674 infants with suspected CMPA [median age 4.5 months (range: 0.1-18.0), males 54%] were enrolled in the study by 466 private physicians (pediatricians: 97%). Family history of atopy was defined as a known history of atopy in at least one first- (father, mother, and/or sibling) and/or second-degree relative (grandparents, uncles, and aunts), as reported by parents to physicians., Results: Atopy in a first-degree relative was more common among infants with documented or high probability of CMPA (in 84% and 80% of cases, respectively, vs. the other subgroups, P=0.005). Most infants experienced digestive (92%) and skin (61%) symptoms suggestive of CMPA. Delayed reactions were reported in 64% of infants. According to a post-classification based on the results of previous diagnostic tests and procedures, 1133 infants (68%) had highly probable (52%) or documented CMPA (16%). In these infants, a history of atopy was reported in first- and/or second-degree relative(s) in 86% of cases (81% in first-degree relatives). Whatever the family history of atopy, the characteristics of the infants were similar, except for fewer pets in the case of negative family atopy (14% vs. 25%, P<0.001). Atopy in a parent was more frequent in infants who presented with the first signs suggestive of CMPA within the first 6 months of life vs. those with later first symptoms (75% vs. 65%, P=0.063)., Conclusion: This French study confirms the high rate of family history of atopy in first-degree relatives of infants with probable or documented CMPA., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Severe delayed drug hypersensitivity reactions comprise different clinical entities and can involve different immune-mediated mechanisms. Common examples are severe cutaneous adverse reactions and druginduced internal organ injuries. The incidence of such reactions is overall low but seems to be on the rise reaching numbers as high as 9 per million individuals-years in the case of SJS/TEN and DRESS. Such conditions carry an important associated morbidity, and mortality can attain 40% in SJS/TEN patients, making these hypersensitivity reactions important targets when implementing preventive measures. Several risk factors have been identified for reaction severity; some are transverse, such as older age and underlying chronic diseases. The recent advances in pharmacogenetics allowed the identification of specific populations with higher risk and permitted strategic avoidance of certain drugs being HLA-B*57:01 screening in patients initiating abacavir the best successful example. In this work, we reviewed the epidemiology of SCARs and liver/kidney/lung drug-induced immune-mediated reactions. We focus on particular aspects such as prevalence and incidence, drugs involved, mortality and risk factors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Heparins are widely prescribed for prevention and therapy of arterial and venous thromboembolic diseases. Heparin-induced skin lesions are the most frequent adverse effect of subcutaneous heparin treatment in non-surgical patients (7.5%-39.8%); no data exist on surgical patients. Commonly, they are due to a delayed-type hypersensitivity reaction (DTH), but may also be a manifestation of life-threatening heparin-induced thrombocytopenia (HIT). Lesions of both entities resemble initially. The risk of HIT is highest among heparin-anticoagulated orthopedic surgery patients., Objective: To determine incidence and causes of heparin-induced skin lesions in major orthopedic surgery patients., Methods: In a prospective cohort study, consecutive patients with subcutaneous low-molecular-weight heparin (LMWH) treatment were examined for cutaneous adverse effects. Further diagnostics (skin biopsy, clinical/laboratory assessment for thrombosis, bleeding, HIT, cross-allergies) were performed., Results: Six of 316 enrolled patients (1.9%; 95% CI: 0.4%-3.4%) developed heparin-induced skin lesions. All were caused by a DTH reaction, and none was due to HIT or other rare heparin-associated skin diseases. Therapeutic use (dosage) of LMWH was identified as only risk factor (odds ratio: 3.1, 95% CI: 1.4-4.9; P = .00141). In addition to DTH, 5 thromboembolic, 4 major bleeding complications but no cases of HIT or cross-allergies were observed., Conclusions and Clinical Relevance: Orthopedic surgery patients have-unlike non-surgical patients-a low risk for heparin-induced skin lesions during LMWH treatment; all lesions were due to a DTH reaction. The risk for DTH differs considerably between individual patient cohorts. No association with HIT was observed. These data help to tailor anticoagulatory treatment individually and to increase patient safety., (© 2018 John Wiley & Sons Ltd.)

Purpose: To assess delayed-type cutaneous reactions (DTCRs) related to drugs, using a case-control approach to qualify drug risks., Methods: The study used the Tunisian pharmacovigilance database of Monastir. The association between drugs and DTCRs was assessed using a case/non-case method. Drugs were grouped according to the ATC Classification System. Patients were defined as "cases" if they have developed DTCRs regardless of the causality assessment. All other reports were "non-cases". Association between reactions and drugs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals (CIs). A p value < 0.05 was considered significant., Results: The analysis was carried out on 1798 reports, of which 867 concerned DTCRs (cases) and 931 concerned non-cases. The calculated risk estimates were significant for cefotaxime (ROR 2.1; 95% CI 1.5 to 3), pristinamycin (ROR 4; 95% CI 2 to 7.9), sulfamethoxazole (ROR 4.4; 95% CI 1.6 to 11.7), oxacillin (ROR 2.2; 95% CI 1.2 to 3.8), doxycycline (ROR 10.8; 95% CI 1.4 to 84.9), carbamazepine (ROR 3.3; 95% CI 1.7 to 6.2), phenobarbital (ROR 2.3; 95% CI 1.03 to 5.1), allopurinol (ROR 3.6; 95% CI 1.8 to 7.2), furosemide (ROR 2.4; 95% CI 1.3 to 6.3), hydrochlorothiazide(ROR 2.9; 95% CI 1.3 to 6.3) and candesartan (ROR 4.7; 95% CI 1.3 to 16.6)., Conclusion: Our findings corroborate risks for a number of drugs, such as antibacterials, antiepileptics and allopurinol in inducing DTCRs. Given the widespread use of these drug classes, awareness should be raised among patients and prescribers about these risks., (Copyright © 2018. Published by Elsevier B.V.)

Background: Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause., Objectives: Characterize occupational ACD by handling systemic antibiotics., Method: A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics., Results: We studied 4 female nurses aged 28-47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job., Conclusions: Occupational ACD caused by β-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between β-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in one case, suggests that patients should avoid future use of the antibiotic to which they are sensitized., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allergy to beta-lactam antibiotics is a common condition and about 10% of patients report being allergic to penicillin. However, this diagnosis is largely overestimated. Two types of allergy should be distinguished and include immediate hypersensitivity that can lead to anaphylactic shock and delayed hypersensitivity, ranging from the most common maculopapular exanthema to severe bullous toxidermia or life-threatening DRESS. Allergy challenge with oriented skin tests according to the clinical features, supplemented with oral challenge in the absence of contraindication, will confirm or invalidate the diagnosis of beta-lactam allergy and will help to identify if necessary safe alternatives to beta-lactams., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Summary: Background. The term of α-Gal syndrome, which includes the delayed allergy to red meat and the allergic reactions following the administration of cetuximab, is associated to the presence of specific IgE to α-Gal. In Italy, only anecdotal cases were reported so far. The Association of Italian Allergists (AAITO) carried out a survey with the aim of evaluating presence, characteristics, clinical features, and distribution of the syndrome in Italy. Methods. A web structured questionnaire was made available on the website of AAIITO from July 2016 to January 2017. It included 31 multiple-choice questions concerning different items, including the site of physicians, the number of patients diagnosed as having cetuximab allergy and/or delayed red meat allergy, recall of tick bites, symptoms, time to reactions, elicitor foods, reactions with foods other than meat, and in-vivo and in-vitro tests used for the diagnosis. Results. Seventy-nine physicians completed the questionnaire. Nine cases of allergy to cetuximab and 40 cases of delayed red meat allergy were recorded across Italy. 22.5% of patients with cetuximab allergy and 62.5% of those with delayed red meat allergy recalled a tick bite. 75% of patients with delayed red meat allergy experienced symptoms after eating beef (butcher's cut in 72.5%). Urticaria was the most frequent clinical manifestation (65% of cases). In 60.6% of cases symptoms appeared 2 - 4 hours after meat ingestion, while in 7.9% symptoms appeared after > 4 hours. The most used diagnostic methods were the intradermal test for cetuximab allergy (88.9%) and the detection of IgE to α-Gal (55.5%) for red meat allergy. Most case reports came from Northern Italy. Conclusions. α-Gal syndrome is present in Italy and beef is the most frequent offending food. In most cases symptoms were not severe.

Background: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh., Objectives: To describe the pattern and prevalence of leprosy reactions in the postelimination stage., Methods: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013., Results: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group., Conclusion: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services., (© 2016 European Academy of Dermatology and Venereology.)

Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries.We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms.Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes.Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Background/aim: Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand., Methods: An online multi-choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Australasian Society of Infectious Diseases (ASID). The 37-item survey was distributed in April 2015 to members of ASCIA, ASID, the Society of Hospital Pharmacists of Australia and the Royal Australasian College of Physicians., Results: Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic-allergic. Forty-two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79, 69 and 61% respectively). Patients with the histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76 vs 41%, P = 0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was a preferred AAT model (53%). Knowledge gaps were identified, with the majority overestimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross-reactivity., Conclusions: A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital-based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving infectious diseases physicians, pharmacists and allergists/immunologists is required., (© 2016 Royal Australasian College of Physicians.)

Background: Occupational contact dermatitis is common in healthcare workers. Although irritant contact dermatitis resulting from wet work is the most frequently reported cause, healthcare workers also constitute high-risk group for the development of allergic contact dermatitis and contact urticaria., Objectives: To evaluate the prevalence of delayed-type and immediate-type hypersensitivity in 120 healthcare workers with hand eczema., Methods: One hundred and twenty healthcare workers from three major hospitals in Denmark with self-reported hand eczema within the last year participated in the study. Patch tests included baseline series plus selected allergens, and prick tests included standard inhalational allergens plus natural rubber latex and chlorhexidine. Levels of IgE specific for latex, chlorhexidine and ethylene oxide were measured., Results: Of the participants, 53% had positive patch test reactions. The most frequent positive patch test reactions were to nickel, thiomersal, fragrances, rubber chemicals, and colophonium. The prevalence of natural rubber latex allergy as diagnosed by prick testing was 2.5%, and chlorhexidine allergy (both contact allergy and IgE-mediated allergy) was found in <1%. Ethylene oxide allergy was not identified in any of the participants., Conclusions: Our results confirm previous reports on contact allergy patterns in healthcare workers. Testing for natural rubber latex allergy is still important, but increased risks of chlorhexidine and ethylene oxide allergy could not be confirmed., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic., Material and Methods: Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period., Results: We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction., Conclusions: The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids., (Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.)

Purpose: To determine which 10 prescription-only drugs used in outpatient treatment in Germany are most frequently reported to induce severe drug hypersensitivity reactions taking into account their prescription numbers. In addition, the reader should be made aware of respective databases available to the public and their limitations., Methods: Reports of anaphylactic and severe cutaneous adverse reactions were identified in the adverse drug reaction database of the German competent authority for the time period January 1998 to December 2012. For frequently reported drugs, the total number of reports was matched with their total number of prescriptions resulting in the reporting rate., Results: Among the 10 drugs with the highest reporting rate for anaphylactic reactions, there were six antibiotics (moxifloxacin, levofloxacin, clindamycin, ciprofloxacin, cefuroxime and amoxicillin), three of which were fluoroquinolones. The other four drugs were glatiramer, metamizole and two angiotensin-converting-enzyme inhibitors. Concerning severe cutaneous adverse reactions, four out of ten drugs were antibiotics (clindamycin, sulfamethoxazol + trimethoprim, ciprofloxacin and amoxicillin), and three were anticonvulsives. Because dental prescription numbers were not available to the public, the real reporting rates for clindamycin and to a lesser extent for amoxicillin are presumably lower., Conclusions: The predominance of antibiotics among the reports of severe immediate and delayed-type drug hypersensitivity reactions is largely in accordance with literature although fluoroquinolones seem to be slightly overrepresented concerning anaphylactic reactions. The reader should be aware of the limitations of adverse drug reaction and prescription databases available to the public, and that over-the-counter drugs, such as non-steroidal anti-inflammatory drugs, and drugs typically administered in hospitals could not be considered., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background and Purpose: It is unclear whether delayed-type hypersensitivity reactions against implanted metals play a role in the etiopathogenesis of malfunctioning total knee arthroplasties. We therefore evaluated the association between metal allergy, defined as a positive patch test reaction to common metal allergens, and revision surgery in patients who underwent knee arthroplasty., Patients and Methods: The nationwide Danish Knee Arthroplasty Register, including all knee-implanted patients and revisions in Denmark after 1997 (n = 46,407), was crosslinked with a contact allergy patch test database from the greater Copenhagen area (n = 27,020)., Results: 327 patients were registered in both databases. The prevalence of contact allergy to nickel, chromium, and cobalt was comparable in patients with and without revision surgery. However, in patients with 2 or more episodes of revision surgery, the prevalence of cobalt and chromium allergy was markedly higher. Metal allergy that was diagnosed before implant surgery appeared not to increase the risk of implant failure and revision surgery., Interpretation: While we could not confirm that a positive patch test reaction to common metals is associated with complications and revision surgery after knee arthroplasty, metal allergy may be a contributor to the multifactorial pathogenesis of implant failure in some cases. In cases with multiple revisions, cobalt and chromium allergies appear to be more frequent.

Background: Patients with allergic contact dermatitis to 1 antigen have been shown to be at increased risk of developing delayed type hypersensitivity reactions to additional antigens. Both environmental and genetic factors likely influence the risk of sensitization., Objective: The aim of this study was to determine whether polysensitization occurs at a higher frequency than would be expected based on chance and whether polysensitization occurs more often in subsets of patients with hand involvement and atopic dermatitis., Methods: From a database of patch test results from a single practitioner, the probability of having positive reactions to 3 or more unrelated allergens was calculated under the assumption that positive reactions are independent and compared with the observed proportion having positive reactions to 3 or more unrelated allergens. The analysis was repeated excluding patients with leg involvement as a proxy for venous insufficiency dermatitis. The proportion of patients from the polysensitized and nonpolysensitized cohorts with either hand involvement or a history of atopic dermatitis was also calculated., Conclusions: Polysensitization occurs more often than expected based on chance. Polysensitized patients were more likely to have hand dermatitis. Atopic dermatitis was not significantly associated with polysensitization in this analysis. Polysensitized individuals may represent a phenotype with increased genetic susceptibility to sensitization.

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Background: Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD., Methods: Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay)., Results: In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium., Conclusions: Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

The number of household pets increased greatly during the twentieth century, with the numbers of new pets (NP, i.e. any pet other than cats and dogs) rising especially sharply over the last decade. Contact with such animals, whose owners do not always know how to look after them properly, expose the population to new risks such as trauma, infection and allergy. While the most common allergies are respiratory, allergic skin reactions, both immediate and delayed, may also result from contact with these new allergens. The animal itself or its environment may be the cause. Herein, we review NPs and reports of allergic dermatitis associated with them., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15-20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.

Background: Patients with atopic dermatitis (AD) have abnormalities in skin barrier function, and are predisposed to developing cutaneous delayed-type hypersensitivity. Soap and detergents are known to exacerbate the breakdown of the skin barrier., Objective: We sought to assess whether atopic patients in our database were more likely than nonatopic patients to patch test positive to the surfactants cocamidopropyl betaine (CAPB) and cocamide diethanolamide (DEA), or to the surfactant precursor amidoamine., Methods: Between January 1, 2001, and the present, a total of 1674 patients underwent patch testing to the North American Contact Dermatitis Group standard screening series. The incidence of positive patch test results to CAPB, cocamide DEA, and amidoamine among patients with AD (n = 242) and without AD (n = 1422) was assessed. Statistical analysis was done using a χ(2) test., Results: AD was associated with contact hypersensitivity to CAPB, but not to cocamide DEA or amidoamine., Limitations: This was a retrospective study of patients evaluated for suspected allergic contact dermatitis and, therefore, matching for gender, age, or other parameters was not possible. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY., Conclusions: Patients with AD should avoid the use of skincare products containing the surfactant CAPB., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Based on ecological analyses we proposed in 2003 the relation of Kawasaki Disease (KD) onset causing acute febrile systemic vasculitis, and pollen exposure. This study was aimed at investigating the correlation between pollen release and the change in the numbers of KD patients from 1991 to 2002 in Kanagawa, Japan. Short-term changes in the number of KD patients and medium- to long-term trends were analyzed separately. Short-term changes in the number of KD patients showed a significant positive cross correlation (CC) with 9- to 10-month delay following pollen releases, and a smaller but significant CC with 3- to 4-month delay. Further, a temporal relationship revealed by positive CC distribution showed that pollen release preceded KD development, suggesting that pollen release leads to KD development. A trend in patient numbers was fitted by an exponential curve with the time constant of 0.005494. We hypothesized that the trend was caused by the cumulative effects of pollen exposure for elapsed months on patients who may develop KD. By comparing the time constants of fitted exponential curve for each pollen accumulation period with 0.005494, the exposure period was estimated to be 21.4 months, which explains why approximately 50% of patients developed KD within 24 months from birth.

Background: Urinary tract infection (UTI) is a frequent, serious complication in kidney allograft recipients., Methods: We reviewed the records of 1166 kidney allograft recipients who received their allografts at our institution between January 2005 and December 2010 and determined the incidence of UTI during the first 3 months after transplantation (early UTI). We used Cox proportional hazards models to determine the risk factors for early UTI and whether early UTI was an independent risk factor for subsequent bacteremia or acute cellular rejection (ACR)., Results: UTI, defined as 10 or more bacterial colony-forming units/mL urine, developed in 247 (21%) of the 1166 recipients. Independent risk factors for the first episode of UTI were female gender (hazard ratio [HR], 2.9; 95% confidence intervals [CI], 2.2-3.7; P<0.001), prolonged use of Foley catheter (HR, 3.9; 95% CI, 2.8-5.4; P <0.001), ureteral stent (HR, 1.4; 95% CI, 1.1-1.8; P=0.01), age (HR, 1.1; 95% CI, 1.0-1.2; P=0.03), and delayed graft function (HR, 1.4; 95% CI, 1.0-1.9; P=0.06). Trimethoprim/sulfamethoxazole prophylaxis was associated with a reduced risk of UTI (HR, 0.6; 95% CI, 0.3-0.9; P=0.02). UTI was an independent risk factor for subsequent bacteremia (HR, 2.4; 95% CI, 1.2-4.8; P=0.01). Untreated UTI, but not treated UTI, was associated with an increased risk of ACR (HR, 2.8; 95% CI, 1.3-6.2; P=0.01)., Conclusions: Female gender, prolonged use of Foley catheter, ureteral stent, age, and delayed graft function are independent risk factors for early UTI. UTI is independently associated with the development of bacteremia, and untreated UTI is associated with subsequent ACR.

The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

When there is the suspicion of an allergic reaction to betalactam-antibiotics, the allergological evaluation is an important tool to confirm the allergy and to test alternative medicaments. As all the testing methods for the allergologic evaluation (cutaneous tests and in-vitro tests) don't have a high sensitivity, a broad case report and the former documentation of the symptoms and diagnostic findings are essential, to enable a high significance of the examination and to assess the indication for the provocation test which is the gold standard in many cases. The documentation of the time flow is basic, to differentiate between immediate reactions (hours after intake) and nonimmediate reactions (several days after intake). The diagnostic evaluation not later than after six months increases the prospects for a successful allergic evaluation.

Background: Literature on the relationship between atopic dermatitis (AD) and cutaneous delayed-type hypersensitivity is inconclusive., Objective: We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD, and, to assess whether atopic patients in our database were more likely to patch test positive to certain classes of allergens., Methods: A total of 2305 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reactions among patients with AD (n = 297) and without AD (n = 2008) was assessed. Statistical analysis was done using a χ(2) test with Yates continuity correction., Results: Compared with nonatopic patients, those with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to nickel, cobalt, and chromium, but was not associated with contact sensitization to fragrances., Limitations: Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City (including Kansas City, MO, Kansas City, KS, and the adjoining suburbs)., Conclusion: Compared with nonatopics, patients with AD are significantly more likely to have at least 1 positive patch test reaction and to develop contact hypersensitivity to metal allergens., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Among the most frequent adverse effects of subcutaneous heparin treatment, heparin-induced skin lesions occur with an incidence of 10.3% in nonpregnant female patients. Clinical observations suggest an even higher risk during pregnancy., Objectives: We sought to determine the incidence and causes of heparin-induced skin reactions during pregnancy in a prospective cohort study., Methods: Pregnant women with subcutaneous heparin treatment were prospectively examined for skin reactions. If a skin lesion was observed, further diagnostics were performed (skin biopsy, subcutaneous provocation, clinical/laboratory assessment for thrombosis, bleeding, and heparin-induced thrombocytopenia [HIT]). Safety parameters were also analyzed (cross-allergies, frequency of thromboembolic and bleeding complications, HIT, and pregnancy outcome)., Results: Among 111 pregnant patients, 22 (19.8%) had heparin-induced skin reactions (95% CI, 13% to 29%). All lesions were caused by allergic delayed-type hypersensitivity (DTH) reactions and not by HIT or other rare conditions. The median time of onset was 50.5 days (range, 5-184 days). The cross-reactivity rate was 33.3%. While nadroparin treatment exhibited a higher DTH risk than dalteparin (hazard ratio [HR], 26.7; 95% CI, 3.4-211.0; P = .00187), enoxaparin treatment was not significantly different from dalteparin treatment (HR, 5.6; 95% CI, 0.3-96.1; P = .238). Three thromboembolic events and 1 major bleeding event occurred., Conclusions: Among patients receiving long-term heparin anticoagulation during pregnancy, heparin-induced skin lesions are frequent (incidence, 19.8%) and are all caused by allergic DTH reactions. Nadroparin has the highest frequency of skin lesions (approximately 65% at 100 days), which is significantly higher than that of dalteparin (HR, 26.7). Therefore nadroparin use should be avoided in pregnancy when possible., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

We evaluated sex, age, nutritional status, and infectious disease (ID) as predictors of two biomarkers of cell-mediated immunity (CMI), delayed-type hypersensitivity to Candida albicans (DTH-Candida), and anti-Epstein-Barr virus antibody (EBV Ab), among 200 children in Kilimanjaro, Tanzania. DTH-Candida, which decreases with compromised CMI, was positively associated with age (OR: 1.27; 95% CI: 1.02, 1.57) and triceps skinfold (TSF; OR: 1.16; 95% CI: 1.02, 1.26), and inversely associated with height-for-age Z score (HAZ; OR: 0.86; 95% CI: 0.68, 1.08) and diagnosed ID (OR: 0.48; 95% CI: 0.22, 1.08). There was significant interaction between TSF and ID: DTH-Candida exhibited a strong inverse association with ID among children with low TSF (OR: 0.16; 95% CI: 0.05, 0.50) and a strong positive association with TSF among children with ID (OR: 2.64; 95% CI: 1.29, 5.42). EBV Ab, which increases with compromised CMI, was inversely associated with male sex (β: -0.47; 95% CI: -0.70, -0.24) and TSF (β: -0.04; 95% CI: -0.08, 0.00), and positively associated with HAZ (β: 0.06; 95% CI: -0.03, 0.15). Among males, EBV Ab was positively associated with anemia. Among normal HAZ children, EBV Ab was inversely associated with TSF. There was no association between DTH-Candida and EBV Ab. While DTH-Candida provides a direct measure of CMI, our results suggest that interpretation of EBV-Ab among Kilimanjaro children was complicated by its indirect relationship with CMI. Among our sample, CMI increased with age and adequate nutrition and was compromised during acute ID. The suggestive CMI-compromising effect of increasing height-for-age may bear further exploration., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Objective: Despite a thorough history and comprehensive testing, many children who present with recurrent symptoms consistent with allergic reactions elude diagnosis. Recent research has identified a novel cause for "idiopathic" allergic reactions; immunoglobulin E (IgE) antibody specific for the carbohydrate galactose-α-1,3-galactose (α-Gal) has been associated with delayed urticaria and anaphylaxis that occurs 3 to 6 hours after eating beef, pork, or lamb. We sought to determine whether IgE antibody to α-Gal was present in sera of pediatric patients who reported idiopathic anaphylaxis or urticaria., Methods: Patients aged 4 to 17 were enrolled in an institutional review board-approved protocol at the University of Virginia and private practice allergy offices in Lynchburg, VA. Sera was obtained and analyzed by ImmunoCAP for total IgE and specific IgE to α-Gal, beef, pork, cat epithelium and dander, Fel d 1, dog dander, and milk., Results: Forty-five pediatric patients were identified who had both clinical histories supporting delayed anaphylaxis or urticaria to mammalian meat and IgE antibody specific for α-Gal. In addition, most of these cases had a history of tick bites within the past year, which itched and persisted., Conclusions: A novel form of anaphylaxis and urticaria that occurs 3 to 6 hours after eating mammalian meat is not uncommon among children in our area. Identification of these cases may not be straightforward and diagnosis is best confirmed by specific testing, which should certainly be considered for children living in the area where the Lone Star tick is common.

Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type hypersensitivity (DTH) response conferring protection against leishmaniasis. The relevance of DTH to sand fly bites in humans living in a leishmaniasis-endemic area remains unknown. Here, we describe the duration and nature of DTH to sand fly saliva in humans from an endemic area of Mali. DTH was assessed at 24, 48, 72, and 96 hours post bite in volunteers exposed to colony-bred sand flies. Dermal biopsies were obtained 48 hours post bite; cytokines were quantified from peripheral blood mononuclear cells (PBMCs) stimulated with sand fly saliva in vitro. A DTH response to bites was observed in 75% of individuals aged 1-15 years, decreasing gradually to 48% by age 45, and dropping to 21% thereafter. Dermal biopsies were dominated by T lymphocytes and macrophages. Abundant expression of IFN-γ and absence of T(H)2 cytokines establishes the T(H)1 nature of this DTH response. PBMCs from 98% of individuals responded to sand fly saliva. Of these, 23% were polarized to a T(H)1 and 25% to a T(H)2 response. We demonstrate the durability and T(H)1 nature of DTH to sand fly bites in humans living in a cutaneous leishmaniasis-endemic area. A systemic T(H)2 response may explain why some individuals remain susceptible to disease.

This was a cross-sectional study which analyzed the prevalence and the clinical and immunological spectrum of canine Leishmania (L.) infantum chagasi infection in a cohort of 320 mongrel dogs living in an endemic area of American visceral leishmaniasis in the Amazonian Brazil by using, mainly, the indirect fluorescence antibody test (IFAT-IgG) and the delayed-type hypersensitivity (DTH), and the parasite research by the popliteal lymph node aspiration. The IFAT and DTH reactivity recognized three different immune response profiles: (1) IFAT((+))/DTH((-)) (107 dogs), (2) IFAT((-))/DTH((+)) (18 dogs), and (3) IFAT((+))/DTH((+)) (13 dogs), providing an overall prevalence of infection of 43% (138/320). Thus, the specific prevalence of IFAT( (+) )/DTH( (-) ) 33.4% (107/320) was higher than those of IFAT( (-) )/DTH( (+) ) 5.6% (18/320) and IFAT( (+) )/DTH( (+) ) 4.0% (13/320). Moreover, the frequency of these profiles among 138 infected dogs showed that the IFAT( (+) )/DTH( (-) ) rate of 77.5% (107/138) was also higher than those of 13.0% (18/138) of IFAT( (-) )/DTH( (+) ) and 9.5% (13/138) of IFAT( (+) )/DTH( (+) ) rates. The frequency of asymptomatic dogs (76%-105) was higher than those of symptomatic (16.6%-23) and oligosymptomatic ones (7.4%-10). A total of 16 (11.6%) L. (L.) i. chagasi isolates were obtained from infected dogs, all from the IFAT( (+) ) /DTH( (-) ) profile: 41% (9/22) from symptomatic, 33.3% (3/9) from oligosymptomatic, and 5.2% (4/76) from asymptomatic dogs. These findings strongly suggested that despite the higher frequency of asymptomatic dogs (76%-105), the majority (72.4%-76) was characterized by the IFAT( (+) ) /DTH( (-) ) profile with a doubtful immunogenetic resistance against infection.

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.

Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity., (© 2011 John Wiley & Sons A/S.)