Negative Skin Test Research Articles

Negative latent tuberculosis at time of incarceration: identifying a very high-risk group for infection.

The main aim was to measure the incidence of latent tuberculosis infection (LTBI) and identify risk factors associated with infection. In addition, we determined the number needed to screen (NNS) to identify LTBI and active tuberculosis. We followed 129 prisoners for 2 years following a negative two-step tuberculin skin test (TST). The cumulative incidence of TST conversion over 2 years was 29·5% (38/129), among the new TST converters, nine developed active TB. Among persons with no evidence of LTBI, the NNS to identify a LTBI case was 3·4 and an active TB case was 14·3. The adjusted risk factors for LTBI conversion were incarceration in prison number 1, being formerly incarcerated, and overweight. In conclusion, prisoners have higher risk of LTBI acquisition compared with high-risk groups, such as HIV-infected individuals and children for whom LTBI testing should be performed according to World Health Organization guidance. The high conversion rate is associated with high incidence of active TB disease, and therefore we recommend mandatory LTBI screening at the time of prison entry. Individuals with a negative TST at the time of entry to prison are at high risk of acquiring infection, and should therefore be followed in order to detect convertors and offer LTBI treatment. This approach has a very low NNS for each identified case, and it can be utilized to decrease development of active TB disease and transmission.

Hypersensibilité aux sels de platine et aux taxanes : intérêt des tests cutanés et des inductions de tolérance

The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.

Bacillus Calmette-Guérin (BCG) vaccination patterns in the province of Québec, Canada, 1956-1974.

In the province of Québec, Canada, the Bacillus Calmette-Guérin (BCG) vaccine was offered to newborns and school-age children from the 1950s to mid-1970s in an organized tuberculosis prevention program. We aimed to describe the annual rates of skin test administration, proportion of skin tests that were positive, and rates of BCG vaccination from 1956 to 1974 according to age, sex, and administrative region. For rates, numerators were extracted from the Québec BCG Vaccination Registry whereas population denominators were obtained from the Canadian Census and governmental publications. Time trends were assessed with linear regression. A total of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly rates of skin tests, routinely administered before vaccination among all except newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9 per 100). The proportion of positive skin tests varied greatly by age, ranging from 10.2% among children <1year to 67.2% among adults ≥20years. The vast majority of individuals who had a negative skin test were subsequently vaccinated, whereas those with a positive result were not, as per recommended guidelines. The average annual vaccination rate was highest among children aged <1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient differences in immunization rates, including positive skin tests and vaccinations, across administrative regions but no difference by sex. This is the first comprehensive description of the tuberculosis prevention program in Québec which offered free, non-mandatory BCG vaccination. Our results confirm that the targeted groups, newborns and school-age children, were preferentially reached. Socioeconomic, demographic, and organizational factors may explain regional differences in immunization rates. Beyond presenting a historical context for this vaccination campaign, our findings are relevant to contemporary uses of the Québec BCG Vaccination Registry in epidemiological research.

Diagnostic challenges, the evaluation of antibiotic allergy.

Antibiotic allergy is commonly reported and often challenging to evaluate. This review highlights recent developments in our understanding of antibiotic allergy, primarily surrounding evaluation, and diagnosis of antibiotic allergy. We provide historical context to establish a framework, lending relevance to the latest studies. Clinicians have typically employed skin testing as a first step in the diagnosis of drug allergy, reserving drug provocation challenge, the gold standard for diagnosis, for those with negative skin tests. Although skin tests have a good negative predictive value, the positive predictive value has never been established. An increasing amount of research is demonstrating that drug provocation challenge is well tolerated as the initial evaluation in patients with non-life-threatening reactions to antibiotics. This research also calls into question the value of skin testing in these patients. Skin testing has long been used as the initial investigation in the diagnosis of drug allergy. New research supports that this may not be necessary in all patients, particularly those with non-life-threatening reactions. Further research into the validity of skin testing is required, along with the development of new diagnostic tests for antibiotic allergy.

The clinical role of purified protein derivative skin test reaction in patients with non-muscle invasive bladder cancer treated with bacillus-Calmette Guerin.

4545 Background: We investigated the association between purified protein derivative (PPD) skin test reaction prior to BCG therapy and clinical outcomes, both oncological outcomes and occurrence of side effects, in BCG-naïve non-muscle invasive bladder cancer (NMIBC) patients. Methods: A total of 288 NMIBC patients who received PPD skin test prior to BCG therapy were included. The PPD skin test reaction was categorized into three groups: positive, slightly positive, and negative. The presence of an induration was positive. If an induration was absent, an erythema 10 mm or more and less than 10 mm corresponds to slightly positive and negative, respectively. Results: Sixty-six (22.9%), 149 (51.7%), and 73 (25.3%) patients had positive, slightly positive, and negative PPD skin test results, respectively. The 5-year recurrence-free survival rate of patients with a positive PPD skin test was 89.4±4.1%, which was significantly higher than that of patients with slightly positive (65.5±4.2%, p = 0.001) and negative (56.4±6.6%, p &lt; 0.001) results. Multivariate Cox regression analysis demonstrated that a positive PPD skin test was independently associated with tumor recurrence (Hazard ratio of 0.213, p &lt; 0.001) but not with stage progression. The occurrence rate of major side effects in patients with a positive BCG skin test (33.3%) was significantly higher than that in patients with slightly positive (26.8%) and negative PPD skin tests (13.7%). The incidence rate of fever persisting beyond 2 days or fever of ≥38°C in patients with a positive PPD skin test (18.2%) was significantly higher than that in patients with slightly positive (8.7%) and negative PPD skin tests (4.1%). Conclusions: NMIBC patients with a positive PPD skin test and who were treated with BCG therapy had a significantly lower tumor recurrence rate and higher incidence of major side effects such as fever persisting beyond 2 days or fever of ≥38°C. Our findings suggest that PPD skin test prior to BCG therapy can predict clinical outcomes following BCG therapy and provide useful information regarding who would experience a strong therapeutic effect for BCG therapy and BCG-related major side effects.

Oral Challenge without Skin Testing Safely Excludes Clinically Significant Delayed-Onset Penicillin Hypersensitivity

Penicillins are the drug family most commonly associated with hypersensitivity reactions. Current guidelines recommend negative skin tests (ST) before re-administering penicillins to patients with previous nonimmediate reactions (NIR). The objective of this study was to examine whether ST are necessary before re-administering penicillin to patients with NIR. Patients with NIR to penicillins starting longer than 1 hour after last dose administration or starting any time after the first treatment day or patients with vague recollection of their reaction underwent penicillin ST. Disregarding ST results, patients were challenged with the relevant penicillins. One-tenth of the therapeutic dose followed by the full dose was administered at 1-hour interval and patients continued taking the full dose for 5 days. A total of 710 patients with alleged BL allergy were evaluated. Patients with a history of immediate reaction (52, 7.3%) or cephalosporin allergy (16, 2.2%) were excluded. Of the remaining 642 patients, 62.3% had negative ST, 5.3% positive ST, and 32.4% equivocal ST. A total of 617 (96.1%) patients were challenged. Immediate reaction was observed in 9 patients (1.5%): 1-positive ST, 7-negative ST, and 1-equivocal ST (P= .7). Late reaction to the first-day challenge occurred in 24 patients (4%). An at-home challenge was continued by 491 patients. Complete 5-day and partial challenges were well tolerated by 417 (85%) and 44 patients (8.9%), respectively, disregarding ST results. Thirty patients (6.1%) developed mild reactions to the home challenge regardless of their ST results. A 5-day oral challenge without preceding ST is safe and sufficient to exclude penicillin allergy after NIR developing during penicillin treatment.

Latent tuberculosis infection screening prior to biological treatment in Tunisian patients

The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35men and 78women. The mean age was 47.67±13.50years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments.

Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study.

Backgroundl-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations.MethodsUnder 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes.ResultsFifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2–4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001).ConclusionChildren with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity.

Drug provocation tests (DPT) are commonly performed as part of β-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects). The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT. During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h. This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.

Skin testing and drug challenge outcomes in antibiotic-allergic patients with immediate-type hypersensitivity

BackgroundThe evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability. ObjectiveTo determine the safety outcomes and risk factors for antibiotic challenge reactions in patients reporting a history of antibiotic immediate-type hypersensitivity. MethodsA 5-year retrospective review of patients evaluated for immediate-type antibiotic allergy was conducted. Data analyzed included patient demographics, index reaction details, and outcomes of skin testing and challenges, classified as single-step or multistep. ResultsAntibiotic hypersensitivity history was identified in 211 patients: 78% to penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to carbapenems. In total, 179 patients completed the challenges (median age 67 years, range 50–76 years, 56% women), and compared with nonchallenged patients, they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions. Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step challenge, 11 of 151 for multistep challenge), and 11 of these patients had negative skin testing results before the challenge. Challenge-reactive patients were significantly younger (P = .007), more often women (P = .036), and had additional reported antibiotic allergies (P = .005). No correlation was detected between the reported index and observed challenge reaction severities (κ = −0.05, 95% confidence interval −0.34 to 0.24). Anaphylactic rates were similar during single-step and multistep challenges (3.6% vs 3.3%). ConclusionIn the present population, younger women with multiple reported antibiotic allergies were at greatest risk for challenge reactions. Negative skin testing results did not exclude reactions, and index severity was not predictive of challenge outcome. The multistep and full-dose methods demonstrated a comparable reaction risk for anaphylaxis.

P025 Retrospective chart review of penicillin challenges in historically penicillin sensitive patients with negative skin testing

Extended challenge to penicillin has been recommended beyond more than 1 dose in office in individuals with history of reaction to penicillin that occurs after the first dose and have negative skin testing to penicillin and single dose challenge in office.We review our experience with oral challenge to penicillin in such patients.

What is the clinical value of negative predictive values of skin tests to iodinated contrast media?

Iodinated contrast media (ICM) can cause hypersensitivity reactions (HSR), yet data are scant about the negative predictive value (NPV) of ICM skin tests. To determine the NPV of skin tests to ICM Methods: We enrolled 73 patients with a history of HSRs to ICM, 136 subjects with no previous exposure to ICM, and, as controls, 47 subjects who had previously tolerated ICM. All the subjects had skin tests with the culprit and/or alternative ICM and were later questioned as to whether they were reexposed and/or reacted to the skin-test-negative ICM. Sixty (82.2%) and 13 (17.8%) patients had a history of immediate HSR and those with a history of nonimmediate HSR, respectively. The sensitivity and specificity of the skin tests were 18% and 97%, respectively, in patients with immediate HSR and were 23% and 99%, respectively, in patients with nonimmediate HSR. Of a total of 237 subjects with negative skin test results, 207 (87.3%) were asked about further ICM administration; 158 (84.9%) confirmed subsequent use either with (n = 15 [9.4%]) or without premedication (n = 143 [90.6%]). Of the 143 individuals, 140 tolerated skin-test-negative ICMs but three (1.9%) reacted to ICMs (two with mild nonimmediate reactions, one with a grade 1 immediate reaction). Of 20 patients who had previous HSR to ICM, 17 tolerated further skin-test-negative ICM without premedication. The NPV of ICM skin tests, therefore, was 97% (95% confidence interval, 7599%). The NPV of skin tests with ICM was high. None of the reactions in patients who had negative skin test results were severe, which may reassure physicians who hesitate to perform further evaluations in patients with negative skin test results.

Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease.

IntroductionThe basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease.MethodsWe screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity.ResultsPositive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks).ConclusionsThe CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life.

Cefalotin as antimicrobial prophylaxis in patients with known intraoperative anaphylaxis to cefazolin

BackgroundThe most common trigger for intraoperative anaphylaxis in Western Australia for the period 2014–5 was an antibiotic used for surgical prophylaxis, cefazolin. In these patients who subsequently present for surgery, alternative cephalosporins are forbidden by current guidelines because of concerns regarding an increased risk of anaphylaxis. However, consideration of the structure–activity relationships relevant to anaphylaxis suggests that cefalotin is a safe alternative because of structural dissimilarities, although there are no pubished clinical data relevant to the perioperative setting. MethodsPatients diagnosed with intraoperative anaphylaxis to cefazolin at the Western Australian Anaesthetic Allergy Clinic were tested with intradermal cefalotin and, if negative, subsequently challenged i.v. If tolerated, cefalotin was recommended for subsequent surgery, and subjects were followed up to determine the safety of subsequent intraoperative doses. ResultsTwenty-one subjects diagnosed with immediate hypersensitivity to cephazolin, including 19 subjects with confirmed anaphylaxis, participated. None tested positive to intradermal cefalotin, and all received a graded i.v. challenge to cefalotin without developing signs or symptoms of anaphylaxis. Three subjects subsequently received intraoperative cefalotin 12–139 days later without adverse events. ConclusionsA negative intradermal cefalotin skin test has a good negative predictive value in patients who have previously suffered anaphylaxis to cefazolin, allowing the rational and desirable use of this alternative cephalosporin for future surgery and the avoidance of less desirable antimicrobial agents.

Autologous serum and plasma skin test to predict 2-year outcome in chronic spontaneous urticaria.

BackgroundAutologous serum skin test (ASST) and autologous plasma skin test (APST) are simple methods to diagnose autoimmune chronic urticaria. However, the association data of ASST or APST with disease severity and long-term outcome are still unclear.ObjectiveThe results of ASST and APST might be used to predict urticaria symptom severity and long-term outcomes among chronic spontaneous urticaria (CSU) patients.MethodsWe evaluated the prevalence of reactive ASST and APST in 128 CSU patients. The patients were characterized by 4 groups: negative, ASST positive, APST positive, and both ASST and APST positive. We observed remission rate among the CSU patients during 2 years.ResultsForty-four of 128 CSU patients (34%) had negative autologous skin test. The CSU patients with positive ASST, positive APST, and both positive ASST and APST were 47 (37%), 6 (5%), and 31 (24%), respectively. No significant difference was found between the groups according to urticaria severity score (USS) and dermatology life quality index (DLQI). Mean wheal diameter of ASST showed positive correlation with DLQI. Also, mean wheal diameter of APST showed positive correlation with USS and DLQI. Both the positive ASST and APST groups had a high proportion of 4-fold dose of H1-antihistamine than the positive ASST (p = 0.03) and negative groups (p = 0.0009). The rate of remission over 2 years in the negative, positive ASST, positive APST, and both positive ASST and APST groups were 81.1%, 62.3%, 60%, and 46.1%, respectively. The urticaria remission rate in patients in the negative group was significantly higher compared with both positive ASST and APST groups (odds ratio, 5.0; 95% confidence interval, 1.61–15.44; p = 0.006).ConclusionASST and APST results could predict remission rates among patients with CSU. Our results suggested investigating ASST and APST among CSU patients before starting treatment.

Potential role for interferon-γ release assays in tuberculosis screening in a remote Canadian community: a case series.

Current Canadian guidelines suggest that neonatal Bacille Calmette-Guérin (BCG) vaccination does not result in false-positive tuberculosis (TB) skin tests, despite a growing body of evidence that interferon-γ release assays may be a more specific alternative in identifying latent tuberculosis infections in vaccinated populations. We set out to evaluate the relationship between TB skin tests and interferon-γ release assays in patients who previously received neonatal BCG vaccine. All children with a positive skin test at age 14 years in a remote community north of Sioux Lookout, Ontario, were considered for interferon-γ release assay testing. Of the 11 children who underwent routine screening at 14 years of age for latent TB infection, 7 had a positive TB skin test (≥ 10 mm). All 7 of these children had received the BCG vaccine as newborns and all had a negative TB skin test during their routine screening at 4 years of age. No potential exposure to active TB could be identified. Chest radiographs were normal, and none of the children had symptoms suggestive of active TB. The 7 children underwent interferon-γ release assay testing using QuantiFERON Gold. All 7 tests were negative. With the addition of interferon-γ release assays to routine skin test screening, we provide evidence that neonatal BCG vaccination may contribute to a false-positive skin test in youth at 14 years of age. Consideration should be given to the possibility that neonatal BCG may contribute to false-positive TB skin tests.

Basophil CD63 expression in chronic spontaneous urticaria: correlation with allergic sensitization, serum autoreactivity and basophil reactivity.

The underlying causes and factors contributing to the disease severity of chronic spontaneous urticaria (CSU) are unknown. Given the important role of basophils in the pathogenesis of urticaria and that CD63 serves as a useful marker for basophil activation and detecting, CD63 expression of basophils is a reliable tool for diagnosing allergy and hypersensitivity reactions to different allergens; the objective of this study was to investigate whether the level of basophil CD63 expression is correlated with allergen sensitization, serum autoreactivity and basophil reactivity in patients with CSU. Basophil-enriched leucocytes were separated from the blood of 64 patients with chronic urticaria (54 CSU patients and 10 symptomatic dermographism patients), 18 healthy control subjects and seven atopic donors without urticaria. Flow cytometry was then used to detect CD63 expression on the cell membrane of basophils from all samples. Analysis was also preformed on basophils incubated with sera from CSU patients with positive or negative autologous serum skin test (ASST). CD63 expression was significantly higher in the basophils from patients with CSU than in those from patients with symptomatic dermographism and the healthy control group. The levels of CD63 expression in CSU patients with ASST+ and/or allergen sensitization were higher than those with ASST- and/or no allergen sensitization patients. Incubation with ASST+ serum resulted in an increased expression of CD63 in the basophils of ASST+ CSU patients, whereas no such response was observed in healthy controls or ASST- CSU patients. The increased CD63 expression in basophils from CSU patients may correlate with allergen sensitization, autoreactivity of serum and basophil reactivity. Our results suggest that CD63 may contribute new insight into the pathogenesis of CSU.

Active tuberculosis in a psoriasis patient treated with tumor necrosis factor inhibitors despite an initial negative tuberculin skin test and no known risk factors

Tumor necrosis factor (TNF) inhibitors are becoming more common in the treatment of moderate-to-severe chronic plaque psoriasis. These medications have a low incidence of serious adverse events and are generally considered safe; however, they do make patients more susceptible to tuberculosis (TB) infection both through latent reactivation and primary infection. We describe a case of a patient who had an initial negative tuberculin skin test (TST), began TNF inhibitor therapy, and then 11 years later was diagnosed with active TB. After the initial screening, the patient did not have any subsequent screenings for TB and no apparent change to his TB risk status. TB is still common in many areas of the United States and travel is not necessary to be exposed. Patients on TNF inhibitors that develop active TB have increased morbidity and mortality than those who are not. It is necessary that dermatologists limit the risk of TB to patients by screening them before initiation and annually when they are on the TNF inhibitor.

Understanding the mechanisms in accelerated drug reactions.

The purpose is to understand the underlying mechanisms of accelerated allergic reactions to drugs, defined here as reactions occurring between 1 and 24 h after drug intake. Recent publications have shown that accelerated reactions are T cell-mediated, although an IgE mechanism cannot be ruled out in some cases. Classification of allergic reactions to drugs is complex. Based on the time interval between drug administration and appearance of the clinical reaction, as well as the type of clinical symptoms, they can be classified as: immediate, typically appearing from less than 1 to 6 h after the last drug administration and nonimmediate, occurring at any time from 1 h after drug administration. Therefore, overlap exists in what the Levine classification defined as accelerated reactions, where clinical symptoms are mainly urticaria and less often exanthema and serum sickness-like reactions. The immunological mechanisms involved suggest that they are T cell-mediated reactions with a Th1 pattern, comprising increased production of IFNγ, TNFα, the chemokine CXCL9 and its corresponding receptor CXCR3. In most cases an IgE-mediated response is ruled out because of negative immediate skin test results, no detection of serum-specific IgE antibodies or tryptase, and no skin-secreted tryptase. However, an IgE-mediated response can be demonstrated in exceptional situations. Finally, serum sickness-like reactions have been reported as an immune complex-mediated accelerated reaction. However, the exact mechanism has not been confirmed.

Introduction of peanuts in younger siblings of children with peanut allergy: a prospective, double-blinded assessment of risk, of diagnostic tests, and an analysis of patient preferences.

The prevalence of peanut allergy in younger siblings of children with peanut allergy has been reported between 7% and 8.5%, but the anaphylactic risk at the time of introduction is currently unknown, which limits our ability to best counsel parents on this issue. To determine the risk of anaphylaxis and working parameters of allergy testing in this context. One hundred and fifty-four peanut-naïve younger siblings of peanut-allergic children underwent double-blinded skin testing, followed by parent-led peanut introduction. Questionnaires were dispensed to parents to investigate preferences with regard to peanut introduction in this subgroup. Eight participants (5.2%) presented unequivocal IgE-mediated reactions to peanut upon introduction, including five anaphylaxes. These participants were significantly older compared to the rest of the cohort (median 4.0 vs 1.9years, P=0.04). The negative predictive value of skin prick test with peanut extract and peanut butter and of specific IgE was 99%, 100%, and 100%, respectively. Six peanut-tolerant participants had positive peanut allergy tests. The option of introducing at home without prior skin testing was associated with high levels of anxiety (median 8.4 on 10-point Likert scale) when compared to supervised introduction (median 3.8, P<0.0001) or home introduction after negative skin test (median 4.3, P<0.0001). There is an increased risk of anaphylaxis upon peanut introduction in siblings of children with peanut allergy, and parents are reluctant to introduce at home without testing. Allergy testing prior to introduction is negative in over 90% of cases and carries a high negative predictive value.