A treatment algorithm for paediatric patients with AE in South Africa is shown in Figure 1.

Epidermal barrier dysfunction, impaired water retention and allergic sensitisation are thought to be important in the onset of AE.^27,28,29 Moisturising the skin twice daily from birth with a bland emollient may therefore be beneficial in those at high risk of developing AE. ‘High-risk patients’ are defined as ‘having a parent or full sibling who has [or had] physician-diagnosed atopic dermatitis, asthma or allergic rhinitis’.²⁷ However, this approach has not been supported by other studies.³⁰ There is no high-quality evidence for the prevention of the development of AE regarding the effectiveness of pre- or probiotics,²² hypo-allergenic infant formula³¹ or the avoidance of certain foods by pregnant and breastfeeding women.^22,32

The anatomical and pathophysiological characteristics of AE in infants are typically different from those observed in older children.¹⁷ In infants, AE begins after the first weeks of life and presents in facial, scalp and extensor regions.¹⁷ This contrasts with older children, in whom flexural involvement predominates.¹⁷ South African guidelines (for all ages)³³ recommend diagnosis of AE according to the original UK Working Party criteria.³⁵ However, these criteria cannot be applied to infants¹⁹ and consequently, revised versions of the UK Working Party criteria^36,37,38 or the Hanifin and Rajka criteria³⁹ should be applied.

Poor access to healthcare and prioritisation of other infectious diseases have led to under-reporting of allergic diseases such as AE in Africa.⁴⁰ In rural settings, healthcare providers may be in short supply and have poor knowledge of allergic conditions.⁴¹ As such, in these areas, ‘teledermatology’ may improve access to healthcare.⁴¹ Another consideration is that allergen tests that have been developed in Europe may be unsuitable for African patients, who may have different allergen sensitivities than European patients.⁴⁰

In agreement with evidence-based guidelines for AE management in South Africa,³³ we recommend that all patients should use an emollient regularly as maintenance therapy. Emollients should be applied over the entire body, in single strokes, in the direction of hair growth at least twice a day.⁴⁷ The choice of emollient is dependent on the patient’s preference, but should be free from fragrances and colorants.^23,48 If cost is a limiting factor, petroleum jelly or glycerine mixed with petroleum may provide effective and affordable alternatives to standard emollients.⁴⁹

Bathing once a day in lukewarm water helps to hydrate and cleanse the skin by removing crusts and/or scales, but bathing time should be limited to 5 min to prevent the skin from drying out.²⁴ Bath additives should be non-irritating and shampoo should be specifically indicated for AE.^24,34 The routine use of household antiseptics or soaps is discouraged and a non-soap cleanser, such as aqueous cream or an emulsifying ointment, should be used.^24,50 After bathing it is best to gently pat, rather than rub, the skin dry and then moisturise the entire body.²⁴ Aqueous cream should not be used as a leave on product as this has been shown to have a negative impact on the skin barrier.⁵¹

Additional measures include: keeping the patient’s nails short, to prevent scratching and secondary infection⁵⁰; not overdressing to keep the skin cool; and using cotton clothing, which is less irritating than clothes made from wool and other rough fibres.⁵² Non-irritating sun protection products should be used and smoking should be avoided near children, as environmental tobacco smoke is a known trigger for acute exacerbations of AE.⁵³ Routine testing for food allergies or food avoidance is not recommended unless there is a clear indication^24,54; specific food avoidance can lead to nutritional deficiencies, exacerbate anxiety in both child and family and may also contribute to the development of a food allergy.^54,55 Food allergies should be treated by a specialist and are beyond the scope of this article.

In South Africa, a high proportion of patients use complementary and alternative therapies, which lack high-quality evidence in support of their efficacy.⁵⁶ Patient education is therefore of particular importance. Nurse practitioners should be educated in childhood AE and trained to provide evidence-based health education to patients and caregivers.^57,58,59

Before therapy begins, it is best to offer either educational material or courses on AE treatment to patients and their caregivers, which should include information regarding common triggers of AE, aspects of basic skin care and potential side effects of treatment.^33,50,54 Patients and caregivers who are informed by educational courses have higher quality of life as they can anticipate side effects, which reduces the likelihood of premature treatment discontinuation.¹⁸ Patients should also be provided with psychological support to improve emotional well-being, although there is a lack of high-quality evidence supporting the efficacy of psychological interventions.^33,60,61

The Allergy Foundation of South Africa (www.allergyfoundation.co.za) has patient-centred, downloadable information materials that may be of use, including a general pamphlet on AE,⁶² an eczema action plan⁶³ and a leaflet on wet-wraps.⁶⁴ Wet-wrap clothing (rather than bandages) is now available in South Africa, simplifying this important treatment method.⁶⁵ Providing patients and caregivers with this information should be prioritised and is as important as other treatment strategies.⁶⁶

Communication with patients is important as a regular follow-up improves the clinical outcome through greater adherence to treatment.⁶⁷ Any change in the treatment plan should be clearly explained to the patient.

A list of the TCSs that are available in South Africa are shown in Table 2.⁶⁹ The costs to use these steroids range from 2.21 (1% hydrocortisone acetate cream) to 17.63 (0.1% methylprednisolone aceponate scalp solution) South African rand (ZAR) per gram.⁷⁰ Topical corticosteroids have been shown to quickly and effectively control flares associated with acute AE.³ There are few side effects for patients when TCSs are chosen appropriately and used in the short term, but local effects may occur when TCSs are used for extended periods of time or at an inappropriate strength.^24,71 These side effects may include striae, skin atrophy, purpura, telangiectasia and impaired epidermal barrier function.⁷¹ Rare systemic side effects of TCSs include hypothalamic–pituitary–adrenal axis suppression and Cushing’s syndrome.^71,72 The systemic side effects of TCSs are of particular concern in children who have a higher surface area-to-body weight ratio, which may lead to increased systemic absorption.⁷¹ Sensitive skin areas, such as the face, eyelids and skin flexures, may be at particularly high risk of developing side effects when TCSs are misused.⁷¹

A growing fear of side effects related to TCSs amongst both patients and healthcare providers, or ‘corticophobia’, has led to widespread lack of adherence and underprescribing of TCSs in recent years. A questionnaire administered to patients in the United Kingdom in 1998 determined that 72.5% experienced corticophobia whilst 24% were non-adherent to corticosteroid treatment.⁷³ The results of another survey of patients in France, published in 2011, found 80.7% of patients experienced corticophobia whilst 36% were non-adherent.⁷⁴ This lack of adherence is a major contributor to TCS treatment failure and persistently uncontrolled AE.^73,74 Educating patients on the correct use of corticosteroids (i.e. the various potencies and correct dosing) and the low risk of side effects associated with appropriate use is therefore critical to improve adherence and to avoid undertreatment.^20,24 If corticophobia is significantly impacting treatment outcome, a referral should be made to a specialist for dermatological advice.³³

In South Africa, pimecrolimus and tacrolimus are indicated for the treatment of mild-to-moderate and moderate-to-severe AE, respectively.³³ Although TCSs are recommended as first-line treatment for most patients because of their superior efficacy, in the American Academy of Dermatology guidelines TCIs are recommended as first-line treatment for patients with AE in sensitive body areas, patients with steroid-induced atrophy and patients who have current long-term uninterrupted topical steroid use.²⁰ In the European AE guidelines, pimecrolimus is recommended for facial lesions and for children, and both pimecrolimus and tacrolimus for long-term maintenance treatment.²⁴

Patients should be informed before treatment begins that application-site erythema and/or a burning sensation are frequent side effects of TCI treatment, but these usually diminish after 3–4 days of use.⁶⁸ These effects may be managed by the systemic use of a non-steroidal anti-inflammatory, such as acetylsalicylic acid, 1 h before application of the product for the first 3–4 days.⁷⁵ Placing the TCI medication in the fridge may also be of help.⁷⁶ In studies with paediatric patients, local burning sensation was experienced by up to 36% of patients treated with tacrolimus and 7.4% of patients treated with pimecrolimus.⁷⁷ Since 2006, TCIs have carried a controversial boxed warning based on a theoretical risk of skin and lymphoma malignancy,⁷⁸ leading to hesitancy for long-term prescription, but this perceived risk has not been supported by rigorous post-marketing surveillance. In a recent systematic review of the last decade of clinical experience, the authors found that there was no evidence that use of TCIs is associated with an increased risk of malignancy.⁷⁸

In a network meta-analysis of clinical studies involving 19 treatment comparisons and 6413 children with AE, pimecrolimus 1% cream and tacrolimus 0.03% and 0.1% ointments were found to have similar efficacy and safety for the treatment of paediatric AE.⁷⁹ Similarly, in a comparative study of both TCIs in 141 children and adolescents with moderate AE, pimecrolimus 1% cream and tacrolimus 0.03% ointment were shown to have similar efficacy for the treatment of AE in different body locations (other than sensitive areas) over 6 weeks.⁶⁸

Topical calcineurin inhibitors are not approved for use in infants (age ≤ 2 years) with mild-to-moderate AE in South Africa.³³ However, extensive evidence from nine studies that were conducted in more than 6700 patients (including 4799 infants and 1312 children) supports the clinical efficacy and safety of pimecrolimus 1% in infants.^{80,81,82,83,84,85,86,87,88} The results of an open-label phase 2 study in 50 infants suggest that tacrolimus 0.03% is also efficacious in this age group, with similar tolerability as in older children.⁸⁹

When prescribing topical medication, it is important to balance efficacy and side effect profiles. Pimecrolimus has been shown to be as effective as a mild-to-medium potency TCSs⁸⁶ but without inducing TCS-related side effects, such as visible skin atrophy and barrier dysfunction.^90,91,92 Furthermore, paediatric studies have demonstrated that pimecrolimus helps in cases where corticophobia is affecting adherence to therapy.^{82,86,87,93,94}

For mild–acute AE flares in paediatric patients, we recommend low or moderate potency TCSs (Table 2) once daily or pimecrolimus twice daily until clear. For moderate AE flares, patients may use an appropriate strength TCSs, either once or twice daily or a TCI twice daily. The potency of TCS should be selected based on the severity of AE. The medication should be applied to all affected areas at the first signs and symptoms of an acute flare up until complete resolution of these symptoms. These signs and symptoms may include transient erythema, bumps, warmth, skin thickening, itching or tingling. If a TCI is selected as first-line therapy and the acute flare is not controlled, a short (7–14 days) course of TCS may achieve control, which can then be gradually reduced or switched to a TCI to maintain results.

We recommend a TCI twice daily for mild-to-moderate AE flares in children and sensitive body areas. In the European AE guidelines, pimecrolimus is recommended as the treatment of choice for facial lesions and children.²⁴ The treatment should be applied twice daily from the first appearance of signs and symptoms until complete resolution.

For the management of severe disease flares, moderate or potent TCSs are recommended (Table 2) as they have been shown to effectively and rapidly control disease flares in paediatric patients with AE.^20,95

Prior to initiating TCS treatment, clear instruction must be given regarding the safe use of the TCS. This guidance may include: the potency of TCS to be used and where on the body it should be applied; frequency of use; the correct amount of cream or ointment to be used per body area as per the ‘fingertip method’ (Figure 2)⁵⁰; avoiding application in sensitive areas such as eyelids, which are more prone to the development of side effects; and washing hands after use (unless the hands themselves are affected). Side effects should be discussed, but it is important to emphasise that these effects are unlikely with short-term usage in the prescribed manner.^73,74 Should tachyphylaxis occur during TCS treatment, an alternative, more potent preparation can be tried if necessary.⁷¹ Cases of severe, chronic AE should be referred to a specialist.⁴⁶