This site is intended for health professionals only!

Published on 1 March 2005

Share this story:

New developments in atopic dermatitis

teaser

Christopher B Yelverton
MD MBA

Steven R Feldman
MD PhD

Alan B Fleischer, Jr
MD
Department of Dermatology
Wake Forest University School of Medicine
Winston-Salem, NC
USA
E:sfeldman@wfubmc.edu

Atopic dermatitis (AD), also known as atopic eczema, is a common disorder characterised by intense pruritus (itching), xerosis (dryness) and lichenification (thickening) of the skin. The condition generally begins in the first year of life with a patchy rash in flexural areas and often progresses to other areas of the body. Epidemiological studies have indicated that AD affects 12–18% of children. Incidence is highest in industrialised nations for reasons that are unclear. Although AD may resolve spontaneously, often near puberty, adult AD is increasing in prevalence.

Clinical features
Patients with AD often have a family or personal history of atopic diseases, such as asthma and seasonal allergies, in addition to AD. This points to a heritable nature for AD, although the exact genetic contribution is still being studied. The diagnosis of AD is clinical, and laboratory workup is typically not necessary. In some cases a scraping is obtained to rule out fungal infection, and skin biopsy may be performed to confirm an unusual case. Histologically, the hallmark of AD is spongiosis (oedema) in the stratum corneum, which is most prominent in the acute phase of the disease. Later, the condition progresses to show acanthosis and lymphocytic infiltrate.(1) Patients may show increased eosinophils in tissue and/or blood. Serum immunoglobulin E (IgE) levels are elevated in a majority of atopic patients, but this finding is not pathognomonic for AD.(2,3)

Pathophysiology
There are a number of theories regarding the development of AD. A complex interplay of genetic, environmental and physical factors is most likely responsible for the condition.(4) The primary event is thought to involve the immune activity of T-helper-2 (Th2) cells, resulting in an overproduction of cytokines (interleukin-4 [IL-4] and others) and IgE that predispose to atopy.(5) Eventually, Th1 activity is also suppressed. Environmental triggers such as dust mite antigens in the home appear to be important modulators of the immune response and may play a role in the development of AD.(6) Studies have shown that patients with AD are frequently colonised with Staphylococcus aureus, but the exact significance of this colonisation is unclear.(7,8) Additionally, individuals with AD are thought to have abnormalities in the stratum corneum, leading to increased water loss and xerosis. The “itch–scratch–itch” cycle of the disease perpetuates the problem, due to further mechanical disruption of the epithelial barrier.(1)

Treatment
A variety of topical and systemic treatments are available for AD. The goals of treatment are to restore moisture, control itch and modulate the inflammatory response. Several excellent reviews have examined the published evidence supporting various AD therapies.(6,8,9)

Topical corticosteroids
Topical corticosteroids have traditionally been the first-line treatment for AD. Topical steroids are classified according to strength and come in a myriad of vehicles, such as creams, ointments, lotions, solutions, shampoos and foams. A discussion of all of the formulations of topical steroids is beyond the scope of this review. The choice of a topical steroid preparation is typically based on location and severity of lesions, age of the patient and tolerability. The advantages of steroids include relatively rapid onset of action, high efficacy and relatively low cost. Typical dosing regimens include either intermittent therapy with mid- to high-potency steroids or daily usage of milder steroids. Inpatients with severe AD are occasionally treated with occlusive wraps using steroids. Long-term use of topical corticosteroids may lead to tachyphylaxis (decreased efficacy due to tolerance), thinning of the skin, telangiectasias and, rarely, adrenal suppression. Skin atrophy, the most worrisome adverse event, was demonstrated at six weeks in several studies.(10)

Topical immune modulators
The most exciting advance in the treatment of AD and many other inflammatory skin conditions is certainly the development of topical immune modulators (TIMs). At present, there are two TIMs available for use in AD: tacrolimus and pimecrolimus. These agents are selective inhibitors of calcineurin,  which inhibits the immune activity of Th2 cells and antigen-presenting cells in the skin (Langerhans cells).(11–13) Tacrolimus (Protopic; Fujisawa) is available as 0.03% and 0.1% ointments for the treatment of moderate-to-severe AD. Pimecrolimus (Elidel; Novartis) is available as a 1% cream for treatment of mild-to-moderate dermatoses. One large, unpublished head-to-head comparison has shown that tacrolimus is more effective than pimecrolimus with a similar adverse effect profile. Another smaller trial already published supports these differences in efficacy, but suggests there may be short-term tolerability differences.(14) The TIMs have several distinct advantages over topical steroids. First, they do not have any effect on collagen synthesis and, therefore, they have no potential for skin atrophy or striae formation. For this reason, they are thought to be safer for use on the face and intertriginous areas. Bioavailability studies of both topical tacrolimus and pimecrolimus have shown minimal systemic absorption in most patients.(6,12,13) These agents represent a significant advance in AD treatment, as they are steroid-sparing and specifically target the cells implicated in AD. Work is underway to develop new vehicle formulations of TIMs that may be more convenient for some patients.

Other topical therapies
Topical emollients are used to moisturise and protect skin in atopic patients, and should probably be used frequently. There is minimal published evidence regarding the efficacy of emollients in reducing the severity of AD, although they are thought to increase patient comfort.(6,8) Topical doxepin has been used to control itch, but data are limited.(8)

Systemic therapies
Systemic therapies for AD are generally reserved for the most severe and resistant cases, out of concern for the adverse effects of these medications. Ciclosporin is one of the most common systemic treatments used for recalcitrant AD. This medication has a mechanism of action similar to that of tacrolimus and pimecrolimus, in that it inhibits calcineurin. It can cause renal, hepatic and haematological dysfunction with prolonged used. Ciclosporin is typically used only for short-term bursts of treatment during severe flares.(6,8,15) Although they have not been studied extensively in AD, systemic corticosteroids are often used in acute flares to control symptoms until transition back to topical therapies is appropriate.(6,8) Systemic steroids have potent anti-inflammatory effects. Concern over long-term adverse effects and rebound flares after discontinuation are the limiting factors in the use of systemic steroids. Systemic antibiotics are sometimes used for superficial infection and skin colonisation, but no studies have shown significant efficacy for these treatments.(6,8) In the same way, oral antihistamines have shown little or no benefit in AD, as histamine is not known to play a prominent role in AD.(8)

Many other systemic therapies have been used for AD, including methotrexate, interferon gamma, azathioprine, mycophenolate mofetil and intravenous immunoglobulin. Methotrexate, which is the most commonly used of these agents, has substantial anecdotal effectiveness in the absence of controlled trials.(6,8) Oral pimecrolimus, which is currently in phase II trials for AD and other immune- mediated skin conditions, has shown great promise. This medication will likely be similar to oral ciclosporin in terms of mechanism of action and adverse effect profile.(16)

Phototherapy
Ultraviolet (UV) light, which is an important mediator of the immune response in the skin, has shown some efficacy in the treatment of AD;(6) UVB or UVA may be used. Recurrence of disease is common following discontinuation of treatment. There is also some concern for increased cutaneous malignancy risk.

Allergen restriction
It is thought that environmental and dietary allergens may play a role in atopic diseases. In truly atopic individuals, particularly those who have undergone allergen testing, attempts to remove allergen triggers may be beneficial. However, the difficulty in effectively removing either environmental allergens (such as dust mites) or food triggers may prove too difficult to accomplish.(6,8) Skin irritants, such as detergents and perfumes, may also play a role.(6) Additional research is ongoing regarding these environmental risk factors.

Implications for hospitals and pharmacies
AD is rarely severe enough to warrant inpatient treatment, but it may be necessary in a few patients who are refractory to attempts at outpatient management.  Moreover, AD is common and can affect a significant proportion of patients admitted for other conditions. A key element of hospital preparedness is the availability of common treatment options. Additionally, availability of minimally irritating linens, soaps and moisturisers will go a long way to improve comfort.

References

  1. Semin Cutan Med Surg 2004;23:39-45.
  2. Allergy 2004;59:561-70.
  3. J Allergy Clin Immunol 2004;114:150-8.
  4. Allergy 2003;58:5-12.
  5. Clin Exp Allergy 2004;34:559-66.
  6. Health Technol Assess 2000;4:1-191.
  7. Acta Derm Venereol 2004;84:32-6.
  8. J Am Acad Dermatol 2004;50:391-404.
  9. Br J Dermatol 2004;151 Suppl 70:3-27.
  10. BMJ 1999;318:1600-4.
  11. J Am Acad Dermatol 2002;46:228-41.
  12. Am Fam Physician 2002;66:1899-902.
  13. J Allergy Clin Immunol 2003;111:1153-68.
  14. J Am Acad Dermatol 2004;51:515-25.
  15. Clin Exp Allergy 2004;34:639-45.
  16. Dermatol Clin 2004;22:461-5,ix-x.

Resource
National Eczema Society (UK)
W:www.eczema.org
Eczema Voice
W:www.eczemavoice.com



Most read




Latest Issue

Be in the know
Subscribe to Hospital Pharmacy Europe newsletter and magazine
Share this story: