Annals Eczema

7/29/2019 Annals Eczema

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Inthe

Clini

cIn the ClinicAtopicDermatitis(Eczema)Prevention page ITC5-2

Diagnosis page ITC5-3

Treatment page ITC5-7

Practice Improvement page ITC5-13

Tool Kit page ITC5-14

Patient Information page ITC5-15

CME Questions page ITC5-16

Physician WriterSusan V. Bershad, MD

Section EditorsDeborah Cotton, MD, MPHDarren Taichman, MD, PhDSankey Williams, MD

The content ofIn the Clinic is drawn from the clinical information and education

resources of the American College of Physicians (ACP), including PIER (Physicians

Information and Education Resource) and MKSAP (Medical Knowledge and Self-

Assessment Program). Annals of Internal Medicine editors develop In the Clinic

from these primary sources in collaboration with the ACPs Medical Education andPublishing divisions and with the assistance of science writers and physician writ-

ers. Editorial consultants from PIER and MKSAP provide expert review of the con-

tent. Readers who are interested in these primary resources for more detail can

consult http://pier.acponline.org, http://www.acponline.org/products_services/

mksap/15/?pr31, and other resources referenced in each issue ofIn the Clinic.

CME Objective: To review current evidence for the prevention, diagnosis, and

treatment of atopic dermatitis (eczema).

The information contained herein should never be used as a substitute for clinical

judgment.

2011 American College of Physicians

wnloaded From: http://annals.org/ by Jose Roel on 10/04/2012


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Can AD be prevented?Efforts at primary prevention of ADhave focused on prenatal and earlychildhood exposure to, or avoidanceof, various dietary and environmentalfactors, including baby formulas and

breast feeding; allergenic foods suchas peanuts, soy, cows milk, and eggs;probiotic supplements; and house-hold pets. By and large, these studieshave not demonstrated the useful-ness of such measures.

When contemplating parenthood,patients with past or current AD,asthma, or other type I allergies

should be aware of the AmericanAcademy of Pediatrics recommen-dations for early nutritionalinterventions to prevent atopicdisease, summarized in a 2008 po-sition paper based on extensive re-

view of high-quality evidence (11)(Box: Recommendations from theAmerican Academy of Pediatricsfor Atopic Disease in High-RiskInfants). Although exclusivebreastfeeding of newborns hasbeen associated with a lower riskfor AD in some studies, othershave shown no benefit, and thisissue remains controversial.

2011 American College of Physicians ITC5-2 In the Clinic Annals of Internal Medicine 1 November 2011

1. Spergel JM. Epidemiol-ogy of atopic dermati-tis and atopic marchin children. ImmunolAllergy Clin North Am.2010;30:269-80.[PMID: 20670812]

2. Su JC, Kemp AS, Vari-gos GA, et al. Atopiceczema: its impact onthe family and finan-cial cost. Arch DisChild. 1997;76:159-62.[PMID: 9068310]

3. Mancini AJ, KaulbackK, Chamlin SL. The so-cioeconomic impactof atopic dermatitis inthe United States: asystematic review. Pe-diatr Dermatol.2008;25:1-6.

[PMID: 18304144]4. Barnes KC. An updateon the genetics ofatopic dermatitis:scratching the surfacein 2009. J Allergy ClinImmunol 2010;125:16-29. [PMID:PMID:20109730]

5. Irvine AD, McLeanWHI, Leung DY. Filag-grin mutations associ-ated with skin and Al-lergic diseases. N EnglJ Med. 2011, (in press)

6. Boguniewicz M, LeungDYM. Atopic dermati-tis: a disease of alteredskin barrier and im-mune dysregulation.

Immunolog Rev.2011;24:233-46. [PMID:21682749]

7. Tokura Y. Extrinsic andintrinsic types ofatopic dermatitis. JDermatol Sci.2010;58:1-7.[PMID: 20207111]

8. Ricci G, Dondi A, PatriziA. Useful tools for themanagement ofatopic dermatitis. AmJ Clin Dermatol.2009;10:287-300.[PMID: 19658441]

Eczemaand atopic dermatitis(AD) are often used synonymously. The dis-tinction is that eczema can mean inflamed skin from any cause, whereasAD is the relapsingremitting pruritic rash that occurs at typical sites,

mainly the face and skin creases, and is associated with other type I allergic dis-orders, such as asthma, food allergies, and allergic rhinitis.

AD is the most common skin condition of early childhood. Its prevalence maybe increasing in developing countries but remains stable at about 17% in theUnited States (1). The disorder begins in the first 18 months of life in approxi-

mately 65% of patients and persists beyond adolescence in 40%. In addition tocausing discomfort, sleep loss, and psychosocial challenges, AD can impose ma-jor financial burdens on families for direct medical care, household accommoda-tions, and missed work (2). In the United States, the total estimated direct costsof AD range from about $400 million to $4 billion per year (3).

AD is a multifactorial disorder involving a genetic predisposition and envi-ronmental triggers. There is no single biological marker. At-risk individualsmanifest at least 19 different associated genes. Mutations in filaggrin, an epi-dermal-barrier protein, occur in about 15% of patients and are consideredmajor predisposing factors (5, 6). Controversy surrounds recent proposalsthat there are 2 types of AD, intrinsic and extrinsic (7). The extrinsic type is

described as classical AD that occurs in conjunction with elevated IgE tovarious airborne and food allergens and is likely to show filaggrin mutation,whereas intrinsic AD is associated with normal IgE levels and a lack of mu-tated filaggrin. In patients who lack allergen-specific IgE, the World AllergyAssociation suggests the term nonatopic eczema, rather than intrinsic AD(8), and some authors prefer the term atopiform dermatitis (9).

The most widely held theory of AD pathophysiology is that it begins with acompromised skin barrier caused by defects in filaggrin or other components ofthe cellular envelope. Epidermal barrier function is further compromised by en-vironmental factors that dry the skin, such as indoor heating and harsh cleansers.Subsequent penetration by allergens, irritants, and bacteria is facilitated, thustriggering the hyperimmune response found in AD (6). Characteristically, skin

dendritic cells bearing IgE receptors become polarized as a result of cytokinesderived from injured epidermal keratinocytes, resulting in Th2-dominated re-sponses in acute AD lesions and Th22 predominance in chronic lesions (10).

Prevention

Recommendations from theAmerican Academy of Pediatrics forAtopic Disease in High-Risk Infants*

Evidence supports:Exclusive breastfeeding for the first 4

months of life

Avoiding food introduction for the first46 months

Breastfeeding plus hydrolyzed (or

elemental) formula after 4 monthsEvidence does not support:Maternal dietary manipulation during

pregnancy and breastfeeding

Delaying food introductionafter 46months

*Those who have first-degree relativeswith histories of Ig-E mediateddisorders, principally atopicdermatitis, asthma, seasonal rhinitis,and/or food allergies.



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2011 American College of PhysiciansITC5-3In the ClinicAnnals of Internal Medicine1 November 2011

In contrast to a prior 2001 systematic re-view of breastfeeding for AD prevention, a

2009 meta-analysis examining 21 studies

found that there is no strong evidence that

breastfeeding has a protective effect, ex-

cept when exclusive breastfeeding was

compared with conventional (cows milk)formula feeding. Comparisons with newer

formulas, inherent lack of blinding, and

observer bias are possible explanations for

the disparity in findings among breast-

feeding-versus-formula studies (12).

distribution, and concomitant find-ings (Table 1).

AD lesions are usually discrete butvaguely delineated, erythematous, andscaly. They can take the form of flatpatches, edematous plaques, or closelygrouped raised papules, on a back-ground of dry skin. Cracking, excori-ations, bleeding, crusting, hyperpig-mentation and lichenification may bepresent as secondary findings that re-flect frictional trauma, consequentbacterial superinfection. and postin-flammatory pigmentary alterations.

In adults, typical AD sites include theface, particularly the eyelids (Figure 1)and perioral area; the antecubital andpopliteal fossae and other flexuralcreases (Figures 2 and 3); extensorsurfaces of the limbs; and the hands(Figure 4) and feet. In infants andchildren, AD has a greater likelihoodto affect the cheeks (Figure 5), chin,forehead, base of the neck, and the di-aper area, in addition to the flexural

surfaces and periorificial areas of theface. AD is almost always bilateral andfairly symmetrical. In severe cases, itcan be widespread.

Nummular dermatitis is a pattern ofAD that consists of 1 or more oval,erythematous patches (Figure 6).Chronic AD is associated with pro-longed scratching that may result in

What items in the history andphysical examination suggest AD?

History and physical examinationare the keys to AD diagnosis.Many versions of the classical crite-ria proposed by Hanifin and Rajkain 1980 (13) have been used toidentify AD for research purposes.Of these, the most extensively vali-dated are the UK Working PartyCriteria (14), which have beenadapted to clinical practice as aconcise list of minimum criteria(Box: Diagnostic Criteria for

Atopic Dermatitis).What elements of the historyshould clinicians focus on inevaluating patients with AD?Elements of the patients history thatstrongly suggest AD are early child-hood onset, generalized dry skin,pruritus and scratching, other familymembers with AD, and a personalor family history of such allergic dis-orders as asthma, allergic rhinitis,and food allergies. If treatment has

been tried with topical corticos-teroids, a full or partial response andsubsequent relapse are exceedinglycommon (Table 1).

How should clinicians carry out askin examination?A thorough skin examinationrequires observation of the mor-phology of the lesions, pattern of

Prevention... Primary prevention of AD is difficult because heredity plays a large

role in its development. Expectant parents with a history of AD, asthma, or foodallergies should be made aware that risk might be decreased or delayed in theiroffspring by exclusive breastfeeding and avoidance of food introduction for 4 to 6months. Extensively hydrolyzed and elemental baby formulas after 4 to 6 monthsseem to be safer than traditional cows milk or soy formulas for high-risk infants.

CLINICAL BOTTOM LINE

Diagnosis

Figure 1. Acute episode of seasonallyrecurring eyelid dermatitis in a 29-year-oldman. This finding is typical in individualswith pollen-specific IgE. Dennie-Morganfolds (extra creases) are apparent in theinfraorbital region. Photo credit: CarolineHalverstam, MD.

Diagnostic Criteria for AtopicDermatitis*

Patient must have pruritus in thepast 12 months, plus 3 or more ofthe following:

History of skin-crease dermatitisor cheek dermatitis (in infants)

Personal history of asthma or hayfever (or first-degree relative if< age 4 y)

History of generalized dry skin inpast year

Visible skin-crease dermatitis (ordermatitis of the cheeks, forehead,or outer limbs if < age 4 y)

Onset before age 2 years (not usedin patients < age 4 y)*Adapted from reference 15.



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lichenification, a grayish to purple-hued skin thickening; patterns of se-vere lichenification include plaques,known as lichen simplex chronicus,and papules, referred to as prurigonodularis (Figure 7).

Associated skin findings that helpconfirm the diagnosis of AD, al-

though they are not always pres-ent, are ichthyosis vulgaris,pityriasis alba, keratosis pilaris,hyperlinear palms, and infraorbitalcreases, also called Dennie-Morgan folds (Figure 1).

How should the severity of AD beclassified?Establishing the severity of AD isan essential element of the initialassessment and follow-up visit.

In general, mild AD causes minimalpruritus and sleep disturbance anddisplays barely noticeable or minorfindings on skin examination. Mod-erate AD is likely to cause episodesof marked pruritus, sleep disruption,and apparent physical signs. SevereAD is associated with extreme orconstant pruritus, sleep deprivation,

and major widespread skin signs thatinclude bleeding, crusting, weeping,and lichenification.

Validated instruments used for clini-cal monitoring and research assess-ments (SCORAD, EASI, andPOEM), are advocated by profes-sional organizations to improve thequality of clinical care of AD (Table2) and to provide reproducible evalua-tion standards. Although each

Figure 2. Chronic antecubital atopicdermatitis showing follicular prominence,lichenification, and hyperpigmentation in ayoung woman. Photo credit: Susan V.Bershad, MD.

Table 1. Elements of the History and Physical Examination for Atopic Dermatitis

Category Element Ask About, or Look for. . . Notes

History Duration Age at onset Onset of AD is usually before age 2 yAcute, intermittent, or chronic

Symptoms Pruritus; sleep disturbance AD is always pruritic

Other allergic disorders Personal history of asthma, seasonal allergies, Ask if suspected food and airborne allergens werefood allergies confirmed by RAST or skin prick tests

Prior treatments Regular emollient use; corticosteroids; Dry skin is a common precipitant of AD; responsecalcineurin inhibitors; oral antihistamines; and relapse to topical medication is typicalantibiotics; natural remedies; other medicines;light treatments (e.g., phototherapy with UVA,

narrow-band UVB)Environment Personal care products; dust; pollen; animal Traditional recommendations include neutral-pH

fibers in clothing; goose down and feathers soap, fragrance-free products, cotton clothing,in bedding hypoallergenic bedding

Family history Atopic dermatitis, asthma, seasonal allergies, Family history is almost always positive for oneand food allergies in first-degree relatives or more type I allergies

Physical examination General skin Dry skin (xerosis)examination

Distribution of lesions Face and scalp; flexural creases; extensor Adults are more prone to AD lesions on drysurfaces; hands and feet; widespread extensor surfaces and are less prone to cheek

and forehead lesions; genital and web spacelesions suggest scabies.

Morphology of lesions Flat scaling patches; edematous plaques; Unusual patterns, such as widespread vesicles,grouped papules; nummular (oval) patches bullae, honey-colored crusts, or pustules, suggest

viral or bacterial infection

Intensity of lesions Degree of erythema; oozing/crusting;excoriation; cracking/fissuring; flaking;bleeding

Concomitant skin Ichthyosis vulgaris; Dennie-Morgan folds;findings pityriasis alba; keratosis pilaris;

hyperlinear palms

Other systems Enlarged lymph nodes; wheezing Lymphadenopathy may indicate chronicsuperinfection; AD patients are at greater riskfor asthma and seasonal allergies

AD = atopic dermatitis; RAST = radioallergosorbent testing; UVA = ultraviolet A; UVB = ultraviolet B



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produces a cumulative score that cor-relates with global severity, they donot provide a strict formula to gradeoverall severity. Describing AD asmild, moderate, or severe is ultimate-ly a matter of judgment that involvesthe patient and caregiver.

SCORAD is the most comprehen-sive, whereas EASI is based solely onthe extent and severity of 4 physicalsigns; both involve a multistep calcu-lation of the total score. POEM isthe simplest to administerthepatient can fill it out in the waitingroom and is takes only a few secondsto score, but it only assesses only thefrequency of 7 characteristic signsand symptoms and not the extent orseverity of lesions.

What other conditions should be

considered in the differentialdiagnosis?When a diagnosis of AD is beingconsidered, the site and distributionof a rash are important distinguish-ing features (Table 3). When theeyebrows, nasoalar creases, innercheeks, scalp, and chest are in-volved, one must consider sebor-rheic dermatitis. In seborrheic

Figure 3. Acute exacerbation of flexuraldermatitis on the wrist of a 29-year-oldfair-skinned man with a history of atopicdermatitis from infancy. Photo credit:Caroline Halverstam, MD.

dermatitis, exfoliated skin scalestend to be larger, whiter, and greas-ier than the fine dry scales or yel-lowish crusts of AD. Althoughboth disorders respond to topicalcorticosteroids, seborrheic dermati-tis responds to more frequent skincleansing and shampooing, whichtend to exacerbate AD.

Psoriasis is another erythematous scal-ing eruption. It affects teenagers andadults more often than infants andchildren. Typically, psoriasis plaquesare more raised and have a thickerscale than AD lesions, and they tendto occur on extensor surfaces, some-times making them difficult to dis-tinguish from the nummular (oval)form of AD. Lesions on the handsand feet may also present diagnostic

challenges when other characteristicAD sites are unaffected.

When a suspected case of AD is re-fractory to treatment, one shouldconsider allergic contact dermatitis.A thorough history may reveal re-cent exposure to a new perfume orgrooming product or a common al-lergen, such as latex, nickel in jewel-ry or belt buckles, or a poison plant.When examining the patient, lookfor a pattern that is asymmetrical orlimited to areas of contact.

It is important to remember that in-fections and infestations are commonand can coexist with AD. When scalypatches are present on the scalp, onemust consider the possibility of der-matophyte infection (tinea capitus)and perform fungal culture of hair andskin scrapings, because treatment re-quires systemic antifungal therapy.Nummular dermatitis can be virtually

indistinguishable clinically from tineacorporis, which generally responds totopical antifungal agents. Likewise,even in a patient with known AD,scabies infestation must be consideredwhen a pruritic eruption involves theskin folds, especially around thewrists, genital area, and finger and toeweb spaces. In such cases, microscopicexamination of skin scrapings is often

Figure 4. Recurrent hand dermatitis withcracking and honey-colored crusts due toStaphylococcus aureussuperinfection in a 40-year-old woman with a long history of atopicdermatitis and dry skin in winter. Photo credit:Jacob Levitt, MD.

Figure 5. An infant girl with atopicdermatitis and secondary Staphylococcusaureus impetigo on the cheeks and neckcreases. Photo credit: Susan V. Bershad, MD.

Table 2. Severity Scoring tools for AD*

Outcome Measure EASI SCORAD POEM

Extent/bodysites affected X X

Symptoms

Pruritus X X

Sleep disturbance X X

Intensity of lesions

Erythema X XEdema/induration X X

Oozing/crusting X X

Excoriation X X

Lichenification X X

Dryness X X

Cracking/fissuring X

Flaking X

Bleeding X

* AD = atopic dermatitis. Adapted from reference16. EASI = Eczema Area and Severity Index (17);SCORAD = SCORing Atopic Dermatitis (18); POEM =Patient-Oriented Eczema Measure (19).



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AD, a condition known as eczemavaccinatum.

What is the role of laboratorytesting in evaluation of AD?Laboratory testing is not needed for adiagnosis of classical AD, but a skin

byStaphylococcusand Streptococcusorganisms, and herpes simplexand varicella-zoster infections(i.e., eczema herpeticum). Small-pox vaccination, although rarelygiven today, can cause seriouswidespread secondary infection of

negative, and empirical treatment witha scabicide is warranted.

AD patients presenting withcrusting or blistering lesions mustbe evaluated for secondary infec-tions, including impetigo caused

Table 3. Differential Diagnosis of Atopic Dermatitis

Disease Typical Demographics Physical examination How to Diagnose Notes

Seborrheic Newborns and Erythema and coarse, greasy Physical examination; positive One of the most common skindermatitis infants; teens scale, located on the face response to frequent cleansing disorders after puberty

and adults (especially eyebrows and and shampooing, which makenasolabial folds), scalp, presternal AD worse; skin biopsy showsarea; canbe widespread (rare) non-specific features

Psoriasis Any age, but seldom Erythematous, raised plaques Physical examination; family Inverse psoriasis shows a flexural orseen in infants; most covered by thick, silvery scale, history is often positive for intertriginous pattern that can becommon in teens located on the scalp, extensor psoriasis; skin biopsy shows confused with AD; guttate psoriasis

and young to surfaces (especially elbows and characteristic features can appear acutely as dozens ofmiddle-aged adults knees), hands, feet, and trunk small lesions, characteristically fol-

lowing an upper respiratory infec-tion; presents on rare occasions asgeneralized erythroderma withwidespread scaling

Allergic Any age; certain Erythema, scaling, blisters, or History of exposure to a contact Poison ivy is the most commoncontact types of workers crusts, sometimes asymmetrical, allergen; physical examination; cause; may also be related to otherdermatitis are more prone following a pattern of contact skin patch testing; skin biopsy plants, costume jewelry, belt

due to occupational with the offending substance is nonspecific buckles, tools, rubber derivatives,exposure to contact cosmetic ingredients, topicalallergens, for medications (especially antibioticsexample: chemicals, and anesthetics), preservatives, andnickel, or latex gloves dozens of other everyday exposures

Tinea capitus Infants, children, Pruritic scaling, crusting, and Scalp scrapings may show fungal False-negative KOH preparations(scalp derma and teens; erythema of the scalp; may be hyphae on direct KOH exam; scalp are common, therefore fungaltophyte relatively rare localized to oval patches or biopsy usually not needed but cultures are needed forinfection) in adults widespread, with possible may show fungal elements on PAS confirmation; requires at least

stain; fungal culture of scrapings 6 weeks of oral antifungal therapyusually positive within 2 weeks

Tinea facei, Any age; tinea Inflammatory type appears as Skin scrapings may show fungal False-negative KOH preparationscorporis, pedis, and cruris are typical ringworm, with active hyphae on direct KOH examination; are common, therefore fungalor cruris (derma- more common red scaling border and central skin biopsy shows fungal elements cultures are needed fortophyte infection after puberty clearing; noninflammatory type on PAS stain; fungal culture of confirmation; localized cases onof the face, appears as dry scaling patches scrapings usually positive within nonhairy areas can be treated withbody, feet, or of skin or maceration between 2 weeks topical antifungal therapygroin area) the toes

Scabies Any age Extremely pruritic, excoriated, History of recent onset of an itchy Burrows are not always seen;infestation small erythematous papules on rash in the index patient and other empirical treatment is

typical sites, such as the axillae, affected household members can be recommended when scabies cannotinner wrists, groin, genitals, highly suggestive; wet preparation be ruled out clinically; can be seen

intergluteal area, and finger and of skin burrow scrapings or skin as a comorbid condition with ADtoe web spaces; may be biopsy may show scabies mites,widespread eggs, or feces; skin biopsy is often

characteristic of arthropod-inducederuptions

Systemic immune Infants and Recalcitrant widespread AD, or History and physical examination The possibility of an immunedisorders (severe children an eruption that resembles AD, for typical features; immunologic, disorder should be considered incombined immune starting during infancy or early metabolic, and genetic evaluations cases of severe refractory ADdeficiency; the childhood, with recurrent as needed; skin biopsy usually when seen in infants and childrenhyper IgE systemic and local infections nonspecific. who fail to thrivesyndrome; theNethertonsyndrome; theWiscott-Aldrichsyndrome;phenylketonuria)

AD = atopic dermatitis; KOH = Potassium hydroxide prep of skin scrapings; PAS = Periodic acidSchiff histologic stain



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biopsy may be helpful in atypical cas-es. Although the histologic findings ofAD are nonspecific, some differentialdiagnoses, particularly psoriasis, sca-bies, and dermatophytosis, usually ex-hibit diagnostic features on micro-scopic examination. Dermatophyteinfections, such as tinea capitus andtinea corporis, can also be diagnosed

by direct microscopic examination ofskin scrapings mounted in potassiumhydroxide.

Certain laboratory tests are usedprincipally to assess complicationsand to guide management. When le-sions are crusted, bacterial cultureand sensitivity are used to select ad-junctive topical or systemic antibiotictreatment. Viral studies, includingdirect fluorescent antibodies and cul-

ture for herpes simplex and varicellazoster, are needed to confirm sus-pected cases of eczema herpeticumrequiring systemic antiviral therapy.

In a patient with refractory dermatitis,allergic contact dermatitis should beconsidered and, if necessary, arrangefor skin patch testing to detect typeIV delayed hypersensitivity to com-mon contact allergens, including nick-el, rubber, and fragrance ingredients.

Radioallergosorbent testing(RAST) for allergen-specific IgEhas a high predictive value for diag-nosis of AD, because more thanhalf of patients with AD have IgEsensitivity to at least one airborneor food allergen. Skin prick testsare also used to identify and con-firm such sensitivities.

In an international study of 2184 infants

with AD, 53% had increased total IgE and

56% showed allergen-specific IgE. Sensitiv-

ity to the most common aeroallergens

(house dust mites, cat dander, grass pollen)

were universal, but specific food sensitivi-

ties varied widely among countries (20).

How common are food allergies,and how are they related?At least 170 foods have been re-ported to cause IgE-mediated al-lergic reactions. Of these, 8 major

food allergens have been identi-fied: peanuts (0.6% prevalence inthe U.S. population); tree nuts(0.4%); fish and crustacean shell-fish (0.6% in children and 2.8% inadults); cows milk (2.2% in aDanish cohort); hens eggs (1.6%in a Norwegian cohort); wheat;and soy (21). The vast majority of

patients eventually develop toler-ance to cows milk, eggs, soy, andwheat, but not to peanuts OR treenuts. Curiously, fish and shellfishallergies are more prevalent inadults than in children.

Although there are no high-quali-ty studies of food allergies inadults, food sensitivity in childrenis more common in atopic versusnonatopic individuals, and it is

also a risk factor for greater sever-ity of disease.

A cross-sectional study of over 2000 pa-

tients with AD aged 1324 monthsshowed the following rates of elevated IgE:

7% to hens eggs, 4% to peanuts, and 3% to

cows milk. There was a direct correlation

between the frequency of positive IgE re-sponses and the severity of AD (22).

The National Institute of Allergyand Infectious Diseases (NIAID)recently developed best practiceclinical guidelines for the diagno-sis and management of food aller-gy (21). The Guidelines distin-guish between food sensitization,meaning laboratory evidence ofelevated allergen-specific IgE, andfood allergy, meaning occurrenceof clinical symptoms from expo-sure to particular foods. Asidefrom systemic symptoms, such aswheezing, tachycardia, nausea,dizziness, and anaphylaxis, foodreactions can include such skinfindings as AD, urticaria, an-gioedema, flushing, and pruritus.

Food allergies are identified by acombination of allergen-specificIgE, skin prick test to the specificfood, improvement with food elim-ination, and relapse with subse-quent oral challenge.

Figure 6. Nummular pattern of atopicdermatitis on the lower extremity of an adultmale, showing grouped papules coalescing intooval plaques. Photo Credit: Jacob Levitt, MD.

9. Bos JD, BrenninkmeijerEE, Schram ME, et al.Atopic eczema oratopiform dermatitis.Exp Dermatol.

2010;19:325-31.[PMID: 20100192]

10. Novak N, Peng W, YuC. Network ofmyeloid and plasma-cytoid dendritic cellsin atopic dermatitis.Adv Exp Med Biol.2007;601:97-104.[PMID: 17712996]

11. Thygarajan A, BurksAW. American Acade-my of Pediatrics rec-ommendations onthe effects of earlynutritional interven-tions on the develop-ment of atopic dis-ease. Curr OpinPediatr. 2008;20:698-

702.[PMID: 19005338]

12. Yang YW, Tsai CL, LuCY. Exclusive breast-feeding and incidentatopic dermatitis inchildhood: a system-atic review and meta-analysis of prospec-tive cohort studies. BrJ Dermatol.2009;161:373-83.[PMID: 19239469]

13. Hanifin JM, Rajka G.Diagnostic features ofatopic dermatitis.Acta Derm Venereol.1980;92:44-47.

14. Brenninkmeijer EE,Schram ME, Leeflang

MM, et al. Diagnosticcriteria for atopic der-matitis: a systematicreview. Br J Dermatol.2008;158:754-65.[PMID: 18241277]

15. Williams HC, BurneyPG, Pembroke AC, etal. The U.K. WorkingPartys Diagnostic Cri-teria for Atopic Der-matitis. III. Independ-ent hospitalvalidation. Br J Der-matol. 1994;131:406-16. [PMID: 7918017]



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dermatologists perform skin patchtesting, which is necessary to diagnosesuspected allergic contact dermatitis.

An allergist should be consulted toperform and interpret RAST or skinprick tests when needed to evaluatepossible airborne or food allergies.

When should a dermatologist oran allergist be consulted fordiagnostic help?A dermatologist can be helpful foratypical cases of AD that fail to re-spond to initial treatment or when askin biopsy is being considered to ruleout other disorders. Certain

16. Schmitt J, Langan S,Williams HC; Euro-pean Dermato-Epi-demiology Network.What are the bestoutcome measure-ments for atopiceczema? A systemat-ic review. J AllergyClin Immunol.2007;120:1389-98.[PMID: 17910890]

17. Hanifin JM, ThurstonM, Omoto M, et al.

The eczema area andseverity index (EASI):assessment of relia-bility in atopic der-

matitis. EASI Evalua-tor Group. ExpDermatol.2001;10:11-8.[PMID: 11168575]

18. Severity scoring ofatopic dermatitis: theSCORAD index. Con-sensus Report of theEuropean Task Forceon Atopic Dermatitis.Dermatology.1993;186:23-31.[PMID: 8435513]

19. Charman CR, VennAJ, Williams HC. Thepatient-orientedeczema measure: de-velopment and initialvalidation of a new

tool for measuringatopic eczema severi-ty from the patientsperspective. ArchDermatol.2004;140:1513-9.[PMID: 15611432]

20. de Benedictis FM,Franceschini F, Hill D,et al. The allergic sen-sitization in infantswith atopic eczemafrom different coun-tries. Allergy.2009;64:295-303.[PMID: 19133917]

21. Boyce JA, Assaad A,Burks AW, et al.Guidelines for the di-agnosis and manage-

ment of food allergyin the United States:summary of the NI-AID-Sponsored Ex-pert Panel report. JAm Acad Dermatol.2011;64:175-92.[PMID: 21167411]

22. Wahn U, Warner J, Si-mons FE, et al. IgE an-tibody responses inyoung children withatopic dermatitis. Pe-diatr Allergy Im-munol. 2008;19:332-6. [PMID: 18422892]

Treatmentceramide-containing lotion for 4 weeks, 20

patients reported complete resolution of

symptoms, and stratum corneum hydration

increased significantly (28).

Over the past decade, wet-wrapdressings have gained in popularityfor AD therapy. While somewhatcumbersome, they have been shownto improve skin barrier function andAD symptoms. Such dressings must

be changed frequently to preventbacterial colonization (29).

Time-tested measures that arecommonly used and believed to behelpful but lack clinical trialsinclude the use of neutral-pHunscented soaps, nonsoap hypoal-lergenic cleansers, and additive-freelaundry detergents; wearing com-fortable clothing made of cottoninstead of wool and syntheticfibers; and avoiding pillows and

bedding that contain feathers,down, or animal fibers.

Is there a role for complementaryand alternative medicine?Traditional Chinese herbal medi-cines and other so-called naturalremedies, such as aloe vera gel,evening primrose oil, and St. Johnswort, are popular nonprescription

What nonpharmacologic measuresshould be used in management?How should patients with AD carefor their skin?Conservative dry-skin care can bevery beneficial for patients with AD.Moisturizers, also known as emol-lients, reduce transepidermal waterloss and reduce skin barrier compro-mise. Daily use of an emollient prod-uct is universally recommended to en-

hance and protect the skin barrier (23,24), but there have been no random-ized, controlled trials (RCTs) of ADtreatment with emollients alone, ex-cept for one study that showed mildefficacy that was inferior to that oftopical corticosteroid cream (25).Clinical trials using emollients as ad-junctive therapy have shown them tobe effective corticosteroid-sparingagents (26, 27). An emollient oint-ment, cream, or lotion is particularly

recommended after bathing. Manydermatologists recommend purepetrolatum or emollients that containa high ratio of petrolatum to water.Medium-quality evidence shows thatAD patients can also be treated suc-cessfully with nongreasy moisturizerscontaining ceramides.

In an uncontrolled trial of 29 patients (ages519 y) with mild-to-moderate AD applying

Diagnosis... AD diagnosis is based on clinical criteria that require a history and physi-cal findings confirming early onset of generalized dry skin with pruritus, predomi-nantly on the face and flexural areas of the limbs. There are several validated instru-ments that are helpful for grading severity. In the differential diagnosis, seborrheicdermatitis, psoriasis, and allergic contact dermatitis can usually be excluded on clini-cal grounds but occasionally require skin biopsy or patch testing. Other laboratorytests are rarely needed for diagnosis but may be helpful to detect bacterial, fungal, orviral comorbid conditions and to identify contributory airborne and food sensitivities.




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23. Hanifin JM, Cooper

KD, Ho VC, et al.Guidelines of care foratopic dermatitis, de-veloped in accor-dance with theAmerican Academyof Dermatology(AAD)/AmericanAcademy of Derma-tology AssociationAdministrative Regu-lations for Evidence-Based Clinical Prac-tice Guidelines. J AmAcad Dermatol.2004;50:391-404.[PMID: 14988682]

24. Saeki H, Furue M, Fu-rukawa F, et al. Guide-lines for manage-

ment of atopicdermatitis. J Derma-tol. 2009;36:563-77.[PMID: 19785716]

25. Sugarman JL, ParishLC. Efficacy of a lipid-based barrier repairformulation in mod-erate-to-severe pedi-atric atopic dermati-tis. J Drugs Dermatol.2009;8:1106-11.[PMID: 20027938]

26. Msika P, De BelilovskyC, Piccardi N, et al.New emollient withtopical corticos-teroid-sparing effectin treatment of child-hood atopic dermati-

tis: SCORAD andquality of life im-provement. PediatrDermatol. 2008 Nov-Dec;25:606-12.[PMID: 19067864]

27. Grimalt R, MengeaudV, Cambazard F. Thesteroid-sparing effectof an emollient thera-py in infants withatopic dermatitis: arandomized con-trolled study. Derma-tology. 2007;214:61-7.[PMID: 17191050]

treatments for AD, although system-atic reviews show no firm evidenceof their effectiveness (30, 31).

Are measures to control airborneallergens and food allergens helpful?Numerous studies have confirmedthe benefit of house dust mite re-duction for controlling AD (32,

33). For patients with positive dust-mite skin prick tests and allergen-specific IgE, such measures asthorough vacuuming, eliminatingold carpeting, and occlusive mat-tress covers may be helpful. Im-munotherapy for dust mites hasbeen successful in patients with ele-vated dust-mitespecific IgE (34),but it has limited usefulness in thegeneral AD population becausethere are many other airborne trig-

gers, such as plant allergens andanimal dander.

Despite evidence that many AD pa-tients have positive IgE to cat anddog dander, there is some evidencethat early pet exposure may be help-ful in reducing the risk for AD.

A cohort study of 4578 German children re-cruited at birth showed a statistically sig-nificant negative association between thedevelopment of AD and exposure to dogsas household pets during the first 2 years of

life. There was a borderline protective effectof keeping small furry animals (hamsters,rabbits, and guinea pigs) as pets duringthe first year (35).

Food and airborne allergens are eval-uated with RAST testing as noted inthe Diagnosis section. In the pres-ence of food allergy (i.e., allergen-specific IgE together with clinicalsymptoms), the NIAID Guidelinesrecommend avoidance of the food,along with nutritional counselingand growth monitoring. Attempts tomodify food-induced reactionsthrough drugs, immunotherapy, ordesensitization are not recommend-ed for the treatment of AD.

What are the roles of sunlightand phototherapy?Moderate exposure to natural sunlightremains a simple and cost-free adjunct

to AD therapy. Moisturizing sun-screens that have a moderate, ratherthan maximum, sun protection factorare recommended, to avoid completelyinterfering with the beneficial effectsof UV rays for AD while still protect-ing against deleterious overexposure.Sunburn, windburn, and overheatingcan worsen AD, and therefore pro-

longed exposure to the elementsshould be avoided.

Phototherapy with PUVA (oral pso-ralens plus ultraviolet A exposure),narrow-band UVB, UVA-1, and com-bined UVA/UVB have all been usedsuccessfully, particularly for adult AD,but these are considered second- tothird-line treatments (36). Their use isgenerally reserved for chronic ADthat responds inadequately to topical

mid-strength to superpotent corticos-teroids and calcineurin inhibitors.Disadvantages include relatively highexpense; inconsistent third-party cov-erage; inconvenient treatment sched-ules (generally 3 times/wk for 48 wk,followed by weekly maintenance);short-term risk for sunburn, causingAD exacerbation; and long-term risksfor freckling, hyperpigmentation, pre-mature aging, and skin cancer.

When and how should topicalcorticosteroids be used?For decades, topical corticosteroidtherapy has remained the corner-stone of AD treatment (23), but itcan be challenging to choose the op-timum preparation from among thedozens that are available over-the-counter and by prescription. BecauseAD is associated with dry skin, cor-ticosteroid ointments are generallypreferred by patients and caregiversover lotions, creams, and foams that

are less moisturizing.

Treatment should be initiated withthe lowest potency corticosteroidthat will clear AD (Table 4). Themore potent the medication, thegreater the risk for side effects, in-cluding local acne-like eruptions,skin atrophy, and stretch marks;systemic effects, such as

Figure 7. Prurigo nodularis resultingfrom chronic excoriation of atopicdermatitis on the forearm extensorsurface of a teenager. Photo credit:Susan V. Bershad, MD.



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Table 4. Classes of Topical Corticosteroids*

Class Description Uses in AD Examples

1 Superpotent Short-term treatment of severe refractory Clobetasol propionate; betamethasone dipropionate ointment;lesions in nonfacial body areas of adults halobetasol propionate; fluocinonide 0.1%

2 Potent Same as class 1 Betamethasone dipropionate cream; mometasone furoate ointment;diflorasone diacetate; halcinonide; fluocinonide gel/ointment;desoximetasone gel

3 Upper mid-strength Longer-term for moderate to severe Fluticasone propionate ointment; fluocinonide-emollient creamnonfacial lesions in adults; short-term 0.05%; betamethasone valerate; desoximetasonefor severe nonfacial lesions in children

4 Mid-strength Same as class 3, plus short-term for Flurandrenolide ointment; mometasone furoate cream/lotion;moderate nonfacial lesions in children triamcinolone acetonide; fluocinolone acetonide ointment;

hydrocortisone valerate ointment

5 Lower mid-strength Same as class 4, plus intermediate-term for Fluocinolone acetonide shampoo; flurandrenolide cream/lotion/nonfacial lesions in children tape; fluticasone propionate cream/lotion; prednicarbate; desonide

lotion; hydrocortisone valerate cream; fluocinolone acetonide cream

6 Mild Intermediate to longer term for all ages and Alclometasone dipropionate; fluocinolone acetonide oil/cream/body areas solution; desonide cream/ointment/foam/gel

7 Least potent Same as class 6 Hydrocortisone acetate lotion/cream/ointment/spray

Source: National Psoriasis Foundation.*The lowest potency corticosteroid that clears AD should be used. AD = atopic dermatitis.

Short-term = 12 weeks; Intermediate-term = 24 weeks; Longer-term = more than 1 month.

Unless otherwise noted, the generic name refers to all commercially available forms. Nonfacial areas do not include areas of thin skin (i.e., flexural creases,neck, axillae, and genital/groin area), which should be treated the same as facial skin.

A systematic review of the clinical andcost-effectiveness of once-daily versustwice-daily therapy found equal benefitsand considerable cost savings for less fre-quent application (38).

What is the role of otherpharmacologic treatments?A summary of drug therapy for AD isfound in Table 5. Adjunctive therapywith oral antihistamines for pruritus isoften recommended, although high-quality evidence of its effectiveness islacking. Nighttime scratching not onlyworsens AD lesions but disrupts sleep,diminishing quality of life.

A sedating antihistamine like diphen-hydramine or hydroxyzine can be usednightly for symptom relief and sleepinduction. During the day, a nonse-dating antihistamine like cetirizine or

loratadine may be taken, although evi-dence supports the use of these agentsonly to alleviate airborne allergies thatmight contribute to AD, not to relievethe pruritus.

An evidence-based Cochrane review foundno large RCTs examining the efficacy of anti-histamines to relieve the pruritus associatedwith AD, and meta-analysis of poorer quali-ty studies was inconclusive (39).

suppression of the hypothalamicpituitaryadrenal axis (37); osteo-porosis; and ocular problems likecataracts and glaucoma that areconcerns when treating the eyelids.

Mid-to high-potency corticos-teroids in classes 1 to 5 can behighly effective for AD but should

be reserved for nonfacial, noninter-triginous skin areas in adults andadolescents. Corticosteroid classes6 and 7, the lowest-strength non-fluorinated compounds, are recom-mended for AD in many clinicalsituations, including the care ofyoung children and treatment ofthe face, neck, groin area, and skincreases in all age groups. Recom-mendations are based primarily onstudies of childhood AD, because

large RCTs of adult AD treatmentare lacking. Although twice-dailyapplication has been the traditionalpractice, evidence suggests thatonce-daily treatment is equally ef-fective and considerably less costly.The drawback of prescribing once-daily topical therapy is that missing1 application can result in subopti-mal therapy.

28. Na JI, Hwang JS, ParkHJ, et al. A new mois-turizer containingphysiologic lipidgranules alleviatesatopic dermatitis. JDermatolog Treat.2010;21:23-7.[PMID: 19626524]

29. Lee JH, Lee SJ, Kim D,et al. The effect ofwet-wrap dressingon epidermal barrier

in patients withatopic dermatitis. JEur Acad DermatolVenereol.2007;21:1360-8.[PMID: 17958842]

30. Zhang W, Leonard T,Bath-Hextall F, et al.Chinese herbal medi-cine for atopiceczema. CochraneDatabase Syst Rev.2004;:CD002291.[PMID: 15495031]

31. Ernst E, Pittler MH,Stevinson C. Comple-mentary/alternativemedicine in derma-tology: evidence-as-sessed efficacy of

two diseases andtwo treatments. Am JClin Dermatol.2002;3:341-8.[PMID: 12069640]

32. Sanda T, Yasue T,Oohashi M, et al. Ef-fectiveness of housedust-mite allergenavoidance throughclean room therapyin patients withatopic dermatitis. JAllergy Clin Immunol.1992;89:653-7.[PMID: 1545086]



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Table 5. Drug Treatment for Atopic Dermatitis

Class (Examples) Mechanism of Action Dosage Benefits Side Effects Notes

Topical Antiinflammatory Apply topically Decreased pruritus Thinning of skin, Class 6 and 7 are thecorticosteroids once to twice daily and redness striae, steroid acne; most versatile and can(see Table 4) to affected areas possible systemic be used on the face and

absorption with skin creases in all ages;HPA axis suppression classes 15 should be

reserved for short-and intermediate-term in older patients;

ointments are moreemolient than creamsor lotions.

Topical calcineurin Antiinflammatory Apply topically Decreased pruritus Local stinging; poten- 0.1% is approved forinhibitors (tacroli- once to twice daily and redness; steroid- tial risk for rare lymph- ages 15 y and older;mus 0.03%, to affected areas sparing; especially use- omas and nonmelanoma considered second-line0,1% ointment; ful around the eyes skin cancers by most third-partypimecrolimus insurers; useful as 1st-1% cream) line therapy for steroid

phobic patients.

Topical antipruritic Tricyclic drug with Apply at bedtime Decreased pruritus HIgh absorption causes Not studied in children.agents (doxepin anthistamine effects drowsinesscream)

Oral antihistamines, Antihistamine Single dose at bed- Decreasd allegic symp- Paradoxic hyperact- Many patients findsedating time; diphenhydra- toms and pruritus; ivity in some children; these agents helpful for(diphenhydramine, mine: 12.525 mg induces sleep in most dry mouth; urine night-time pruritus, buthydroxine) (children 6 y and retention systematic reviews

older), 2550 mg have not confirmed(adults); hydroxine: efficacy in AD.5 mg (under 20 lb)10 mg (children over20 lb) 1025 mg(adults)

Oral antihistamines, Antihistamine Check recommend- Decreased allergic symp- Dry mouth; urine re- No high-qualitynonsedating (lora- ed dose for age and toms; possible relief of tention; drowsiness evidence of efficacytidine, cetirazine, weight pruritus or hyperactivity; lora- in AD.fexofenadine, tidine and fexofenidineacrivastine) are the least sedating

Topical antibac- Antibacterial Apply to crusted FDA-approved to treat Potential resistance Bacterial culture andterial agents against areas, pustules, impetigo, which com- sensitivity testing of (mupirocin Staphylococcus surrounding skin, monly occurs secondary lesions is recommended

2% cream and Streptococcus nostrils, and finger- to AD lesions; promotes before using antibacter-and ointment; nails twice daily healing; reduces the ial medications;retapamulin spread of infection colonization tends to1% ointment) recur rapidly on

discontinuation oftreatment; dilutedbleach baths help todelay this risk

Oral antibiotic Antibacterial Choose the appro- Reduced bacterial Potential resistance; Limit oral antibiotic(oxacillin, priate drug based on infection, usually S. allergic reactions, use to the treatmentcephalexin, culture and sensitivity aureus that excerbates such as pruritus, GI of culture-positiveaxithromycin, testing; dosage and pruritus and inflamma- distress, diarrhea, infection withdoxycycline) number of days as tion; promotes healing; and vomiting; sulfa crusting, exudates,

recommended for reduced spread of drugs are associated and/orpustulessoft tissure infection infection with the Stevens-

Johnson syndrome;

tetracyclines are notfor pediatric use dueto dental andbone absorption

Oral cortico- Antiinflammatory Single morning dose Rapid induction of GI distress; steroid Occasional judicious usesterois (predni- with food, rapidly temporary remission acne; temporary can effect dramaticsone tablets; tapering to 0 over in recalcitrant AD elevations of blood improvement; rebound isprednisolone 710 d; predni- sugar and blood likely without strictoral solution) sone 0.51 mg/kg pressure; mood dis- adherence to a topical

on day 1; prednisol- orders; HPA axis regimenlone 0.61.2 mg/kg suppressionon day 1



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accomplished by adding one-half cupof household chlorine bleach to a 40-gallon bathtub of warm water. Thelong-term safety of exposure to dilut-ed bleach has not been established.

What are calcineurin inhibitors,and when should they be used?Calcineurin is a calcium-dependent

phosphatase that activates theT-cells and dendritic cells responsiblefor AD inflammation. There are 2U.S. Food and Drug Administration(FDA)approved topical drugs in thecalcineurin-inhibitor class, tacrolimusand pimecrolimus. Their mechanismof action is similar to cyclosporine, anoral calcineurin inhibitor. As immune-system modulators, they are usefulsteroid-sparing agents and are suitablefor corticosteroid-resistant AD in pa-

tients older than 2 years of age. Evi-dence suggests that they are more ef-fective than class 7 topicalcorticosteroids (44). In several studies,tacrolimus was found to be superior topimecrolimus (45). Tacrolimus isavailable in a high-potency ointmentfor adults and a milder formulationfor ages 2 to 15 years; pimecrolimuscream comes in 1 formulation for ages2 and up.

On areas of very thin skin, such as the

face, neck, and groin, calcineurin in-hibitors can be beneficial to avoid skinatrophy. These inhibitors are especiallyuseful on the eyelids, where long-term corticosteroids may thin the skinand create risks for cataracts and glau-coma.

Topical tacrolimus and pimecrolimus,generally considered to be second-line

The topical antipruritic agent dox-epin, a tricyclic drug, provides effectiverelief but has systemic effects, such assedation, due to high absorption (40).

What are the best approaches totreat and prevent bacterialsuperinfection?Staphylococcus aureusskin colonization

occurs in most patients with AD, afinding first noted by Leyden andcoworkers in 1974 (41) and subse-quently confirmed by others (42).Guidance from the AAD indicatesthat bacterial superinfection should betreated with topical and/or oral antibi-otics (23). Mupirocin cream or oint-ment, applied twice daily, can be alter-nated or layered under corticosteroidpreparations on fissured and crustedareas to treat culture-proven localized

infection. Studies have shown thatAD patients carry these organisms intheir nostrils and under the finger-nails; these areas should be treatedwith twice-daily topical applicationsof mupirocin for 7 to 10 days to re-duce risk for reinfection. Widespreadcrusted lesions require appropriate oralantibiotic therapy based on bacterialculture and sensitivity results.

Recently, diluted bleach baths havebecome popular for prophylaxis of

bacterial colonization of AD. Thispractice by itself has not been studiedin RCTs, but it was used successfullyin combination with intermittent in-tranasal application of mupirocin oint-ment for 3 months in an RCT de-signed to reduce the severity of AD inpatients with clinical signs of second-ary bacterial infections (43). Inexpen-sive and easy to use, this method is

33. Tan BB, Weald D,Strickland I, et al.Double-blind con-trolled trial of effectof housedust-mite al-lergen avoidance onatopic dermatitis.Lancet. 1996;347:15-8. [PMID: 8531541]

34. Werfel T, Breuer K,Ruff F, et al. Useful-ness of specific im-munotherapy in pa-tients with atopicdermatitis and aller-

gic sensitization tohouse dust mites: amulti-centre, ran-domized, dose-re-sponse study. Allergy.2006;61:202-5.[PMID: 16409197]

35. Zirngibl A, Franke K,Gehring U, et al. Ex-posure to pets andatopic dermatitis dur-ing the first two yearsof life. A cohort study.Pediatr Allergy Im-munol. 2002;13:394-401.[PMID: 12485314]

36. Meduri NB, Vander-griff T, Rasmussen H,et al. Phototherapy in

the management ofatopic dermatitis: asystematic review.Photodermatol Pho-toimmunol Pho-tomed. 2007;23:106-12. [PMID: 17598862]

37.www.fda.gov/ohrms/dockets/ac/05/slides/2005-4099S1_03_FDA-Cook.ppt

38. Green C, Colquitt JL,Kirby J, et al. Clinicaland cost-effective-ness of once-dailyversus more frequentuse of same potencytopical corticos-

teroids for atopiceczema: a systematicreview and econom-ic evaluation. Health

Technol Assess.2004;8:iii,iv, 1-120.[PMID: 15527669]6]

39. Klein PA, Clark RA. Anevidence-based re-view of the efficacyof antihistamines inrelieving pruritus inatopic dermatitis.Arch Dermatol.1999;135:1522-5.[PMID: 10606058]

Table 5 (continued). Drug Treatment for Atopic Dermatitis

Oral immuno- Immune suppression Check appropriate May be useful in Serious and life- Use only in consultationmodulators dosage for age and severe refractory AD threatening effects with a specialist in

weight; begin at low are possible, including severe inflammatoryend of the range immune suppression, skin disease

anemia, hepatotoxicity,nephrotoxicity, andopportunistic infections;check individualdrug side effects

AD = atopic dermatitis; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; HPA = hypothalamicpituitaryadrenal.



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40. Drake LA, Fallon JD,Sober A. Relief of pru-ritus in patients withatopic dermatitis af-ter treatment with

topical doxepincream. The DoxepinStudy Group. J AmAcad Dermatol.1994;31:613-6.[PMID: 8089287]

41. Leyden JJ, MarplesRR, Kligman AM.Staphylococcus au-reus in the lesions ofatopic dermatitis. Br JDermatol.1974;90:525-30.[PMID: 4601016]

42. Hon KL, Lam MC, Le-ung TF, et al. Bogu-niewicz M, Leung DY.Recent insightsinto atopic dermatitisand implications for

management of in-fectious complica-tions. J Allergy ClinImmunol. 2010;125:4-13. [PMID: 20109729]

43. Huang JT, Abrams M,Tlougan B, et al. Treat-ment ofStaphylococ-cus aureus coloniza-tion in atopicdermatitis decreasesdisease severity. Pedi-atrics. 2009;123:e808-14. [PMID: 19403473]

44. Reitamo S, Harper J,Bos JD, et al. 0.03

Tacrolimus ointmentapplied once ortwice daily is moreefficacious than 1%

hydrocortisone ac-etate in children withmoderate to severeatopic dermatitis: re-sults of a randomizeddouble-blind con-trolled trial. Br J Der-matol. 2004;150:554-62. [PMID: 15030341]

45. Paller AS, Lebwohl M,Fleischer AB Jr, et al.

Tacrolimus ointmentis more effective thanpimecrolimus creamwith a similar safetyprofile in the treat-ment of atopic der-matitis: results from 3randomized, compar-ative studies. J Am

Acad Dermatol.2005;52:810-22.[PMID: 15858471]

46. Berger TG, Duvic M,Van Voorhees AS, Theuse of topical cal-cineurin inhibitors indermatology: safetyconcerns. Report ofthe American Acade-my of DermatologyAssociation TaskForce. J Am AcadDermatol.2006;54:818-23.[PMID: 16635663]


recalcitrant to topical antibacterialagents. For vesicular and crusted le-sions that test positive for herpessimplex or varicella zoster, rapidinitiation of treatment with sys-temic acyclovir, famciclovir, or vala-cyclovir is critical.

What are the complications?

The most common complicationof AD is bacterial superinfection,also referred to as impetiginization,from the word impetigo, meaning asuperficial skin infection with strainsofStaphylococcus or Streptococcus. Theusual clue to this diagnosis is ahoney-colored crust overlying areasof AD, particularly those that havebeen subjected to excoriation andfriction. Bullous impetigo, a blister-ing form of the infection, is relatively

rare, but may occur. When vesiclesand bullae are present, an urgentconsideration is eczema herpeticum,a serious form of disseminated her-pes simplex or varicella zoster.

AD is also frequently associatedwith development of asthma andallergic rhinitis.

When should a dermatologist beconsulted for management of apatient with AD?

A dermatologist should be consult-ed for management of recalcitrantAD when topical treatment op-tions, including corticosteroids andcalcineurin inhibitors, have failedand the patient requires systemictherapy with corticosteroids, PUVAor other light treatments, or im-munomodulators.

How long should therapy becontinued?The duration of treatment for AD

varies greatly among patients. Al-though moisturizers should be usedcontinuously for areas of dry skin inAD patients, drug therapy is re-quired only for sites with active der-matitis. Once AD is under control,maintenance regimens, other thanemollients and allergen avoidance,are unnecessary and potentiallyharmful.

therapy, may be employed as first-lineoptions when patients express so-called steroid phobia, an irrationallyheightened but not uncommon fear ofcorticosteroid side effects.

The only local side effect of cal-cineurin inhibitors is occasional mildstinging. The prescriber should be

aware that these drugs carry an FDAblack box warning stating that topi-cal use has been associated with rarecases of lymphoreticular and skin can-cer. However, professional task forcesof the AAD and the AAAI have dis-puted a causal relationship (46, 47).

When should systemic therapy beconsidered?AD usually responds quickly to a top-ical corticosteroid with or without acalcineurin inhibitor, but treatment-resistant AD may require systemiccorticosteroid therapy. Although ex-perts agree that a short 7- to 10-dayrapidly tapering course of oral pred-nisone or prednisolone can bringabout dramatic remission, RCTS arelacking (23). Rapid rebound is a fre-quent consequence, particularly whenpatients do not adhere to an emollientregimen for dry skin and topical med-ications for active lesions. Long-termsystemic corticosteroids are con-

traindicated for AD.

In a select group of adult andteenaged patients with very severerefractory AD, evidence-based prac-tice guidelines recommend carefullyweighing the risks and benefits ofusing systemic immunomodulatingagents (23, 48). Effective drugs inthis group include cyclosporine, tu-mor necrosis factor inhibitors, inter-feron gamma, mycophenolatemofetil, and azathioprine. This typeof therapy should be considered onlyin consultation with a physician whospecializes in severe inflammatoryskin conditions. In experiencedhands, the vast majority of cases canbe managed less aggressively.

Systemic antibiotic therapy is war-ranted for culture-positive AD le-sions that are widespread or



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47. Fonacier L, Spergel J,Charlesworth EN, etal. Report of the Topi-cal Calcineurin In-hibitor Task Force ofthe American Col-lege of Allergy, Asth-ma and Immunologyand the AmericanAcademy of Allergy,Asthma and Im-munology. J AllergyClin Immunol.2005;115:1249-53.[PMID: 15940142]

48. Leung DY, Nicklas RA,Li JT, etal. Diseasemanagement ofatopic dermatitis: anupdated practice pa-rameter. Joint TaskForce on Practice Pa-rameters. Ann AllergyAsthma Immunol.2004;93(3 Suppl2):S1-21.[PMID: 15478395]

49. www.aad.org/educa-tion/CPATinfo.htm.

In

the

ClinicTool Kit

In the Clinic

AtopicDermatitis(Eczema)

PIER Modulehttp://pier.acponline.org/physicians/diseases/d922/d922.html

PIER module on atopic dermatitis from the American College of Physicians (ACP).PIER modules provide evidence-based, updated information on current diagnosis andtreatment in an electronic format designed for rapid access at the point of care.

Patient Informationwww.annals.org/intheclinic/toolkit-atopic-dermatitis.xhtml

Patient information that appears on the following page for duplication and distributionto patients.www.nlm.nih.gov/medlineplus/eczema.htmlwww.nlm.nih.gov/medlineplus/ency/article/000832.htmwww.nlm.nih.gov/medlineplus/ency/article/000870.htm

Information on eczema, dyshidrotic eczema, and nummular eczema from NationalInstitutes of Healths MedlinePLUS.www.niams.nih.gov/Health_Info/Atopic_Dermatitis/atopic_dermatitis_ff.aspwww.niams.nih.gov/Portal_En_Espanol/Informacion_de_Salud/Dermatitis_atopica/default.asp

Easy-to-read information on eczema, in English and Spanish, from the NationalInstitute of Arthritis and Musculoskeletal and Skin Diseases.www.skincarephysicians.com/eczemanet/proper_treatment.html

Guidelines of care for atopic dermatitis due out soon from the American Academy ofDermatology.http://guidance.nice.org.uk/CG57

Management of atopic eczema in children from birth up to the age of 12 years, fromthe National Institute for Health and Clinical Excellence, released in 2007.

1 November 2011Annals of Internal MedicineIn the ClinicITC5-14 2011 American College of Physicians

What do professionalorganizations recommendregarding the management ofpatients with AD?Official guidelines for treatingAD have been established by theAAD (23) and the Joint TaskForce on Practice Parameters thatrepresents 3 societies: the Ameri-can College of Allergy, Asthmaand Immunology; the AmericanAcademy of Allergy, Asthma, andImmunology; and the Joint Coun-cil of Allergy, Asthma and Im-munology (48).

How is quality of care for ADevaluated in the United States?The AAD, as part of its programfor maintaining professional certifi-cation, has recently developed theClinical Performance AssessmentTool (CPAT) for dermatology, a setof Web-based disease-specificmodules to evaluate quality of carein medical practices. Evidence-based treatment guidelines andevaluation standards for AD diag-nosis and management, which in-clude the severity scoring instru-ments listed in Table 5, areincorporated into the CPAT mod-ule titled Atopic Dermatitis (49).

PracticeImprovement

Treatment... First-line treatment of AD consists of daily nonprescription emollientsfor dry skin and low-potency topical corticosteroids (classes 6 and 7) applied to facialand intertriginous active lesions. In adults and older children, lesions on other sitesmay be treated with limited courses of mid-strength to superpotent (classes 1 to 5)corticosteroids. Fissured and crusted areas frequently require topical or oral antibiotictherapy, based on culture and sensitivity results. Sedating antihistamines are indicat-ed at bedtime for patients whose sleep is disrupted by pruritus. Second-line therapyincludes topical calcineurin inhibitors, PUVA and other light treatments, and oral cor-ticosteroids. The latter two modalities, as well as third-line therapy for severe recalci-

trant AD with such immunomodulators as cyclosporine, may be considered in collab-oration with a dermatologist specializing in inflammatory skin disorders.




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In the Clinic

Annals of Internal Medicine

PatientIn

formation

THINGS YOU SHOULDKNOW ABOUT ATOPICDERMATITIS (ECZEMA)

What is atopic dermatitis (eczema)? A chronic skin disease that causes dry, irritated skin.

The cause is unknown, but it is believed to run infamilies.

Occurs most often in babies and children, but canappear at any age.

Is not contagious.

What are the symptoms? An itchy rash, which appears most commonly on the

face, hands and feet, behind the knees, and inside

the elbows.

Scratching may cause redness, swelling, scaling, andcracked, crusting, thick skin.

Symptoms tend to come and go, worseningsometimes and improving or clearing up other times.

People with atopic dermatitis (eczema) are morelikely to have asthma and allergies, such as hayfever.

What factors can worsen atopicdermatitis (eczema)? Irritants, like wool, soap, perfume, chlorine, or

smoke.

Allergens like dust mites, mold, pollen, or pet dander.

Eating certain foods, such as fish, soy, wheat, milk,or peanuts.

Skin infections.

Long, hot baths or showers or anything else thatdries the skin.

How is it treated? Practice a skin care routine to keep skin well-

moisturized.

Avoid things that lead to flares, such as allergens orirritants.

Follow your doctors advice for using skin creams orointments to control swelling and reduce allergicreactions.

Take antibiotics as directed for any infection relatedto the skin disorder.

Antihistamines may reduce nighttime scratching.

Light therapy, sometimes combined with a drug

called psoralen, may reduce symptoms.

Consult a specialist before getting the the smallpoxvaccine because it can cause serious problems.

For More Information

www.skincarephysicians.com/eczemanet/daily_care.htmlwww.skincarephysicians.com/eczemanet/moisturizing_cleansing.htmlArticles on skin care for people with eczema, from the American

Academy of Dermatology.

www.niams.nih.gov/Health_Info/Atopic_Dermatitis/default.aspPatient handout on atopic dermatitis from the National Institute

of Arthritis and Musculoskeletal and Skin Diseases.

www.skincarephysicians.com/eczemanet/index.htmlEczemaNet is a comprehensive online resource for patients and

caregivers from the American Academy of Dermatology.

www.nationaleczema.org/The National Eczema Association provides sponsors support

networks and education on eczema



16/16

CME Questions

1 November 2011Annals of Internal MedicineIn the ClinicITC5-16 2011 American College of Physicians

Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP, accessed at

http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/

to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.

1. A 35-year-old man is evaluated for anacute rash on his face. The rash is painfuland somewhat pruritic, and his left eye isswelling shut. He has a history of long-

standing atopic dermatitis, which hasbeen reasonably well-controlled withregular use of emollients and topicalcorticosteroids. His current medicationsare triamcinolone ointment, tacrolimusointment, and hydroxyzine. Lately he hasbeen nonadherent to his medicationregimen because of recent travel andtherefore has been scratching more. He isallergic to sulfa.

On physical examination, vital signs arenormal. The conjunctivae are inflamed,but no purulence is noted. No grossabnormalities of the cornea are visible.The left preauricular lymph nodes areslightly enlarged and tender.

Which of the following is the most likelydiagnosis?

A. Acute allergic contact dermatitis

B. Acute atopic dermatitisC. Eczema herpeticumD. Staphylococcus aureus pyoderma

2. A 51-year-old woman is evaluated for aseveral-year history of persistent handdermatitis. She has worked as a

hairdresser for years, and, while she hashad rashes in the past, she has neverbefore experienced such a persistentproblem. Her hands are itchy andsometimes have very painful cracks.Regular emollient use has improved therash in the past but is not helping at thistime. She wears gloves at work most ofthe time, but she is not sure if they arelatex or vinyl. She notes improvement onweekends when she does not work,although the dermatitis does notcompletely clear. Symptoms improvedsignificantly when she went on vacation.

She has allergic rhinitis and hypertensionand has a history of mild eczema duringchildhood. Her mother had asthma. Shecurrently takes hydrochlorothiazide and

nasal corticosteroids intermittently andhas no known drug allergies.

On physical examination, the skin on thehands is thickened and hyperkeratotic,

especially on the palms, where there arepoorly defined plaques, dry scale, andfissures but no pustules. Skin on thedorsal hands is red and scaly. The surfaceof the nails is rough. Other areas of skin,including the soles of the feet, are notinvolved.

Which of the following is the mostappropriate diagnostic test?

A. Epicutaneous patch testingB. Lymphocyte stimulation assayC. Prick testing

D. Radioallergosorbent test

3. A 65-year-old man is evaluated for ageneralized, intensely pruritic eruption thathas been slowly progressing over the last 6months. He has been treated with topicalcorticosteroids for 4 months for widespreadeczema without relief of pruritus or changein clinical appearance. He has never had askin biopsy. He does not have a personal orfamily history of asthma, atopic dermatitis,allergic rhinitis, or psoriasis.

On physical examination, temperature is37.5C (99.5F), blood pressure is

135/85 mm Hg, pulse rate is 84/min,and respiration rate is 14/min. Skinexamination reveals erythema with scaleaffecting greater than 90% of the bodysurface area. Alopecia, nail dystrophy,and ectropion (turning inside out of theeyelid) are present. There is thickeningand fissuring of the skin on the palmsand soles. Bilateral axillary and inguinallymphadenopathy is present. The mucousmembranes are not involved.

Which of the following is the mostappropriate next step in management?

A. Antinuclear antibody assayB. CyclosporineC. PhototherapyD. Rapid plasma reagin test

E. Skin biopsy

4. A 30-year-old woman is evaluated for apustular rash on her central face. She hasa 5-year history of dandruff and arecurrent, red, scaly, itchy rash behind

and in her ears and on the medialaspects of her cheeks. For several monthsshe has been self-treating the rash withdaily application of her husbandseczema cream (triamcinolone acetonide0.1%). The rash was initially controlledusing this treatment, but for the pastmonth a new acne-like rash hasappeared. She began using thetriamcinolone twice daily within the lastweek but has noted no improvement.

On physical examination, papules andpustules on an erythematous base areobserved in a perioral distribution. Theremainder of the examination is normalexcept for atopic dermatitis involving thepopliteal fossae.

In addition to discontinuingtriamcinolone, which of the following isthe most appropriate treatment?

A. Clobetasol cream

B. Benzoyl peroxide gelC. Neomycin ointmentD. No further treatment

5. A 20-year-old male college student is

having trouble sleeping because of anitchy rash on his hands and on the innercreases of his elbows. His pruritus hasbeen recurring for several years,becoming more severe in the winterdespite his use of a daily moisturizer. Hishistory is remarkable for seasonalallergies, and the only medication heuses is a nasal corticosteroid in the fall.

Which of the following is the mostappropriate treatment for this patientscondition?

A. Topical corticosteroids

B. Topical tacrolimusC. Oral antibioticsD. Topical antifungals

E. Oral corticosteroids

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