Evidence-Based Treatment of Atopic Eczema in General Practice

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Evidence-based treatment of atopic eczema in general practice

NONHLANHLA P Atopic eczema is a common chronic condition KHUMALO characterised by dry, itchy skin associated with MB ChB, FCDerm

Division of flares and remissions. Dermatology Groote Schuur Hospital and The prevalence of atopic eczema (AE) in tion); this combination of signs is some- Red Cross War Western societies is estimated at 10 - 20% times referred to as lichenification. Memorial Children’s in children under 14 years of age. South Hospital African rural, peri-urban and urban fig- The clinical presentation of AE differs Cape Town ures are 0.7%, 1.1% and 3.7%, respec- somewhat according to the age of the tively (Professor G Todd — personal com- patient. Nonhlanhla Khumalo completed her MB munication). Although there may be indi- ChB degree in 1989 vidual variations, patients with AE gener- Infantile AE at the University of ally have a higher incidence of asthma and The onset may be as early as within the Natal Medical School hay fever, as well as a history of similarly first few weeks of life.There is a predilec- in Durban. She affected family members. The exact cause received clinical and tion for involvement of the head and neck, research training at is unknown but a combination of genetic especially the face (Fig. 1). Distinction Groote Schuur and environmental factors probably inter- from infantile seborrhoeic dermatitis may Hospital and at the acts. The importance of environmental be difficult, but the latter is characterised Churchill Hospital in factors is emphasised by the observation by the presence of a greasy scale (so- Oxford, UK. Her main of a higher incidence of AE in relatives interests are diseases called ‘cradle cap’) and the absence of who have moved from rural to more of the vulva, hair and evidence-based der- urban communities. matology.

PATRICIA CLINICAL FEATURES R LAWRENCE Acute eczema is characterised by red, MB ChB, MMed (Derm) itchy skin and often by vesicles that ooze Division of serum, resulting in crust formation. Dermatology Scratching may result in secondary infec- Groote Schuur tion and associated complications. Hospital and Red Cross War In chronic eczema recurrent scratching Memorial Children’s Hospital results in thickening of the skin, promi- Cape Town nence of skin marking and colour change (hyperpigmentation or hypopigmenta- Pat Lawrence has been a dermatologist in hospital practice since June 1991, and The clinical presentation has a special interest in paediatric of AE differs somewhat dermatology. according to the age of

the patient. Fig. 1. Child with moderately severe atopic eczema.

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itch, which may be difficult to trials are flawed in terms of the assess in the very young. There are many sample size or study design. Based on the literature alone, the efficacy Childhood AE remedies in use, of antihistamines remains to be After the age of 2 years the skin and consequently adequately investigated. lesions tend to have a predilection many claims of use - Anecdotally, sedating antihistamines have sometimes been useful for the folds, especially the antecu- fulness are made by bital and popliteal fossae of the by virtue of their soporific effect arms and legs, respectively (Fig. 2). both patients and and bedtime use may be warrant- ed.There is no evidence to support d o c t o r s . the effectiveness of expensive non- sedating agents.’

UP TO THE YEAR 2000 AFTER THE YEAR 2000 RCTs of interventions for AE are The following abstracts of a num- comprehensively summarised in a ber of RCTs published after the systematic review by Hoare and abovementioned review1 may be co-workers.1 This review is exten- useful to the general practitioner: sive and summarises data from 272 • ‘Moisturizers are widely used in RCTs covering 47 different inter- AE.The use of 20% glycerin ventions.The authors state that cream was compared with the ‘there was reasonable RCT evi- urea-saline cream. No differ- dence to support the use of oral ences were found regarding skin cyclosporin, topical corticosteroids, reactions such as stinging, itch- Fig. 2. Typical flexural involvement. psychological approaches and UV ing and dryness/irritation.’ The therapy’ (as quoted by Bigby). 2 study concluded that a ‘glycerin Adult AE containing cream appears to be There was either insufficient or no a suitable alternative to In the older patient skin involve- RCT evidence for many other urea/sodium chloride in the ment may be similar to childhood interventions, such as maternal treatment of atopic dry skin’.4 eczema or localised to one area, allergy avoidance for disease pre- • Short bursts of a potent corti- e.g. hand dermatitis. vention, oral antihistamines, costeroid (0.1% betamethasone evening primrose oil, emollients, valerate applied for 3 days fol- In more severe disease, involve- avoidance of enzymatic washing lowed by the base ointment for ment in all age groups may be powders, cotton as opposed to syn- 4 days) were compared with a more extensive and in some cases thetic fibres for clothing, and the mild steroid (1% hydrocortisone may encompass more than 90% of use of twice-daily as opposed to applied for 7 days) in mild or the integument (if acute and red, once-daily topical corticosteroids. moderate AE in patients recruit- sometimes referred to as erythro- It is important, however, always to ed from general practices and dermic eczema). remember that the absence of evi- from a hospital outpatient clinic. dence does not necessarily mean The study5 concluded that: ‘A EVIDENCE-BASED that the intervention is not success- short burst of a potent topical MANAGEMENT ful. corticosteroid is just as effective as prolonged use of a milder There are many remedies in use, An RCT which we think may be of preparation for controlling mild and consequently many claims of particular value for general practi- or moderate AE in children.’ usefulness are made by both tioners, is one which examined the The study duration was 18 patients and doctors. This article effect of antihistamines in relieving weeks. only looks at evidence from dou- pruritus. This study3 concluded the • House dust mite allergy is com- ble-blind, randomised controlled following:‘Although antihistamines mon in AE and, although closely trials (RCTs), which are largely are often used in the treatment of associated with hay fever (aller- regarded as the best evidence for atopic dermatitis, little objective gic rhinitis), it has also been sus- the effectiveness of interventions. evidence exists to demonstrate pected of increasing the severity relief of pruritus. The majority of of AE. Oosting et al.6 investigat-

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ed this association and conclud- atopy. This effect is lessened in ointment was similar to that of ed that: ‘Use of house dust the general population and neg- 0.1% hydrocortisone butyrate mite-impermeable encasings ligible in children without first- ointment and was lower for resulted in a significant decrease order atopic relatives. Breast- 0.03% tacrolimus ointment. No in allergen concentrations. feeding should be strongly rec- serious safety concerns were However, this reduction in aller- ommended to mothers of identified.’ (Please note that gen load did not result in signifi- infants with a family history of 0.1% hydrocortisone butyrate cant changes in clinical parame- atopy, as a possible means of ointment is a potent corticos- ters between the groups.’ preventing AE.’8 teroid with similar strength to • The effect of early supplementa- betamethasone valerate.) In tion with gamma-linoleic acid another study11 the same group The wet-wrap dress - (GLA) (i.e. oil of evening prim- compared tacrolimus to 1% rose) given as borage oil supple- hydrocortisone acetate (a mild ing technique has ment (containing 100 mg GLA) corticosteroid) and concluded proved to be benefi - or sunflower oil supplement as a that: ‘Tacrolimus, 0.03% and cial in cases of exac - placebo daily for the first 6 0.1%, was significantly more months of life was investigated effective than 1% hydrocorti- erbated atopic der - by Van Gool and co-authors.9 sone acetate and 0.1% matitis (AD) skin The main outcome measures tacrolimus was more effective were the following: the inci- than 0.03% tacrolimus in the l e s i o n s . dence of AD in the first year of treatment of moderate-to-severe life (by UK Working Party crite- AD in children. No safety con- ria), the severity of AD cerns were identified.’ • The wet-wrap dressing tech- (SCORing Atopic Dermatitis; •A recent study12 on the effective- nique has proved to be benefi- SCORAD), and the total serum ness of pimecrolimus compared cial in cases of exacerbated immunoglobulin E (IgE) con- with placebo showed impressive atopic dermatitis (AD) skin centration at the age of 1 year. results: ‘First flare was 144 days lesions.The aim was to investi- The results showed a favourable in the pimecrolimus group and gate the effect of wet-wrap trend for severity of AD associ- 26 days in the control group dressings in a controlled trial ated with GLA supplementation (p < 0.001). Pimecrolimus treat- comparing a steroid-containing (SCORAD ± SD: 6.32 ± 5.32) ment was also associated with (mometasone furoate 0.1%) and in the GLA-supplemented improvement in signs and symp- a steroid-free (vehicle) prepara- group compared with 8.28 ± toms of AD, pruritus, patients' tion in an inpatient comparison 6.54 in the placebo group (p = self-assessment and quality of study.Twenty children aged 2 - 0.09; p = 0.06 after adjustment life.’ The authors concluded 17 years with exacerbated AD for total serum IgE at baseline, that: ‘Pimecrolimus cream 1% were treated twice daily with age 1 week). However, there bid is an effective, well-tolerat- wet-wrap dressings over a 5-day were no significant effects on ed, long-term treatment for AD period. The study concluded the other atopic outcomes.The in adults, substantially reducing that ‘Application of the wet- authors’ conclusion was that the number of flares compared wrap dressing technique for ‘Early supplementation with to a conventional therapy and exacerbated AD lesions is effec- gamma linoleic acid in children consequently reducing or elimi- tive, combination with a topical at high familial risk does not nating the need for corticos- steroid being superior to a prevent the expression of atopy teroid.’ steroid-free application without as reflected by total serum IgE, • Azathioprine has been used bearing the risk of a bacterial but it tends to alleviate the anecdotally and has now been superinfection.’7 severity of atopic dermatitis in proved in an RCT to be ‘an • A systematic review of the bene- later infancy in these children.’ effective and useful drug in fit of breast-feeding in prevent- • Two recent RCTs examined the severe AD although it is not ing AE concluded that: effectiveness of tacrolimus (a always well-tolerated. 'Exclusive breast-feeding during synthetic immune modulator Monitoring of the full blood the first 3 months of life is asso- with cyclosporin-like effects) in count and liver enzymes is ciated with lower incidence rates AE.The study by Reitamo and advisable during treatment.’13 of AD during childhood in chil- co-workers10 concluded that: dren with a family history of ‘The efficacy of 0.1% tacrolimus

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SUGGESTED PRACTICAL MANAGEMENT OF AE • Diagnosis. Making the correct diagnosis is largely dependent on the history (personal and family history of atopy, i.e. asthma, hay fever) and examination (acute ver- sus chronic eczema and areas of predilection).

• Moisturisers. Although there are no RCTs on the effect of soap, we have found the substitution of soap with aqueous cream very helpful (less drying and therefore less like- ly to induce itch and scratching). We recommend petroleum jelly or emulsifying base as a moisturis e r . These are oily and may not be acceptable to all patients, in which case water-based moisturisers such as aqueous, cetomacrogol, liquid paraffin and other creams containing glycerin or urea 4 may be more acceptable. Generally, lotions are not very useful. To reduce the risk of added irritants we warn our Fig. 4. Wet wraps in an older child. patients to avoid antiseptic, topical Fig. 3. Wet-wrap treatment of a baby. Note relative sparing of the face. antihistamine and perfume-containing creams and ointments. The quantity of topical steroid is • Newer macrolide treatments. • Topical steroids.For acute measured according to the ‘finger There is an excellent chapter by flares, we recommend the use of tip’ method.14 Williams et al.15 on the evidence- 1% hydrocortisone acetate to the based treatment of AE. It sum- face and neck and topical • Antihistamines. The effect of marises data from 7 RCTs on tra- betamethasone to the body as well antihistamines on itch has not been colimus as follows:‘About a third as wet wraps7 (we use two layers of proved beyond doubt, but sedating of study participants with moder- cotton tubular bandage as a dress- antihistamines are useful by virtue ate-to-severe AE achieve excellent ing, a wet (damp — warm water) of their soporific effect.There is no results, defined as at least 90% layer underneath and a dry layer evidence to support the effective- improvement in the physician’s on top) for up to a maximum of 5 ness of expensive non-sedating global assessment. A transient days (see Figs 3 and 4). It is agents. burning sensation is a common important to continue with the side-effect that occurs in about half liberal use of moisturiser. The use • Oil of evening primrose may of adults investigated, but is sel- of wet wraps may be continued be helpful, but more RCTs are dom severe enough to necessitate even without topical corticos- needed to confirm the beneficial stopping treatment.’ teroids (i.e. with moisturiser effects, particularly in view of the Tacrolimus is recommended for alone).The advantages of wet cost involved.Therefore oil of moderate to severe disease, where- wraps include increased contact evening primrose is not routinely as pimecrolimus is effective in mild with the skin during treatment recommended in our centre but to moderate disease. In the USA, (topical steroid is not rubbed off neither is it discouraged in the pimecrolimus is approved for onto bed linen), and reduction of individual patient who inquires ‘short-term intermittent therapy in the skin temperature — thus about its usefulness (discuss the the treatment of mild-to-moderate reducing warmth, sweating and insufficient evidence with the AD in non-immunocompromised itch and indirectly improving sleep. patient or parent). patients 2 years or older, in whom

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the use of alternative, conventional 3. Klein PA, et al. Arch Dermatol 1999; 135: 11. Reitamo S, et al. J Allergy Clin Immunol 1522-1525. 2002; 109: 539-546. therapies is deemed inadvisable . .. 4. Loden M, et al. Acta Derm Venereol 2002; 12. Meurer M, et al. Dermatology 2002; 205: or in patients who are not ade- 82: 45-47. 271-277. quately responsive or are intolerant 5. Thomas KS, et al. BMJ 2002; 324: 768. 13. Berth-Jones J, et al.Br J Dermatol 2002; 6. Oosting AJ, et al. J Allergy Clin Immunol 147: 324-330. to conventional therapies.’16 2002; 110: 500-506. 14. Long C, et al. Clin Exp Dermatol 1991; 7. Schnopp C, et al. Dermatology 2002; 204: 16: 444-447. 56-59. 15. Williams H, et al. Evidence-based Note that the effect of these treat- 8. Gdalevich M, et al. J Am Acad Dermatol Dermatology. London: BMJ Books, 2003: ments is equivalent to moderately 2001; 45: 520-527. 144-225. 9. Van Gool CJ, et al. Am J Clin Nutr 2003; 16. Anon. FDA licensing review of pimecrolimus potent topical steroids.Topical 77: 943-951. www.fda.gov/cder/foi/nda/2001/21- steroids are safe and effective, pro- 10. Reitamo S, et al. J Allergy Clin Immunol 302.Elidel.htm. vided they are used for short, inter- 2002; 109: 547-555. mittent periods as recommended above.The use of the newer bio- logical treatments is limited by the IN A NUTSHELL on evidence from randomised con- cost and availability. trolled trials (RCTs). Atopic eczema (AE) is a common Practical management consists of the chronic condition characterised by a What about patients who do not correct diagnosis, moisturising the dry, itchy skin, associated with flares skin with aqueous cream or petrole- respond? They should be referred and remissions. to a dermatologist for considera- um jelly, topical steroids and wet The exact cause of AE is unkown, wraps in acute flare-ups, and the use tion of other treatment which may but a combination of genetic and of the newer macrolide treatments in include ultraviolet light (with or environmental factors probably inter- patients with moderate to severe AE. without topical or oral psoralens), acts. The importance of the latter is However, use of the latter is limited azathioprine, and cyclosporin. Oral emphasised by the observation of an by cost and availability. increased incidence in relatives who steroids are best avoided for the Breast-feeding by a mother with a have moved from a rural to an urban treatment of AE. history of atopy may go some way environment. towards preventing a child from We wish to thank Dr S Jessop for her The clinical presentation varies developing eczema later in life. helpful comments on the manuscript. according to the age of the patient. The usefulness of antihistamines to References Many remedies are usually tried by prevent itch has not been proved 1. Hoare C, et al. Health Technol Assess 2000; both the patient and the doctor, but beyond doubt, nor has that of 4: 1-191. we only consider treatments based evening primrose oil. 2. Bigby M. Arch Dermatol 2001; 137: 1635- 1636.

SINGLE SUTURE Using household possessions to identify the poor Information on income and expenditure are difficult and time-consuming to obtain, but those working on child-health interventions need information on household economic status. An alternative is to use information on household possessions and characteristics of a family’s house. For example, households owning a car can be judged to be wealthier than those owing a motorcycle, which in turn are deemed wealthier than those owning only a bicycle. Electricty implies wealth, as does ownership of a television rather than just a radio. Such information, which is available in demographic, health and other surveys, can be combined into one index of wealth by various means.

(Victoria CG, et al.Lancet 2003; 362: 233-241.)

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