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

Br J Dermatol. 2014 Aug;171(2):388-96. doi: 10.1111/bjd.12910. Epub 2014 Jul 23.

Virgili A, Borghi A, Toni G, Minghetti S, Corazza M

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.

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Immediate hypersensitivity reaction with mango

Ashok Shah, Kamal Gera

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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

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

Stanford RH1, Shah M, D'Souza AO.

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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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

Jeanette Lund Madsen, Stine Kroghsbo, Charlotte Bernhard Madsen, Irina 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.

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Contact urticaria syndrome caused by haptens

Postepy Dermatol Alergol. May 2014; 31(2): 108–112.

Published online Apr 22, 2014. doi:  10.5114/pdia.2014.40915

PMCID: PMC4112244

Krzysztof Gomułka and Bernard Panaszek

Abstract:

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

Research article

Susanna Esposito^1*, Carlotta Galeone², Mara Lelii¹, Benedetta Longhi¹, Beatrice Ascolese¹, Laura Senatore¹, Elisabetta Prada¹, Valentina Montinaro¹, Stefano Malerba³,Maria Francesca Patria¹ and Nicola Principi¹

• *Corresponding author: Susanna Esposito susanna.esposito@unimi.it

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BMC Pulmonary Medicine 2014, 14:130  doi:10.1186/1471-2466-14-130

Published: 7 August 2014

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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Bitter Taste Receptors in The Wrong Place: Novel Airway Smooth Muscle Targets For Treating Asthma

Trans Am Clin Climatol Assoc. 2014;125:64-75.

Liggett SB.

• Tampa, Florida.

Abstract

There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (β-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than β-agonists. We have found that human and mouse ASM express six bitter taste receptor (TAS2R) subtypes, previously thought only to exist in taste buds of the tongue. Agonists acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism. TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis upon repetitive dosing, and relaxes even under extreme desensitization of relaxation by β-agonists. Taken together, TAS2Rs on ASM represent a novel pathway to consider for development of agonists in the treatment of asthma and chronic obstructive lung disease.

PMID:

 

25125719

 

[PubMed - in process] 

PMCID:

 

PMC4112707

 

Respiratory symptoms and pulmonary function tests in security and safety products plant workers

Int J Clin Exp Med. 2014 Jul 15;7(7):1883-6. eCollection 2014.

Balbay EG, Toru U, Arbak P, Balbay O, Suner KO, Annakkaya AN

Abstract

OBJECTIVE:

Lock and key factory workers are under the risk of metal pneumoconiosis and occupational asthma. In this cross-sectional study, it's aimed to evaluate the relationship between metal dust exposure and respiratory symptoms, pulmonary function tests of workers in different section of lock and key factory.

METHODS:

54 male workers (mean age, 32.8 ± 5.4) in a security and safety products plant were evaluated for respiratory symptoms, pulmonary function tests and smoking habits. Results have been interpreted by comparison of the painting (28/54) and grinding group workers (26/54).

RESULTS:

There was no significant difference between painting (32.1 ± 4.8) and grinding (33.6 ± 6.1) groups regarding mean age (P > 0.05). Smokers were in significantly higher in grinding group (18/26). Cough and sputum were reported 14.3% (4/28) in painting and 3.8% (1/26) in grinding workers (P > 0.05). Chest tightness was seen in 7.1% and 7.7% of painting and grinding workers, respectively (P > 0.05). But no chest tightness was reported in both groups when they were away work. Breathlessness was seen in 10.7% and 7.7% of painting and grinding workers, respectively (P > 0.05). Breathlessness was similar in both groups (7.1% vs. 3.8%) when they were away work. When comparing painting and grinding workers respiratory functions no significant difference observed. Chest radiography in painting and grinding workers showed hyperlucency (3.6% vs.11.4%), respectively.

CONCLUSION:

Painting groups in lock and key factory workers had more but statistically insignificant respiratory complaints. Interestingly, chest tightness was only observed when both groups were at work. It was thought that ventilation and using personal protective equipment in factory could provide significant benefits.

KEYWORDS:

Lock and key factory workers; respiratory functions; respiratory symptoms

PMID:

 

25126195

 

[PubMed] 

PMCID:

 

PMC4132159

 

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Microbiota in Healthy Skin and in Atopic Eczema

Biomed Res Int. 2014;2014:436921. Epub 2014 Jul 13.

Baviera G, Leoni MC, Capra L, Cipriani F, Longo G, Maiello N, Ricci G, Galli E.

Abstract

The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.

PMID: 25126558 [PubMed - as supplied by publisher] PMCID: PMC4122000

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The Association between Platelet Count and Acute Phase Response in Chronic Spontaneous Urticaria

Biomed Res Int. 2014;2014:650913. doi: 10.1155/2014/650913. Epub 2014 Jun 16.

Kasperska-Zając A, Grzanka A, Jarzab J, Misiołek M, Wyszyńska-Chłap M, Kasperski J, Machura E.

Abstract

Background. The platelet parameters and C-reactive protein (CRP) are markers reflecting a systemic inflammatory response. Among those, CRP is one of the major proteins helpful in determination of severity/activity of chronic spontaneous urticaria (CSU). Aim. To determine relationships between platelet activation indices and serum concentration of CRP, the best marker of acute phase response, and their potential clinical use in CSU patients.

Methods. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet count as well as serum CRP concentration were measured in CSU patients, showing different degrees of urticarial severity, and in the healthy subjects.

Results. No significant differences were found in MPV and PDW between CSU group and the healthy subjects. The platelet count was significantly higher in moderate-severe CSU than that of the controls and mild CSU patients. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects and significantly correlated with the platelet count in CSU patients.

Conclusions. Acute phase response in CSU is associated with the increased number of circulating platelets in patients with more severe symptoms. It seems that simple determination of platelet size indices is not a reliable indicator of CSU severity/activity.

PMID: 25025065 [PubMed - in process] PMCID: PMC4084584 

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Pathogenesis of chronic urticaria: an overview

Dermatol Res Pract. 2014;2014:674709. doi: 10.1155/2014/674709. Epub 2014 Jul 10.

Jain S.

Author information

• Skin Care Clinic, 108 Darya Ganj, New Delhi 110002, India.

Abstract

The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria.

PMID:

 

25120565

 

[PubMed] 

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