|Other common terms: AD, atopic eczema, eczema|
|ICD-10 classification:L20.0, L30.0|
|Prevalance: Varies between populations from 2-20% of total population|
|Symptoms: Blackheads, whiteheads and inflammatory papules and pustules on the skin, most commonly on the face and shoulders, but can occur anywhere. Severe acne can causes scarring of the skin.|
|Treatments/cures: A range of over the counter and prescription medications. Antibiotics and hormonal therapies in moderate-severe cases. Chemical skin peeling, scar and cyst removal or photodynamic therapy in very severe cases.|
|Differential diagnosis: Allergic reactions, seborrheic dermatitis|
Atopic dermatitis (AD), also known as atopic eczema, is one of the most common chronic inflammatory skin diseases. It is characterised by itchiness (pruritis) and associated defects in the skin barrier. AD is a complex disease with significant genetic and environmental influences, but its precise mechanisms are poorly understood. Its prevalence is rising in developed countries and, although predominantly a childhood disease, a small proportion of adults do suffer AD. Over 80% of adult AD patients suffer from hayfever or asthma.
A majority of patients with AD have mild disease. A significant minority, however, have moderate to severe AD, which is difficult to manage and requires second-line therapies.
The prevalence of atopic dermatitis varies between different populations. If affects less than 2% of children in China and Iran, whilst the prevalence can be as high as 20% in northern and western Europe, Australia and the USA. The prevalence of adults with AD is as low as 0.9% in the USA and can be up to 10% in other countries. AD affects all races and affects both sexes, although females are slightly more frequently affected than males.
The prevalence of AD has increased dramatically in the past three decades. Some studies report that the incidence and prevalence of AD may have stabilized in recent years.
The increase in recent years can be attributed to environmental influences. A higher incidence in AD has been observed in industrialized and urban settings, higher socioeconomic status and a smaller family size. The “hygiene hypothesis” has been proposed to explain recent increases in AD. This hypothesis suggests that absence of infections early in life in the above-mentioned populations predisposes individuals to developing AD. The support for this hypothesis, however, has been equivocal. Also, the role of dietary factors in AD has been far from proven. A family history of AD, asthma or allergic rhinitis may increase susceptibility to developing AD.
The precise causes of atopic dermatitis are unknown, but AD considered to be caused by complex interactions of deficient innate and adaptive immune responses as well as a result of genetic predisposition. The following factors are thought to play a causal role in AD:
- A family history of AD, asthma or hayfever is common, suggesting a role for genetic variants in the development of AD;
- Defects in the immune system are thought to play in the hypersensitivity reaction that characterises AD;
- Allergies may play a role in the exacerbation of AD. Although patients with AD develop allergies to food and environmental allergens, it is not clear if allergies cause or maintain AD;
- Environmental irritants, such as detergents, may cause flare-ups of AD;
- Itching may further damage the skin barrier and cause flare-ups of AD and secondary infections;
- Overgrowth of Staphylococcus aureus (S aureus) may lead to recurrence of AD;
- Dry skin, temperature changes, stress and exposure to water may worsen the symptoms of AD.
Genetic predisposition to atopic dermatitis
AD has a strong genetic component and linkage studies have identified chromosomal loci 1q21, 3q21, 3q24-22, 3q26-24 and 17q25 as possible regions of interest in AD. Specific regions that predispose to AE with increased allergen-specific IgE and concomitant asthma have also been identified. These loci are thought to contain genes or gene families that modulate immune reactions in the skin and mucosa. The genetic variants in these loci are thought to be involved in epidermal barrier dysfunction, via regulating epidermal differentiation, inflammation and atopy.
Impaired barrier defence
The epidermis of the skin functions as a physical barrier and an immunological organ. The barrier confers protection against allergens, microbes and irritants. In AD, a modified skin barrier with increased transepidermal water loss and dehydration of the skin is the hallmark feature. The dysfunctional barrier allows allergens, microbes and irritants to enter the skin and causes an immune response that characterises AD. Impaired epidermal differentiation is believed to be responsible for epidermal dysfunction in AE. During differentiation, keratinocytes move from a proliferative cell type in the basal layer of epidermis through the granular layer where the cornified envelope is formed, to an association of flattened, dead cell remnants (corneocytes) in the uppermost layer of the skin, the stratum corneum (SC). The cornified envelope prevents water loss and acts as a barrier against allergens and microbes. Altered enzymatic activities have been postulated to affect SC integrity, cohesion and permeability barrier function. Impaired barrier defences can also occur due to abnormal expression of structural proteins involved in the cornification process.
Innate immune responses are the first-line cellular and biochemical defence mechanisms that respond to microbial invasion via their recognition by pattern-recognition receptors (PRR). PRR plays a crucial role in activating innate immune response and trigger adaptive immune responses. Impaired PRR responses have been implicated in the pathogenesis of AD. Furthermore, impaired innate immune mechanisms with deficiency of antimicrobial proteins are believed to be responsible for the increased susceptibility to skin infections seen in patients with AD.
In addition to innate immunity, keratinocytes are crucial in mediating adaptive immunity via cytokines. In patients with AD, keratinocytes produce increased amounts of proinflammatory mediators. Because of the underlying barrier dysfunction and increased production of cytokines, minimal exogenous skin trauma (such as scratching) is sufficient to activate disease in hitherto clinically uninvolved skin. Memory and effector T cells migrate to the inflammed skin and cause atopy.
AD is a biphasic disease. Initially, T helper type 2 (Th2) cytokines predominate. As the disease progresses to a chronic phase, T helper type 1 (Th1) cytokines predominate. Immunoglobulins (IgE), produced by B lymphocytes, are under the support of Th2 cytokines. Marked Th2 production and the resultant increase in IgE levels characterise AD. Modified regulatory T cells, and altered levels of immune modulators such as Interferon predispose patients with AD to viral infections (e.g. herpes simplex virus) and allergic sensitizations.
Atopic dermatitis is characterised by the following symptoms:
- Intense itching (pruritis);
- Skin rash;
- Papular rashes (more common in darker skinned individuals;
- Oozing or crusting blisters;
- Moist or ‘weeping’ skin;
- Dry skin (xerosis);
- Discharge or bleeding from the ears;
- Altered skin tone;
- Inflamed or red skin;
- Thickened (lichenified) skin; and/or
- Rough and flaky skin.
Although atopic dermatitis can occur anywhere, particular patterns are usually observed at different ages. Initially, the face is usually affected. In crawling infants, the forearms, extensor aspects of the knees and the ankle flexures are the most affected. In infants, the skin lesions are ill-defined, scaly and crusted patches.
In older children, the flexor aspects of the elbow and the knees are the most affected.
The clinical course of AD fluctuates with intermittent flare-ups, although the causes may not always be discernible.
In adults, lesions become diffuse and erythematous. Xerosis is common and skin thickening may occur. A brown macular ring, which is localized deposition of amyloid, around the neck may be present. About 80% of adults with AD suffer from allergic rhinitis or asthma.
Infective complications can occur, particularly due to Staphylococcus infections, which may present as bullous impetigo or as exacerbated eczema with redness and oozing. Occlusion can occur from wet dressings and cause staphylococcal folliculitis. Herpes simplex virus infections are also common in patients with AD.
Recurrent bacterial, viral and fungal infections often afflict patients with AD. In patients with AD, up to 90% of microbial flora on the skin is colonized by S aureus, compared to about 10% in healthy individuals. In addition to promoting pruritis, S aureus can cause glucocorticoid resistance in patients with AD. Other complications of AD include allergies to food and other air-borne allergens, due to IgE sensitization and specific T cell mediated immune responses. Autoreactivity of IgE has been postulated in the involvement of progression to chronic and severe AD.
Atopic dermatitis is diagnosed based on the appearance of the skin and on family history. Excluding other conditions such as scabies, contact dermatitis, psoriasis and other morphologically similar diseases enables a more accurate diagnosis of AD. It is also important to rule out other, often rare, condition that present with AD, such as Comel-Netherton syndrome. Clinicians often use the SCORAD index, developed by the European Taskforce on Dermatitis and validated in children and adults, to assess the severity of AD. The SCORAD index can be used to derive a score, based on the severity and distribution of symptoms. This score can then be used to ascertain the progression and severity of AD. In patients with moderate to severe AD, where required, a validated stepwise allergy test (using food, contact allergens and atopens) may be helpful.
A range of treatments exist for atopic dermatitis, depending on the severity of the disease. In addition to treatment, wearing soft clothing, exposure to cool temperatures and clothes washed with mild detergents and without a fabric softener reduce flare-ups of AD.
For mild to moderate atopic dermatitis, emollients (substances that soften and soothe the skin – e.g. petroleum based gels) and topical steroids are the mainstay of treatment. In addition, avoiding allergens and irritants and educating family members and patients about AD may improve treatment outcomes.
Topical corticosteroids have been the mainstay of treatment for atopic dermatitis flare-ups. A number of agents are available in varying doses and concentrations. Low-potency agents should be used on the face, groin and axillae, and in infants, to minimize side-effects, such as acne. Topical corticosteroids should be used for the shortest time possible to control flare-ups in order to minimize adverse effects. Once flare-ups are controlled, preventative strategies should be employed to control AD. Systemic side-effects, such as reduced linear growth in children and altered bone density in adults, can occur, but are rare.
Secondary bacterial infections due to overuse of topical steroids should be clinically reviewed.
For moderate to severe AD, topical or systemic calcineurin inhibitors, such as pimecrolimus, may be effective. These agents inhibit calcineurin in the skin, and blocks early T cell activation and release of cytokines. These drugs have side-effects including, skin irritation and burning sensations. The long-term safety of calcineurin inhibitors is unclear amid reports of cancer development in some patients.
Phototherapy with exposure to ultraviolet B light may help in some cases of atopic dermatitis, but the risk of skin cancer with such exposure should be considered.
For severe forms of AD, systemic treatments may be warranted. Short-term systemic corticosteroid therapy may be effective in controlling AD in adults. Rebound flare-ups and reduced effectiveness is of concern and may limit use. Immune modulators such as cyclosporine and interferon-gamma-1b may be effective in treating severe AD. On the other hand, the efficacy of other immune modulators, such as azathioprine and intravenous immunoglobulins, are unclear. Side effects of these agents include kidney and liver damage, increased risk of developing certain forms of cancer, and immune suppression.
Treatment of infections
Antibiotic treatments (such as cephalexin) and anti-viral treatments (e.g. acyclovir) may be used to treat secondary bacterial (particularly, S aureus) and viral (herpes simplex virus) infections respectively. Concerns about antibiotic resistance should be weighed up. Use of antiseptic baths and washes should be avoided.
Atopic dermatitis is a chronic disease and cannot be prevented or cured. Steps can be taken to manage symptoms and reduce flare-ups. Wearing soft clothing (such as cotton or other smooth fabrics), exposure to cool temperatures and clothes washed with mild detergents and without a fabric softener can reduce flare-ups of AD. Use of emollients and/or moisturizers twice a day to prevent dry skin is crucial in reducing the exacerbations of AD. Bathing in warm water using a mild, unscented soap or soap-free cleansers is helpful. Lubricating ointments may be used at night-time, because of their superior hydrating potential. Patients may develop allergies to foodstuffs and, where necessary, epinephrine / adrenaline (EpiPen) injections should be readily available. Avoiding known environmental triggers is beneficial.
Atopic dermatitis is a chronic condition that cannot be cured, but the symptoms can be controlled with treatment and appropriate preventative methods, such as moisturisation. Educating patients about the need to control and manage symptoms, and avoid allergens and irritants is vital in reducing the risk of flare-ups and complications. In children, AD usually resolves by adulthood. In adults, however, the disease is often recurring. Patients may develop complications, including bacterial and viral infections, asthma and allergic rhinitis and these should be managed appropriately. Regular follow-ups may be required to assess the progress of the disease and modify treatment regimes accordingly.
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- Atopic Dermatitis (Eczema) fact sheet from the University of California (Berkeley) Health Service
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