Department of Biomedical and Surgical Sciences
Section of Dermatology
University of Verona
Atopic dermatitis (AD) is an inflammatory, chronic-relapsing, usually itching skin disease characterised by eczematous lesions with a specific distribution varying according to age. The pathogenesis of the disease is complex, involving both genetic and environmental factors. Allergens, such as house-dust mites and foods, may be important in some cases, but nonallergic factors, such as rough clothing, skin colonisation by Staphylococcus aureus infections, excessive heat and exposure to irritants that disrupt the function of the skin barrier, may also be important.
The management of patients with AD requires pharmacological treatment, skincare procedures and identification/avoidance of triggering factors. The objective of therapy is to reach a rapid control of the acute symptoms of the disease and to maintain long-term control by reducing the frequency and severity of flares.(1)
There are no effective strategies to prevent AD development in patients at risk. There is no clear evidence that a restricted diet in the last three months of pregnancy in atopic women reduces the risk of AD development in the newborn, or that exclusive breastfeeding can prevent it. Randomised controlled clinical trials showed that perinatal administration of probiotics may reduce the incidence of AD in children at risk during the first four years of life,(2) but other trials failed to confirm these findings.(3)
Educational programmes and counselling, although time-consuming, are particularly important. Although it is time-consuming, it is important to answer the questions that patients and their parents may want to ask and give them instructions to avoid unnecessary, and sometimes expensive, measures and constraints. Experience with parents of children suffering from AD indicates the usefulness of counselling programmes in the therapy.(4) Moreover, early detection of bronchial asthma in patients with AD is part of the global management of the disease.
AD is associated with skin barrier anomalies that lead to easier allergen penetration through the skin and increased likeliness of cutaneous inflammation. Lack of important stratum corneum intercellular lipids and enhanced proteolytic activity in the stratum corneum worsen transepidermal water loss, leading to skin dryness. There is evidence that regular and continuous use of the appropriate quantity of emollients (150–200g per week in young children and up to 500g in adults) reduces the need for topical corticosteroids (TCSs) and enhances therapeutic response.(5,6)
More than 80 randomised controlled trials have documented the efficacy of TCSs in inducing rapid remission of flares in AD.(7) The potency of these drugs is defined as their potential for vasoconstriction, a surrogate for clinical efficacy and skin thinning. In general, only preparations that have very weak or moderate strength are used on the face, genital and folds, whereas those with moderate or potent strength are used on other body areas. Lower-potency TCSs are preferred in infants and younger children. Preparations are generally used in phases of three to seven consecutive days to achieve control, and subsequently stopped and reapplied as needed (intermittent regimen).
Long-term studies of the use of TCSs in AD are scarce. A four-month trial of patients aged 12 to 64 years with moderate-to- severe disease showed that the application of fluticasone to previously active and new-site AD for two consecutive days per week reduced flares significantly, compared with a group receiving emollient only.(8) A matter of concern with the use of TCSs is the occurrence of side-effects, including irreversible skin thinning, striae distensae, teleangectasia, glaucoma and cataract for the application on the eyelid, whereas secondary adrenal suppression is very rare. Although inappropriate use of TCSs possibly induces side-effects, the concern expressed by patients (and parents) is often out of proportion.
Topical immunomodulators (TIMs) include tacrolimus and pimecrolimus, both of which are calcineurin inhibitors (CNIs). These drugs bind to cytoplasmic proteins, and the resulting complex binds calcineurin, inhibiting its ability to dephosphorylate the nuclear factor of activated T-cells (NF-AT). NF-AT is a nuclear transcription factor that facilitates the transcription of several growth factors and inflammatory genes. Pimecrolimus has a selective action on T-cells and mast cells, whereas tacrolimus also acts on dendritic cells, eosinophils and keratinocytes. A recent meta-analysis has documented that tacrolimus ointment 0.03% (for children) and 0.1% (for adults) and pimecrolimus cream 1% are effective in the short- and long-term control of AD, both in children and in adults.(9)
The most frequent adverse reactions to TIMs are application site reactions. Local side-effects of topical CNIs commonly reported by patients are feelings of warmth/burning/ stinging, increase of erythema or irritation, and increased itching. These reactions are usually transitory and occur only during the first days of use.
The major concern about the safety of topical CNIs is related to the potential risk of cancer. On 15 February 2005, the Pediatric Advisory Committee of the FDA recommended “black box” warnings for pimecrolimus cream and tacrolimus ointment because of potential safety risks (including skin cancer and lymphoma).(10) However, there is no evidence that topical use of pimecrolimus causes malignancies, as emphasised by many experts and scientific societies.(11–13) Over the last decade, TIMs have been extensively studied in clinical trials involving hundred thousands of patients; millions of patients, more than half of them children, have been treated with these medications since their approval. Moreover, TIMs do not induce skin atrophy, and pimecrolimus is not associated with an increased risk of cutaneous infection, even after long-term application.
Oral antihistamines are commonly used in acute flares to control itch, although evidence is lacking to support their wide use. Sedative anti-H(1) molecules are preferred, to permit sleep.
Randomised clinical trials have shown that ultraviolet (UV) light (UVB, narrow-band UVB and high-intensity UVA) is beneficial for AD in the short term. Carcinogenicity is a major concern for long-term treatment. Phototherapy is usually used as a second- or third-line treatment.
Systemic immunosuppressive agents
The use of systemic immunosuppressive drugs, including oral corticosteroids, ciclosporin, azathioprine and mycophenolate, is generally limited to patients with severe disease who do not respond to other measures.
Patients and families should be educated regarding the nature, course and treatments of AD. A single cause and a single cure are unlikely, but a good control is very often possible.
- Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med 2005;352:2314-24.
- Kalliomaki M, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869-71.
- Isolauri E. Dietary modification of atopic disease: use of probiotics in the prevention of atopic dermatitis. Curr Allergy Asthma Rep 2004;4:270-5.
- Gieler U, et al. Counselling of parents with children with atopic dermatitis. Hautarzt 1992;43 Suppl 11:37-42.
- Lucky AW, et al. Use of an emollient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children. Pediatr Dermatol 1997;14:321-4.
- Kantor I, et al. Efficacy and safety of emollients as adjunctive agents in topical corticosteroid therapy for atopic dermatitis. Today Ther Trends 1993;11:157-66.
- Hoare C, et al. Systematic review of treatments for atopic eczema. Health Technol Assess 2000;4:1-191.
- Berth-Jones J, et al. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. BMJ 2003;326:1367.
- Ashcroft DM, et al. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: metanalysis of randomised controlled trials. BMJ 2005;330:516-22.
- Food and Drug Administration Pediatric Advisory Committee February 15, 2005), Briefing Information. Available from: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4089b2.htm
- Fonacier LM, et al. Report of the topical calcineurin inhibitor task force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2005;115:1249-53.
- Bieber T, et al. Consensus statement on the safety profile of topical calcineurin inhibitors. Dermatology 2005;211:77-8.
- Girolomoni G, et al. The safety profile of topical pimecrolimus in the treatment of atopic dermatitis. G Ital Dermatol Venereol 2005;140:456-7.