The term "atopy" is derived from the Greek word meaning "placeless, unusual" and implies a genetic predisposition to developing eczema, asthma and allergic rhinitis (hay fever is a subtype of this and results in seasonal rhinitis as a result of reactions to grass or tree pollens).
Atopic eczema (AD, also called atopic dermatitis) is a chronic, pruritic, inflammatory skin disease that affects 10-20% of children in developed countries. It is a relapsing-remitting condition.
AD frequently appears in the first year of life, with around 70% of affected infants and infants experiencing clinical remission of all symptoms and signs by age 11 years.
This remission may not be permanent as many individuals will relapse at some stage in adulthood, for example, by developing irritating hand eczema. Atopic diseases have a strong genetic component.
Individuals from families with atopy have a predisposition to develop eczema, asthma and hay fever. Many children with AD continue to develop asthma and allergic rhinitis, in a sequence referred to as the ’atopic march’.
While atopic disease in general (particularly asthma) is slightly more common in males, AD appears to affect boys and girls equally with some studies reporting a slightly higher prevalence in females.
| Etiology |
> Genetics of atopic diseases
There is strong evidence to suggest that genetic factors are important in predisposition to AD. Twin studies have shown much higher disease concordance for monozygotic twins (approximately 50% concordance) than for dizygotic twins (15-20% concordance).
In the last decade, the importance of a few critical barrier function genes has been elucidated. The most important of these is filaggrin (FLG). A loss-of-function mutation in the FLG gene on chromosome 1 strongly predisposes to ichthyosis vulgaris and atopic eczema. This loss of function reduces the integrity of the epidermal barrier, allowing the loss of moisture and allergens into the body.
> Environmental triggers and epigenetic effects: dirt is good, indoor life is bad
Of course, the human genome is very stable. It only changes very slowly over thousands of years. Therefore, genetics alone does not explain the increase in the prevalence of AD observed in recent decades, which should be attributed to environmental factors, epigenomic changes or the interaction of the genome with environmental factors.
There are many practical examples. Most studies seem to confirm that migration to developed economies and urban (as opposed to rural) living increases the risk of developing and expressing atopic diseases.
A study of migrants has shown that black Caribbean children living in London were around three times more likely to have AD than similar children living in Jamaica.
The "hygiene hypothesis" , which describes the observation that asthma prevalence, rhinitis prevalence, skin test reactivity, and allergen-specific IgE levels are often elevated in "cleaner" population groups , may also be valid in the EA. Studies have shown a higher prevalence of AD in advantaged socioeconomic groups.
Environmental triggers can cause an AD flare in a susceptible child and these do not necessarily have to be an allergen. For example, irritation from common soaps, the use of wool next to the skin, overheating at night, and contact with water and dusty materials can cause deterioration in AD in childhood.
The use of soaps and detergents raises the local pH of the skin and increases the activity of epidermal protease enzymes, which further compromise the skin barrier. Staphylococcus aureus and house dust mites generate exogenous proteases, which impair skin function and have superantigen properties that stimulate an immune response.
| Clinical features |
Eczema is the clinical manifestation of an inflammatory reaction in the skin that can be caused by a series of factors, both internal (for example, atopy, seborrhea) and external (for example, contact with allergens, irritation).
It is characterized histologically by inflammation of the superficial dermis and epidermal spongiosis, the presence of edema in the epidermis, which is clinically observed as serous fluid. From this appearance the name eczema is derived from the Greek for boil .
The main characteristic of eczema is itching/pruritus, which affects the sleep of both the child and the parents. Repeated scratching stimulates local cytokine production and generates more itching, in a process known as the itch-scratch cycle, which further erodes the skin barrier and can also introduce infection.
The morphology of skin lesions in AD is variable and depends on the stage and severity of the lesion. Dry skin (xerosis) is an almost universal feature of AD, characterized by fine scales and roughness on palpation, even in non-inflamed skin.
There is reduced water content in the stratum corneum, with decreased secretion of sebum and sweat. Clinical examination during an acute flare may show ill-defined erythema, papules, papulovesicles, erosions, swelling, and general irritability. Such features are present during infancy, while later in childhood there may also be signs of chronic skin rubbing.
The skin may become thickened and hyperpigmented, with an accentuation of skin fold lines in the inflections, called lichenification. Prolonged rubbing can lead to the development of thickened lichenified purple plaques and fibrotic papules (prurigo).
In long-standing AD, individuals may manifest all of the above features at the same time or at different times, reflecting the relapsing-remitting nature of eczema.
Although often diffuse in pattern, EA can take the form of discrete lesions.
A discoid or nummular eczema pattern describes the formation of sharply demarcated circular or coin-shaped plaques, with papules and vesicles at the periphery. These can be generalized in distribution, or located in the trunk or in the extensor areas of the extremities.
Staphylococcal infection is often implicated in this pattern of eczema, with mild cases often responding to topical steroid-antibiotic combination. A skin swab is useful to confirm heavy growth of S. aureus and exclude antibiotic resistance, before prescribing oral antibiotics in recalcitrant cases. This clinical appearance could be confused with tinea corporis, especially in younger children with few lesions, and can be excluded with a negative skin scraping.
| Variations with age |
Infantile AD generally begins in the first 3 months of life, generally affecting the face and scalp first, then spreading to involve the extensor surfaces of the limbs and trunk in a symmetrical distribution.
Trunk lesions are diffuse, while extremity lesions tend to be discrete and localized. The diaper area is often spared. Seborrheic dermatitis, caused by the overgrowth of Malassezia yeast , is a differential diagnosis although EA can develop on the scalp after it clears.
Around 2-3 years of age, the distribution of AD changes from an extensor pattern to a primarily flexor pattern, affecting the wrists, antecubital fossae, popliteal fossae, and anterior regions of the ankles.
During childhood, cheilitis may develop with dry cracked lips and perioral margins. It is frequently due to irritating exposure of saliva due to repeated lip licking.
There may be an increased number of infraorbital folds (Dennie-Morgan lines), caused by swelling in the delicate periorbital skin, which is a sign that the child’s facial eczema is active.
After puberty, AS tends to affect the face, hands, back, wrists, and the backs of the feet. The hands and fingers are frequently involved, possibly due to constant irritant exposure.
Fissures can develop over the joints of the fingers, which can be painful and limit function. Nipple eczema may become prominent in girls during this period.
| Diagnosis |
The diagnosis of AD is clinical. There is no definitive test or laboratory marker available that serves as a reference standard. Despite its visual nature, AD is a difficult disease to define due to its variation in distribution, morphology, and time course.
The EA is usually flexural in distribution, but is sometimes extensor and often poorly demarcated. The morphology of the lesions varies from acute exudation and vesicles to lichenification. The time course may oscillate as AD is usually an intermittent disease and therefore presents to the community clinician at variable intervals.
Table 1 gives the current consensus characteristics required for the diagnosis of eczema in children in the UK.
> Medical history
During the clinical evaluation, a specific medical history should include the following characteristics:
• time of onset, pattern and severity of eczema
• response to previous and current treatments
• possible triggers, whether irritants (soaps, shampoos, bubble baths, washing liquids) or allergies (pets, dust, metals)
• food allergens and dietary history (including parental dietary restrictions)
• growth and development
• personal and family history of atopic diseases
• the impact of eczema on parents or carers.
> Severity of the disease
The severity of the disease can be evaluated from the clinical signs, the extent of the disease, and the patient’s symptoms. These 3 domains are together in the SCORAD (SCORing Atopic Dermatitis) criteria, one of the many systems used to grade the severity of AD.
Clinical signs include dry skin, redness, excoriation, exudation, bleeding and cracking. The area of affected skin can be measured according to the "rule of 9s", as in the evaluation of burns.
Symptoms experienced may include frequent itching/scratching and loss of sleep, presented to the patient on a visual analogue scale. The combination of scores for each domain gives a value, which is classified as mild, moderate or severe.
Other tools include the POEM (Patient Oriented Eczema Measure) score, the DLQI (Dermatology Life Quality Index) and its adaptation for children (the CDLQI), which are validated questionnaires for the assessment of disease severity and monitoring response to treatment.
> Diagnostic tests
Immunological abnormalities in the atopic individual include increased serum total IgE and IgE antibodies specific to ingested or inhaled antigens, such as dust mite allergens.
Routine measurement of total and specific IgE is not performed in clinical practice and does not correlate with the severity of the patient’s symptoms.
Performing a RAST blood test, or allergen skin testing, is only beneficial when there is a high index of suspicion towards a particular allergen, as a positive result may have no clinical significance for the patient.
| When to refer to a specialist |
Recent NICE guidelines for the management of AD in children list indications for referral to secondary care.
Referral is recommended if the diagnosis is uncertain, if the disease is not satisfactorily controlled with appropriate first-line treatments, if there are severe or recurrent skin infections, if facial eczema is uncontrolled, if there are serious psychological problems, if caregivers need specialist advice on treatment applications, or if the child(ren) or parent(s) has a serious illness associated with psychological problems.
Additionally, children with moderate to severe food allergy or growth retardation should be referred.
| Follow-up |
AD is a chronic condition that requires support from health professionals to manage not only the acute episodes but also the daily difficulty in managing a variable condition.
Educational support groups are available nationally and often locally, and parents should be directed to these for advice from similarly affected families.
Many hospital departments are supported by specialist dermatology nursing and referral can be made for an initial consultation to educate parents on appropriate treatment techniques.
In secondary care, children can continue with regular review appointments if they are known to have a predisposition to frequent flares, or if they have started systemic therapy.
Regular monitoring on a growth chart can be a useful indicator of a child’s skin health, with a drop across percentile measurements indicating poor long-term control.
| Treatments |
AD is a chronic condition for which there is no cure and therefore management is based on the prevention and control of outbreaks. Severe eczema can be physically and psychologically demanding for both the child and caregiver and requires a holistic strategy in both the short and long term.
Table 2 lists NICE recommendations for the optimal management of children at community level. As with asthma, a gradual approach is taken to manage AE according to the severity of symptoms.
> Emollients
Emollients form the backbone of the therapy and should be used even when the skin is free of eczema. As such, it can be considered a "preventive" measure, along with steroids, which are the "treatment."
Moisturizers should be applied regularly every 2-4 hours to keep the skin hydrated, a child would need to use 500g of moisturizers every week or so. There are smaller 250g containers available to take to nursery or school.
Using a spatula, rather than your fingers, reduces contamination of the emollient inside an open pot or knob. Unscented emollients are also available for bathing and washing.
Since 2007, aqueous cream is no longer recommended due to evidence that it causes increased transepidermal water loss due to its sodium lauryl sulfate (LSS) content.
> Steroids
Topical corticosteroids have anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects. They are available in mild, moderate and high potency preparations which should be used for mild, moderate and severe breakouts accordingly.
In delicate areas of the face, armpits, and groin, mild-strength steroids are generally used to avoid the complications of skin atrophy, stretch marks, and hypopigmentation.
Moderate potency steroids should only be used in these areas for 7 days as a short-term treatment to control a flare, before tapering to a mild potency formulation. Strong corticosteroids can be used in children in the short term, but long-term use should only be under the guidance of a specialist.
Application of mildly potent topical steroids twice a week as maintenance therapy for the eczema-prone site has been shown to be beneficial in reducing the speed and severity of flares.
Steroids are fat-soluble, cross the cell membrane and affect DNA transcription for more than 24 hours. As such, they should be applied once, or at most twice a day. Ointments have a higher concentration of oil compared to water-based creams, providing better hydration of the skin and improving the potency of the steroids.
Parents should be educated on the ’fingertip unit’ (FTU), where a line of cream or ointment from the distal phalanx crease to the tip of the finger will contain approximately 0.5g of product. This should be used to cover two areas of skin the size of an adult hand, which is equivalent to 2% of the surface area of the adult body.
Adjustments are made for the different body surface proportions in children. In an infant, for example, 1 FTU will cover the face and neck and 2 FTUs will cover an arm or leg.
Topical and systemic side effects are rarely encountered in dermatological practice and are usually seen where there is prolonged treatment without clinical need. Less treatment of the child’s skin will prolong the duration of the disease; Therefore, parents must be sure that correctly applied steroid treatment will not harm the child.
> Calcineurin inhibitors
Calcineurin inhibitors are topical immunomodulatory agents that do not contain steroids and thus avoid the side effects associated with long-term steroid use. They are useful in cases of eczema refractory to standard topical therapy and also in delicate areas (groin, axilla, head and neck), where large amounts of steroid preparations can cause skin atrophy.
Systemic macrolide immunosuppressants were first used in 1994 to prevent organ transplant rejections and are now available for topical treatment as tacrolimus 0.03% or 0.1% and pimecrolimus 1%.
Topical tacrolimus is licensed as a twice-weekly maintenance therapy to prevent AD flares at susceptible sites after acute treatment, proactively analogous to the use of inhaled steroids to prevent acute asthma episodes.
> Complementary therapy
Occlusive dressings are useful in children to improve skin hydration and treatment effectiveness. Wrapping the extremities in wet bandages or stockings improves skin hydration, prevents chafing, and has a soothing effect on the child’s itching. Wraps consist of a bottom (wet) and top (dry) layer.
Moisturizers can be applied under the bandage to increase skin hydration, which is helpful for the dry, thickened skin seen in chronic lichenified eczema. Adding steroid creams/ointments under occlusion can increase potency up to 4 times, making it a useful short-term (7-14 days) option for managing difficult eczema. Occlusion should not be applied to infected skin due to the risk of exacerbation and septicemia.
The recent BATHE study (Saunter et al BMJ 2018), which examined the effectiveness of bath additives, has shown that there is no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children, compared with pure water. However, ’leave-on’ emollients and soap substitutes remain important in the management of eczema.
Bleach baths (diluting 150 ml of bleach in 10 cm depth of water in an adult bathtub, or 2 ml of bleach per liter of water in a baby bathtub) are recommended in eczema patients prone to infections. recurrent infections, and have been shown to reduce secondary infection rates.
Some dermatologists in the UK also recommend using saltwater baths as a second-line treatment.
> Other treatments
Phototherapy is useful in a proportion of children with generalized eczema who are resistant to conventional treatment, since ultraviolet B (UVB) radiation has an immunosuppressive effect on the skin. Patients attend treatments three times a week, lasting from thirty seconds to ten minutes in the phototherapy chamber. Younger children may not be able to comply with the practical aspects of treatment.
Systemic immunomodulatory drugs are required in about 2% of patients whose disease does not respond to topical treatment or phototherapy. Available pharmacologic agents include prednisolone, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil.
Antihistamines are generally not helpful. They have no effect on eczematous skin pathology and therefore the itching returns quickly as the skin is still inflamed.
Sedating antihistamines (e.g., chlorphenamine, hydroxyzine) may be useful to allow both the child and caregivers to rest at night, once appropriate topical treatment has been applied. If these sedative antihistamines no longer have the desired effect, alimemazine would be a suitable sedative antihistamine alternative. However, the high cost of alimemazin oral solution must be taken into account.
| Complications |
> Impetigo
The structure of dry skin under microscopy resembles cracked pavement, acting as a portal of entry for bacteria and providing anchoring points for viruses and allergens. Secondary infection with staphylococcal and streptococcal bacteria can cause impetigo in eczematous skin.
Clinical examination may reveal excessive crying, pustules, folliculitis, and honey-yellow scabs. The child may have rapidly worsening eczema that does not respond to therapy, with increased erythema, drainage, and pain. There may be generalized features such as fever and malaise.
Oral flucloxacillin has good skin penetration compared to erythromycin and can be used in conjunction with a topical antimicrobial wash containing chlorhexidine or benzalkonium. Combined corticosteroid and antimicrobial ointments can be used for short periods in infected eczema, but a course of oral antibiotics is equally effective and bacterial resistance may be less likely to develop.
In severe cases, nasal swabs from both the child and family are useful to exclude concurrent infection with MRSA. Decontamination treatment with nasal mupirocin and chlorhexidine baths may reduce the risk of a serious infectious episode in the future.
> Eczema herpeticum
Herpes infection must be actively excluded, as steroid application will exacerbate this superficial viral infection. There may be groups of monomorphic vesicles, with the appearance of cold sores in the early stage.
Older vesicles may become stripped, leaving uniform circular erosions, which may coalesce into larger ulcerations. The child will have a rapid deterioration of the painful eczema, with possible lethargy, fever and malaise. Hospital admission may be required to receive intravenous acyclovir, along with antibiotics to cover any added bacterial infection.
Topical steroids can be reintroduced 48 hours after intravenous antimicrobials, as active treatment of eczema reduces the risk of secondary infection.
> Molluscum contagiosum
Molluscum contagiosum is a poxvirus skin infection that is commonly found but completely harmless. It causes single or grouped, small, shiny, white or skin-colored papules, which characteristically have a central umbilication and are commonly found at sites of active dermatitis.
> Food allergy
Eczema rashes are not usually caused by specific allergies, but are due to irritation from external triggers. Therefore, most children do not require testing for an allergy. The two most common causes of an allergic reaction are dust mites and certain foods, including eggs, dairy products, fish, nuts, and citrus fruits.
A food allergy should be suspected if symptoms occur immediately after repeated exposure to certain foods. Symptoms may include an eczema flare-up or gastrointestinal features such as cramping, vomiting, altered bowel habits, or failure to thrive.
If suspected, the offending food should be avoided for 6 weeks and then reintroduced into the diet while symptoms are observed. Allergy to the protein found in cow’s milk is the most common food allergy reported.
In bottle-fed infants, a 6-week trial may be offered when replacing cow’s milk formula with a hydrolyzed protein formula. Substitution, not exclusion, from the diet should be emphasized and the child’s growth chart should be recorded. Specialist advice is required if following such a diet for more than 8 weeks. There is little evidence that changing the mother’s diet affects breastfed babies with AD.
| What’s next in atopic eczema? |
EA is a chronic condition that requires both patient and family education to allow treatment of acute eruptions and a prolonged period of preventive therapy. Studies are being done to find the best supportive treatments for AD.
One paper in Nottingham showed no benefit from installing water softeners in hard water areas. Pharmacological agents should be developed in the future to augment the current available systemic treatments, which carry the risk of potentially serious side effects.
Alitretinoin, a retinoid and vitamin A derivative, has recently been developed to treat chronic hand eczema in adults and provided an additional avenue for research. Knowledge about the synthesis and function of filaggrin may encourage strategies aimed at increasing its expression.
Biological treatments, such as Dupilumab, a human monoclonal antibody against the IL4 receptor reduces the inflammation processes that manifest as AD, are currently being studied in clinical trials in patients with moderate-severe AD who have failed systemic treatments.
New treatments will be developed but, like asthma, AD cannot be cured. Patients’ expectations and morale must be managed accordingly, with the goal of treatment being an improvement in their quality of life.
Comment
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Table 1
The UK diagnostic criteria for AD for use in epidemiological studies. Adapted from the UK working group diagnostic criteria for atopic dermatitis, Williams et al., 1994. Should have • Any itchy skin condition (or parent report of scratching or redness) in the past 12 months Plus three or more of the following • History of skin fold involvement (elbows, behind the knees, front of the ankles, around the neck or eyes) • Personal history of asthma and hay fever (or history of atopic disease in a first-degree relative if the child is under 4 years old) • History of generally dry skin in the • Visible flexural dermatitis (this includes dermatitis affecting the cheeks or forehead and other outer aspects of the limbs in children under 4 years of age) |
Table 2
Recommendations for the optimal management of AE in a community setting. Adapted from: Atopic eczema in children, NICE quality standards QS44, September 2013 1. Children with atopic eczema are offered counseling at the time of diagnosis that includes a detailed summary of their medical and treatment history and the identification of potential triggering factors. 2. Children with atopic eczema are offered treatment based on recorded severity of eczema using the stepped care plan, compatible with education 3. Psychological well-being (and that of their families) and quality of life are discussed and recorded at each eczema consultation in children with atopic eczema. 4. Children with atopic eczema are prescribed sufficient quantities (250 to 500g weekly) of a choice of unscented emollients for daily use 5. Children with uncontrolled or unresponsive atopic eczema, including recurrent infections, or psychosocial problems related to atopic eczema, are referred to dermatological specialists 6. Infants and young children with moderate or severe atopic eczema that have not been controlled with optimal treatment are referred for specialized investigation to identify possible food and other allergies 7. Children with atopic eczema who have suspected eczema herpeticum receive immediate treatment with systemic acyclovir and are referred for dermatological advice by the specialist on the same day |
