Elina Jerschow

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.

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.

Fatal Anaphylaxis: Mortality Rate and Risk Factors

Up to 5% of the US population has suffered anaphylaxis. Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. Fatal drug anaphylaxis may be increasing, but rates of fatal anaphylaxis to venom and food are stable. Risk factors for fatal anaphylaxis vary according to cause. For fatal drug anaphylaxis, previous cardiovascular morbidity and older age are risk factors, with beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections the commonest triggers. Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk. For fatal venom anaphylaxis, risk factors include middle age, male sex, white race, cardiovascular disease, and possibly mastocytosis; insect triggers vary by region. Upright posture is a feature of fatal anaphylaxis to both food and venom. The rarity of fatal anaphylaxis and the significant quality of life impact of allergic conditions suggest that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

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.

Fixed drug eruption caused by mesna

1. Grigoriadou S, Longhurst HJ. Clinical immunology review series: an approach to the patient with angio-oedema. Clin Exp Immunol. 2009;155:367–377. 2. Agostoni A, Cicardi M. Drug-induced angioedema without urticaria. Drug Saf. 2001;24:599–606. 3. Bas M, Adams V, Suvorova T, Niehues T, Hoffmann TK, Kodja G. Nonallergic angioedema: role of bradykinin. Allergy. 2007;62:842–856. 4. Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P. Angiotensin converting enzyme inhibitor induced angio-edema: a review of the pathophysiology and risk factors. Clin Exp Allergy. 2009;40:50–61. 5. Davis AE III. Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol. 2008;100(suppl 2):S7–S12. 6. Binkley KE. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions. Allergy Asthma Clin Immunol. 2010;6:16. 7. Duan QL, Binkley K, Rouleau GA. Genetic analysis of factor XII and bradykinin Figure 1. Bradykinin regulation pathways and interaction with sex h degradation of bradykinin and des-Arg-bradykinin, whereas estrogens ha enzyme (ACE), aminopeptidase P (APP), C1 esterase inhibitor (C1-IN respectively. Asterisk indicates that bradykinin and its metabolite, des-Ar to angioedema.

Isotretinoin treatment in a patient with known peanut allergy and positive IgE test results for soybean

Isotretinoin is a retinoid that is approved by the US Food and Drug Administration for the treatment of acne vulgaris and used off label for other dermatologic conditions, including hidradenitis suppurativa (HS). Isotretinoin decreases comedones and sebum production, influences cell-cycle progression, and reduces inflammation.1 Prescribing information leaflets state that oral isotretinoin is contraindicated in patients with known allergy to isotretinoin, peanut, or soya.2 Soybean oil is found within the capsules; thus, patients with peanut allergy might be considered at risk because of the known cross-reactivity between soybean and peanut.3 Currently, all isotretinoin products on the market contain soybean derivatives; therefore, patients with known allergy to soybean or peanut could be at risk of developing an allergic response if they are treated with oral isotretinoin. Peanut and soybean are derived from the same plant family of legumes. These legumes contain allergenic protein fractions, specifically, Ara h 1, Ara h 2, and Ara h 3 in peanuts and Gly m 1 and G2 glycinin in soy, that exhibit in vitro and in vivo cross-reaction.4,5 However, clinical observations have revealed a low rate of crossreactivity between peanut and soy.5 In addition, it has been documented that proteins present in the oil of soybean have little clinical significance with regard to soybean allergy.6 Two prior case reports by Pierret et al7 and Hulstaert et al8 reported successful isotretinoin treatment in 2 patients with documented peanut allergy who had negative allergy test results to soybean. We present the case of HS, a history of peanut allergy, and positive test results for soy allergy in a 23-year-old man whose treatment of choice was isotretinoin. A 23-year-old man with history of longstanding eczema, acne, asthma, and peanut allergy was referred to the allergy clinic by a dermatologist who recommended treatment of the patient’s acne and HSwith isotretinoin. On the basis of the results of an IgE test for peanut of more than 18.00 kUA/L (class 5) performed when the patient as a child, the patient was advised to avoid peanuts and prescribed an epinephrine autoinjector. The patient has been avoiding peanuts ever since and has never had an allergic reaction. The patient denied a prior history of allergic reactions to soy and reported that he was not avoiding soy in his diet. Physical examination findings were remarkable for eczema, xerosis, and hidradenitis lesions in his axillae and right groin. In addition, his face had some scarring and scattered inflammatory papules on his cheeks. The results of skin prick tests for peanut and soybean were positive at 4þ and 1þ, respectively. Laboratory tests revealed elevated

Contrast Is the New Penicillin, and Possibly Worse

Surprising to many clinicians, less than 20% of purported penicillin allergies are validated in those undergoing skin testing [1]. Reporting a false penicillin allergy is not benign. Patients are deprived of a class of drugs that are effective, available, and potentially lifesaving. In addition, they open themselves to complications from alternative antibiotics that are potentially less effective, have more side effects, and are more expensive. Unnecessary use of newer-generation antibiotics hastens the inevitable emergence of antibiotic-resistant pathogens, with potentially grave long-term public health consequences. Fortunately, in less than 30 minutes, patients with suspected penicillin allergies may undergo skin testing to confirm or disprove an immunoglobulin-E (IgE)emediated allergy with a high level of confidence [2]. As with penicillin, allergic or allergiclike reactions to iodinated intravascular contrast media are well documented and can range from minor cutaneous eruptions to fatal anaphylaxis. The mechanism of reaction remains controversial, with some reactions demonstrating an IgE or T-cell dependence and others not [3]. A gradual adoption of nonionic contrast material has taken place, owing to market forces, patent expiration, and most importantly, an improved safety profile. Use of nonionic iodinated contrast (either low-osmolar or isoosmolar) is the current standard of care [4,5]. Still, among identified culprit drugs, contrast remains second to only antibiotics as a cause of medicationinduced fatal anaphylaxis in the United States [6]. Interestingly, despite the perceived safety of gadolinium-based

Nonimmediate Hypersensitivity Reaction After Trastuzumab Infusion: A Suspected Drug-Virus Interaction

Introduction Hypersensitivity reactions to commonly used chemotherapeutic agents range from mild cutaneous eruptions to fatal anaphylaxis. These are mostly immediate reactions that may be amenable to desensitization procedures. Nonimmediate reactions are less frequently reported and are challenging to manage. Trastuzumab (Herceptin; F. Hoffmann-La Roche/Genentech, Nutley, NJ) is a humanized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2). Treatment with trastuzumab in combination with adjuvant chemotherapy improves disease-free and overall survival in patients with HER2-positive, earlystage breast cancer compared with chemotherapy alone. In addition to the immediate immunoglobulin E (IgE) –mediated drug reactions (time of onset 1 hour), there are nonimmediate and/or delayed drug-induced hypersensitivity reactions (time of onset 1 hour). Rates of severe immediate hypersensitivity reaction to trastuzumab range from 0.6% to 5%. Most of these reactions occur after multiple exposures and can be avoided during subsequent treatments by using desensitization procedures. In contrast, desensitization treatments for delayed hypersensitivity reactions are not consistently successful. Although diagnosis of an immediate allergic reaction to monoclonal antibodies can be confirmed by skin testing, skin tests are rarely informative in the case of a nonimmediate type of reaction because of low sensitivity. Therefore, confirmation of diagnosis of nonimmediate types of reactions to medications, including those to monoclonal antibodies, presents particular challenges. Such considerations are important if the initial allergic reaction occurred during a viral syndrome and a drug-virus interaction cannot be excluded. Herein, we report our management of a nonimmediate hypersensitivity reaction to trastuzumab in a young woman with potentially curable, HER2-positive, early-stage breast cancer.

Correlations between cystic fibrosis genotype and sinus disease severity in chronic rhinosinusitis: Cystic Fibrosis Genotype and Sinus Disease

Cystic fibrosis (CF) patients commonly develop chronic rhinosinusitis (CRS). The impact of the most common cystic fibrosis transmembrane conductance regulator (CFTR) mutation, F508del, on the severity of sinonasal disease remains inconclusive. The objective of this study is to evaluate the impact of CFTR genotype functional classification on sinonasal disease severity in patients with CRS.

Depression symptoms and quality of life among individuals with aspirin-exacerbated respiratory disease

Abstract Objective: Patients with aspirin-exacerbated respiratory disease (AERD) have high disease burden due to the severity of asthma and sinonasal symptoms. There is limited research on the psychological well-being and subjective experiences of patients with AERD. This study examined levels of depression symptoms, asthma-related quality of life and asthma control among AERD patients. Methods: Thirty-two adults with AERD and 39 patients without AERD (asthma-only) were recruited from outpatient asthma/allergy clinics. The sample was largely comprised of ethnic minority, inner-city patients who ranged in age from 19 to 84 years old. Participants completed the Beck Depression Inventory (BDI), the Mini Asthma Quality of Life Questionnaire (Mini AQLQ), a self-report rating of asthma severity and spirometry testing. Asthma control and severity were determined following national guidelines. Results: AERD patients reported lower levels of depression symptoms (p = 0.049), better overall asthma-related quality of life (p < 0.001), and perceived their asthma to be less severe (p = 0.01) compared to asthma-only patients. However, clinician ratings of asthma severity were more severe for AERD than asthma-only patients (p = 0.006). No significant differences were found between the groups on asthma controller medications or oral corticosteroid bursts for asthma. Conclusions: AERD patients may be resilient given their low levels of depression symptoms and positive views of asthma-related impairment despite higher clinician-rated asthma severity. The adult onset nature of asthma in AERD might be a protective factor on mental health. Future studies should explore mechanisms linking AERD and positive psychological health outcomes and subjective perception of asthma.