August 29, 2014

Hypersensitivity Reactions to Biological Drugs



J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225
M Corominas,1 G Gastaminza,2 T Lobera3
1Allergy Unit-Internal Medicine Department, Hospital Universitari de Bellvitge-IDIBELL, L’Hospitalet de Llobregat, Spain
2Allergy and Clinic Immunology Department, Clinica Universidad de Navarra, Navarra, Spain
3Department of Allergy, Hospital San Pedro/San Millán, Logroño, Spain
The authors are all members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (Biological Drugs Section)

 Abstract

Strictly speaking, biological drugs are defined as drugs obtained using biotechnology that act on the immune system. They encompass monoclonal antibodies, fusion proteins, and cytokines. Although they are restricted to specific diseases, they have been increasingly used in recent years, with the consequent reporting of adverse reactions, many of which occur during the postmarketing phase. Because of the characteristics of
adverse reactions, a new classification has been proposed. Hypersensitivity reactions are beta-type reactions and include infusion reactions and injection site reactions. In some cases, an immune mechanism mediated by IgE, IgG, or T cells is involved. Clinical symptoms vary widely, from skin reactions to anaphylaxis. Diagnostic studies are based on skin tests and in vitro tests (specific IgE, basophil activation test). Most are not standardized and are conducted in small groups of patients, thus making it impossible to obtain sensitivity and specificity values. With some biological drugs, desensitization protocols have proven successful. In this review, we discuss hypersensitivity reactions to biological drugs and the diagnostic tests used to assess these reactions.

Key words: Biological drugs. Hypersensitivity. Skin tests. Diagnosis. Monoclonal antibodies.
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August 28, 2014

WHO recommendations for the viruses used in the 2013–2014 Northern Hemisphere influenza vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013 ☆

Volume 32, Issue 37, 20 August 2014, Pages 4713–4725
WHO Report
Under a Creative Commons license
  Open Access

Abstract

In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013–2014 Northern Hemisphere influenza vaccine composition.

Article outline

August 27, 2014

First randomized trial on clobetasol propionate and mometasone furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability



Abstract

BACKGROUND:

A 3-month topical application of clobetasol propionate (CP) represents the recommended and accepted first-line treatment for vulvar lichen sclerosus (VLS); however, to date, no randomized controlled trials have compared the efficacy and safety of CP with other topical corticosteroids.

OBJECTIVE:

To compare the effectiveness and tolerability of two different topical corticosteroids, CP 0·05% ointment and mometasone furoate (MMF) 0·1% ointment, in the treatment of VLS.

METHODS:

Fifty-four patients with VLS were enrolled in a 12-week active treatment phase (ATP) and randomized to apply either CP or MMF in a tapering regimen. The main efficacy parameters were the response rate, the rate of patients achieving an improvement from baseline of ≥ 75% in the subjective and objective scores, and the mean reduction in subjective and objective scores throughout the treatment.

RESULTS:

By the end of the 12-week ATP, 24 (89%) patients were considered to be responders among the CP patients and 24 (89%) among the MMF patients; 59% and 37% of patients in the CP group and 67% and 48% in the MMF group achieved an improvement of at least 75% in subjective and objective scores, respectively. The decrease in mean symptom and sign scores was significant compared with baseline with both treatments. No significant differences were found in any of the assessed efficacy endpoints between CP and MMF. Both treatments were well tolerated.

CONCLUSIONS:

Clobetasol propionate and MMF appeared similarly efficacious and well tolerated for the treatment of VLS and both may represent the first-line treatment for the disease.
© 2014 British Association of Dermatologists.

August 25, 2014

Immediate hypersensitivity reaction with mango


Ashok Shah, Kamal Gera

Abstract

Hypersensitivity to the fruit mango is extremely rare and can exhibit either as immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate type I reactions and 12 with delayed) have been documented with allergy to mango. History of atopy and geographical region may influence the type of reaction. Immediate reactions occured most often in patients with history of atopy, while delayed reactions developed in non-atopic individuals. Clustering of delayed hypersensitivity reports from Australia and immediate reactions from Europe has been documented. We report a 50-year-old man with immediate type I hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised itching and abdominal discomfort after ingestion of mango. Life threatening event can also happen making it imperative to diagnose on time, so as to prevent significant morbidity and potential mortality

Keywords

allergy, anaphylaxis, bronchial asthma, contact dermatitis, mango, urticaria

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Fluticasone propionate-salmeterol versus inhaled corticosteroids plus montelukast: outcomes study in pediatric patients with asthma


 2013;6:1-10. doi: 10.2147/JAA.S34582. Epub 2012 Dec 28.

Author information

  • 1GlaxoSmithKline, Research Triangle Park, Durham, NC.

Abstract

BACKGROUND:

The purpose of this study (GSK ADA111194) was to compare asthma-related health care utilization and costs associated with fluticasone propionate (an inhaled corticosteroid [ICS]) and salmeterol (a long-acting beta-agonist) in a single inhalation device (fluticasone propionate-salmeterol) versus the combination of ICS + montelukast in the treatment of pediatric patients with asthma.

METHODS:

This was a retrospective, observational cohort study using a large health insurance claims database spanning January 1, 2000 to January 31, 2008. The target population was patients aged 4-11 years with at least one pharmacy claim for fluticasone propionate-salmeterol, any ICS, or montelukast during the study period. The date of first claim for the medication of interest was deemed the index date. Patients were required to be continuously eligible to receive health care services one year prior to and 30 days after the index date, and have at least one claim with an ICD-9-CM code for asthma (493.xx) in the one-year pre-index period. Patients with prescriptions for fluticasone propionate-salmeterol, ICS + montelukast, or long-acting beta-agonists during the pre-index period were excluded. Patients were matched on a 1:1 basis according to three variables, ie, pre-index use of oral corticosteroids, ICS, and presence of pre-index respiratory-related hospitalizations/emergency department visits. The risk of asthma-related hospitalization, combined hospitalization/emergency department visit, and monthly asthma-related costs were assessed using multivariate methods.

RESULTS:

Of the 3001 patients identified, 2231 patients were on fluticasone propionate-salmeterol and 770 were on ICS + montelukast. After matching, there were 747 pairs of fluticasone propionate-salmeterol and ICS + montelukast patients, which were well matched for baseline characteristics. Patients who started fluticasone propionate-salmeterol compared with patients on ICS + montelukast had a significantly (P < 0.02) lower rate of asthma-related hospitalizations (0.3% versus 3.5%) and asthma-related hospitalizations/emergency department visits (3.5% versus 5.7%). After controlling for baseline and patient characteristics, fluticasone propionate-salmeterol users were associated with a significantly lower risk of an asthma-related hospitalization (adjusted hazard ratio 0.039; 95% confidence interval 0.004-0.408) or hospitalization/emergency department visit (hazard ratio 0.441; 95% confidence interval 0.225-0.864), and $151 (95% confidence interval 67-346) lower asthma-related monthly costs compared with ICS + montelukast.

CONCLUSION:

In patients aged 4-11 years with asthma, use of fluticasone propionate-salmeterol was associated with lower asthma-related health care utilization and costs compared with use of ICS + montelukast.

KEYWORDS:

asthma; fluticasone propionate; inhaled corticosteroids; montelukast; outcomes; pediatric; salmeterol
PMID:
 
23300347
 
[PubMed] 
PMCID:
 
PMC3536350
 
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August 22, 2014

The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats

Research


Open Access
Jeanette Lund MadsenStine KroghsboCharlotte Bernhard MadsenIrina Pozdnyakova,Vibeke Barkholt and Katrine Lindholm Bøgh
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Clinical and Translational Allergy 2014, 4:25  doi:10.1186/2045-7022-4-25
Published: 18 August 2014

Abstract (provisional)

Background

Characterisation of the specific antibody response, including the epitope binding pattern, is an essential task for understanding the molecular mechanisms of food allergy. Examination of antibody formation in a controlled environment requires animal models. The purpose of this study was to examine the amount and types of antibodies raised against three cow's milk allergens; beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and beta-casein upon oral or intraperitoneal (i.p.) administration. A special focus was given to the relative amount of antibodies raised against linear versus conformational epitopes.

Methods

Specific antibodies were raised in Brown Norway (BN) rats. BN rats were dosed either (1) i.p. with the purified native cow's milk allergens or (2) orally with skimmed milk powder (SMP) alone or together with gluten, without the use of adjuvants. The allergens were denatured by reduction and alkylation, resulting in unfolding of the primary structure and a consequential loss of conformational epitopes. The specific IgG1 and IgE responses were analysed against both the native and denatured form of the three cow's milk allergens, thus allowing examination of the relative amount of linear versus conformational epitopes.

Results

The inherent capacity to induce specific IgG1 and IgE antibodies were rather similar upon i.p. administration for the three cow's milk allergens, with BLG = ALA > beta-casein. Larger differences were found between the allergens upon oral administration, with BLG > ALA > beta-casein. Co-administration of SMP and gluten had a great impact on the specific antibody response, resulting in a significant reduced amount of antibodies. Together results indicated that most antibodies were raised against conformational epitopes irrespectively of the administration route, though the relative proportions between linear and conformational epitopes differed remarkably between the allergens.

Conclusions

This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens, indicating that the structural characteristics of proteins may heavily affect the induced antibody response.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

August 20, 2014

Contact urticaria syndrome caused by haptens

PMCID: PMC4112244

In the group of urticaria, contact urticaria syndrome is a particular variety. In these patients, appearance of typical skin lesions is preceded by contact of the skin and mucous membranes with various inhaled allergens, nutrients or contact details. Furthermore, symptoms connected with contact urticaria syndrome are characterized by gradual, stepwise waveform, which can be easily generalized – patients may develop systemic symptoms similar to those found in the angioedema, asthma or anaphylactic shock. It is an attribute of contact urticaria syndrome in the course of which potentially life-threatening symptoms may develop after contact of the skin with the allergen. The underlying mechanisms are poorly understood; both immunological and non-immunological mechanisms are taken into account, therefore contact urticaria syndrome can be classified into two categories – allergic and non-allergic. An intriguing phenomenon seems to be the immediate reaction after exposure to low molecular weight allergens – haptens, such as metals, which are usually the cause of delayed allergic reactions. Diagnosis is based on clinical presentation indicating a coincidence of the onset of allergy with contract with allergen, and helpful exposure tests. Treatment consists of supportive antihistamines and corticosteroids – locally and systemically. In the case of anaphylaxis, appropriate treatment intensification of the integration of pressor amines and hydration is necessary. It is also regarded that prevention is advisable, which consists of relevant information to avoid situations connected with contact with well-known factors. In this paper we describe a case of a 57-year-old female admitted to the Department of Internal Medicine, Geriatrics and Allergology, Medical University in Wroclaw to undergo diagnostic tests of chronic urticaria and angioedema. According to information obtained from the clinical presentation and after the diagnostic procedures, contact urticaria syndrome due to exposure to metals was diagnosed.
Keywords: contact urticaria syndrome, haptens, immediate contact reaction

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August 19, 2014

Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma

Research article

Open Access

Susanna Esposito1*Carlotta Galeone2Mara Lelii1Benedetta Longhi1Beatrice Ascolese1Laura Senatore1Elisabetta Prada1Valentina Montinaro1Stefano Malerba3,Maria Francesca Patria1 and Nicola Principi1
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Abstract

Background

Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms.

Methods

This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants.

Results

Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p = 0.005) and cough (p - 0.001), episodes of rhinitis (p = 0.04) and tracheitis (p = 0.01), asthma attacks (p - 0.001), episodes of pneumonia (p - 0.001) and hospitalizations (p = 0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR] = 1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR = 0.50; 95% CI, 0.31 -0.80). An increase of 10 μg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR] = 1.08, 95% CI: 1.00-1.17 for PM10; continuous RR = 1.08, 95% CI: 1.01-1.17 for NO2).

Conclusions

There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.
Keywords: 
Air pollution; Asthma; NO2; PM10; Respiratory disease; Traffic-related pollutant; Wheezing 

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