Gabriele de Vos

Selective Effect of Mercury on Th2-Type Cytokine Production in Humans

Mercury induces autoimmune disease and increases IL-4 production and IgE levels in certain rodent strains. The object of this study was to determine if mercury was capable of inducing Th2 cytokine production in human leucocytes. Human peripheral blood mononuclear cells (PBMC) were incubated with PMA/ionomycin or Con A in the presence or absence of methyl mercury (CH3Hg) or mercuric chloride (HgCl2). IL-4 and gamma-IFN were measured by ELISA. RESULTS: IL-4 production significantly increased at low concentrations of CH3Hg (0.5 uM, p < 0.01), while gamma-IFN production was suppressed starting at CH3Hg 2 uM (p = 0.004). Inorganic mercury (HgCl2) increased IL-4 only at concentrations 10–20 times higher than CH3Hg. These findings suggest a mechanism by which mercury could trigger or potentiate TH2 cytokine production in humans.

Skin Testing Versus Serum-Specific IgE Testing: Which Is Better for Diagnosing Aeroallergen Sensitization and Predicting Clinical Allergy?

An accurate diagnosis of aeroallergen sensitization is pivotal to clinical practice and research. Given the recent technological advances in analyzing serum allergen-specific IgE, the question of which testing method, skin or serum testing, is superior in diagnosing allergic sensitization must be readdressed, as well as their value in predicting clinical disease. This review article provides a detailed summary of recent studies addressing these questions. Conclusively, most studies show substantial discordance between serum-specific IgE and skin testing results, suggesting that the two testing methods compliment each other and cannot be used interchangeably. On average, using only one testing method may misdiagnose every fourth allergically sensitized patient as non-sensitized. In addition, depending on the allergen tested, skin prick testing and serum-specific IgE testing appear to be the methods of choice in predicting outcomes of experimental allergen challenge, while intradermal testing is less contributory.

Dichlorophenol-containing pesticides and allergies: results from the US National Health and Nutrition Examination Survey 2005-2006

BACKGROUND Epidemiologic studies support the hypothesis that reduced microbial exposure in westernized societies promotes atopy. Dichlorophenols are widely used as pesticides and for chlorination of water. They have a strong bactericidal effect that could affect microflora in the environment. However, it is unknown whether their use is associated with a higher prevalence of allergies. OBJECTIVE To test the association between exposure to environmental pesticides represented by dichlorophenols and allergic sensitization measured by allergen-specific serum IgE levels in a US nationally representative sample of 2,211 persons 6 years and older in the National Health and Nutrition Examination Survey 2005-2006. METHODS Exposure to dichlorophenols was defined as high if their levels in urine were present at the 75th percentile and above. Association of the high exposure to dichlorophenols with sensitization to food and environmental allergens was assessed in logistic regression models after adjustment for sample weights and potential confounders. RESULTS Sensitizations to 1 or more food allergens were more common in those with exposure to 2 dichlorophenol metabolites. After multivariable adjustment, urine dichlorophenol levels at the 75th percentile and above were associated with the presence of sensitization to foods (odds ratio, 1.8; 95% confidence interval, 1.2-2.5; P = .003). No significant association was found between dichlorophenol exposure and sensitization to aeroallergens alone. CONCLUSION High urine levels of dichlorophenols are associated with the presence of sensitization to foods in a US population. Excessive use of dichlorophenols may contribute to the increasing incidence of food allergies in westernized societies.

Discordance between aeroallergen specific serum IgE and skin testing in children younger than 4 years.

BACKGROUND Atopic sensitization to aeroallergens in early life has been found to be a strong risk factor for the development of persisting asthma in young children with recurrent wheeze. OBJECTIVE To assess the yield of skin prick test (SPT) compared with allergen specific serum IgE (sIgE) testing at identifying aeroallergen sensitization in atopic children younger than 4 years. METHODS Concordance between SPT and allergen-specific sIgE testing for 7 common aeroallergens was analyzed in 40 atopic inner-city children 18 to 48 months of age (mean [SD], 36 [9] months) with recurrent wheezing and family history of asthma and/or eczema. RESULTS In 80% of children one or more allergen sensitizations would have been missed if only SPT had been performed, and in 38% of children one or more sensitizations would have been missed if only sIgE testing had been performed. Agreement between the SPT and sIgE test was fair for most allergens (κ = -0.04 to 0.50), as was correlation between sIgE levels and SPT grade (ρ = 0.21 to 0.55). Children with high total sIgE (≥300 kU/L) were more likely to have positive sIgE test results, with negative corresponding SPT results (P = .02). CONCLUSION Our study revealed a significant discordance between allergen-specific SPT and sIgE testing results for common aeroallergens, suggesting that both SPT and sIgE testing should be performed when diagnosing allergic sensitization in young children at high risk of asthma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01028560.

The association between asthma-related emergency department visits and pollen and mold spore concentrations in the Bronx, 2001–2008

Abstract Background: The incidence of asthma morbidity and mortality is highest among minority inner-city populations. Among New York City’s five boroughs, the Bronx has the highest rate of asthma-related hospitalizations and mortality. Outdoor air pollutants have been associated with increased asthma-related ED visits (AREDV) in this borough. Objective: To better understand the contribution of pollen and mold to asthma severity in the Bronx. Methods: The numbers of daily adult and pediatric AREDV and asthma-related hospitalizations (ARH) from 2001 to 2008 were obtained from two Bronx hospitals. AREDV and ARH data were acquired retrospectively through the Clinical Looking Glass data analysis software. Daily counts for tree, grass and weed pollen and mold spore counts from March 2001 to October 2008 were obtained from the Armonk counting station. All data were statistically analyzed and graphed as daily values. Results: There were a total of 42 065 AREDV and 10 132 ARH at both Bronx hospitals. There were spring and winter peaks of increased AREDV. Tree pollen counts significantly correlated with total AREDV (rho = 0.3639, p < 0.001), and pediatric (rho = 0.33, p < 0.001) and adult AREDV (rho = 0.28, p < 0.001). ARH positively correlated with tree pollen counts (Spearman rho = 0.2389, p < 0.001). Conclusions: There exists a significant association between spring AREDV and ARH and tree pollen concentrations in a highly urbanized area such as the Bronx. Early anticipation of spring pollen peaks based on ongoing surveillance could potentially guide clinical practice and minimize asthma-related ED visits in the Bronx.

A case of common variable immunodeficiency syndrome associated with Takayasu arteritis

BACKGROUND Association of common variable immunodeficiency (CVID) with Takayasu arteritis has rarely been reported. OBJECTIVE To describe a case of Takayasu arteritis in a 53-year-old Hispanic woman with CVID undergoing long-term (3-year) intravenous immunoglobulin (IVIG) treatment. METHODS The patients serum immunoglobulin levels and antibody titers to measles, mumps, and rubella were measured. She also underwent angiography of the large vessels. RESULTS Low to undetectable serum IgA, IgM, and IgG levels and low antibody titers to mumps, measles, and rubella were consistent with the diagnosis of CVID. The angiogram showed narrowing of the proximal left subclavian artery (2-3 mm in diameter). CONCLUSIONS This patient developed Takayasu arteritis while receiving IVIG for CVID. She clinically improved after her IVIG dose was increased. To our knowledge, this is the second reported case of Takayasu arteritis associated with CVID.

Fear of repeated injections in children younger than 4 years receiving subcutaneous allergy immunotherapy

BACKGROUND Allergy immunotherapy during early childhood may have potential benefits for the prevention of asthma and allergy morbidity. However, subcutaneous immunotherapy has not yet been prospectively researched in children younger than 4 years, primarily because of safety concerns, including the fear and psychological distress young children may experience with repeated needle injections. OBJECTIVE To quantify fear in atopic children younger than 4 years with a history of wheezing who are receiving subcutaneous immunotherapy. METHODS Fear of injection was graded during a total of 788 immunotherapy injection visits in 18 children (age, 37 months; SD, 9 months) receiving subcutaneous allergy immunotherapy. The parent and the injection nurse assigned fear scores on a scale of 0 to 10 after each injection visit. RESULTS At the time of analysis, children had a median of 49 injection visits (range, 12-88) during a median study period of 81.5 weeks (range, 15-165 weeks). Fifteen children (83%) lost their fear of injections during the study. A fear score of 0 was achieved after a mean of 8.4 visits (SD, 7.4). The more injection visits were missed, the more likely children were to retain fear of injections (hazard ratio, 0.13; 95% confidence interval, 0.02-1.02; P=.05). Age, adverse events, number of injections at each visit, and change of injection personnel were not associated with increased fear. CONCLUSION Our analysis suggests that most children receiving weekly subcutaneous immunotherapy lose their fear of injections during the treatment course. Children with increased intervals between visits may be at higher risk of experiencing fear of injections. CLINICAL TRIAL REGISTRATION clinicaltrial.gov identifier NCT01028560.

Increased allergic sensitization to mugwort in chronic urticaria.

Background: Mugwort pollen is known to cross-react with a variety of spices and vegetables that are typically part of elimination diets used in the treatment of chronic urticaria (CU). Objective: We sought to investigate the association between CU and allergic sensitization to mugwort pollen. Methods: We conducted 2 case-control studies comparing aeroallergen skin prick test results between patients with and without CU and with or without allergic rhinitis (total n = 202). Results: CU patients with coexisting allergic rhinitis were more than twice as likely to be sensitized to mugwort as subjects not suffering from CU (67 vs. 30%; p = 0.004). Ragweed, cat, rat and mite sensitization were also significantly associated with CU. Overall, patients with CU had more positive aeroallergen skin tests than patients without CU (p < 0.005). Conclusion: Mugwort sensitization was associated with CU, possibly contributing to beneficial effect of elimination diets.

Diagnosing Environmental Allergies: Comparison of Skin-Prick, Intradermal, and Serum Specific Immunoglobulin E Testing:

Background Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. Objective To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. Methods SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. Results A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357–4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. Conclusion IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

Hyper–immunoglobulin E-like syndrome in a patient with multiple genetic mutations

A 44-year-old African-American woman with hidradenitis suppurativa, scoliosis, and idiopathic avascular necrosis of the hips presented to the emergency department with transient monocular visual loss, purulent discharge at the site of a gold-plate implant in the left upper eyelid for lagophthalmos secondary to Bell palsy, and a right thigh abscess. Since her diagnosis of hidradenitis suppurativa at 16 years old, she developed multiple abscesses in the axilla, groin, thighs, and nape of the neck requiring incision and drainages, skin grafting, and antibiotics. As a child, she did not have recurrent infections, delayed shedding of her primary teeth, or a history of eczema. Her family history was noteworthy for recurrent abscesses in hermother with diabetes, 2 daughters in their 30s, and a teenage son. Physical examinationwas notable for left facial droop and a gold plate protruding from the left eyelid associated with crusting. Multiple comedones with folliculitis were noted on her face and chest. A 3to 4-cm abscess was present on the lateral aspect of her right thigh in addition to multiple tender and nontender subcutaneous nodules in her axillae, groin, and nape of the neck. Healing lesions in the intergluteal fold with some granulation tissue were present. Complete blood cell count showed microcytic anemia with a normal white blood cell count and differentials, including eosinophils. Erythrocyte sedimentation rate and C-reactive protein were increased at 106 mm/h (normal 0e20 mm/h) and 6.7 mg/L (0e5.0mg/L), respectively. Culture of pus from the right thigh abscess grew Staphylococcus lugdunensis. Culture of the eyelid discharge grew Corynebacterium amycolatum and Staphylococcus epidermidis. The allergy and immunology service was consulted to evaluate for a potential underlying immunodeficiency. Laboratory analysis was notable for an increased serum immunoglobulin (Ig) E level of 3,185 IU/mL (normal 180 IU/ml). IgM was normal with increased IgG (2,196 IU/mL, normal 700e1,600 IU/mL) and IgA (1,217 IU/mL, normal 70e400 IU/mL) levels. Neutrophil oxidative burst, thyroid function, syphilis, human immunodeficiency virus, and hepatitis serologies and complement levels were unremarkable. Antinuclear antibody was 1:160 and speckled with negative double-stranded DNA and extractable nuclear antigens. Chest x-ray showed dextroscoliosis of the thoracic spine. Bone densitometry showed osteopenia in the hip and lumbar regions. The patient was treated for 4 weeks with amoxicillin plus clavulanic acid, doxycycline, and topical clindamycin, benzoyl peroxide, and tretinoin cream. Two weeks after discharge, a new abscess appeared at the nape of her neck, for which amoxicillin plus clavulanic acid was continued. She subsequently remained on prophylactic therapy with trimethoprim plus sulfamethoxazole.