Khumalo, NP

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The prevalence of atopic eczema (AE) inWestern societies is estimated at 10 - 20%in children under 14 years of age. SouthAfrican rural, peri-urban and urban fig-ures are 0.7%, 1.1% and 3.7%, respec-tively (Professor G Todd — personal com-munication). Although there may be indi-vidual variations, patients with AE gener-ally have a higher incidence of asthma andhay fever, as well as a history of similarlyaffected family members. The exact causeis unknown but a combination of geneticand environmental factors probably inter-acts. The importance of environmentalfactors is emphasised by the observationof a higher incidence of AE in relativeswho have moved from rural to moreurban communities.CLINICAL FEATURESAcute eczema is characterised by red,itchy skin and often by vesicles that oozeserum, resulting in crust formation.Scratching may result in secondary infec-tion and associated complications.In chronic eczema recurrent scratchingresults in thickening of the skin, promi-nence of skin marking and colour change(hyperpigmentation or hypopigmenta-tion); this combination of signs is some-times referred to as lichenification.The clinical presentation of AE differssomewhat according to the age of thepatient.Infantile AEThe onset may be as early as within thefirst few weeks of life.There is a predilec-tion for involvement of the head and neck,especially the face (Fig. 1). Distinctionfrom infantile seborrhoeic dermatitis maybe difficult, but the latter is characterisedby the presence of a greasy scale (so-called ‘cradle cap’) and the absence ofMAIN TOPICC M E S e p t e m b e r  2 0 0 3   Vo l . 2 1   N o . 9   529Evidence-based treatmentof atopic eczema in general practiceAtopic eczema is a common chronic conditioncharacterised by dry, itchy skin associated withflares and remissions.NONHLANHLA PKHUMALOMB ChB, FCDermDivision ofDermatologyGroote SchuurHospital and Red Cross WarMemorial Children’sHospitalCape TownNonhlanhla Khumalocompleted her MBChB degree in 1989at the University ofNatal Medical Schoolin Durban. Shereceived clinical andresearch training atGroote SchuurHospital and at theChurchill Hospital inOxford, UK. Her maininterests are diseasesof the vulva, hair  andevidence-based der-matology.PATRICIA R LAWRENCEMB ChB, MMed (Derm)Division ofDermatologyGroote SchuurHospital and Red Cross WarMemorial Children’sHospitalCape TownPat Lawrence hasbeen a dermatologistin hospital practicesince June 1991, andhas a special interestin paediatric dermatology.The clinical presentationof AE differs somewhataccording to the age ofthe patient. Fig. 1. Child with moderately severe atopiceczema.itch, which may be difficult toassess in the very young.Childhood AEAfter the age of 2 years the skinlesions tend to have a predilectionfor the folds, especially the antecu-bital and popliteal fossae of thearms and legs, respectively (Fig. 2).Adult AEIn the older patient skin involve-ment may be similar to childhoodeczema or localised to one area,e.g. hand dermatitis.In more severe disease, involve-ment in all age groups may bemore extensive and in some casesmay encompass more than 90% ofthe integument (if acute and red,sometimes referred to as erythro-dermic eczema).EVIDENCE-BASEDMANAGEMENT There are many remedies in use,and consequently many claims ofusefulness are made by bothpatients and doctors. This articleonly looks at evidence from dou-ble-blind, randomised controlledtrials (RCTs), which are largelyregarded as the best evidence forthe effectiveness of interventions.UP TO THE YEAR 2000RCTs of interventions for AE arecomprehensively summarised in asystematic review by Hoare andco-workers.1 This review is exten-sive and summarises data from 272RCTs covering 47 different inter-ventions. The authors state that‘there was reasonable RCT evi-dence to support the use of oralcyclosporin, topical corticosteroids,psychological approaches and UVtherapy’ (as quoted by Bigby). 2There was either insufficient or noRCT evidence for many otherinterventions, such as maternalallergy avoidance for disease pre-vention, oral antihistamines,evening primrose oil, emollients,avoidance of enzymatic washingpowders, cotton as opposed to syn-thetic fibres for clothing, and theuse of twice-daily as opposed toonce-daily topical corticosteroids.It is important, however, always toremember that the absence of evi-dence does not necessarily meanthat the intervention is not success-ful.An RCT which we think may be ofparticular value for general practi-tioners, is one which examined theeffect of antihistamines in relievingpruritus. This study3 concluded thefollowing:‘Although antihistaminesare often used in the treatment ofatopic dermatitis, little objectiveevidence exists to demonstraterelief of pruritus. The majority oftrials are flawed in terms of thesample size or study design. Basedon the literature alone, the efficacyof antihistamines remains to beadequately investigated.Anecdotally, sedating antihista-mines have sometimes been usefulby virtue of their soporific effectand bedtime use may be warrant-ed.There is no evidence to supportthe effectiveness of expensive non-sedating agents.’AFTER THE YEAR 2000The following abstracts of a num-ber of RCTs published after theabovementioned review1 may beuseful to the general practitioner:• ‘Moisturizers are widely used inAE.The use of 20% glycerincream was compared with theurea-saline cream. No differ-ences were found regarding skinreactions such as stinging, itch-ing and dryness/irritation.’ Thestudy concluded that a ‘glycerincontaining cream appears to bea suitable alternative tourea/sodium chloride in thetreatment of atopic dry skin’.4• Short bursts of a potent corti-costeroid (0.1% betamethasonevalerate applied for 3 days fol-lowed by the base ointment for4 days) were compared with amild steroid (1% hydrocortisoneapplied for 7 days) in mild ormoderate AE in patients recruit-ed from general practices andfrom a hospital outpatient clinic.The study5 concluded that: ‘Ashort burst of a potent topicalcorticosteroid is just as effectiveas prolonged use of a milderpreparation for controlling mildor moderate AE in children.’The study duration was 18weeks.• House dust mite allergy is com-mon in AE and, although closelyassociated with hay fever (aller-gic rhinitis), it has also been sus-pected of increasing the severityof AE. Oosting et al.6 investigat-MAIN TOPIC530 C M E S e p t e m b e r  2 0 0 3   Vo l . 2 1   N o . 9Fig. 2. Typical flexural involvement.There are manyremedies in use,and consequentlymany claims of use -fulness are made byboth patients andd o c t o r s .ed this association and conclud-ed that: ‘Use of house dustmite-impermeable encasingsresulted in a significant decreasein allergen concentrations.However, this reduction in aller-gen load did not result in signifi-cant changes in clinical parame-ters between the groups.’• The wet-wrap dressing tech-nique has proved to be benefi-cial in cases of exacerbatedatopic dermatitis (AD) skinlesions.The aim was to investi-gate the effect of wet-wrapdressings in a controlled trialcomparing a steroid-containing(mometasone furoate 0.1%) anda steroid-free (vehicle) prepara-tion in an inpatient comparisonstudy.Twenty children aged 2 -17 years with exacerbated ADwere treated twice daily withwet-wrap dressings over a 5-dayperiod. The study concludedthat ‘Application of the wet-wrap dressing technique forexacerbated AD lesions is effec-tive, combination with a topicalsteroid being superior to asteroid-free application withoutbearing the risk of a bacterialsuperinfection.’7• A systematic review of the bene-fit of breast-feeding in prevent-ing AE concluded that:'Exclusive breast-feeding duringthe first 3 months of life is asso-ciated with lower incidence ratesof AD during childhood in chil-dren with a family history ofatopy. This effect is lessened inthe general population and neg-ligible in children without first-order atopic relatives. Breast-feeding should be strongly rec-ommended to mothers ofinfants with a family history ofatopy, as a possible means ofpreventing AE.’8• The effect of early supplementa-tion with gamma-linoleic acid(GLA)  (i.e. oil of evening prim-rose) given as borage oil supple-ment (containing 100 mg GLA)or sunflower oil supplement as aplacebo daily for the first 6months of life was investigatedby Van Gool and co-authors.9The main outcome measureswere the following: the inci-dence of AD in the first year oflife (by UK Working Party crite-ria), the severity of AD(SCORing Atopic Dermatitis;SCORAD), and the total serumimmunoglobulin E (IgE) con-centration at the age of 1 year.The results showed a favourabletrend for severity of AD associ-ated with GLA supplementation(SCORAD ± SD: 6.32 ± 5.32)in the GLA-supplementedgroup compared with 8.28 ±6.54 in the placebo group (p =0.09; p = 0.06 after adjustmentfor total serum IgE at baseline,age 1 week). However, therewere no significant effects onthe other atopic outcomes.Theauthors’ conclusion was that‘Early supplementation withgamma linoleic acid in childrenat high familial risk does notprevent the expression of atopyas reflected by total serum IgE,but it tends to alleviate theseverity of atopic dermatitis inlater infancy in these children.’• Two recent RCTs examined theeffectiveness of tacrolimus (asynthetic immune modulatorwith cyclosporin-like effects) inAE.The study by Reitamo andco-workers10 concluded that:‘The efficacy of 0.1% tacrolimusointment was similar to that of0.1% hydrocortisone butyrateointment and was lower for0.03% tacrolimus ointment. Noserious safety concerns wereidentified.’ (Please note that0.1% hydrocortisone butyrateointment is a potent corticos-teroid with similar strength tobetamethasone valerate.) Inanother study11 the same groupcompared tacrolimus to 1%hydrocortisone acetate (a mildcorticosteroid) and concludedthat: ‘Tacrolimus, 0.03% and0.1%, was significantly moreeffective than 1% hydrocorti-sone acetate and 0.1%tacrolimus was more effectivethan 0.03% tacrolimus in thetreatment of moderate-to-severeAD in children. No safety con-cerns were identified.’• A recent study12 on the effective-ness of pimecrolimus comparedwith placebo showed impressiveresults: ‘First flare was 144 daysin the pimecrolimus group and26 days in the control group (p < 0.001). Pimecrolimus treat-ment was also associated withimprovement in signs and symp-toms of AD, pruritus, patients'self-assessment and quality oflife.’ The authors concludedthat: ‘Pimecrolimus cream 1%bid is an effective, well-tolerat-ed, long-term treatment for ADin adults, substantially reducingthe number of flares comparedto a conventional therapy andconsequently reducing or elimi-nating the need for corticos-teroid.’• Azathioprine has been usedanecdotally and has now beenproved in an RCT to be ‘aneffective and useful drug insevere AD although it is notalways well-tolerated.Monitoring of the full bloodcount and liver enzymes isadvisable during treatment.’13MAIN TOPICC M E S e p t e m b e r  2 0 03   Vo l . 2 1   N o . 9   531The wet-wrap dress -ing technique hasproved to be benefi -cial in cases of exac -erbated atopic der -matitis (AD) skinl e s i o n s .SUGGESTED PRACTICALMANAGEMENT OF AE• Diagnosis. Making the correctdiagnosis is largely dependent onthe history (personal and familyhistory of atopy, i.e. asthma, hayfever) and examination (acute ver-sus chronic eczema and areas ofpredilection).• Moisturisers. Although there areno RCTs on the effect of soap, wehave found the substitution of soapwith aqueous cream very helpful(less drying and therefore less like-ly to induce itch and scratching).We recommend petroleum jelly oremulsifying base as a moisturi s e r.These are oily and may not beacceptable to all patients, in whichcase water-based moisturisers suchas aqueous, cetomacrogol, liquidparaffin and other creams contain-ing glycerin or urea 4 may be moreacceptable. Generally, lotions arenot very useful. To reduce the riskof added irritants we warn ourpatients to avoid antiseptic, topicalantihistamine and perfume-con-taining creams and ointments.• Topical steroids. For acuteflares, we recommend the use of1% hydrocortisone acetate to theface and neck and topicalbetamethasone to the body as wellas wet wraps7 (we use two layers ofcotton tubular bandage as a dress-ing, a wet (damp — warm water)layer underneath and a dry layeron top) for up to a maximum of 5days (see Figs 3 and 4). It isimportant to continue with the liberal use of moisturiser. The useof wet wraps may be continuedeven without topical corticos-teroids (i.e. with moisturiseralone).The advantages of wetwraps include increased contactwith the skin during treatment(topical steroid is not rubbed offonto bed linen), and reduction ofthe skin temperature — thusreducing warmth, sweating anditch and indirectly improving sleep.The quantity of topical steroid ismeasured according to the ‘fingertip’ method.14• Antihistamines. The effect ofantihistamines on itch has not beenproved beyond doubt, but sedatingantihistamines are useful by virtueof their soporific effect.There is noevidence to support the effective-ness of expensive non-sedatingagents.• Oil of evening primrose maybe helpful, but more RCTs areneeded to confirm the beneficialeffects, particularly in view of thecost involved.Therefore oil ofevening primrose is not routinelyrecommended in our centre butneither is it discouraged in theindividual patient who inquiresabout its usefulness (discuss theinsufficient evidence with thepatient or parent).• Newer macrolide treatments.There is an excellent chapter byWilliams et al.15 on the evidence-based treatment of AE. It sum-marises data from 7 RCTs on tra-colimus as follows:‘About a thirdof study participants with moder-ate-to-severe AE achieve excellentresults, defined as at least 90%improvement in the physician’sglobal assessment. A transientburning sensation is a commonside-effect that occurs in about halfof adults investigated, but is sel-dom severe enough to necessitatestopping treatment.’Tacrolimus is recommended formoderate to severe disease, where-as pimecrolimus is effective in mildto moderate disease. In the USA,pimecrolimus is approved for‘short-term intermittent therapy inthe treatment of mild-to-moderateAD in non-immunocompromisedpatients 2 years or older, in whomMAIN TOPIC532 C M E S e p t e m b e r  2 0 0 3   Vo l . 2 1   N o . 9Fig. 3. Wet-wrap treatment of a baby.Fig. 4. Wet wraps in an older child.Note relative sparing of the face.the use of alternative, conventionaltherapies is deemed inadvisable . . .or in patients who are not ade-quately responsive or are intolerantto conventional therapies.’16Note that the effect of these treat-ments is equivalent to moderatelypotent topical steroids. Topicalsteroids are safe and effective, pro-vided they are used for short, inter-mittent periods as recommendedabove.The use of the newer bio-logical treatments is limited by thecost and availability.What about patients who do notrespond? They should be referredto a dermatologist for considera-tion of other treatment which mayinclude ultraviolet light (with orwithout topical or oral psoralens),azathioprine, and cyclosporin. Oralsteroids are best avoided for thetreatment of AE.We wish to thank Dr S Jessop for herhelpful comments on the manuscript.References1. Hoare C, et al. Health Technol Assess 2000;4: 1-191.2. Bigby M. Arch Dermatol 2001; 137: 1635-1636.3. Klein PA, et al. Arch Dermatol 1999; 135:1522-1525.4. Loden M, et al. Acta Derm Venereol 2002;82: 45-47.5. Thomas KS, et al. BMJ 2002; 324: 768.6. Oosting AJ, et al. J Allergy Clin Immunol2002; 110: 500-506.7. Schnopp C, et al. Dermatology 2002; 204:56-59.8. Gdalevich M, et al. J Am Acad Dermatol2001; 45: 520-527.9. Van Gool CJ, et al. Am J Clin Nutr 2003;77: 943-951.10. Reitamo S, et al. J Allergy Clin Immunol2002; 109: 547-555.11. Reitamo S, et al. J Allergy Clin Immunol2002; 109: 539-546.12. Meurer M, et al. Dermatology 2002; 205:271-277.13. Berth-Jones J, et al.Br J Dermatol 2002;147: 324-330.14.  Long C, et al. Clin Exp Dermatol 1991; 16: 444-447.15.  Williams H, et al. Evidence-basedDermatology. London: BMJ Books, 2003:144-225.16. Anon. FDA licensing review of pimecrolimuswww.fda.gov/cder/foi/nda/2001/21-302.Elidel.htm.MAIN TOPIC534 C M E S e p t e m b e r  2 0 0 3   Vo l . 2 1   N o . 9IN A NUTSHELLAtopic eczema (AE) is a commonchronic condition characterised by adry, itchy skin, associated with flaresand remissions.The exact cause of AE is unkown,but a combination of genetic andenvironmental factors probably inter-acts. The importance of the latter isemphasised by the observation of anincreased incidence in relatives whohave moved from a rural to an urbanenvironment.The clinical presentation variesaccording to the age of the patient.Many remedies are usually tried byboth the patient and the doctor, butwe only consider treatments basedon evidence from randomised con-trolled trials (RCTs).Practical management consists of thecorrect diagnosis, moisturising theskin with aqueous cream or petrole-um jelly, topical steroids and wetwraps in acute flare-ups, and the useof the newer macrolide treatments inpatients with moderate to severe AE.However, use of the latter is limitedby cost and availability.Breast-feeding by a mother with ahistory of atopy may go some waytowards preventing a child fromdeveloping eczema later in life.The usefulness of antihis tamines toprevent itch has not been provedbeyond doubt, nor has that ofevening primrose oil.SINGLE SUTUREUsing household possessions to identify the poorInformation on income and expenditure are difficult and time-consuming to obtain, but those working onchild-health interventions need information on household economic status. An alternative is to use informa-tion on household possessions and characteristics of a family’s house. For example, households owning a carcan be judged to be wealthier than those owing a motorcycle, which in turn are deemed wealthier than thoseowning 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 oneindex of wealth by various means.(Victoria CG, et al.Lancet 2003; 362: 233-241.)  

Evidence-based treatment of atopic eczema in general practice

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Evidence-based treatment of atopic eczema in general practice

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