Negative Skin Test Research Articles

Component‐resolved diagnosis of wasp (yellow jacket) venom allergy

Wasp venom allergy is a potentially life-threatening condition with serious consequences of diagnostic error. To assess whether component-resolved diagnosis, using non-glycosylated recombinant allergen components from yellow jacket can add to the diagnosis of wasp venom allergy. In total, 148 patients with a wasp (yellow jacket) allergy were included, 91 with unequivocal tests, 26 with double positivity of serum-specific IgE (sIgE) to both venoms, 21 with discrepant sIgE and skin test results and finally 10 having their diagnosis only confirmed by basophil activation test (negative sIgE and skin test results). Specific IgE to recombinant species-specific allergen components Ves v 1 and Ves v 5 from yellow jacket, Api m 1 from honeybee and Ves v 5 complemented wasp venom were tested by ImmunoCAP. Overall, combined use of sIgE to rVes v 1 and rVes v 5 allowed correct diagnosis in 139 of the 148 patients (94%) and rApi m 1 was demonstrable in only one patient. Supplementing the traditional yellow jacket allergosorbent with rVes v 5 allowed to correctly diagnose wasp allergy in patients sensitized to Ves v 5 but demonstrating a negative sIgE to wasp venom. Component-resolved diagnoses with the wasp-specific recombinant allergen components Ves v 1 and Ves v 5 is a reliable method to diagnose yellow jacket allergy and can help to take out the sting of difficult cases. However, as the number of patients with doubt after conventional tests is small, larger collaborative studies are needed to draw more definitive conclusions. Whether the rVes v 5 supplemented yellow jacket allergosorbent constitutes an asset in the diagnostic management of wasp venom allergy remains to be further established.

Mycobacterium bovis detection from milk of negative skin test cows

Mycobacterium bovis is the bovine tuberculosis (bTB) agent, which is still an important infection in bovine herds. Apart from this, bTB is also a zoonotic disease, and human beings can...

Co-existence of Chronic Urticaria and Metabolic Syndrome: Clinical Implications

A systemic pro-inflammatory and pro-coagulating state occurs in subjects who have both chronic urticaria and metabolic syndrome. To investigate the prevalence and clinical impact of metabolic syndrome in Korean patients with chronic urticaria, a hospital-based cross-sectional study of 131 patients was performed. Metabolic syndrome was assessed by the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Urticaria disease activity was assessed by total urticaria activity score (range 0-15). Thirty-nine patients (29.8%) had metabolic syndrome compared to 17.8% in a matched control group (p=0.001). Patients with chronic urticaria and metabolic syndrome were older, had a higher mean urticaria activity score and serum levels of eosinophil cationic protein, tumour necrosis factor-α, and complements, and showed a higher rate of negative autologous serum skin tests compared with those with-out metabolic syndrome. Logistic regression analysis indicated that an urticaria activity score of ≥ 13 (p=0.025) and the presence of metabolic syndrome (p=0.036) were independent predictors of uncontrolled chronic urticaria. We conclude that patients with severe and uncontrolled chronic urticaria should be evaluated for metabolic syndrome in order to reduce cardiovascular risk and improve chronic urticaria outcomes.

ANTIHISTAMINE THERAPY EFFICACY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA

Background. Estimation of efficacy of antihistamines in patients with various severity levels and various clinical and laboratory variants of chronic idiopathic urticaria (CIU) . Methods. The retrospective study of the anamnestic clinical laboratory findings in 196 patients with CIU was performed. Results. The frequency of patients with full effect of antihistamines was 69%, partial efficacy — 11%, lack of efficacy — 20%. Lack of efficacy was dominated in patients with severe course of the disease and the presence of clinical manifestations of autoimmune disorders, non-specific inflammation and / or signs of cutaneous vasculitis. The full effect of antihistamines was dominated in patients with mild to medium CIU, with a normal clinical blood count and with a negative skin test with autologous serum. Conclusion. Lack of efficacy of of antihistamines in patients with severe course of disease, signs of autoimmune disorders specify on others nonhistamine mediators in CIU pathogenesis and application of the second and third line therapy of CIU.

Spiking venom with rVes v 5 improves sensitivity of IgE detection in patients with allergy to Vespula venom

Spiking venom with rVes v 5 improves sensitivity of IgE detection in patients with allergy to Vespula venom

Epidemiological aspects of tuberculosis in children and adolescents in Rio de Janeiro

To describe the epidemiological aspects of childhood tuberculosis (TB) in a Brazilian reference hospital. This was a retrospective study (1999-2008) of 473 subjects (0-14 year olds) with confirmed TB, or with clinical improvement by the fourth month of treatment under the unit's care, including the review of medical records, monitoring reports and notifications by the TB unit. Among 473 TB cases included in the study, positive tuberculin skin test was observed in 52%, history of contact with a patient with pulmonary tuberculosis in 66%, mostly intra-household, and with the father/stepfather most commonly involved; and disseminated TB in 22%. The result of HIV testing was obtained in 265 (56%) cases, being positive in 45 (17%). The diagnosis of TB was confirmed in 31% of cases, most frequently in children older than 5 years, with negative tuberculin skin test, and in disseminated forms. Of the 65 cultures positive for TB performed in the study, drug sensitivity testing to anti-TB drugs was done in 30 (46%) clinical samples, among which 10 (33%) were resistant to one or more anti-TB drugs, and 2 (0.8%) were multi-drug-resistant. Among patients with confirmed pulmonary TB, 31% did not meet the criteria for starting anti-TB treatment according to the scores of the Ministry of Health (≤ 25 points). The high proportion of drug-resistant TB and co-infection with HIV identified in this study highlight the necessity to carry out additional studies in order to evaluate the impact of TB control activities on childhood TB.

Old questions and novel clues: Complexity of IgE repertoires

Old questions and novel clues: Complexity of IgE repertoires

Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity reactions to iodinated contrast media

Nonimmediate hypersensitivity reactions to iodinated contrast media (CM) are common. Allergological evaluation is necessary to confirm the diagnosis and to find a tolerated alternative. The aim of this study was to establish the role of skin testing and the drug provocation test (DPT) in the diagnosis of nonimmediate reactions to CM. Skin intradermal testing and patch testing with delayed readings were carried out with different CM (iobitridol, iomeprol, iodixanol, iohexol, ioversol, iopramide and ioxaglate). Single-blind placebo-controlled DPT was carried out in those cases with a negative skin test. In seven cases, a skin biopsy was obtained from positive skin tests and positive DPT. Of the 161 subjects evaluated, 34 (21.1%) were skin-test positive, 21 (50%) to Iomeprol, 7 (16.7%) to Iodixanol, 5 (11.9%) to Iobitridol, 4 (9.5%) to Ioxaglate, 3 (7.1%) to Iohexol and 1 (2.4%) to Iopramide. DPT was positive in 44 cases (34.6%) that were skin-test negative, 38 (76%) to Iodixanol, 8 (16%) to Iomeprol and 4 (8%) to Iohexol. Of 78 cases (48.4%) with confirmed hypersensitivity, 34 (43.6%) were identified by skin testing and 44 (56.4%) by DPT. Skin biopsies showed a perivascular mononuclear cell infiltrate, mainly in the dermis, with higher levels of CD4 than CD8 T lymphocytes, with expression of activation markers and skin homing receptors. Patients with nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT in 56.4%. The method to confirm the diagnosis differed depending on the CM involved.

Paracetamol Hypersensitivity: Clinical Features, Mechanism and Role of Specific IgE

Background: Paracetamol is a common antipyretic/analgesic and a component of many prescription and over- the- counter preparations. Hypersensitivity reactions to paracetamol appear to be increasing, but there are few prevalence data. The mechanism is poorly understood. We identified the clinical features of 32 patients with suspected paracetamol allergy, investigated the underlying mechanism and examined co-existing non-steroidal anti-inflammatory drug (NSAID) tolerance. Methods: A clinical history was taken and skin tests and an oral challenge were performed in 32 patients with suspected paracetamol allergy. Results: Patients presented with a combination of urticaria, angio-oedema (face, hands), erythema (cutaneous features in 94%), dyspnoea (including laryngeal oedema), rhinoconjunctivitis, cough, abdominal pain and anaphylaxis. Two patients had a positive skin prick test (SPT) and unequivocal history of acute urticaria/facial angio-oedema/conjunctivitis/cough after paracetamol with no other triggers. One patient had a positive intradermal test. Oral challenge was positive in 15 of 31 patients (including self-challenge in 4), triggering (a combination of) rhinitis, conjunctivitis, pruritus, erythema, urticaria, angio-oedema, dyspnoea and abdominal pain. Sensitivity was evident in 1 patient on the basis of the patient’s history. Overall, paracetamol hypersensitivity was confirmed in 16 of the 32 patients (50%). Twelve of the 16 paracetamol-allergic patients (75%) tolerated NSAIDs (negative challenge in 6, negative history in 6). Four of these 16 patients (25%) were intolerant of NSAIDs (positive challenge in 1, self-challenge in 3). Conclusions: In past reports on paracetamol hypersensitivity, only single cases of a positive SPT and detectable specific IgE have been described. Our data confirm that specific IgE may be a mechanism underlying paracetamol hypersensitivity, as in this series 18.8% of the patients had specific IgE. In 81.2% of patients, negative skin tests did not exclude paracetamol hypersensitivity, suggesting that it may be mediated by leukotrienes. However, three quarters of our patients tolerated NSAIDs, implicating an alternative mechanism. In patients with suspected paracetamol allergy, skin tests should be performed in addition to clinical history and oral challenge.

Clinical Outcome in the Use of Cephalosporins in Pediatric Patients with a History of Penicillin Allergy

Background: The risk of cephalosporin administration in patients with a history of penicillin allergy is unclear. Few studies have looked at the risk of cephalosporin administration in children following penicillin skin testing for suspected penicillin allergy. The goal of this study was to determine whether children with penicillin allergy were at increased risk for adverse drug reactions when administered a cephalosporin. Methods: A retrospective chart review was conducted in pediatric patients (≤18 years) with a history of penicillin allergy and a positive or negative penicillin skin test who were administered a cephalosporin after testing. Charts were reviewed for adverse drug reactions to the cephalosporin. Results: A total of 173 patients (91 males) were included in this study. The mean age of the patients was 4.1 ± 3.1 years. Twenty-one patients (12%) tested positive in a penicillin skin test and 152 patients (88%) tested negative. One patient with a negative penicillin skin test (0.7%) had an adverse drug reaction (eye swelling) to cephalexin. None of the patients with a positive penicillin skin test who received a course of cephalosporin had an adverse drug reaction. Conclusion: Among all patients with a history of penicillin allergy (penicillin skin test positive and negative), only 1 person had an adverse drug reaction. Further large prospective studies examining the safety of administering cephalosporins in pediatric patients with confirmed penicillin allergy are needed.

Multicytokine Detection Improves Latent Tuberculosis Diagnosis in Health Care Workers

In a low-incidence setting, health care workers (HCW) are at a higher risk of tuberculosis than the general population. The suboptimal sensitivity of the QuantiFERON-TB Gold In-Tube (QFT) test remains a critical issue when identifying occupational latent tuberculosis infection (LTBI) in HCW. The aim of this study was to identify additional biomarkers in order to overcome the limits of gamma interferon (IFN-γ) release assays (IGRAs) and improve the performance of LTBI diagnosis within this population. Seventy Bacille Calmette-Guérin-vaccinated HCW regularly exposed to Mycobacterium tuberculosis were grouped according to QFT results into an LTBI-positive group (positive QFT, n = 8), an LTBI-negative group (normal QFT and negative tuberculin skin test [TST], n = 21), and an undetermined group (subpositive QFT and/or positive TST, n = 41). The secretion of 22 cytokines in response to QFT-specific stimulation was quantified using a multiparameter-based immunoassay. As a result, thresholds discriminating LTBI-positive from LTBI-negative HCW were established by comparing areas under the receiver operating characteristic curves for interleukin-2 (IL-2), IL-15, IFN-γ-induced protein 10 (IP-10), and the monokine induced by IFN-γ (MIG), which are biomarkers differentially secreted by the two groups. The combination of IL-15 and MIG provided a sensitivity of 100% and a specificity of 94.1% in distinguishing LTBI-positive from LTBI-negative HCW. When using IL-15 and MIG among the undetermined group, 6/45 HCW could be classified in the LTBI-positive group. The use of additional biomarkers after IGRA screening could improve the diagnosis of LTBI. The performance of these biomarkers and their use in combination with TST and/or QFT, as well as the cost-effectiveness of such a diagnostic strategy, should be evaluated in further larger clinical trials.

Outpatient penicillin use after negative skin testing and drug challenge in a pediatric population

The practice of elective penicillin skin testing could be compromised by the fact that patients, their parents, or their physicians remain reluctant to reuse penicillin-class antibiotics (PCAs) despite a negative evaluation by an allergist. This study addresses reuse of PCAs in a pediatric population after negative penicillin skin testing and drug challenge and factors associated with its reluctance. All children evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between January 1998 and June 2000 with negative skin testing and drug challenge were included in the study. A telephone survey was conducted between May and October 2002 to assess the perception of the initial reaction by the parents, subsequent use of antibiotics, and antibiotic-related adverse reactions. Among the 200 children selected, parents of 170 (85%) children completed the survey. Since the allergist evaluation, 130 (76%) children had received antibiotics. PCA was used in 59 (45%) children. Parents of 24 (18%) children refused PCAs because they still feared an adverse reaction. They were more likely to have been very frightened by their child's allergic reaction than other parents whose children had used PCAs (p = 0.008). Although elective penicillin skin testing is useful and safe in the pediatric population, a significant proportion of parents still refuse PCAs even though they are needed. Identification of parents that were very frightened by their children's allergic reactions and additional reassurance could improve this situation.

Facteurs prédictifs des récidives de tuberculose pulmonaire en Tunisie : une étude rétrospective

Tuberculosis is still endemic in Tunisia. Even though recurrent TB (RT) is rare, there is an increased risk of resistance. The purpose of this study is to investigate predictors of RT. This was a case controlled retrospective study, comparing two groups of patients with confirmed pulmonary tuberculosis: a relapse group (GR) of 64 patients with RT and a control group (GT) of 105 patients. Between September 1995 and December 2007, the incidence of RT was 9.48%. All the patients were male. There was no difference in the average age of the two groups. A smoking history of greater than 20 pack-years was more common in the GR (44.89% versus 21.4%, P=0.055). No difference was found regarding the history and clinical signs except that chest pain and dyspnoea were more frequent in the GR. A low haemoglobin was more common in the GR (11.33 ± 1.57g/dL versus 12.41 ± 1.66g/dL, P=0.008). The tuberculin skin test was negative in 73.7% of GR versus 31.1% of GT (P=0.001). Adverse liver reactions are more frequent in the GR (27.3% versus 8.6%, P<0.05). Discontinuation of TB treatment was more common in the GR (36.7% versus 3.8%, P<0.001). The achievement of sputum negativity was delayed in the GR (46.32 ± 54.01 versus 9.35 ± 11.84 days, P<0.001). Despite this, we have noted no significant difference in drug resistance. In multivariate analysis, hepatic cytolysis and a negative tuberculin skin test were independent predictive factors for RT. All tuberculous patients should have a carefully adapted treatment regimen, particularly the presence of factors predictive for recurrence.

Value Of Skin Testing Solely With Penicillin G In Children With a History Of Penicillin Allergy

For most part of the last decade, PrePen® has been unavailable commercially. This situation has compromised the evaluation of many patients with a history of penicillin allergy. During this period, evaluation of children with a history of penicillin allergy continued in our center using penicillin G as the sole reagent for skin testing. We aimed to determine the negative predictive value and safety of this approach. We reviewed the files of all patients evaluated for a history of penicillin allergy between December 2006 and December 2009 at the CHU Sainte-Justine Allergy Clinic. Evaluation consisted of skin testing with penicillin G 10,000 IU/mL followed if negative by a graded challenge to the culprit penicillin. We evaluated 563 patients during this period. Among these, 185 (32.9%) had a positive skin test to penicillin G and 378 (67.1%) had a negative skin test. A reaction occurred in 4.8% (18/375) of patients following challenge. Three patients were not challenged. All reactions were mild and generally limited to the skin. The negative predictive value of skin testing solely with penicillin G was calculated at 95.2% (92.5-97.1%). This study raises questions about the relevance of skin testing children with a history of penicillin allergy with a large array of skin test reagents as the negative predictive value of penicillin G alone approximates that of the recommended approach. Also, it offers support for a simpler and safe alternative to skin testing in these children using penicillin G as the sole skin test reagent.

357 Tear IL-4 is Decreased in Allergic Conjunctivitis Patients with Negative Skin Test After Dialyzable Leukocyte Extracts Treatment

BackgroundIt has been suggested that sublingual immunotherapy induces immune regulation, however in patients with clinical ophthalmological diagnosis as allergic conjunctivitis with negative skin test reactivity (ACNST) this treatment is not useful. Dialyzable leukocyte extracts (DLE) have been used in atopic dermatitis and asthma. The aim of this work was to evaluate treatment of ACNST with DLE and to analyze the microenvironment provided by tear and serum cytokines in patients before and after DLE treatment.Methods10 ACNST-patients with negative skin test were included in this study. ACNST diagnosis was based on a clinical history and full ophthalmologic examination according to the diagnosis standards of the American Academy of Ophthalmology. Coproparasitoscopic negative for parasites was documented This study was approved by Scientific and Ethics Committees if Institute of Ophthalmology “Conde de la Valenciana “, Mexico City an all subjects gave their informed consent to obtain samples. Tear and Serum Samples were collected to determine cytokines IL2, IL-4, IL-5, IFN-g, TNF-a, IL-10 by cytometric bead arrays (CBA), following manufacturer's instructions.ResultsPatients showed lower significant levels of L-4 after 6 months of treatment, without changes in IL2, IL5, TNFa and IL10. Significant Clinical improvement was also observed since 3 months of treatment and was maintained until the end of 6 months.ConclusionsDLE could be an excellent therapeutic tool to improve the clinical outcome in ACNST patients; it is possible that clinical improvement could be Tear IL-4 dependent.

371 Cutaneous Response to Patch Tests with Dermatophagoides Farinae and Dermatophagoides Pteronyssinus in Patients with Chronic Rhinitis

BackgroundRhinitis is characterized clinical by chronic runny nose, sneezing, nasal itching, congestion and postnasal discharge, among other symptoms. It´s classified as allergic and non allergic. Skin prick testing is the principal diagnosis method for allergic rhinits. However, there is a group of patients with chronic rhinopathy that have negative skin tests, the objective of this study was to determine the cutaneous response to patch tests with Dermatophagoides farinae and Dermatophagoides pteronyssinus in patients with chronic rhinitis.MethodsIt was a cross-sectional, observational and descriptive study. We included patients over 18 years old. They were divided into 3 groups; Group A patients who came for the first time with a history of chronic rhinopathy over 18 months of evolution and positive skin tests for aeroallergens; group B patients with chronic rhinitis with at least one year of evolution and negative skin tests; group C healthy volunteers. Patch test with farinae and pteronisyinnus were done in the subjects of all 3 groups, with readings at 48 and 72 hours.ResultsA total of 37 patients were studied, mean age 26.1 years. Twenty two were male subjects (60%). The mean lenghtof chronic rhinophaty was 10.8 years. Six patients had positive patch test to any of the mites tested; 2 (33%) in group A, 2 (33%) in group B and 2 (33%) of the control group, but it was not statistically significant (P > 0.05).ConclusionsAlthough the results were not statistically significant, there were patients with chronic rhinitis wich had positive patch test for mites. This sensitization could be clinically significant for those patients.

Systemic Mycobacterium avium Complex Infection During Antitumor Necrosis Factor‐α Therapy in Pediatric Crohn Disease

Systemic <i>Mycobacterium avium</i> Complex Infection During Antitumor Necrosis Factor‐α Therapy in Pediatric Crohn Disease

404 Allergen Specific Immunotherapy as a Treatment for Eosinophilic Esophagitis

BackgroundEosinophilic Esophagitis (EoE) is an inflammatory disease that reduces the ability of the esophagus to pass food, often leading to dysphagia. A relationship between EoE and food allergies has been determined. However, there have been several documented cases in which patients had negative prick skin testing (PST) results for food allergens and positive results for airborne environmental allergens, and still have a confirmed diagnosis of EoE. Recently, airborne allergens have been implicated in the onset of this condition. Studies have shown that patients sensitive to airborne allergens such as pollen have a seasonal biannual component in which the severity of EoE symptoms increase, coinciding with high pollen seasons.MethodsWe followed a 65-year-old man with a history of allergies complaining of an increase in his symptoms of allergic rhinitis and asthma. He also noted dysphagia and occasional vomiting. We noted the disease and medication course over 5 years of treatment.ResultsThe patient underwent an esophagogastroduodenoscopy with biopsy, in which midesophageal rings as well as an 8 mm sessile polyp were found, suggesting EoE. Histological analysis confirmed EoE, having found >20 intraepithelial eosinophils/HPF. The patient was treated with a short term prednisone regimen, as well as maintenance medications consisting of inhaled corticosteroids and antihistamines. The patient returned 6 months after the initial consultation and still presented symptoms of EoE, at which point the patient was prescribed proton pump inhibitors. In addition, allergen specific immunotherapy was initiated for confirmed airborne allergens. The patient was examined after 5 years of immunotherapy treatment. Not only did he report that his allergic rhinitis and asthma symptoms were controlled, but his EoE symptoms had resolved.ConclusionsResults suggest that immunotherapy for airborne allergens could be a successful treatment for EoE. A larger study is needed to determine if allergen specific immunotherapy is a viable treatment option for EoE in similar cases. Such a study could include patients with EoE and confirmed airborne allergies treated with immunotherapy while monitoring a number of eosinophilic and lymphocytic markers.

Advances in upper airway diseases and allergen immunotherapy in 2011

The purpose of this review is to highlight recently published important articles on upper airway diseases and allergen immunotherapy. We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases.

Clinical and investigative assessment of patients with positive versus negative autologous serum skin test: A study of 80 south Indian patients

Background:Chronic urticaria (CU) is defined as urticaria persisting daily as or almost daily for more than 6 weeks and affecting 0.1% of the population. Mast cell degranulation and histamine release is of central importance in the pathogenesis of CU. About 40-50% of the patients with chronic idiopathic urticaria demonstrate an immediate wheal and flare response to intra-dermal injected autologous serum. This led to the concept of autoimmune urticaria.Aims:To determine the occurrence, clinical features, associated clinical conditions, comorbidities of autoimmune urticaria and to compare this with chronic spontaneous urticaria. This study aimed to find the frequency of autologous serum skin test (ASST) positive patients among patients with CU and to identify the clinical and laboratory parameters associated with positive ASST.Materials and Methods:Prospective correlation study was done on 80 chronic urticaria patients, more than 6 weeks duration, attending outpatient department of dermatology during a period of November 2007 to January 2010. Patients were subjected to ASST, complete blood count, urine routine examination, liver function tests, renal function tests, thyroid function tests, H. pylori antibody tests, C3 and C4 complement level estimation, antinuclear antibody, and urine analysis.Results:ASST was positive in 58.75% and negative in 41.25% of the patients, respectively. Out of 33 patients with history of angioedema, 9 (27.3%) patients were in ASST negative group and 24 were in positive group, this was statistically significant. Both groups showed no statistically significant difference for epidemiological details.Conclusion:ASST is considered a screening test for an autoimmune urticaria, which decreases the rate of diagnosis of “idiopathic” form of chronic urticaria. Patients with an autoimmune urticaria have more severe urticaria, more prolonged duration, more frequent attacks, and angioedema. Identification of autoimmune urticaria may permit the use of an immunotherapy in severe disease unresponsive to anti-histamine therapy.