Atopic dermatitis and eczema

What is atopic dermatitis?

Atopic dermatitis, also known as atopic eczema is a chronic, relapsing, inflammatory skin condition characterised by an itchy red rash that favours the skin creases such as the folds of the elbows or behind the knees.¹

Atopic dermatitis is often used synonymously with the term 'eczema', although some disease ontologies consider atopic dermatitis to be a specific subtype of eczema.²

How common is atopic dermatitis? (Epidemiology)³

• Atopic dermatitis is common and the prevalence is increasing.

• Estimates vary due to the different populations examined, but figures suggest that it affects about 10–30% of children, and about 2–10% of adults.

• It presents most frequently in childhood, but can present at any age. Around 70–90% of cases occur before 5 years of age, with about 45% of cases beginning in the first 6 months of life.

• There is an increased prevalence of atopic eczema in children with an affected parent (about 80% of children where both parents are affected, and 60% if only one parent is affected).

• There is an increased rate of atopic eczema in urban areas, smaller families, and higher socio-economic classes.

Trigger factors^{4 5}

Environmental irritants and allergens

• Irritants - eg, soaps and detergents (including shampoos, bubble baths, shower gels and washing-up liquids).

• Skin infections: Staphylococcus aureus is believed to be an important exacerbating factor in atopic eczema.

• Contact allergens.

• Extremes of temperature and humidity. Most patients improve in summer and are worse in winter. Sweating induced by heat or exercise can provoke an exacerbation.

• Abrasive fabrics - eg, wool.

• Dietary factors aggravate atopic eczema in about 50% of children but much less frequently in adults. Food allergy should be suspected in children with atopic eczema who have reacted previously to a food, with immediate symptoms, or in infants and young children with moderate or severe atopic eczema that has not been controlled by optimum management, particularly if associated with gut dysmotility (colic, vomiting, altered bowel habit) or failure to thrive.

• Inhaled allergens - eg, house dust mites, pollens, pet dander and moulds. Inhaled allergy should be suspected in children with seasonal flares of atopic eczema, associated asthma and rhinitis, or children aged over 3 years with atopic eczema on the face.

Endogenous factors

• It is thought that genetic mutations affect the production of filaggrin. Filaggrin is a protein critical to the conversion of keratinocytes to the protein/lipid squames that compose the stratum corneum, the outermost barrier layer of the skin. Therefore, in at least some patients with atopic eczema, there is a genetic predisposition that increases their sensitivity to external environmental triggers.

• Stress may exacerbate atopic eczema, which itself may be a cause of psychological distress.

• Hormonal changes in women - eg, premenstrual flare-ups, deterioration in pregnancy.

Diagnostic criteria

The diagnosis of atopic dermatitis is typically relatively straightforward, and based on the appearance and feel of the rash combined with the history given by the patient.

The National Institute for Health and Care Excellence (NICE) suggests the following diagnostic criteria:⁵

• Must have an itchy skin condition (or report of scratching or rubbing in a child) plus three or more of the following:

  • A previous history of itchiness in skin creases such as folds of the elbows, behind the knees, fronts of ankles, or around the neck (or the cheeks in children aged 18 months or under).

  • History of asthma or hay fever (or history of atopic disease in a first-degree relative in children aged under 4 years).

  • General dry skin in the preceding year.

  • Visible flexural eczema (or eczema affecting the cheeks or forehead and outer limbs in children aged under 4 years).

  • Onset in the first two years of life (not always diagnostic in children aged under 4 years).

• If it does not itch it is very unlikely to be eczema.

• Note that in Asian, Black Caribbean, and Black African children, atopic eczema may be more likely to affect extensor surfaces, rather than the flexures. Discoid or follicular patterns may be more common.

Atopic dermatitis symptoms (presentation)

Eczema on arms

By Jambula at English Wikipedia, Public domain, via Wikimedia Commons

• The distribution tends to vary with age and the appearance of persistent lesions may alter with scratching.

• A tendency to dry skin persists throughout life.

• Acute flare-ups vary in appearance from vesicles to areas of poorly demarcated redness. Other possible features include crusting, scaling, cracking and swelling of the skin.

• Repeated scratching often leads to thickening of chronic lesions.

• During infancy, atopic eczema primarily involves the face, the scalp and the extensor surfaces of the limbs. It is usually acute. The nappy area is usually spared.

• In children and in adults with long-standing disease, eczema is often localised to the flexure of the limbs.

• Adults: often generalised dryness and itching.

• Chronic eczema on the hand may be the primary manifestation.

• Bacterial infection is suggested by:

  • Crusting, weeping, pustulation and/or surrounding cellulitis with erythema of otherwise normal-looking skin.

  • A sudden worsening of the condition.

• Eczema herpeticum is suggested by:⁵

  • Areas of rapidly worsening, painful eczema.

  • Clustered blisters consistent with early-stage cold sores.

  • Punched-out erosions (circular, depressed, ulcerated lesions) usually 1-3 mm that are uniform in appearance (may coalesce to form larger areas of erosion with crusting).

  • Possible fever, lethargy or distress.

Assessment of severity and well-being in a child with atopic eczema⁵

In assessment of severity, psychological and psychosocial well-being and quality of life, take into account the impact of atopic eczema on parents or carers, as well as the child and provide appropriate advice and support. The following assessment tools can be used (see links under 'Further Reading', below):

• Visual analogue scales (0-10) capturing the child/parent/carer's assessment of severity, itch and sleep loss over the previous three days and nights.

• Patient-oriented Eczema Measure (POEM).

• Children's Dermatology Life Quality Index (CDLQI).

• Infants' Dermatitis Quality of Life Index (IDQOL).

• Dermatitis Family Impact (DFI) Questionnaire.

Differential diagnosis⁶

• Psoriasis.

• Contact dermatitis.

• Seborrhoeic dermatitis.

• Fungal infections.

• Lichen simplex chronicus.

• Scabies and other infestations.

Diagnosing atopic dermatitis (investigations)

• Investigations are rarely required to establish the diagnosis.

• Most children with mild atopic eczema do not need clinical testing for allergies.⁵

• There is no evidence of the value of high-street or internet allergy tests in the management of atopic eczema.⁵

• Estimation of immunoglobulin E (IgE) and specific radioallergosorbant tests (RASTs) only confirm the atopic nature of the individual.

• Swabs for bacteriology may be useful if flares do not respond to treatment, or if there are very frequent flares, in order to identify antibiotic-resistant strains of Staphylococcus aureus (S. aureus) or to detect additional streptococcal infection.

Associated diseases

Atopic eczema is associated with other atopic disease such as asthma, hay fever and allergic rhinitis.

Management of atopic dermatitis^{5 7 8}

• Provide information about the condition, the factors that may provoke it, the role of different treatments and their effective and safe use. It is important to emphasise the correct quantities of topical treatments to use. Use written information to reinforce information discussed.

• Include information on how to recognise flares of atopic eczema (increased dryness, itching, redness, swelling and general irritability).

• Information should also include how to recognise the symptoms and signs of bacterial infection with staphylococcus and/or streptococcus (weeping, pustules, crusts, atopic eczema failing to respond to therapy, rapidly worsening atopic eczema, fever and malaise).

• Provide support: living with skin disease, especially the potential psychosocial difficulties, can be very difficult.

• Provoking factors should be identified and avoided when practical. Avoid anything that is known to increase disease severity: advise avoidance of extremes in temperature and humidity, avoid irritating clothes containing wool or certain synthetic fibres (use non-abrasive clothing fabrics, such as cotton).

• Advise keeping nails short and avoid use of soaps or detergents; replace with emollient substitutes (use gloves when unable to avoid handling irritants such as detergents).

• Keep the skin hydrated: use of baths and bath additives and reduction of water loss by the use of sufficient appropriate emollient therapy, used liberally.

• A stepped approach should be used for managing atopic eczema in children, ie tailoring the treatment step to the severity of the atopic eczema. Management can then be stepped up or down, according to the severity of symptoms.

• Emollients should form the basis of atopic eczema management and should always be used, even when the atopic eczema is clear.

Emollients and moisturisers

• These are best applied when the skin is moist but they should also be applied at other times.

• They should be applied as liberally and frequently as possible and continual treatment with complete emollient therapy (combinations of cream, ointment, bath oil and emollient soap substitute) will help to provide maximal effect.

• Ideally the frequency of application of emollients should be every four hours or at least 3-4 times per day.

• They should be prescribed in large quantities, with the recommended quantities used in generalised eczema being 500 g/week for an adult and 250 g/week for a child.

• Intensive use of emollients will reduce the need for topical steroids.

• Education on how to use emollients is essential to ensure maximal rehydration of the skin.

A Cochrane review found that most moisturisers showed some beneficial effects, prolonging time to flare, and reducing the number of flares and amount of topical corticosteroids needed to achieve similar reductions in eczema severity. There was no reliable evidence that any one moisturiser was better than another.⁹

The Medicines and Healthcare products Regulatory Agency (MHRA) has published warnings about the risk of severe and fatal burns with the use of all paraffin-based emollients, regardless of paraffin concentration. Data suggest there is also a risk for paraffin-free emollients. Advise patients who use these products not to smoke or go near naked flames, and warn about the easy ignition of clothing, bedding, dressings and other fabric that have dried residue of an emollient product on them.¹⁰

Topical steroids

• Mild corticosteroids are generally used on the face and on flexures; potent corticosteroids are generally required for use on adults with discoid or lichenified eczema or with eczema on the scalp, limbs and trunk.

• It is recommended that topical corticosteroids for atopic eczema should be prescribed for application only once or twice daily.¹¹

• Use mild potency for mild atopic eczema, moderate potency for moderate atopic eczema and potent for severe atopic eczema.

• Use mild potency for the face and neck, except for short-term (3-5 days) use of moderate potency for severe flares.

• Use moderate or potent preparations for short periods only (7-14 days) for flares in vulnerable sites such as the axillae and groin.

• Do not use very potent preparations in children, without specialist dermatological advice.

• Patients using moderate and potent steroids must be kept under review for both local and systemic side-effects.

• Chronic eczema in adults: this often requires a potent steroid together with emollients and allergen avoidance.

• Regular long-term use of topical corticosteroids, particularly potent or super-potent ones, can lead to harms such as skin atrophy, striae, perioral dermatitis, and changes in skin pigmentation. In rare cases (eg, large areas of skin treated with high-potency steroids), they can lead to systemic steroid side-effects, including hypothalamic-pituitary-adrenal axis suppression.¹²

• For this reason, topical corticosteroids are usually prescribed for short courses only (eg, once or twice a day for up to 14 days) to treat eczema flares.

• Topical corticosteroids can, however, also be used for 'maintenance' therapy once the eczema flare has settled, with the aim of preventing future flares. A common regime is 'weekend steroids', ie application of topical steroids on two consecutive days per week.¹³ This may be useful for people with frequent flares in whom as-needed topical steroid therapy is insufficient.

• Fingertip units (FTUs) are a useful guide for patients on how much topical steroid to use. One fingertip unit is the amount of steroid cream or ointment squeezed out of a tube, in a straight line, between the tip of an adult's index finger to the first crease in the finger (over the distal interphalangeal joint). This is enough topical steroid to cover the area of two adult hands with the fingers together.

Topical corticosteroid (TCS) withdrawal

^{14 15 16}
TCS withdrawal is a potential complication of topical steroid treatment, particularly where there has been an inappropriate long-term use of moderate-to-potent steroid.

Symptoms include:

• Red skin.

• Burning pain or stinging.

• Itch.

• Skin peeling and oozing.

• Papules.

• Pustules, or erosions.

• Excessive sweating.

Severe and prolonged symptoms may lead to depression. The outlook is variable. Symptoms may be mild and short-lived or may be severe and last for months or even years. In some cases, severe symptoms may settle after several days or a few months, followed by a prolonged period of dry, itchy skin but with gradual improvement.

Topical calcineurin inhibitors¹⁷

• Three products are available in this category: Elidel® (pimecrolimus) cream, Protopic® (tacrolimus) 0.03% ointment, and Protopic® (tacrolimus) 0.1% ointment.

• Their main advantage is that they are steroid-sparing agents, and do not cause skin atrophy or glaucoma (as long-term topical steroids can). This makes them especially useful for repeated or longer-term use on sites with thin skin that are particularly susceptible to topical steroids, such as the eyelids, face, and neck.

• They are considered to be second-line options where topical corticosteroid use is insufficient, mainly because eczema flares respond slower to calcineurin inhibitors than topical corticosteroids.

• The BNF states that topical calcineurin inhibitors are for 'specialist initiation only'.¹⁸ Many ICBs have similar policies. This is based on a theoretical safety concern (extrapolated from oral tacrolimus use) that topical calcineurin inhibitor use may increase the risk of developing cutaneous lymphoma.

• However, extensive post-marketing surveillance has been very reassuring, and has not shown a causal link with the development of skin cancer.¹⁷

• The SmPCs for Elidel® and Protopic® were updated in 2022 to remove cancer as a potential adverse effect of use.¹⁷

• Various dermatology societies, including the Primary Care Dermatology Society, are of the opinion that topical calcineurin inhibitors can be safely initiated by any clinician experienced in treating eczema, including GPs.¹⁷

• Both tacrolimus and pimecrolimus can be used twice daily for a short time (usually up to six weeks) to treat a flare of eczema, with or without topical corticosteroids.

• Tacrolimus is also licensed for use twice-weekly as maintenance therapy to reduce the risk of eczema flares.

Bacterial infection

• The role of antibiotics in eczema is relatively limited. In people who are not systemically unwell, there is limited benefit in using antibiotics alongside topical steroids, compared to using topical steroids alone.¹⁹

• NICE recommends that topical or oral antibiotics should not routinely be used in flares of eczema if the patient is not systemically unwell.

• Oral antibiotics should be used for people who are systemically unwell with a secondary bacterial infection of eczema.

• If antibiotic therapy is still felt to be required in someone who is not systemically unwell (eg, if there is a strong clinical suspicion of a significant bacterial infection), NICE recommends:¹⁹

  • First-choice topical antibiotic: topical fusidic acid 2%, applied three times a day for 5-7 days.

  • First-choice oral antibiotic: flucloxacillin.

  • Alternative oral antibiotic if penicillin allergy or if flucloxacillin is unsuitable: clarithromycin.

  • Alternative oral antibiotic if penicillin allergy or if flucloxacillin is unsuitable, and the person is pregnant: erythromycin.

  • If meticillin-resistant: consult a microbiologist.

• Penicillin should be given if beta-haemolytic streptococci are isolated.

• Steroid-antibiotic combinations are effective in clinical practice although there is no evidence for greater efficacy.

Lichenification

• Results from repeated scratching.

• Initially treated with a potent corticosteroid.

• Bandages containing ichthammol paste (to reduce pruritus) and other substances such as zinc oxide may be applied over the corticosteroid.

• Coal tar and ichthammol can be useful in some cases of chronic eczema.²⁰

Exudative eczema

• Initially, this requires a potent corticosteroid.

• Infection may also be present and requires treatment.

• Potassium permanganate solution (1 in 10,000) can be used in exudative eczema, for its antiseptic and astringent effect.

Diet⁵

• Hydrolysed formulas should not be offered to infants in preference to breast milk for the prevention of atopic eczema.

• Do not use diets based on unmodified proteins of other species' milk (for example, goat's or sheep's milk) or partially hydrolysed formulas for the treatment of suspected cow's milk allergy. Diets including soya protein can be offered to children aged over 6 months, with specialist dietary advice.

• Refer for specialist dietary advice children who follow a cow's milk-free diet for more than eight weeks.

• It is not known whether altering a breast-feeding mother's diet is effective in reducing the severity of the condition. A trial of an allergen-specific exclusion diet under dietary supervision may be considered.

• Parents should be advised that where there is a family history of atopy, exclusive breastfeeding for the first three months reduces the risk of infantile eczema.

• There is little evidence to support the use of various exclusion diets in unselected people with atopic eczema. However, if food allergy is diagnosed by using thorough diagnostic procedures such as oral food allergy challenges, exclusion of specific trigger foods can make a significant clinical difference. Significant dietary manipulation should always be managed in conjunction with a dietician and/or paediatric allergy specialist.²¹

Managing flare-ups

• Settle inflammation with topical corticosteroids.

• Treat clinically apparent bacterial infection with oral antibiotics as outlined above.

• Urgently refer or admit someone with severe unresponsive disease. Admit anyone with suspected infection with herpes simplex virus (eczema herpeticum).

Managing frequent flare-ups

• Change the emollient to one with a higher lipid content.

• Advise the person to apply the emollient more often.

• Recommend applying more emollient each time.

• Review the factors that might be provoking flare-ups; avoid environmental irritants and stresses where possible.

• Consider maintenance therapy at weekends with topical corticosteroids and/or topical calcineurin inhibitors.

Tacrolimus and pimecrolimus for atopic eczema

• NICE has recommended that topical pimecrolimus and tacrolimus are options for atopic eczema not controlled by maximal topical corticosteroid treatment or if there is a risk of important corticosteroid side-effects (particularly skin atrophy).²²

• Topical pimecrolimus is recommended for moderate atopic eczema on the face and neck of children aged 2-16 years.

• However, a Cochrane review concluded that topical pimecrolimus is less effective than moderate and potent corticosteroids and 0.1% tacrolimus and that the therapeutic role of topical pimecrolimus is uncertain due to the absence of key comparisons with mild corticosteroids.²³

• Topical tacrolimus is recommended for moderate-to-severe atopic eczema in adults and in children aged over 2 years.

Referral criteria⁵

An immediate (same-day) referral for specialist dermatological advice should be made if eczema herpeticum is suspected.

Urgent (within two weeks) referral for specialist dermatological advice should be made for children with atopic eczema if:

• Atopic eczema is severe and has not responded to optimum topical therapy after one week.

• Treatment of bacterially infected atopic eczema has failed.

Referral for specialist dermatological advice is recommended for children with atopic eczema if:

• The diagnosis is, or has become, uncertain.

• Management has not controlled the atopic eczema satisfactorily based on a subjective assessment by the child, parent or carer (eg, 1-2 weeks of flares per month or is reacting adversely to many emollients).

• Atopic eczema on the face has not responded to appropriate treatment.

• The child or parent/carer may benefit from specialist advice on treatment application (eg, bandaging techniques).

• Contact allergic dermatitis is suspected (eg, persistent atopic eczema or facial, eyelid or hand atopic eczema).

• Atopic eczema is causing significant social or psychological problems for the child or parent or carer (eg, sleep disturbance, poor school attendance).,

• Atopic eczema is associated with severe and recurrent infections, especially deep abscesses or pneumonia.

Children with atopic eczema that has responded to optimum management but for whom the impact of the atopic eczema on quality of life and psychosocial well-being has not improved, should be referred for psychological advice.

Children with moderate or severe atopic eczema and suspected food allergy should be referred for specialist investigation and management of the atopic eczema and allergy.

Children with atopic eczema who fail to grow at the expected growth trajectory, as reflected by UK growth charts, should be referred for specialist advice relating to growth.

Treatments provided in secondary care

Systemic drugs acting on the immune system (eg, ciclosporin, azathioprine, and mycophenolate mofetil), and phototherapy are available for the management of some cases of severe refractory eczema, used under specialist supervision.

Dupilumab is licensed for the treatment of moderate- to-severe atopic eczema in patients requiring systemic therapy.²⁰

Tralokinumab is recommended by NICE as a treatment option in adults if at least one systemic immunosuppressant has been ineffective, or if these are unsuitable.²⁴

Alitretinoin is recommended as a treatment option for adults with severe chronic hand eczema that has not responded to potent topical corticosteroids, if the person has severe disease and a Dermatology Life Quality Index (DLQI) score of 15 or more.²⁵

JAK inhibitors²⁶²⁴

Three Janus kinase (JAK) inhibitors are endorsed by NICE for use in moderate-to-severe atopic dermatitis: baricitinib (in adults), abrocitinib and upadacitinib (the latter two in over-12s).

These are recommended as an option if moderate-to-severe atopic dermatitis has not responded to at least one systemic immunosuppressant, or if these are not suitable.

Complications of atopic dermatitis

Infection

• S. aureus infection may present with typical impetigo or as worsening of the eczema with increased redness, oozing and crusting.

• Herpes simplex infection, indicated by grouped vesicles and punched-out erosions, can also occur. Disseminated herpes simplex viral infection, eczema herpeticum, presents with widespread lesions that may coalesce to large, denuded, bleeding areas that can extend over the entire body.

• Superficial fungal infections are also more common in people with atopic eczema.

Psychosocial impact

• Disturbed sleep patterns.

• Reduced self-esteem because of chronic visible disease.

• Isolation from other children - eg, when they are unable to take part in swimming.

• Adverse effects on a child's behaviour and development: poor sleep, reduced self-esteem and social isolation.

Prognosis³

• Usually a relapsing course, with a tendency to gradual improvement in adult life.

• Atopic eczema can be expected to clear in about 65% of children by the time they are 7 years of age, and in about 74% of children by 16 years of age, although relapses may occur.

• Predictors of a worse prognosis include early onset of disease and in children with associated asthma.

Prevention of atopic dermatitis²⁷

• Systematic reviews of prevention strategies (eg, promoting exclusive and prolonged breastfeeding, or reducing ingested or airborne allergens during pregnancy and after birth) have generally not shown convincing benefit.

• Maternal/infant supplements such as vitamin D have also not shown any benefit with the possible exception of omega-3 fatty acids.

• Systematic reviews suggest that probiotics could reduce the incidence of atopic dermatitis by about 20%, although the studies are quite variable.

• Skin barrier enhancement from birth to prevent atopic dermatitis and food allergy has received recent interest, and results from national trials are awaited.

• It is possible that trying to influence major immunological changes through infant-directed interventions may be too late, and more attention to strategies before birth may be more successful.