ECZEMA: PREVENZIONE E TERAPIA

Le influenze ambientali: è possibile una prevenzione?

“In-door”

Dr.ssa Maria Chiara Leoni

Pédiatre Allergologue

Service de Pédiatrie - Hôpital Intercommunal de Créteil (Paris)

Università degli Studi di Pavia (Pavia)

AD: a multifactorial disorder

Genetic predisposition

Environmental triggers

• allergen exposure • polluants • microbes • diet • stress

Prevenzione In - door

In-door

Edificio Lavori domestici

Ventilazione

Origine biologica: acari, epitelio di animali domestici, pollini, muffe.

Attività umane Abitudini di vita: fumo di tabacco

Agenti chimici

In-door allergens

Airborne allergens sensitization

In AD patients, the early epidermal barrier impairment may facilitate the epicutaneous penetration of molecules of environmental allergens, such as Der p 1, synergizing with their proteolytic activity. Boralevi F et al, Allergy 2008: 63: 205–10. In fact, recent advances suggest that the dust mite, more than foods, is a major cause of allergic AD. Fuiano N et al, Allergol Int 2012: 61:231–43.

A cross-sectional study has recently shown that early sensitization to cat among children with AD may be linked to an increased risk of sensitization to a broader spectrum of allergen components from early life.

Wisniewski JA et al, Clin Exp Allergy 2013: 43: 1160–70.

Given that initial skin lesions are more prominent on air-exposed areas and that sensitization to aeroallergens occurs very early in life, infantile AD may reflect the allergen penetration phase.

Amongst the aeroallergens involved in the sensitization of AD patients, house dust mite (HDM), pet dander, and pollens from trees and plants are the most prevalent.

The greater the TEWL, the higher the prevalence of sensitization to aeroallergens, which points to a possible causative role of epidermal barrier impairment in the sensitization to atopens in AD infants.

Allergology International.

2012;61:231-243

Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1.

Patients with AD have a baseline-impaired barrier function that allows proteins to enter into the viable epidermis. In AD, airborne proteins have the ability to penetrate into the epidermis and worsen AD severity through 3 mechanisms: - inherent proteolytic enzyme activity - activation of proteinase-activated receptors-2 (PAR-2) - immunoglobulin E (IgE) binding inflammation

Several intervention studies could show that the reduction in the HDM allergen exposure is accompanied by a marked reduction in the clinical severity.

Accepted article Pediatr Allergy Immunol

Despite a lack of evidence for its efficacy, dust mite avoidance is commonly recommended for the prevention and treatment of atopic dermatitis.

Conclusion: dust mite avoidance provided no benefit in the prevention of AD.

(Relative risk (RR)=1.08, 95% Confidence Interval (CI)=0.78 to 1.49, I2=73%)

Our strongest evidence is therefore that the common denominator, mite impermeable mattress covers alone, are ineffective in the primary prevention of atopic dermatitis.

Impermeable dust mite covers in the primary and tertiary prevention of allergic disease: a metaanalysis.

Arroyave WD, Rabito FA, Carlson JC, Friedman EE, Stinebaugh SJ Ann Allergy Asthma Immunol 2014: 112: 237-248.

Dust mite avoidance was limited to home environment in all studies; it is possible that dust mite reduction in other areas of one’s environment (outdoors, day care, or car) may be needed for a protective effect.

Ricci G, Patrizi A, Specchia F, et al. Effect of house dust mite avoidance measures in children with atopic dermatitis. Br J Dermatol 2000: 143: 379–84. Nishioka K, Yasueda H, Saito H. Preventive effect of bedding encasement with micro fine fibers on mite sensitization. J Allergy Clin Immunol 1998: 101(1 Pt 1):28–32. Tan BB, Weald D, Strickland I, et al. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet 1996: 347: 15–8.

Mite avoidance

Excessive avoidance of natural exposure to allergens without justification can lead to impaired immunologic tolerance and a poorer quality of life of children and their families.

Makela MJ, Pelkonen A, Valovirta E, Haahtela T.

Household ventilation rates are important in maintaining adequate indoor air quality and regulating the diversity and concentrations of environmental exposures.

Childhood exposure to a mildew/musty odour increased risk of reporting current asthma, but not eczema or allergy.

Reporting of a mildew/musty odour was associated with increased risk of adults reporting current eczema, allergy and asthma.

Fungal contamination is of interest because sensitisation to different fungal species (and HMD) is associated with increased risk of asthma and reduced pulmonary function, and is associated with atopic eczema and allergy.

Household ventilation

An interesting link between AD and a variety of air pollutants, such as environmental tobacco smoke, volatile organic compounds, formaldehyde, toluene, nitrogen dioxide, and particulate matter, has also been suggested.

Indoor air polluants

These air pollutants may act as risk factors for the development or aggravation of AD by inducing oxidative stress in the skin, leading to skin barrier dysfunction or immune dysregulation.

Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic czema in children.

Weiland S, Husing A, Strachan D, Rzehak P, Pearce N, Group IPOS. Occup Environ Med 2004;61:609–15

Indoor air quality measurements: Indoor temperature Humidity Particulate materials (PM10) CO Carbon dioxide (CO2) Formaldehyde (HCHO)

Indoor environments have a range of air pollutants from sources that include tobacco smoke, stoves, construction materials, furniture, and electronic devices.

Indoor air pollutants include VOCs, PM, and combustion pollutants,such as sulfur dioxide, CO, and NO2.

Benzene, toluene, ethylbenzene, xylene, formaldehyde, and many other compounds are VOCs commonly found at home or in other buildings.

Allergens and biologic materials, such as house dust mites, animal dander, mold spores, and bacteria, are the sources of biologic pollutants that are found ubiquitously indoors.

From a health perspective, concerns regarding indoor air pollution are increasing because people spend most of their time indoors in their homes, schools, and public buildings.

Indoor PM originates partly from the outside, depending on the degree of ventilation of the building, whereas there are many indoor sources of PM as well.

Eberlein-Konig B et al. Influence of airborne nitrogen dioxide or formaldehyde on parameters of skin function and cellular activation in patients with atopic eczema and control subjects. J Allergy Clin Immunol 1998;101:141-3.

Subsequent to the completion of the indoor air quality improvement program, the mean PM10 level was significantly decreased from 182.7 to 73.4 μg/m3. After the completion of the program, the prevalence of AD and the mean EASI were decreased, and the changes were both statistically significant. The mean number of hospital visits decreased from 1.3 per month during the first survey to 0.7 per month during the second survey, which was statistically significant.

Wen HJ et al.,

Predicting risk for early infantile atopic dermatitis by hereditary and environmental factors.

Br J Dermatol 2009;161:1166-1172.

Arnedo-Pena A et al,

Air pollution and recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren

aged between 6 and 7 years. Arch Bronconeumol 2009;45:224-229.

Data from the ISAAC study indicated that the prevalence of AE is negatively associated with the mean annual temperature and the indoor relative humidity.

Le risque d’avoir un test de course positif, d’avoir une dermatite atopique le jour de l’examen et d’avoir des antécédents d’asthme atopique durant les 12 derniers mois était significativement élevé chez les enfants fréquentant les écoles exposées aux valeurs de PM2,5 supérieures à la valeur médiane. De même, le risque d’être sensibilisé vis-à-vis des allergènes domestiques était significativement plus élevé chez ces enfants. Par ailleurs, le pourcentage d’enfants polysensibilisés était plus important aussi dans ce sous-groupe. En revanche, l’inclusion dans le modèle du taux de NO2 ne modifiait pas ces résultats.

Archives de pédiatrie 16 (2009) 299–305

Barrier Enhancement for Eczema Prevention (BEEP) pilot study

The evidence for most existing disease prevention strategies, such as avoidance of allergens and dietary interventions, has been unconvincing and inconsistent.

The hygiene hypothesis posits that reduced exposure to specific microorganisms during key periods of development leads to immunologic modification favoring acquisition or maintenance of an atopic phenotype.

One systematic review found no evidence of improvement when house dust levels were reduced. Garritsen FM et al., Br J Dermatol. 2013;168:688-91. Some studies even found a paradoxical increase in the risk of AD in families who avoided the allergen, much in the same way as when endotoxins are avoided.

Harris JM et al., Br J Dermatol. 2007;156:698-704. Gehring U et al., Allergy. 2012;67:248---56.

Therefore, in practical terms, strict avoidance of house dust mites should not be recommended as a strategy for prevention or treatment, since it is difficult, impractical, and, possibly, erroneous.

The presence of pets during the first year of life could protect against AD. Several studies show a uniform protective effect with dogs; however, this effect is less clear with cats, and findings are contradictory. The risk is greater in children with mutations in the filaggrin gene, suggesting that alterations in the barrier function could facilitate sensitization to cat dander and development of AD.

Theoretical framework of therapeutic patient education

GADIS (German Atopic Dermatitis Intervention Study)

It is impossible to prevent a disease as complex and multifactorial as AD by eliminating a single risk factor: AD requires an integral approach!