Inpatient management ofatopic dermatitisdth_1400 249..255

Shelley D. Cathcart & Amy TheosDepartment of Dermatology, University of Alabama at Birmingham,Birmingham, Alabama

ABSTRACT: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that is generallymanaged on an outpatient basis. However, a significant percentage of patients may develop complica-tions severe enough to require inpatient treatment. The most common complications of AD that mayrequire hospital admission include erythroderma, eczema herpeticum, and systemic bacterial infec-tion. Hospital admission can also be useful for chronic and severe disease that has not responded tostandard therapy or in situations where nonadherence is suspected as the cause of treatment failure. Inthese cases, inpatient treatment can offer an opportunity for caretaker education and allow for anobjective evaluation of a patients response to a structured treatment plan. This article will review theindications for inpatient management of AD and the therapies that can be used to acutely managesevere disease and associated complications.

KEYWORDS: atopic dermatitis, eczema herpeticum, erythroderma, hospitalized patient, wet wraptherapy

Introduction

Atopic dermatitis (AD) is a chronic inflammatoryskin disease that affects approximately 17% of chil-dren and 13% of adults (1). Traditional therapyconsists of emollients, mild to moderate potencytopical corticosteroids, or topical calcineurininhibitors, along with avoidance of irritants andallergens. Although this treatment strategy resultsin significant improvement for most patients, asmall percentage will require more intensivetherapy. The most common complications of ADthat may require inpatient management includeerythroderma, eczema herpeticum, and systemicor severe bacterial infection. Hospital admissioncan also be useful for chronic and severe diseasethat has not responded to standard therapy or insituations where nonadherence is suspected as thecause of treatment failure. In these cases, inpatient

treatment can offer an opportunity for caretakereducation and allow for an objective evaluation of apatients response to a structured treatment plan.This article will review the indications for inpatientmanagement of AD and the therapies that can beused to acutely manage severe disease and associ-ated complications.

Erythroderma

Acute decompensation of moderate to severe ADcan lead to erythroderma, which is defined as thepresence of erythema and scaling involving greaterthan 80% of the body surface area. AD is one ofthe more common causes of erythroderma, butmany other causes exist (Table 1). Regardless of theunderlying disease, complications of erythrodermacan be life-threatening and can include tempera-ture instability, hypoproteinemia, hypovolemia,hypernatremia, and high-output congestive heartfailure. Inpatient management of erythroderma isoften necessary.

The first step in the management of a patientpresenting with erythroderma is a thorough

Address correspondence and reprint requests to: Amy Theos,MD, Department of Dermatology, University of Alabamaat Birmingham, EFH 414, 1530 3rd Ave S, Birmingham, AL35294-0009, or email: amy.theos@chsys.org.

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workup to identify the underlying etiology. Acareful history should be taken at presentation,giving special attention to preceding illnesses,recent fevers, new medications, and relevant pastmedical and family history. Physical examinationshould include evaluation of the mucosal surfaces,testing for a positive Nikolsky sign (sloughing of theepidermis with light lateral friction on the skinsurface), and palpation of the lymph nodes. Base-line laboratory evaluation should consist of liverfunction tests, chemistry panel, and completeblood count. Preexisting dermatitic lesions, severepruritus, lichenification, personal or family historyof atopy, elevated serum levels of immunoglobulinE, or eosinophilia can be helpful features thatsupport the diagnosis of AD. Helpful clues on his-tological examination include mild to moderateacanthosis and spongiosis, dermal eosinophils,and parakeratosis.

Although definitive treatment of erythrodermadepends on the underlying cause, all patients

should be managed for fluid loss, electrolyteabnormalities, and temperature instability (2).Nutritional support is also critical. The large body-surface-to-body-mass ratio in children combinedwith an impaired skin barrier and cutaneousvasodilation leaves them especially vulnerable tohypernatremic dehydration, high-output cardiacfailure and hypothermia (3). Secondary bacterialinfection with Staphylococcal aureus is common inerythrodermic atopic patients and should be rec-ognized and treated promptly. Once the cause oferythroderma has been established, proper treat-ment of the underlying condition can be initiated.In the case of AD, wet wrap therapy can achieverapid improvement.

Wet wrap therapy

Wet wrap treatment is defined as any treatmentconsisting of the application of a topical agent witha double layer of bandages or gauze, first with amoist layer and then a dry second layer. The effec-tiveness of wet wrap therapy in AD is thought to bemultifactorial. Wet wraps have been shown to healthe disrupted skin barrier of AD patients, repairthe lamellar structure of intercellular lipid, anddecrease transepidermal water loss (4). It is alsosuggested that the dressings create a physicalbarrier to scratching, which allows the skin to healin addition to providing a moist environment inwhich topical medications are more easilyabsorbed (5). Although most regimens includethe use of a topical corticosteroid, there are alsoreports of improvement with emollient alone. Atrial by Schnopp et al. comparing wet wrap therapywith either mometasone or a bland emollientshowed significant improvement in both arms ofthe study; however, the effect was significantlybetter in the mometasone-treated group (6). Theeffectiveness of steroid-free treatment does,however, lend support to the idea that improvedpenetration of topicalmedications is only one facetof the effectiveness of wet wrap therapy.

Regarding the practical details of wet wraptherapy, a basic protocol that includes the featurescommon to most wet wrap regimens is presentedin Table 2. A variation in which the first layer issoaked in warm steroid cream instead of water hasalso been reported to be effective; in this variation,the steroid-soaked wet layer replaces the applica-tion of a topical steroid (7). The steroid of choice aswell as the frequency of wet wrap application alsovaries by institution. Table 3 shows several topicalsteroids and frequencies of application that havebeen reported effective. Regarding the duration of

Table 1. Differential diagnosis of common causesof erythroderma

DiseaseCharacteristic clinicalfeatures

Atopic dermatitis Severe pruritus,lichenification, personal orfamily history of atopy,elevated immunoglobulinE, eosinophilia

Seborrheic dermatitis Infants, greasy yellow scale,diaper area involved

Psoriasis Silvery scale, preexistingpsoriatic lesions, nailchanges, + family historyof psoriasis

Staphylococcal scaldedskin syndrome

Infants and young children,superficial blisters, +Nikolskys sign, skin foldand perioral accentuation,painful

Ichthyosis Congenital, possiblecollodion membrane

Netherton syndrome Onset in infancy, sparse hair(trichorrhexis invaginata),failure to thrive, atopy

Immunodeficiencies Early onset, alopecia, failureto thrive, recurrentinfections

Drug History of medication intakeCutaneous T cell

lymphomaAdults, severe pruritus,

keratodermaPityriasis rubra pilaris Keratoderma, islands of

sparing, salmon-colorederythrema

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therapy, all studies showed significant improve-ment of AD after 1 week of wet wrap therapy, withless improvement seen in the second week andthereafter(610). Therefore, the present authorsrecommend a treatment period of no more than 7days to balance the risk of side effects while achiev-ing themaximal benefit available with this therapy.

The major risk of wet wrap therapy is suppres-sion of the hypothalamic-pituitary-adrenal (HPA)axis. Several studies have shown that wet wraptherapy can lead to a temporary drop in earlymorning serum cortisol levels (7,8). However, cor-tisol levels returned to normal within 2 weeks ofdiscontinuing therapy, and no adverse eventsoccurred in either study as a result of this suppres-sion. Several investigators have examined the effectof dilution of steroid with emollient as a way todecrease the total amount of steroid delivered tothe skin and have found that there was no differ-ence in efficacy between various dilutions of fluti-casone proprionate (see Table 3 for dilutionsstudied) (8,9). Wolkerstorfer et al. also examinedwhether or not HPA axis suppression could beminimized if a more dilute steroid cream wasapplied (9). They found that more HPA axis sup-pression did occur in patients treated with highersteroid concentrations. Therefore, increasing thedilution of potent steroids appears to result inlower risk of HPA axis suppression while maintain-ing efficacy of higher steroid concentrations.

The two most common adverse effects associ-ated with wet wrap treatments are poor toleranceof the process and folliculitis likely secondary toocclusion. Using creams instead of ointments mayreduce the incidence of folliculitis. The increasedrisk of bacterial or herpetic infections with wetwrap therapy is controversial but appears to berare. Although some studies report an increase in

the incidence of secondary bacterial infection,others actually report a decrease in the coloniza-tion of S. aureus on the skin of AD patients after wetwrap treatment (6,8). The present authors suggestthat wet wraps not be applied to any obviouslyinfected areas until proper antimicrobial treatmenthas been initiated and improvement is seen.

Eczema herpeticum (EH)

EH occurs when skin previously affected by ADbecomes secondarily infected with herpes simplexvirus (HSV). EH can lead to serious and even fatalcomplications, especially in the case of dissemi-nated viremia andmultiorgan involvement (11,12).For this reason, EH is another complication thatcan require inpatient management. Disseminationof the herpes virus in patients with AD is thought tobe a result of the impaired skin barrier, which facili-tates viral invasion and binding to cellular recep-tors (13). Children affected by EH will often havea history of a more severe disease, an earlier onsetof AD, and a higher rate of coexistent food allergyor asthma (14). Elevated serum immunoglobulinE has also been implicated as a risk factor for EH(15). Athough topical corticosteroids have beenimplicated in the past as a potential cause of thiscomplication, further research has refuted thisassertion (15).

EH presents as umbilicated vesicles progressingto punched-out crusted ulcers occurring primarilyin skin affected by AD (FIG. 1). The head and neckare preferentially involved. The infection can be aresult of either dissemination of recurrent HSV or aresult of inoculation from an infected person (15).The skin lesions can be extremely painful and are atrisk for secondary bacterial infection. New lesionstypically appear for the first 710 days, and thelesions will typically resolve in 26 weeks (16). Theprimary episode is often associatedwith fever, lym-phadenopathy, and malaise. Systemic viremia canlead to multiorgan involvement, most commonlythe liver, lungs, central nervous system, andadrenal glands. The diagnosis can be confirmedwith viral changes seen on skin biopsy, direct fluo-rescent antibody (DFA) staining, viral culture, orpolymerase chain reaction for viral DNA on asmear or tissue sample. Diagnosis can also bemade performing a Tzanck test. The Tzanck testrefers to a procedure in which the base of a freshlyunroofed vesicle is scraped and the cells aresmeared onto a glass slide. After staining the slidewithWright or Giemsa stain, the presence of multi-nuclear viral cells or balloon cells with typical viral

Table 2. Wet wrap protocol

General wet wrap protocol

Using tubular bandages, cut the appropriate size tocover the arms, trunk, legs, and (if needed) a maskfor the face. You will need enough for two layers.

Gently bathe skin with lukewarm water for 510minutes. Pat dry gently.

Apply steroid cream or ointment to the skin. Soak the first layer of bandages in lukewarm water,

wring out, and apply to skin wrapping theextremities and trunk.

Apply second layer of dry bandages. Leave in place at least 2 hours and repeat every 12

hours. Children may sleep overnight in dressings iftolerated.

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cytopathic change, such as nuclear molding andcondensed chromatin, confirms the diagnosis (17).DFA staining is the most rapid and reliable testif available in your local hospital lab. DFA alsorequires scraping the base of the lesions andsmearing on a glass slide in six to eight differentwells for the DFA technician to test with HSV andvaricella zoster virus reagents.

The cornerstone of EH therapy is antiviralmedication (Table 4). Intravenous acyclovir is pre-ferred in EH because of the lower bioavailability(1530%) of oral acyclovir (13). Therefore, oral acy-clovir should be restricted to the treatment ofmild disease. For children

acute phase has resolved. Another rare but poten-tially serious complication of EH is keratocon-junctivitis (19). Patients should receive anophthalmologic examination, especially if there isfacial involvement.

Bacterial infection

Bacterial colonization is a common complicationof AD (FIG. 2). A study by Leyden et al. showed that90% of patients with AD had S. aureus colonizationof diseased skin (20). When compared with psori-atic plaques, which were colonized only 50% of thetime in a similar study. This colonization rate mayindicate a specific vulnerability of atopic skin tobacterial colonization (21). Although the reasonsfor this are not completely understood, decreasedexpression of endogenous antimicrobial peptidesin atopic skin may cause a localized immunodefi-ciency in atopic skin (22). Chronic colonizationwith S. aureus can exacerbate disease and makedisease clearance more difficult. Treatment withtopical or oral antistaphylococcal antibiotics canfacilitate recovery (23). Interestingly, patients withADdo not appear to bemore likely than the generalpopulation to be carriers of resistant strains of S.aureus (23).

In addition to colonization, S. aureus, and lesscommonly streptococcus, can cause clinical infec-tion. Active infectionmanifests as pustules, honey-crusted papules, abscesses, or cellulitis. Patientswith AD are also at risk for serious infectionsincluding sepsis, endocarditis, septic arthritis, andosteomyelitis (24). Not surprisingly, patients withmore severe AD are at greater risk for bacteremia.Invasive S. aureus infection should be consideredin all atopic patients presenting with an acute

FIG. 1. Eczema herpeticum. Umbilicated vesicles andhemorrhagic-crusted papules characteristic of eczema her-peticum. Note significant periorbital edema.

Table 4. Management of eczema herpeticum

Antiviral treatmenta

Intravenous acyclovir12 years of age: 510 mg/kg/dose every 8 hours

Oral acyclovirb

Child: 20 mg/kg/dose every 6 hours (maximumdose 800 mg)

Adults: 800 mg five times a day (treat children asadults when mg/kg dosing is 800 mg)

Other antivirals (dosing schedules not established inpediatric patients)Valacyclovir 1 g three times a dayFamciclovir 500 mg three times a day

Adjunctive treatmentPain controlAvoidance of topical corticosteroids and topical

calcineurin inhibitors to active areas of infectionAvoidance of systemic immunosuppressives during

acute infectionIdentify and treat secondary bacterial infectionNormal saline or Burrows compresses twice a dayBland emollientsOphthalmologic consult if facial involvement present

aAll treatment is administered for a minimum of 710 days.bIntravenous acyclovir is preferred except in cases of mild

disease.

FIG. 2. Atopic dermatitis and secondary bacterial infection.Erosions and crusted papules superimposed over lichenifiedeczematous plaques.

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unexplained febrile illness or fever and localizedpain. In such cases, early recognition andtreatment with appropriate antibiotics can belifesaving.

Oral antibiotics can be used for most cases ofactive infection. The prevalence of methicillin-resistant S. aureus (MRSA) varies by communityand makes the implementation of generalizedtreatment recommendations difficult. Empirictherapy should be based on local patterns of anti-biotic resistance. Care should be taken to identifyany fluctuant areas in need of surgical drainage.Cellulitis that fails oral treatment should be treatedon an inpatient basis with intravenous antibiotics.Goals for discharge include decreasing size,redness, and tenderness of the affected area. Aculture should be obtained whenever possible tohelp tailor antibiotic therapy. Depending onculture results, patients can be discharged on oralantibiotics or maintained on home intravenousinfusions for a full course of treatment with theappropriate antibiotic. More serious infectionswill require hospital admission and treatmentwith intravenous antibiotics. Consultation with aninfectious disease specialist may be beneficial.Empiric antibiotic therapy should provide cover-age against MRSA until cultures and sensitivitiesare available. MRSA causes more serious and viru-lent infections compared with methicillin-sensitive S. aureus (MSSA). Patients requiringhospitalization for their staphylococcal infectionswere found to be more likely to grow MRSA thanMSSA (25).

Conclusions

Inpatient treatment of AD can be a helpful andimportant part of long-term management ofpatients with this chronic condition. Erythrodermacan be a life-threatening complication thatrequires careful attention to fluid status and rapidcorrection of the underlying dermatitis. Althoughmany protocols for wet wrap therapy exist, thebasic structure of steroid application under a wetand then a dry dressing has been shown in severalstudies to lead to rapid improvement of AD. EH isanother serious complication of chronic AD requir-ing in most cases intravenous antiviral medicationand inpatient monitoring for potential complica-tions. Awareness of community-acquired MRSAis also important when treating AD patients.Although S. aureus colonization of atopic skin is acommon occurrence, the existence of pathogenicstrains capable of causing more severe infections

that are resistant to traditional therapies is a recentdevelopment complicating the management ofthese patients. Intravenous therapy should be con-sidered for any AD patient with a severe bacterialskin infection that is resistant to oral antibiotics.Although most AD patients will not require acuteinpatient therapy, it is important to recognize thatthere are certain subsets of our AD population whomay benefit greatly from it. Prompt recognition ofthese patients and institution of the proper therapycan improve patient outcomes and prevent moreserious complications.

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