ATOPIC DERMATITIS

Atopic dermatitis is one of the fastest emerging skin disorders through out the world. With the increase in pollution related problems, skin disorders are just increasing. Here is a little about the disorder which was a part of my dissertation work…

Dermatitis simply means skin inflammation, but it embraces a range of ailments. In most cases the early stages are characterized by dry, red, itchy skin, although acute attacks may result in crusty scales or blisters that ooze fluid.

The categories of dermatitis:

Contact dermatitis typically causes the skin to develop a pink or red rash, which may or may not itch. Pinpointing the exact cause of contact dermatitis can be difficult. The leading culprits are poison ivy, poison oak, detergents, soaps, some synthetic fibers etc.

Nummular dermatitis consists of distinctive coin-shaped red patches that are most commonly seen on the legs, hands, arms, and torso.

Seborrheic dermatitis consists of greasy, yellowish, or reddish scaling on the scalp and other hairy areas.

Stasis dermatitis is caused by poor circulation and can happen in people with varicose veins, congestive heart failure, or other conditions.

Atopic dermatitis (AD) is a chronically relapsing skin disease that occurs most commonly during early infancy and childhood. It is frequently associated with elevated serum IgE levels and a personal or family history of AD, allergic rhinitis, and/or asthma. There is no single distinguishing feature of AD or a diagnostic laboratory test. Thus, the diagnosis is based on the constellation of clinical findings.

HISTORICAL ASPECTS

This disorder was probably first reported by Robert Willan, in 1808, as a prurigo-like condition.

In 1923, Coca and associates introduced the term atopy , meaning “ out of place” or “strange”, to signify the hereditary tendency to develop allergies.

Atopic dermatitis is also known as atopic eczema, infantile eczema, flexural eczema and disseminated neurodermatitis.

EPIDEMIOLOGY

• The prevalence of AD in adults is approximately 1 to 3 percent.

• There is also a female preponderance for AD, with an overall female/male ratio of 1.3:1.

• Although the tendency to develop AD is inherited, inheritance patterns do not follow strict Mendelein patterns and the overall prevalence of AD is increasing.

ETIOLOGY AND PATHOGENESIS

• Complex interactions among genetic, environmental, skin barrier, pharmacologic, and immunologic factors contribute to the pathogenesis of AD.

• The concept that AD has an immunologic basis is supported by the observation that patients with primary T cell immunodeficiency disorders frequently have elevated serum IgE levels and eczematoid skin lesions indistinguishable from AD.

Systemic Immune Abnormalities

• Increased synthesis of IgE

• Increased specific IgE to multiple allergens, including foods, aeroallergens, microorganisms, bacterial toxins, autoallergens

• Increased expression of CD23 on B cells and monocytes

• Increased basophil histamine release

• Impaired delayed-type hypersensitivity response

• Eosinophilia

• Increased secretion of IL-4, IL-5 and IL-13 by T_H2 cells

• Decreased secretion of IFN-γ by T_H1 cells

• Increased soluble IL-2 receptor levels

lmmunologic Triggers

FOODS:

• Induce eczematous dermatitis

• Common allergens are: milk, egg, wheat, soy and peanut.

• Increase in histamine levels and eosinophil activation.

AEROALLERGENS:

• E.g. dust mites, weeds, animal dander and molds.

AUTOALLERGENS:

• IgE against auto antigens are made in the skin.

• Auto antigens trigger IgE or T- cell mediated responses.

Immune Response in AD Skin

ROLE OF CYTOKINES :

• T_H2- and T_H1-type cytokines contribute to the pathogenesis of skin inflammation in AD.

• Increased number of cells expressing IL-4 and IL-13, but not IL-5, IL-12, or IFN-γ .

• Activated T cells infiltrating the skin of AD patients have also been found to induce keratinocyte apotosis contributing to the spongiotic process found in AD skin lesions.

PERSISTENT SKIN INFLAMMATION:

• Mechanical trauma induces the release of TNF-α and many other proinflammatory cytokines from epidermal keratinocytes.

• Chronic scratching plays a role in the perpetuation and elicitation of skin inflammation in AD.

CHEMOATTRACTANT FACTORS :

• IL-16, a chemoattractant for CD4+ T cells, is more highly expressed in acute than chronic AD skin lesions.

• It was shown that TARC and MDC levels in AD sera significantly correlate to disease activity.

• The results obtained were:

Ø serum MDC levels in AD patients were significantly higher than those in psoriasis vulgaris patients or healthy controls

Ø serum MDC levels in the severe group of AD patients were significantly higher than those in the mild or moderate groups

GENETICS

• Familially transmitted with a strong maternal influence

• Potential role of chromosome 5q31-33 because it contains a clustered family of cytokine genes-IL-3, IL-4, IL-5, IL-13, and GM-CSF-which are expressed by T_H2 cells.

CLINICAL MANIFESTATIONS

Diagnosis of AD is based on the constellation of clinical features:

Clinical Features of Atopic Dermatitis

• Major Features

Facial and extensor eczema in infants and children

Chronic or relapsing dermatitis

Personal or family history of atopic disease

• Associated features

Xerosis

Nonspecific dermatitis of the hands or feet

Ichthyosis, palmar hyperlinearity

Nipple eczema

Anterior subcapsular cataracts, keratoconus

Elevated serum IgE levels

Positive immediate-type allergy skin tests

Early age of onset

Dennie-Morgan infraorbital folds, orbital darkening

Facial erythema or pallor

Course influenced by environmental and\or emotional factors

LABORATORY FINDINGS

• Serum IgE levels are elevated in majority of patients with AD

• 85% patients have positive immediate skin tests directed to a variety of food, inhalant and microbial allergens.

• Serum levels of eosinophil cationic protein and urinary eosinophil protein X are elevated in AD.

TREATMENT AND PROGNOSIS

• Topical Therapy

Ø CUTANEOUS HYDRATION

Ø TOPICAL GLUCOCORTICOID TREATMENT

• TOPICAL IMMUNOMODULATORS

Ø Tacrolimus

Identification and Elimination of Triggering Factors

• SPECIFIC ALLERGENS

• EMOTIONAL STRESSORS

• INFECTIOUS AGENTS

• TAR PREPARATIONS

• PHOTOTHERAPY

• OTHER THERAPIES

• PROGNOSIS

CONCLUSION

• Focus has, meanwhile, shifted to new research on the role of the skin barrier in AD, with particular interest in groundbreaking research showing that genetic mutations appear to play a critical role in the skin barrier function as it relates to atopic dermatitis.

• The barrier research, the role of immunity and antimicrobial peptides and the whole role of S. aureus are the big areas of interest right now.