Atopic Dermatitis: A Short Review

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Atopic dermatitis is a chronic skin inflammation with pruritus as its most frequent symptom. Attempts to relieve the itch by scratching worsen the rash, creating a vicious circle ("an itch that rashes"). The disease course marked by exacerbations and remissions (reminiscent of disease course in asthma).

Pathogenesis and Etiology

A genetic abnormality causes increased levels of cyclic adenosine monophosphate (cAMP) phosphodiesterase, which leads to low levels of intracellular cAMP. This causes basophils and mast cells to be hyperreactive, with increased histamine and leukotriene production and release.

Prevalence

Atopic dermatitis is common and historically affected 10 percent of children. The prevalence of atopic dermatitis has increased 2-3 times in the last three decades, affecting 15 to 20 percent of young children.

Prognosis

Atopic dermatitis resolves by adolescence in 50 percent of affected children. Poor prognostic features include a family history of atopic dermatitis, early disseminated infantile disease, female gender and coexisting allergic rhinitis and asthma.

Diagnosis

Diagnosis is based on history and physical examination -- the diagnostic criteria are listed below. Elevated IgE levels are found in 80 percent of affected patients but this is not specific.

Diagnostic features of atopic dermatitis are listed below. The diagnosis requires 3 major features and 3 minor features

Major features

Pruritus

Chronic or relapsing dermatitis
Personal or family history of atopic disease
Typical distribution and morphology of atopic dermatitis rash:
Facial and extensor surfaces in infants and young children
Flexure lichenification in older children and adults

Minor features

Eyes

Cataracts (anterior subcapsular)
Keratoconus
Infraorbital folds affected
Facial pallor
Palmar hyperlinearity
Xerosis
Pityriasis alba
White dermatographism
Ichthyosis
Keratosis pilaris
Nonspecific dermatitis of the hands and feet
Nipple eczema
Positive type I hypersensitivity skin tests
Propensity for cutaneous infections
Elevated serum IgE level
Food intolerance
Impaired cell-mediated immunity
Erythroderma
Early age of onset

Pruritus is a universal and dominant finding in atopic dermatitis (""the itch that rashes" rather than the "rash that itches"). Children with atopic dermatitis lose an average of 1.9 hours of sleep per night whereas their parents lose an average of 2.1 hours per night.

Xerosis (dry skin) is another typical finding in atopic dermatitis

XP
Xerosis
Pruritus

The lesions of atopic dermatitis have a characteristic distribution which changes with age. In infants and young children, pruritus is present on the scalp, face (cheeks and chin) and extensor surfaces of the extremities. Older children and adults typically have involvement of the flexor surfaces (antecubital and popliteal fossa), neck, wrists and ankles.

Anterior subcapsular cataracts develop in 4-12 percent of patients with atopic dermatitis. Posterior cataracts are usually a side effect of oral corticosteroid therapy.

Secondary Infections

Staphylococcal and streptococcal infections are common complications in atopic dermatitis.

Differential Diagnosis

Lesions in atopic dermatitis can take many forms:
papules
vesicles
plaques
nodules
excoriations

The differential dagnosis includes seborrheic dermatitis, psoriasis, contact dermatitis, scabies, dermatitis herpetiformis, dermatophyte infection.

Treatment

Bathing and Moisturizers

Emollients are the mainstay of maintenance therapy for atopic dermatitis. Bath once daily with warm (not hot) water for 5-10 minutes. Soap should not be used. Immediately after bathing (and before the skin is completely dry), patients should apply a moisturizer/emollient (e.g., Aquaphor, Eucerin, Moisturel).

Topical corticosteroids

Topical corticosteroids should are the first-line treatments for patients with atopic dermatitis flare-ups. More than 30 topical corticosteroids are available, ranging from low to high potency.

Only low-potency should be used on the face, groin, and axillae to minimize local side effects such as acne, striae, telangiectasia, and atrophy. Current treatment guidelines do not recommend more than twice-daily application of topical corticosteroids.

Topical corticosteroids are safe and effective for the treatment of flare-ups when used for up to 4 weeks Topical corticosteroids do not cure atopic dermatitis.

Topical calcineurin inhibitors

Calcineurin inhibitors (pimecrolimus, Elidel and tacrolimus, Protopic) are immunosuppressants developed for oral administration to prevent allogeneic transplant rejection. They inhibit calcineurin in the skin, which blocks early T-cell activation and the release of cytokines.


Pimecrolimus. Image source: Wikipedia, public domain. Tacrolimus is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.

Topical formulations were developed as alternatives to topical corticosteroids.

Generally, topical calcineurin inhibitors should not be used in patients younger than two years or in those who are immunosuppressed. The most common local adverse effects are skin burning and irritation.

The Food and Drug Administration recommends avoiding long-term use of topical calcineurin inhibitors in all patient populations and limits use to children older than 2 years because of possible risk of local or distant malignancy.

A suggested approach to topical treatment of moderately severe atopic dermatitis.Bleach (sodium hypochlorite)The typical recommendation is to add half a cup of bleach (e.g. Clorox) to one bathtub each week.

Antihistamines

It makes a theoretical sense to treat the pruritus with antihistamines but they have been shown to be ineffective when compared with placebo. Sedating antihistamines are indicated have sleep disturbances and concomitant allergic conditions.

Antibiotics

Antibiotics should be used to treat secondary infections, appropriate choices include dicloxacillin, first-generation cephalosporins and macrolide antibiotics.The use of antiseptic baths and washes also should be avoided.

Phototherapy

Phototherapy may be effective in treating refractory atopic dermatitis

Systemic therapy

Systemic therapy may be rarely indicated in severe, resistant disease. Short course of systemic corticosteroids are effective at controlling atopic dermatitis exacerbations in adults but their usefulness is limted by rebound flare-ups and diminishing effectiveness.

Cyclosporine may be effective for severe atopic dermatitis. There is no evidence to support the use of leukotriene inhibitors, methotrexate, desensitization injections, theophylline, or oral pimecrolimus.

How does cyclosporine work?

Cyclosporin binds to the cytosolic protein cyclophilin (immunophilin) of T-lymphocytes. This complex of cyclosporin and cyclophylin inhibits calcineurin, which is responsible for the transcription of interleukin-2. Cyclosporin inhibits lymphokine production and interleukin release and leads to a reduced function of effector T-cells.


Ciclosporin (INN), cyclosporine (USAN) or cyclosporin (former BAN). Image source: Wikipedia, public domain.


Cyclophilin. Image source: Wikipedia, public domain.

This mode of action is similar to pimecrolimus (Elidel), an ascomycin macrolactam derivative, which binds to macrophilin-12 and inhibits calcineurin. Thus pimecrolimus inhibits T-cell activation by inhibiting the synthesis and release of cytokines from T-cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from mast cells.

Cyclosporin is an immunosuppressant drug used in post-allogeneic organ transplant. Initially isolated from a Norwegian soil sample, Cyclosporin A is a cyclic peptide of 11 amino acids produced by the fungus Tolypocladium inflatum Gams, and contains D-amino acids, which are rarely encountered in nature.

References

Atopic Dermatitis: A Review of Diagnosis and Treatment. AFP, 1999.
Treatment Options for Atopic Dermatitis. AFP, 2007.
Atopic Dermatitis. NEJM, 4/2008.
Allergy and the skin: eczema and chronic urticaria. Constance H Katelaris and Jane E Peake. MJA 2006; 185 (9): 517-522.
Drugs acting on immunophilins: Cyclosporine, Tacrolimus, Sirolimus

Related Reading

FIT Corner Questions. Chapter 86 of the 6th edition of Middleton’s Allergy Principles and Practice, edited by N. Franklin Adkinson, et al., January 17, 2007, Chapter 86: Atopic Dermatitis.

Atopic dermatitis (eczema) skin care: When should I use Aquaphor instead of Eucerin?

Published: 07/12/2008
Updated: 12/15/2009