Definition - Inflammatory skin condition characterised by dry, pruritic skin with a chronic relapsing course.
- Can affect all age groups, but it is most commonly diagnosed before 5 years of age and affects 10% to 20% of children.
- Patients often have a personal or family history of other atopic diseases such as asthma or allergic rhinitis.
- Food allergens may occur at increased rates in this population.
- Atopic dermatitis can be described as acute or chronic.
- Acute atopic dermatitis is used to describe a flare-up of symptoms.
- Chronic is used to describe the condition when the patient develops signs of chronic inflammation (e.g., lichenification).
- The period of time before the condition is termed chronic is not clearly defined.
Risk Factors - Age <5 years
- 45% of patients with atopic dermatitis are diagnosed by 6 months of age,
and 70%-85 % of patients are diagnosed by the age of 5 years.
- FHx
- Concordance rates of 77% in monozygotic twins and 15% in dizygotic twins. [8]
- Studies have estimated prevalence in siblings at 22%-24%. [15]
- Allergic rhinitis
- Occurs in 50%-80% of children with atopic dermatitis. [1] [3]
- Allergen sensitisation and immune dysregulation are thought to be important components in atopic disease.
- Asthma
- Occurs in 40%-50% of children with atopic dermatitis. [1] [3]
Differential diagnosis - Seborrhoeic dermatitis
- Characteristic greasy scale that is not pruritic.
- Often affects cheeks
on face, scalp, extremities and trunk.
- Unlike atopic dermatitis, the
nappy area is often affected.
- Irritant contact dermatitis
- Common in nappy area, face, and extensor surfaces in children resulting
from exposure to irritating substances.
- Typically less pruritic than
atopic dermatitis.
- Allergic contact dermatitis
- Well-circumscribed erythematous lesions, often with spongiotic papules,
vesicles, and crusting.
- Lesions are usually pruritic.
- Eruptions are due
to contact with specific allergen, and removal of offending agent
results in resolution of symptoms.
- Scabies
- Severe pruritus, particularly at night.
- In addition to papules or
vesicles, burrows may be evident and will help to make the diagnosis.
- The wrists, ankles, palms, soles, interdigital spaces, axilla, waist and
groin are the most commonly affected sites.
- Patients will often report
similar symptoms in family members or other close contacts. [3]
- Psoriasis
- Well-circumscribed, erythematous lesions with silver scale that show a
predilection for extensor surfaces, particularly elbows and knees.
- The
nail pitting seen in psoriasis has smaller pits and is more common than
that seen in patients with atopic dermatitis.
- Mycosis fungoides
- The initial stages of mycosis fungoides (cutaneous T cell lymphoma) may
look similar to atopic dermatitis.
- Erythematous plaques in random
distribution are common and scale is often present.
- As opposed to
patients with atopic dermatitis, patients with mycosis fungoides tend to
be older at the time of diagnosis, with an average age of 50 years.
Epidemiology - Atopic dermatitis usually presents in childhood, with 45% of patients
diagnosed by 6 months of age, and 70% to 85% by 5 years of age. [1] [2] [3]
- Remission is noted by the age of 15 in 60% to 70% of cases, although relapse may occur later in life. [1] [2] [4]
- Atopic dermatitis affects males and females equally.
- The prevalence is 10% to 20% in US children, and 1% to 3% in adults. [5]
- This is significantly higher than the prevalence reported several
decades ago, and mirrors that seen in many industrialised nations. [3]
- The prevalence in European and Japanese children has been estimated to be 15% and 24% respectively. [1]
- In addition, atopic dermatitis occurs more commonly in urban areas and
in smaller families, supporting the theory that environment plays a
significant role in disease development.
Aetiology - Atopic dermatitis has a multifactorial aetiology, with a combination of genetic susceptibility and environmental factors contributing to disease development.
- Defects in the skin's barrier function and immune dysregulation following allergen exposure are thought to be key components in the development of this disease.
- It has been linked to mutations in genes that are crucial for normal epidermal differentiation as well as to genes involved in immune-system regulation. [6] [7]
- This genetic predisposition is supported by the increased incidence in family members, and by studies showing concordance rates of 77% in monozygotic twins and 15% in dizygotic twins. [8]
- The aetiopathogenesis of atopic dermatitis has been increasingly attributed to abnormal skin barrier function. [9]
- Evidence to support that both inherited and acquired insults to the barrier worsen the overall disease state has become increasingly strong. [10]
- Common loss of function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
- The loss-of-function mutation in the structural protein filaggrin predisposes the affected individual to a less effective mechanical barrier against the environment. [11]
- The stratum corneum of those individuals with loss-of-function mutations in the filaggrin gene have lower levels of natural moisturising factor in their stratum corneum. [12]
- Additionally, the skin of those affected with atopic dermatitis is deficient in extra-cellular lipids including ceramides. [13]
- Breaks in the epidermal barrier allow increased exposure and sensitisation to antigens.
- Mutations in genes that are crucial to normal epidermal barrier function have been identified and are thought to predispose patients to the development of atopic dermatitis.
- Links have also been identified between atopic dermatitis and areas of the genome that are known to encode cytokines and receptors involved in the Th2-mediated immune response that predominates in atopic dermatitis. [8]
- The role of environmental factors in the development of this skin disorder is supported by the increased rate of disease seen in urban areas, smaller families and higher socio-economic classes.
- In a recent study, the prevalence of atopic dermatitis in Jamaican children living in London was twice as high as that of Jamaican children living in Jamaica. [2]
- In addition, it has been noted over the last several decades that the prevalence of atopic dermatitis has increased significantly. [3]
Clinical features - Pruritis
- Xerosis
- Sites:
- Infants typically show involvement of the cheeks, forehead, scalp,
and extensor surfaces.
- Affected skin is often oedematous, with prominent
weeping and crusting.
- Children typically have involvement of flexures, particularly the wrists, ankles, antecubital and popliteal fossae. [2] [6]
- In addition to the areas affected by acute
disease, chronic atopic dermatitis often affects the neck, upper back,
and arms, as well as the hands and feet. [1] [3] [5] [23]
- Erythema
- Scaling
- Vesicles
- Papules
- Keratosis pilaris
- Excoriations
- Lichenification
- Hypopigmentation
Pathophysiology - Impairment of the skin's barrier function leads to an increased sensitisation to cutaneous antigens and is a major factor in the pathophysiology. [5]
- Recent studies have demonstrated that the development of atopic dermatitis shows genetic linkage to chromosome 1q21, which contains the genes of the epidermal differentiation complex (EDC).
- These genes are integral to the formation of the epidermal layer, and several mutations have been identified that lead to the impaired barrier function seen in atopic dermatitis.
- Mutations in the filaggrin gene, which encodes a protein necessary for terminal differentiation of epidermis, have been shown to predispose patients. [6] [7] [7]
- Filaggrin mutations that result in impairments in the barrier function of the epidermis result in increased exposure and sensitisation to cutaneous antigens.
- In the acute phase of atopic dermatitis, the immune response following sensitisation is predominantly Th2 mediated, with over-expression of IL-4, IL-5, and IL-13.
- These interleukins lead to an increased production of IgE and peripheral eosinophilia. [1] [3] [14]
- Susceptibility has been linked to polymorphisms in the gene encoding a subunit of the IgE receptor as well as to a region on chromosome 5q31-33 that includes genes for cytokines expressed by Th2 cells. [8]
- Persistent inflammation and scratching can eventually lead to chronic atopic dermatitis, with thick, lichenified skin.
- Lesions demonstrate a different complement of immune cells and cytokines, with a predominant Th1 response, and increased levels of IL-12. [3]
Investigations- Allergy testing
- Allergy testing may be beneficial in assisting the patient to avoid
exacerbating allergens, but up to 60% of children with atopic dermatitis
do not have demonstrable IgE-mediated sensitivity to allergens
- IgE levels
- Early atopic sensitisation has been associated with a poorer prognosis in patients with atopic dermatitis.
- Skin biopsy
- May be used to differentiate atopic dermatitis from
allergic contact dermatitis and psoriasis
- This is less frequently
employed than a careful skin examination
- Careful attention to the
primary lesions, their distribution, the associated symptomatology and
the duration and associations at the time of onset of the skin disease.
Managementa) conservativeb) medical - Treatment is carried out in a step-wise approach starting with emollients and then progressing to topical corticosteroids and calcineurin inhibitors
- In this way symptom control is achieved in most patients, but a few with particularly treatment-resistant dermatitis will need other treatments such as coal tar, UV light therapy or systemic immunosuppressants.
- The use of oral corticosteroids is not advocated in the treatment of atopic dermatitis.
c) surgicalPrognosis- Atopic dermatitis is a chronic disease with a varying course.
- Approximately 60% of children will have symptom resolution as they enter puberty, but relapse may occur in 50%. [2]
- Although it can be difficult to predict the course of this disease, certain factors place patients at risk for a more aggressive course.
- A prospective study of 1314 German children evaluated the natural course of atopic dermatitis from birth to the age of 7 years.
- It found that disease severity and early atopic sensitisation were associated with a poorer prognosis.
- Atopic sensitisation was quantified by measuring specific IgE levels, and although there was a strong association between IgE level and disease severity, no prognostic cutoff values were established. [67]
- Many patients with milder disease are able to be maintained on emollient treatment with intermittent use of other topical agents during flares.
- Patients with more severe disease often require combination treatment that includes coal tar, UV light therapy and systemic immunosuppressants.
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