Atopic Dermatitis Causes/Eczema is a common, chronic, non-infectious skin condition. The main symptom of this inflammatory disease is a very itchy rash. It often affects children. In many cases eczema gets better as the years go by, and it may go away for a while or disappear altogether. Acute flare-ups can really affect quality of life. The itching can be especially bad, making it difficult to concentrate and sleep well. Some people are embarrassed if their rash is visible to others. By taking good care of your skin, using medication and avoiding irritants and other things that can trigger the eczema, it is usually possible to relieve the symptoms at least enough to live a fairly normal life.
World Allergy Organization (WAO) revised nomenclature in 2003, eczema (also known as atopic dermatitis) is a chronic, relapsing, and itchy inflammatory skin condition. In the acute stage, eczematous lesions are characterised by poorly defined erythema with surface change (oedema, vesicles, and weeping). In the chronic stage, lesions are marked by skin thickening (lichenification). Although lesions can occur anywhere on the body, infants often have eczematous lesions on their cheeks and outer limbs before they develop eczema in the typical flexural areas such as behind the knees and in the folds of the elbow and neck. About 50% of people suffering from eczema also become sensitised to environmental allergens, such as house dust mite, and may then be classified as having atopic eczema under the revised WAO nomenclature.
Types of Eczema
Atopic dermatitis can be grouped into three clinical stages, although these may be difficult to reproduce in the individual patient [rx].
- Atopic Dermatitis of Infancy – Infants experience eczema that is often localised to the face, scalp, and extensor aspects of the arms and legs, but it can also be widespread. The lesions are characterised by erythema, papules, vesicles, excoriations, oozing, and formation of crusts.
- Atopic Dermatitis of Childhood – In toddlers and older children, the eczema lesions tend to shift location so that they are often confined to the flexures of the elbows and knees as well as the wrists and ankles, although it can occur at any site. In general, the eczema becomes drier and lichenified with excoriations, papules, and nodules.
- Atopic Dermatitis of Adolescence and Adulthood – In adult patients, the lesions frequently localise to the face and neck, head-and-neck dermatitis, and a considerable portion of patients, around 30%, develop atopic hand eczema, which may interfere with workplace activities.
There are at least 11 distinct types of skin conditions that produce eczema. In order to develop a rational treatment plan, it is important to distinguish them. This is often not easy.
- Atopic dermatitis – This health condition has a genetic basis and produces a common type of eczema. Atopic dermatitis tends to begin early in life in those with a predisposition to inhalant allergies, but it probably does not have an allergic basis. Characteristically, rashes occur on the cheeks, neck, elbow and knee creases, and ankles.
- Irritant dermatitis – This occurs when the skin is repeatedly exposed to excessive washing or toxic substances.
- Allergic contact dermatitis – After repeated exposures to the same substance, an allergen, the body’s immune recognition system becomes activated at the site of the next exposure and produces a dermatitis. An example of this would be poison ivy allergy.
- Stasis dermatitis – It commonly occurs on the swollen lower legs of people who have poor circulation in the veins of the legs.
- Fungal infections – This can produce a pattern identical to many other types of eczema, but the fungus can be visualized with a scraping under the microscope or grown in culture.
- Scabies – It’s caused by an infestation by the human itch mite and may produce a rash very similar to other forms of eczema.
- Pompholyx (dyshidrotic eczema) – This is a common but poorly understood health condition which classically affects the hands and occasionally the feet by producing an itchy rash composed of tiny blisters (vesicles) on the sides of the fingers or toes and palms or soles.
- Lichen simplex chronicus – It produces thickened plaques of skin commonly found on the shins and neck.
- Nummular eczema -his is a nonspecific term for coin-shaped plaques of scaling skin most often on the lower legs of older individuals.
- Xerotic (dry skin) eczema – The skin will crack and ooze if dryness becomes excessive.
- Seborrheic dermatiti – It produces a rash on the scalp, face, ears, and occasionally the mid-chest in adults. In infants, in can produce a weepy, oozy rash behind the ears and can be quite extensive, involving the entire body.
Pathophysiology
A number of molecular mechanisms and cell types are thought to be important in atopic eczema and these are reviewed in detail elsewhere.[x] Microscopically, the characteristic appearance of eczema is fluid between the cells in the epidermis (spongiosis). When severe, this fluid eventually disrupts the adjacent cells in the epidermis to form small collections of fluid, which are visible to the naked eye as vesicles. In the chronic phase, atopic eczema is characterised by gross thickening of the epidermis (acanthosis) and a lymphocytic infiltrate in the dermis. The pathophysiology of atopic eczema may be related to abnormal gene expression of immune cells as they infiltrate and remain in the mucosal surfaces and skin. There appears to be a failure to switch off the natural predominance of type 2 helper (Th2) lymphocytes that normally occurs in infancy, leading to an abnormal response of cytokines (chemical messengers) to a variety of stimuli. This failure to achieve the normal balance of type 1 helper (Th1) and Th2 cells may be a result of mutations in the interleukin-18 gene[x ]r other genes,[x] for example those that produce receptors for the innate immune system. Defects in the composition of the skin barrier leading to dry skin and enhanced penetration of irritants and allergens are also thought to be critical.[x,[x]
Causes of Eczema
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Irritants – wool or synthetic clothing, soaps, detergents, perspiration, disinfectants and topical antimicrobials, and many chemical reagents
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Contact allergens – preservatives in topical medications, perfume-based products, metals and latex
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foods/dietary factors – cow’s milk, eggs, peanuts, tree nuts, wheat, soya, fish, shellfish and (rarely) others such as sesame, kiwi and legumes
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Inhalant allergens (aero-allergens) – house dust mites (Dermatophagoides pteronyssinus and D. farinae), animal dander, cockroach, tree and grass pollens, and moulds
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Microbial colonisation and/or infection – Staphylococcus aureus, streptococcus species, Candida albicans, Pityrosporum yeasts, herpes simplex (colonisation and infection associated with atopic eczema in children is considered separately in
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Climate – extremes of temperature and humidity, and seasonal variation in the pattern of atopic eczema
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Environmental factors – hard water, cooking with gas, proximity to road traffic, and environmental tobacco smoke
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Familial factors – genetics, family size and sibling order
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Social class (higher incidence in more affluent social classes)
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Concurrent illness and disruption to family life – teething, psychological stress and lack of sleep.
Symptoms of Eczema
Clinical features of atopic dermatitis
Major features
- Dry, sensitive skin
- Red, inflamed skin
- Very bad itching
- Dark colored patches of skin
- Rough, leathery or scaly patches of skin
- Oozing or crusting
- Areas of swelling
- Pruritus – Facial and extensor involvement in infants and children; flexural involvement with lichenification in adults
- Chronic or chronic, relapsing course – Personal or family history of atopy, including asthma, allergic rhinitis, atopic dermatitis
- Xerosis – Palmar hyperlinearity, ichthyosis, keratosis pilaris
- Immediate skin test reactivity, elevated serum IgE – Cutaneous infection, including Staphylococcus aureus and Herpes simplex virus
- Nipple eczema – Cheilitis, Pityriasis alba
- White dermatographism, delayed blanching
- Perifollicular accentuation
- Anterior subcapsular cataracts
- Itch when sweating
- Non-specific hand or foot dermatitis
- Recurrent conjunctivitis
- Dennie-Morgan folds
- Keratoconus
- Facial erythema or pallor
Diagnosis of Eczema
| An individual must have an itchy skin condition (or parental report of scratching or rubbing) in the last 12 months, plus three or more of the following: |
| (i) a history of involvement of the skin creases (fronts of elbows, behind knees, fronts of ankles, around neck, or around eyes) |
| (ii) a personal history of asthma or hay fever (or history of atopic disease in a first-degree relative if a child is aged under 4 years) |
| (iii) a history of a generally dry skin in the last year |
| (iv) onset under the age of 2 years (not used if a child is aged under 4 years) or visible flexural dermatitis (including dermatitis affecting cheeks or forehead and outer aspects of limbs in children under 4 years) |
Research criteria for assessing severity in eczema
| Symptom severity scoring systems |
| The SCORing Atopic Dermatitis (SCORAD) index |
| Total score is calculated from: |
| Extent of affected areas: calculated as a percentage of total body area (from chart) |
| Intensity of a typical lesion (each scored 0 = none, 1 = mild, 2 = moderate, 3 = severe): |
| Erythema |
| Oedema/papulation |
| Oozing/crust |
| Excoriation |
| Lichenification |
| Dryness of unaffected areas |
| Subjective symptoms: |
| Pruritus (0–10 visual analogue scale) |
| Sleep loss (0–10 visual analogue scale) |
| SCORAD = extent score/5 + 7 × intensity score/2 + subjective symptoms score |
| Half of all people with eczema score between 28 and 54 points. For a simple guide to using SCORAD in practice, see http://adserver.sante.univ-nantes.fr/Scorad_Course/How.html (last accessed 8 March 2011) |
| Six Area, Six Sign Atopic Dermatitis severity index (SASSAD) |
| Six sites of the body are assessed for each of 6 features, each one scoring 0 to 3 for increasing severity: |
| Erythema |
| Exudation |
| Excoriation |
| Dryness |
| Cracking |
| Lichenification |
| The SASSAD scale correlates with global assessments of disease severity, but not with quality-of-life scores |
| Eczema Area and Severity Index (EASI) |
| Includes an assessment of the extent of disease of different anatomic sites on a Likert scale |
| Includes an assessment of the intensity of lesions, i.e., erythema, oedema/induration/papulation, excoriation, and lichenification, each one scoring 0 to 3 for increasing severity |
| Total EASI score ranges from 0 to 72 with higher scores indicating more severe eczema |
| Patient-oriented Eczema Measure (POEM) |
| Measures the frequency of occurrence of the following eczema signs and symptoms during the previous week |
| Dryness |
| Itching |
| Flaking |
| Cracking |
| Sleep loss |
| Bleeding |
| Weeping |
| POEM score ranges from 0 to 28, with higher scores indicating more severe eczema |
Atopy patch test
- Compared with the DBPCFC[rx] test, the atopy patch test (erythema[rx]usually with infiltration) had high specificity (81–96%) for any reaction (immediate, delayed, or immediate and delayed combined) to cow’s milk, egg and soya. Specificity for any reaction to wheat was more variable (35–94%). Compared with an open food challenge, the specificity results for any reaction were more variable for cow’s milk, egg, wheat and peanut.
- Compared with DBPCFC or an open food challenge, sensitivity results for any reaction to a single food (cow’s milk, egg, wheat, soya and peanut) were more variable. Sensitivity and specificity results compared with DBPCFC were both more variable when considered for several foods together (no data compared with an open food challenge).
Skin prick test
- Compared with the DBPCFC test the skin prick test (wheal size 3 mm or greater) had high sensitivity (90–95%) for diagnosing an immediate response to fish and peanut, or to several foods together (results from one study); specificityresults for these foods were more variable.
- The sensitivity and specificity for detecting any reaction (immediate, delayed, or combined and compared with DBPCFC) to all other allergens tested (cow’s milk, wheat and soya) were more wide-ranging across studies. Compared with an open food challenge, sensitivity and specificity results for any reaction (immediate, delayed, or combined) to all allergens were also more variable.
Specific IgE
- The sensitivity of specific IgE (more than 0.35 ku/l) for detecting any reaction (immediate, delayed, or combined) to cow’s milk and egg was high (83–100%) compared with the DBPCFC test. Sensitivity for detecting an immediate reaction to wheat, soya, fish and peanut compared with DBPCFC was also high (94–97%; one study only). Sensitivity for a combined immediate and delayed reaction to wheat or soya was more variable (no data for delayed reactions).
- Specificity results for each of the allergens alone or when considered together were more variable. Compared with an open food challenge, both sensitivity and specificity results were less consistent across all foods tested. The specific IgE level indicative of a positive test ranged from 0.35–99 ku/l in the open challenge studies.
Effect of changing test parameters
- The available data for each type of test do not show consistency in sensitivity or specificity results. This might reflect the way the particular tests were undertaken or the criteria used to define positive test results. Several studies have considered whether changing certain parameters of a test affects their diagnostic accuracy in children with atopic eczema.[x,rx,rx]
- The accuracy of the atopy patch test varied according to the size of the chamber used for occlusion, the vehicle and concentration used to apply the allergen to the skin, and according to which skin sign was taken to indicate a positive test. [rx = 3/EL = DS III]
Differential diagnosis for atopic dermatitis
- Contact dermatitis
- Seborrheic dermatitis
- Drug reactions
- Infantile psoriasis
- Scabies
- Nutritional deficiencies – zinc/biotin
- Acrodermatitis enteropathica
- Netherton syndrome
- Icthyosis vulgaris
- Peeling skin disorder, type B
- Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome
- Primary immunodeficiency diseases* & Omenn syndrome
- Lymphocytic-variant Hypereosinophilic syndrome (HES)
- Cutaneous T cell lymphoma
Treatment of Eczema
Eczema is a chronic condition. Treatment cannot cure it, but regular skin care and medication can help to keep the itching and rash at bay. The main treatment options are:
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Basic treatment – Lipid-replenishing and moisturizing products (emollients) are generously applied to the skin at least twice a day to keep it from drying out. This can help relieve itching and protect the skin from germs and irritants.
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Special soaps, liquid cleansers and shampoos – Normal soaps and products like shampoo or shower gel contain various substances that can dry out your skin. Special cleansing products without these substances are available to get around this problem. But basic treatment with emollients can usually compensate for the loss of moisture caused by normal soaps.
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Steroid creams – Eczema flare-ups are usually treated with steroid creams because they can relieve the itching and inflammation. They are typically used only for acute symptoms. But they are sometimes used at regular intervals together with moisturizing skin care products (basic treatment): for example, as a “weekend treatment” where a steroid cream is applied on one or two days a week.
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Pimecrolimus and tacrolimus – Pimecrolimus and tacrolimus are two other medicines that can be used to treat eczema. They are not approved for use in children under the age of two years, though. These two medicines are also applied to the skin in a cream or ointment, and can be used if steroid products are not an option. This might be the case if steroid treatment is not tolerated or is ineffective. Pimecrolimus and tacrolimus may also be an option for long-term treatment of sensitive skin in the face and neck area. They can also be used on one or two days per week only, as described above.
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Other eczema treatment options include wet wrap – radiation and medications that suppress certain immune responses. Tablets containing these medicines are used if other treatments don’t work, or if the eczema is very severe or affects large areas of skin. Because they have an effect throughout the entire body, they may have more extensive side effects than topical treatments.
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Allergy medications (antihistamines)-are also commonly used to relieve itching. But research has now shown that they are not suitable for treating eczema, whether used as tablets or a cream.
People often try out herbal products or dietary supplements, such as evening primrose oil, borage oil, vitamin B6, vitamin E and zinc. But research hasn’t shown that these products are effective.
Dealing with dryness
- Bath oils and products containing oatmeal are useful and prevent the drying of the skin that bathing can induce. Bath oils that contain antiseptic may have added benefit in certain cases but have a tendency to overdry and sometimes actually irritate the skin. The child should have either a bath with additive or a short shower. It is essential to find a suitable moisturiser that can be applied all over twice a day whether or not there is active eczema. Creams containing cetomacrogol, emulsifying ointment, and creams or ointments with lanolin can be used. If a product stings the skin it must be abandoned. The most likely irritant in emollient creams is the stabiliser propylene glycol. Products that contain urea almost always sting broken skin and are unsuitable in these children.
Use of wet dressings
- Wet dressings are useful in children with severe widespread eczema.[x] This is essentially an inpatient procedure but can be used for short periods at home. A water based emollient is applied all over; a corticosteroid cream (rather than ointment in this case because cream is more water miscible) is applied to the areas of active eczema. The creams are covered with a double layer of wrapping, the innermost of which is wetted with tepid water. The material may be cotton sheeting covered with a crepe bandage, though an easier alternative is the use of a double layer of tubular elasticated bandage. The procedure is repeated three times a day. This treatment is usually effective in clearing the eczema in three or four days.
Avoidance of allergens
- House dust mite is the most important allergen. Avoidance measures have to be carried out assiduously and must include encasing the mattress and pillows as well as dealing with the top covers, either by encasement or by hot (>60°C) washing.
- If food allergy is suspected, the child should be referred to a paediatric dietician. In general, it is children with severe atopic eczema who have food allergy or food intolerance. Children with flexural eczema are unlikely to have food allergy, unless the history suggests otherwise.
Topical corticosteroids
- It is often necessary to spend some time counselling the parents that topical steroid preparations used appropriately are safe. The strength chosen depends on the severity of the eczema and the site affected. The frequency of application depends on the individual product.
Topical antibacterials
- Staphylococcus aureus is commonly cultured from eczematous skin, and there may be obvious signs of infection. For localised infections, fusidic acid ointment may be effective. To prevent infections it is useful to bathe the child in preparations containing triclosan9 or benzalkonium chloride.
Calcineurin Inhibitors
- Pimecrolimus cream and tacrolimus ointment—also termed topical calcineurin inhibitors—are newer formulations used both for the treatment of acute flares and for maintenance therapy of atopic dermatitis [25]. Pimecrolimus has the potency of a mild corticosteroid cream, whereas tacrolimus corresponds to a moderate to strong topical corticosteroid. The side effects of corticosteroids, such as thinning of the skin, are not seen with topical calcineurin inhibitors, and this allows daily treatment for longer periods. Topical calcineurin inhibitors can also be used in the proactive treatment strategy.
Phototherapy
- Widespread eczema benefits from treatment with UV light. Narrowband UVB light is particularly suitable for treating adults with recalcitrant eczema. Broadband UVA light and a combination of UVA light and the photosensitizing drug psoralene can also be used to treat severe recalcitrant eczema. Difficult-to-treat atopic dermatitis often clears with 1-2 months’ phototherapy three to five times a week, preferably combined with topical corticosteroids. Nevertheless, as phototherapy causes premature aging of the skin and increases the risk of skin cancer in the long run, it should be prescribed with caution.
Topical immunosuppressants
- Tacrolimus is a potent immunosuppressive drug used in organ transplantation. A topical formulation has been shown to be effective in trials in patients with moderate to severe atopic dermatitis. Two studies specifically related to childhood eczema have confirmed its efficacy.[x],[x]]The main side effect is a sensation of burning. A concern has been raised as to whether application to skin exposed to sun could increase the long term risk of skin cancer.
- Pimecrolimus (an ascomycin derivative) is a newer immunosuppressive agent, similar to tacrolimus. Preliminary studies in children look encouraging.[x]
Outline of available treatments in atopic dermatitis
| Topical | Phototherapy and systemic therapy |
|---|---|
| Class: Corticosteroids Examples Low-potency
Mid-potency
High-potency
Very-high potency
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Class: Corticosteroids Example: Prednisone Class: Calcineurin inhibitor Example: Cyclosporine A Class: Anti-metabolites Examples: Methotrexate Azathioprine Mycophenolate mofetil |
| Class: Calcineurin inhibitors Examples
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Phototherapy Example:
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*For a comprehensive list of topical corticosteroids, organized by potency, available in Canada and available dosage forms, contact the Eczema Society of Canada for the “Topical Treatments in Atopic Dermatitis—Health Care Provider Resource Chart.”
| Education | Explain/demonstrate how to apply emollients |
| Various topical medications should be used with intervals | |
| In children > 12 months, use shampoos recommended in AD | |
| When talking to the patient (guardian), make sure the recommendations are understood and followed | |
| Revision of recommendations at least once a year | |
| Prevention | Avoid allergens and irritants: |
| Tobacco smoke | |
| Infections | |
| Wool clothing | |
| Stress | |
| Skin cleansing | Delicate and precise, mechanical cleansing |
| Detergents with/without aseptic substances | |
| Suitable galenic forms | |
| pH in the range of 6 | |
| Fast bath ≤ 5 min, including 2-min bathing in oil at 27–30°C | |
| Adding 1/2 cup of sodium hypochlorite to the bath eliminates itching | |
| Bath salts – facilitate the removal of exfoliated skin, skin scales, particularly beneficial in severe impetiginization | |
| Emollient therapy | Application min. 2–3 times a day! |
| Glycerol is better tolerated than urea or sodium chloride | |
| Propylene glycol can easily cause irritation in young children < 2 years of age and should not be used in these patients | |
| In children < 2 years of age it is recommended to use emollients without protein allergens and haptens | |
| Do not use emollients containing peanut extracts which increase the risk of sensitization and allergies! | |
| Emollients are poorly tolerated in inflammation sites – use the appropriate doses of emollients (250–500 g/week) |
Topical corticosteroids.
| Mild (Class I) | |
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| Moderate (Class II) | |
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| Strong (Class III) | |
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| Very strong (Class IV) | |
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- Cyclosporine – is a calcineurin inhibitor that controls T-cell–mediated inflammation by preventing the transcription of inflammatory cytokines.[rx] Cyclosporine A has been found to be effective in the management of severe and refractory AD in adults and children[rx] However, the risk of serious adverse effects, including hypertension, renal dysfunction and an increased risk of infection, limit it to short-term use[rx] Cyclosporine A may interact with a number of different medications, and so care must be taken to avoid interactions.
- Methotrexate azathioprine and mycophenolate mofetil are antimetabolite medications that work as a folate antagonist, purine analog and purine synthesis inhibitor, respectively. These medications have been shown to be variably effective in treatment-resistant AD[rx] As with cyclosporine, they are immunosuppressive and therefore can increase the risk of infection. They are also each associated with the potential for end-organ damage, including hepatotoxicity and cytopenias. Methotrexate should be used in conjunction with folic acid supplementation to reduce the risk of hematologic adverse events[rx]
- Azathioprine – a safer drug for long term use, though it does have several side effects, including nausea, fatigue, myalgia, and liver dysfunction. It is used by paediatric dermatologists in the United Kingdom.15 It is essential to assay for thiopurine methyl transferase before treatment starts as children deficient in this enzyme will experience marked bone marrow suppression. In most children it is effective at low dosage. The main long term side effect that could theoretically occur (as with ciclosporin) is the development of lymphoma. The advantage of this drug is that it can be used continuously.
Other possibilities include the leukotriene inhibitors zafirlukast[x] and montelukast, given orally. Chinese herbal medicines have also been used successfully but are not without danger[rx]
Antihistamines
- Sedating antihistamines such as alimemazine and promethazine given at bedtime are both useful. The sedation is an important feature of their antipruritic action. It is still debatable whether non-sedating antihistamines such as cetirizine and loratadine are useful because generally the role of histamine in eczema is somewhat limited. However, a large study of the use of cetirizine in adults with atopic eczema showed a significant reduction of clinical manifestations in those treated.[x]
Cetirizine
- One double-blind placebo-controlled randomised trial considered the effectiveness of cetirizine in the treatment of mild to moderate pruritus in children aged 6–12 years with atopic eczema (nrx = 22).[x] The dosage of cetirizine given was dependent on body weight: 5 mg/kg daily was given to those weighing 30 kg or less, and 10 mg/kg daily to those over 30 kg. After 8 weeks’ treatment there were significant differences between the two groups in terms of clearance of all signs and symptoms of atopic eczema (73% cetirizine versus 18% placebo, P < 0.02), and in use of concomitant therapy (disodium cromoglicate or topical corticosteroids: 18% cetirizine versus 82% placebo, P < 0.01). Severity of pruritus and erythema was also measured in the study, but no numerical results were reported.[x] [rx] = 1+]
Chlorphenamine
- One double-blind RCT compared the effectiveness of chlorphenamine with placebo in children aged 1–12 years who had nocturnal itching and scratching associated with atopic eczema (n = 151).[x] Treatment was given for 4 weeks. The dosage of chlorphenamine given was 1 mg once daily for children aged 1–5 years and 2 mg once daily for children aged 6–12 years. Where itching was not reduced by the initial dose, a second identical dose was permitted from 3 hours after administration of the first dose. If itching had not improved at the end of the first 2 weeks of treatment then the dosage was doubled (2 mg and 4 mg for children aged 1–5 years and 6–12 years, respectively). Use of emollients and hydrocortisone 1% was permitted during the trial.[x]
Hydroxyzine versus cyproheptadine
- One double-blind RCT evaluated the effects of hydroxyzine and cyproheptadine on pruritus (day and night) in children aged 2–16 years (mean age approximately 8 years) with an acute exacerbation of atopic eczema (n = 20).[x]
- The doses taken were 1.25 mg/kg three times daily (t.d.s.) of hydroxyzine (up to 30 mg t.d.s.), and 0.25 mg/kg t.d.s. cyproheptadine (up to 6 mg t.d.s.). The doses used were higher than those generally used in UK practice. The children were also using an emollient preparation three times daily, but no other medications were permitted.
Clemastine versus ketotifen
- A double-blind RCT compared the effectiveness of clemastine and ketotifen in children (mean age 9 years) with atopic eczema (n = 284 randomised, 255 analysed).[x] After 4 weeks’ treatment, the proportion of children whose condition was moderately improved based on the investigator’s rating was significantly higher with ketotifen; no other differences in the other six ratings were noted. In terms of individual symptoms, improvement in itching, erythema/papule and excoriation/scratch was found in significantly more children treated with ketotifen (itching 79% versus 57%, erythema/papule 73% versus 58%, excoriation/scratch 70% versus 54%).
Loratadine versus placebo
- A study evaluating the use of loratadine in conjunction with topical mometasone furoate 1% cream in children with atopic eczema was identified (n = 50). Although the volume (and not strength) was reported in the paper, it was assumed that the only available proprietary preparation of loratadine was used (5 mg/5 ml).
- The dose given was 5 ml for children who weighed up to 30 kg, and 10 ml for those weighing more than 30 kg. After 15 days’ treatment, there were no significant differences between groups in any outcome (improvement in severity (SCORAD) scores, physician’s assessment of global improvement or pruritus score). Dizziness was reported by one child in each group; there were no reports of drowsiness or difficulty in awakening.[x] [EL = 2+]
Antihistamines used preventatively in children with atopic eczema
- The Early Treatment of the Atopic Child (ETAC) study considered whether cetirizine could prevent the onset of asthma, and also provided longer term safety data for cetirizine. In this double-blind RCT, 18 months’ treatment with cetirizine was compared with placebo in children aged 12–24 months with active atopic eczema (n = 795).rx The dosage of cetirizine given was 0.25 mg/kg twice daily. Both groups were permitted to use topical or systemicmedication if required.
- Pityrosporum ovale and tinea (ringworm) infections are no more common in children with atopic eczema than other children[rx,rx] [sing topical corticosteroids can alter the clinical appearance of tinea infections, allowing low-grade spread of the causal fungus.
Interferon gamma
- One placebo-controlled double-blind RCT,[x] an associated long-term follow-up study459 and five case series or case report[rx;rx] described the use of interferon gamma to treat atopic eczema[rx]
- The RCT included children and adults (age range 3–65 years), with some data reported separately for those aged 3–20 years (n = 83, 25% aged 3–20 years).[x] [EL = 1+] However, the relative proportion of people aged 3–20 years differed between groups, with six treated with interferon gamma and 15 treated with place[x].
- Interferon gamma 50 μg/m2/day by subcutaneous injection was self-administered by patients (or carers in the case of children, presumably) for 12 weeks. At the end of treatment, the proportions reporting at least 50% improvement were significantly higher in the interferon gamma than the placebo group (45% versus 21%, P = 0.016 based on the investigator’s assessment, and 53% versus 21%, P = 0.002 based on the patient’s or carer’s assessment). In those aged 3–20 years, the patient/carer ratings were 67% versus 20% (investigator’s assessment was not reported).
Intravenous immunoglobulin
- One narrative review described literature identified in relation to the use of intravenous (IV) immunoglobulin in children with atopic eczema, which consisted of three publications.[x] In four children, IV immunoglobulin was used to treat Kawasaki syndrome or idiopathic thrombocytopenia purpura, in which improvement (‘remission’) of their coexisting atopic eczema was noted within 7 days.
- A case report of an 8-month-old boy treated for thrombocytopenia did not find improvement of his atopic eczema. The third publication reported improvement in ‘skin score’ and in levels of cytokines (including interleukin and interferon levels) in five children with atopic eczema who were treated with IV immunoglobulin.[x] [EL = 3]
Mycobacterium vaccae
- One double-blind RCT evaluated the effects of killed Mycobacterium vaccae on atopic eczema in children with moderate to severe disease (n = 166, 93% completed and analysed, aged 5–16 years).[x] [EL = 1−] At 12 or 24 weeks following a single intradermal injection of the preparation (either 1 mg or 0.1 mg, or placebo), there were no significant differences between groups in any outcome (severity (SASSAD), body surface area affected, patient’s global assessment, pruritus, sleep, topical corticosteroid use, or quality of life (CDLQI)). Overall, 19% had injection-site reactions (induration and erythema), and 13% had atopic eczema that was believed to be due to the injection given (32% reported atopic eczema as an adverse effect overall).
Alclometasone dipropionate 0.05% (moderately potent) versus clobetasone butyrate 0.05% (moderately potent)
- One double-blind RCT compared the effectiveness of alclometasone dipropionate 0.05% with clobetasone butyrate 0.05% (n = 43). In this small study, improvement in severity of signs and symptoms was not significantly different between groups. Investigator’s rating of the global condition was similar in both groups. Stinging was reported in two children treated with alclometasone.[x] [EL = 1+]
Triamcinolone acetonide cream 0.1% (potent) versus hydrocortisone valerate cream 0.2% (moderately potent)
- A within-patient (left–right) [x] compared 2 weeks’ triamcinolone acetonide 0.1% treatment with hydrocortisone 0.2% (n = 66, 54 completed and analysed). Severity was reported to be improved in both groups, but data were only shown in graphs. Clearance or an ‘excellent response’ was seen in 74% in both groups. Transient stinging was reported in 3% in both groups.[x [EL = 1−]
Hydrocortisone butyrate 0.1% cream (potent) versus hydrocortisone 1% ointment (mild)
- One RCT evaluated two hydrocortisone preparations in a left–right comparison (hydrocortisone butyrate 0.1% cream versus hydrocortisone 1% ointment, n = 40). Treatment was given for 4 weeks. Significantly greater improvements in the global severity of the condition were reported in children treated with hydrocortisone butyrate 0.1%: mean (%) reduction in global severity score after 4 weeks of 2 (73%) versus 1.6 (62%), P < 0.05. Details of any adverse effects were not reported.[x] [EL = 1+]
Betamethasone valerate 0.1% (potent) versus hydrocortisone 1% (mild)
- One double-blind RCT compared the effectiveness of 3 days’ treatment with betamethasone valerate 0.1% with 7 days’ treatment with hydrocortisone 1% ointment in children with mild to moderate atopic eczema (n = 207).[x]Treatment was used when needed during an 18 week period.
- The population consisted predominantly of children from the community in whom atopic eczema was milder than in the 16% recruited from a hospital outpatient clinic. Several outcomes were only reported for the community subgroup
Mometasone furoate 0.1% (potent) versus various hydrocortisone preparations
- Two RCTs compared mometasone furoate 0.1% with various hydrocortisone preparations in children with moderate to severe atopic eczema.
- In the first study the comparator was hydrocortisone valerate 0.2% cream (moderate potency n = 219).[x] The children had failed to respond to treatment with a hydrocortisone preparation (assumed to be a mild preparation) over the previous 7 days. It was reported that there were no significant differences between mometasone furoate 0.1% and hydrocortisone valerate 0.2% groups in global improvement (87% versus 78%, P = 0.01) after 3 weeks’ treatment. However, no baseline data were reported and thus it was not possible to determine whether groups were similar other than in the intervention being give.
Fluticasone propionate 0.05% (potent) versus hydrocortisone 1% (mild) or hydrocortisone 17-butyrate 0.1% (potent)
- One publication reported the outcomes of two RCTs which compared fluticasone propionate 0.05% cream with hydrocortisone 1% (n = 137) or hydrocortisone 17-butyrate 0.1% (n = 128) in children experiencing a flare of atopic eczema.[x] Treatment was applied twice a day for 2–4 weeks until the atopic eczema was stabilised, followed by intermittent use as required up to twice a day, for up to 12 weeks. Emollients could be used as required.
Prebiotics in the treatment of AD
- Prebiotics have not been extensively studied in the treatment of AD. One small RCT did find that prebiotics alone lowered the SCORAD index in children with AD [rx]. Overall, however, minimal evidence exists to support the use of prebiotics as a stand-alone therapy.
Synbiotics (combination therapy)
- A combination of prebiotics and probiotics, known as synbiotics, appears to hold promise in the treatment of AD. A recently published meta-analysis examined all published RCTs of synbiotics for the treatment of AD, using the SCORAD index to evaluate efficacy [rx]. The final analysis included 6 studies with 369 children.
- The authors concluded that the use of synbiotics for at least 8 weeks with mixed-strain bacterial species had a significant effect on improving the SCORAD index. This effect held only for children aged 1 year or older. Probiotics containing single strains of bacteria did not show a significant effect.
- The studies included in the analysis used a variety of bacterial strains, some single-strain and some mixed-strain, at differing doses and dosing regimens. The studies also used a variety of prebiotics, such as fructo-oligosaccharides, galacto-oligosaccharides, potato starch and lactose [rx].
- We don’t know whether vitamin E or multivitamins reduce symptoms in adults with eczema or whether pyridoxine, zinc supplementation, exclusion diets, or elemental diets are effective in children with eczema, as there are insufficient good-quality studies.
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Probiotics do not seem to reduce symptoms in children with established eczema.
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Essential fatty acids, such as evening primrose oil, blackcurrant seed oil, or fish oil, do not seem to reduce symptoms in people with eczema.
We don’t know whether control of house dust mites or maternal dietary restriction can prevent the development of eczema in children.
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Observational data suggest that exclusive breastfeeding for at least 3 months does not reduce eczema risk and there is no evidence to suggest that exclusive breastfeeding alleviates eczema symptoms, unless a child is allergic to cow’s milk protein.
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Introduction of probiotics in the last trimester of pregnancy and during breastfeeding may reduce the risk of eczema in the baby, although it remains unclear whether both antenatal and postnatal supplementation together yields the strongest protective effect. It is equally unclear which strains of probiotics are most effective.
Vitamin and mineral supplementation
- Two placebo-controlled RCTs considered the effectiveness of zinc or vitamin E for atopic eczema.[x,1rx] The trial involving zinc included children aged 1–16 years who continued with their usual treatments for atopic eczema (emollients and topical corticosteroids). Itch scores were significantly higher in children treated with zinc than with placebo, otherwise there were no significant differences in any outcome at 8 weeks (sleep disturbance, redness, surface area or combined disease severity scores, or in use of other treatments; n = 50, 84% analysed).220 [EL = 1−]
- The trial of vitamin E included children and adults (n = 96, aged 10–60 years).[x] Treatment with emollients was continued. Vitamin E or placebo was given for 8 months, after which the global assessment of the condition (classifications not defined) found worsening in 8% of the vitamin E group versus 78% in the placebo group; no change in 12% versus 11%, slight improvement in 20% versus 9%, great improvement in 46% versus 2%, and almost complete remission in 14% versus 0%. No statistical analysis of the data was presented and no adverse effects were reported.[1rrxEL = 1−]
Probiotics
- Three double-blind RCTs considered the effectiveness of a milk substitute supplemented with probiotics for the treatment of atopic eczema in infants with suspected cow’s milk allergy.rx]x[] The cow’s milk substitute in all three studies was a hydrolysed whey formula, with Lactobacillus added in the intervention group. Two studies had an additional intervention group: one received a mixture of probiotics (Lactobacillus, Bifidobacterium, Propionibacterium) and the other received Lactobacillus rhamnosus. Control groups received the hydrolysed whey formula only. Two studies evaluated 1 month’s use. Of these, the study with three treatment arms found no significant differences between the groups treated with probiotics and the control group in changes in SCORAD severity scores (n = 252, 91% completed and analysed).rx [EL = 1−]
Prevention
- Moisturise your skin as often as possible, ideally at least 2-3 times each day. The most greasy, non-perfumed moisturiser tolerated is best. This is the most important part of your skin care. Smooth it on in the direction of hair growth. Do not put your fingers back and forth into the pot of moisturiser, as it may become contaminated and be a source of infection. It is best to remove an adequate amount to cover the skin with a spoon or spatula and put this on a saucer or piece of kitchen roll.
- Wash with a moisturiser instead of soap (known as a soap substitute), and avoid soap, bubble baths, shower gels and detergents.
- Wear non-powdered non-rubber gloves (e.g vinyl gloves) to protect your hands and avoid contact with irritants, such as when doing housework.
- Rinse well after swimming and apply plenty of your moisturiser after drying. Make sure that the shower at the swimming pool contains fresh water and not chlorinated water from the swimming pool.
- Wear comfortable clothes made of materials such as cotton and avoid wearing wool next to your skin.
- Try to resist the temptation to scratch. It may relieve your itch briefly, but it will make your skin itchier in the long term. Smooth a moisturiser onto itchy skin.
- Avoid close contact with anyone who has an active cold sore as patients with eczema are at risk of getting a widespread cold sore infection.
- Do not keep pets to which there is an obvious allergy.
- Keep cool. Overheating can make eczema itch more.
- Treat eczema early – the more severe it becomes, the more difficult it is to control.
- Wash clothes with a non-biological washing powder and use a double rinse cycle to remove detergent residues from the clothing.
References
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