**1. Introduction**

The treatment of atopic dermatitis (AD) can be challenging for dermatologists and other healthcare professionals. Conventional treatments consisting of emollients and topical corticosteroids are often insufficient for severe and/or refractory AD. Other therapies include systemic corticosteroids, photochemotherapy using psoralen and ultraviolet-A light, and cyclosporine. However, all of these approaches have potentially serious side effects and relative contraindications, especially in children. Over the past two decades, occlusive therapy has been advocated as a safe and effective treatment modality for individuals with acute erythrodermic AD and those with severe and/or refractory AD. (Nicol 1987; Goodyear et al. 1991; Bridgman 1995; Devillers and Oranje 2005)

Occlusive therapy usually involves the application of emollients, antiseptics, or topical corticosteroids under either wet wrap dressings (WWD) or dry wrap dressings (DWD). This consists of moistened open-weave cotton tubular bandages (eg. Tubifast, Tubigauz) in WWD occlusion, versus dry gauze, plastic wraps, or hydrocolloid dressings (eg. Duoderm) in DWD occlusion. (Nicol 1987; Goodyear et al. 1991; Bridgman 1995)

More recently, however, occlusion alone using a hydrogel patch has been utilized. The theory is that a major component in the pathophysiology of AD is barrier dysfunction. In fact, many current therapies target this barrier defect (i.e., pseudoceramide moisturizers and skin barrier emulsions). As such, an ideal repair mechanism would completely eliminate microbe and allergen penetration and transepidermal water loss in AD, both of which lead to xerosis, hypersensitivity, pruritus, and inflammation. The hydrogel patch, therefore, offers an innovative approach to *complete* barrier repair. (Park et al. 2011)

Regardless of the treatment approach, occlusive therapy offers many advantageous such as a cooling effect on inflamed skin, increased penetration of topical agents, enhanced skin hydration, and a barrier to external antigens and trauma (i.e. scratching). Reported disadvantages include the cumbersome and time-consuming nature of the application process, risk of allergic reaction to the occlusive material itself, and possible increased risk of infectious complications such as folliculitis, furunculosis, or cellulitis. An additional concern is that occlusion may cause skin maceration if used incorrectly, or can paradoxically

promote skin dryness if too little topicals are applied. (Nicol 1987; Goodyear et al. 1991; Bridgman 1995; Krakowski et al. 2008)

Occlusion alone of both normal and lesional eczematous skin can result in increased density of cutaneous microbial flora. (Aly et al. 1978; Rajka et al. 1981) Moreover, there is a positive association between *Staphylococcus aureus* (*S. aureus*) colonization and disease severity. (Williams 2000) These findings suggest that occlusion, by increasing the density of *S. aureus*, might push already colonized eczematous skin into the realm of clinical infection. In addition, innate production of cutaneous anti-microbial peptides, such as sphingosine and -defensin, is depressed in patients with AD such that eczematous skin possesses decreased natural resistance to bacterial invasion (Arikawa et al. 2002; Ong et al. 2002) Thus, evidence of clinically apparent skin infection may be a contraindication to occlusive therapy, as it may exacerbate the infection. (Aly et al. 1978) However, the possibility that *S. aureus* colonization may complicate occlusive therapy has not been adequately addressed to date.

Another concern is that the use of topical corticosteroids under occlusion may relate to an increased potential for absorption and greater incidences of possible adverse effects. Most attention has been focused on the risk of skin atrophy and striae, hypothalamic-pituitaryadrenal (HPA) axis suppression, as well as growth impairment in children.

Ultimately, this chapter aims to examine current evidence on the safety and efficacy of occlusive therapy in the treatment of AD.

#### **2. Methods**

Studies on the use of occlusive therapy for the treatment of atopic dermatitis were identified in PubMed and Embase Medline databases from January 1966 to April 2011, using the key terms "occlusion," "occlusive dressings", "occlusive therapy," "wet wrap," "wet dressings," "dry wrap," "dry dressings," "atopic dermatitis," "dermatitis," and "eczema." Key terms were also searched in combination. Reference lists of relevant publications were manually searched for additional relevant studies. The search was limited to original studies and review articles published in English or with English abstracts, in humans. Studies of small size and those that did not use a controlled or randomized study design were included due to the dearth of published literature on this topic. Publications meeting these criteria were then reviewed for study design, population, disease severity or type, study size, efficacy, and safety. The topical agent used, dilution, and type and period of occlusive therapy were also noted, when such information was made available in the publication. In addition, response to therapy was seen as improvement in disease severity or symptoms from baseline, improvement in SCORing Atopic Dermatitis (SCORAD), and/or improvement in Eczema Area and Severity Index (EASI) score, depending on what information was provided. Of note, SCORAD is composite score of eczema severity based on the surface area involved, intensity of symptoms, and subjective symptoms such as sleep disturbance and pruritus. EASI is a 12-point scoring system of disease severity assessing erythema, induration, lichenification, pruritus, and excoriation. Finally, conclusions were drawn from the results of these studies bearing in mind standard clinical practice.

#### **3. Studies on occlusive therapy**

There are a total of 19 studies evaluating the use of occlusive therapy in AD (Table 1). Fourteen studies used WWD, 5 of which were randomized controlled trials. All WWD


270 Atopic Dermatitis – Disease Etiology and Clinical Management

promote skin dryness if too little topicals are applied. (Nicol 1987; Goodyear et al. 1991;

Occlusion alone of both normal and lesional eczematous skin can result in increased density of cutaneous microbial flora. (Aly et al. 1978; Rajka et al. 1981) Moreover, there is a positive association between *Staphylococcus aureus* (*S. aureus*) colonization and disease severity. (Williams 2000) These findings suggest that occlusion, by increasing the density of *S. aureus*, might push already colonized eczematous skin into the realm of clinical infection. In addition, innate production of cutaneous anti-microbial peptides, such as sphingosine and -defensin, is depressed in patients with AD such that eczematous skin possesses decreased natural resistance to bacterial invasion (Arikawa et al. 2002; Ong et al. 2002) Thus, evidence of clinically apparent skin infection may be a contraindication to occlusive therapy, as it may exacerbate the infection. (Aly et al. 1978) However, the possibility that *S. aureus* colonization

Another concern is that the use of topical corticosteroids under occlusion may relate to an increased potential for absorption and greater incidences of possible adverse effects. Most attention has been focused on the risk of skin atrophy and striae, hypothalamic-pituitary-

Ultimately, this chapter aims to examine current evidence on the safety and efficacy of

Studies on the use of occlusive therapy for the treatment of atopic dermatitis were identified in PubMed and Embase Medline databases from January 1966 to April 2011, using the key terms "occlusion," "occlusive dressings", "occlusive therapy," "wet wrap," "wet dressings," "dry wrap," "dry dressings," "atopic dermatitis," "dermatitis," and "eczema." Key terms were also searched in combination. Reference lists of relevant publications were manually searched for additional relevant studies. The search was limited to original studies and review articles published in English or with English abstracts, in humans. Studies of small size and those that did not use a controlled or randomized study design were included due to the dearth of published literature on this topic. Publications meeting these criteria were then reviewed for study design, population, disease severity or type, study size, efficacy, and safety. The topical agent used, dilution, and type and period of occlusive therapy were also noted, when such information was made available in the publication. In addition, response to therapy was seen as improvement in disease severity or symptoms from baseline, improvement in SCORing Atopic Dermatitis (SCORAD), and/or improvement in Eczema Area and Severity Index (EASI) score, depending on what information was provided. Of note, SCORAD is composite score of eczema severity based on the surface area involved, intensity of symptoms, and subjective symptoms such as sleep disturbance and pruritus. EASI is a 12-point scoring system of disease severity assessing erythema, induration, lichenification, pruritus, and excoriation. Finally, conclusions were drawn from

There are a total of 19 studies evaluating the use of occlusive therapy in AD (Table 1). Fourteen studies used WWD, 5 of which were randomized controlled trials. All WWD

may complicate occlusive therapy has not been adequately addressed to date.

adrenal (HPA) axis suppression, as well as growth impairment in children.

the results of these studies bearing in mind standard clinical practice.

Bridgman 1995; Krakowski et al. 2008)

occlusive therapy in the treatment of AD.

**3. Studies on occlusive therapy** 

**2. Methods** 


\*Dilution and concentration noted when provided in the article

Table 1. Studies on Occlusive Therapy (HCT = Hydrocortisone, RCT = randomized control trial)

Occlusive Therapy in Atopic Dermatitis 273

occlusion studies demonstrated efficacy in severe or acute, moderate and chronic AD. Among the 4 studies examining DWD, only one used a randomized controlled design. All, except one, DWD studies demonstrated improvements in AD. There is also one study that used an impermeable hydrogel patch consisting of about 50% water content. The hydrogel patch alone demonstrated improvements in AD, comparable to that of corticosteroid use alone. Increased cutaneous bacterial counts or clinical infections were reported in 4 out of

The following is a detailed description of the 14 studies evaluating the efficacy of WWD in the treatment of AD (Table 2). Occlusive therapy was first introduced by Goodyear et al. in 1991. Goodyear et al. (1991) evaluated the inpatient use of WWD occlusion for acute erythrodermic eczema. This WWD technique involved the application of open-weave cotton tubular dressings (Tubegauz) impregnanted with hydrocortisone 1% cream (if child <2 years of age) or 10% dilution of bemethasone valerate (if child > 2 years of age) twice daily. All 30 children responded well to WWD occlusion, with no relapses noted at 2 weeks follow-up. Interestingly, an attempt at long-term home therapy using WWD, following the inpatient therapy, in 5 patients was unsuccessful due to reports of inconvenience, increased

Mallon et al. (1994) studied the use of WWD in chronic severe eczema in 21 children. Eczema was managed using topical steroid creams (i.e. hydrocortisone 0.5% or 10% dilution betamethosone 0.1% cream) and emollients under WWD daily for less than 5 days. All patients responded well to WWD therapy. The treatment was also well-tolerated. Majority of parents (20/21) reported decreased use topical steroid per week following the

Abeck et al. (1999) treated 6 patients (3 children and 3 adults) with acute exacerbated atopic eczema with basic emollients in combination with chlorhexidine-soaked dressings for 3 days. The study observed improvements in disease severity based on SCORAD score. Patients also reported decreased itch and sleep loss following WWD therapy. In addition, there was a

In a study of 31 children with severe refractory AD, Wolkerstorfer et al. (2000) investigated the efficacy of various cortiocosteroid dilutions under WWD occlusion. Participants were divided into 3 treatment groups. The first group consisted of 18 children, who were treated with 50% dilution of fluticasone propionate 0.05% (FP) cream under WWD for 2 weeks. In the second group, 5 children with symmetrically localized AD were treated with different dilutions (10%, 25% and 50%) of FP cream on the left and the right side of the body under WWD for one week and then 10% dilution of FP cream under WWD the following week. In the third group, 8 children were treated with 0% (i.e. only emollient), 5%, 10%, or 25% dilutions of FP cream applied to the entire body under WWD. After just one week of therapy, significant improvement in disease severity was observed, without noticeable differences between 5%, 10%, or 25% dilutions of FP cream under WWD. Less improvement was observed in the second week of therapy. In terms of skin infections, mild-to-moderate folliculitis was reported in a large proportion of the children, with 33% (6/18) children in the first group, 40% (2/5) children in the second group, and 63% (5/8) children in the third group. There was also one case of furunculosis in the third group. Interestingly, generalized folliculitis was noted in both of the children treated with only emollient during the first week. These findings suggests that although WWD occlusion may foster bacterial growth,

bacterial infections, and prolonged HPA axis suppression. (Goodyear 1991)

reduction of *S. aureus* counts that paralleled skin improvement. (Abeck et al. 1999)

the 15 studies using WWD and all 4 studies using DWD.

introduction of WWD therapy. (Mallon et al. 1994)

**3.1 Wet wrap dressings** 

\*Dilution and concentration noted when provided in the article

control trial)

Table 1. Studies on Occlusive Therapy (HCT = Hydrocortisone, RCT = randomized

occlusion studies demonstrated efficacy in severe or acute, moderate and chronic AD. Among the 4 studies examining DWD, only one used a randomized controlled design. All, except one, DWD studies demonstrated improvements in AD. There is also one study that used an impermeable hydrogel patch consisting of about 50% water content. The hydrogel patch alone demonstrated improvements in AD, comparable to that of corticosteroid use alone. Increased cutaneous bacterial counts or clinical infections were reported in 4 out of the 15 studies using WWD and all 4 studies using DWD.

#### **3.1 Wet wrap dressings**

The following is a detailed description of the 14 studies evaluating the efficacy of WWD in the treatment of AD (Table 2). Occlusive therapy was first introduced by Goodyear et al. in 1991. Goodyear et al. (1991) evaluated the inpatient use of WWD occlusion for acute erythrodermic eczema. This WWD technique involved the application of open-weave cotton tubular dressings (Tubegauz) impregnanted with hydrocortisone 1% cream (if child <2 years of age) or 10% dilution of bemethasone valerate (if child > 2 years of age) twice daily. All 30 children responded well to WWD occlusion, with no relapses noted at 2 weeks follow-up. Interestingly, an attempt at long-term home therapy using WWD, following the inpatient therapy, in 5 patients was unsuccessful due to reports of inconvenience, increased bacterial infections, and prolonged HPA axis suppression. (Goodyear 1991)

Mallon et al. (1994) studied the use of WWD in chronic severe eczema in 21 children. Eczema was managed using topical steroid creams (i.e. hydrocortisone 0.5% or 10% dilution betamethosone 0.1% cream) and emollients under WWD daily for less than 5 days. All patients responded well to WWD therapy. The treatment was also well-tolerated. Majority of parents (20/21) reported decreased use topical steroid per week following the introduction of WWD therapy. (Mallon et al. 1994)

Abeck et al. (1999) treated 6 patients (3 children and 3 adults) with acute exacerbated atopic eczema with basic emollients in combination with chlorhexidine-soaked dressings for 3 days. The study observed improvements in disease severity based on SCORAD score. Patients also reported decreased itch and sleep loss following WWD therapy. In addition, there was a reduction of *S. aureus* counts that paralleled skin improvement. (Abeck et al. 1999)

In a study of 31 children with severe refractory AD, Wolkerstorfer et al. (2000) investigated the efficacy of various cortiocosteroid dilutions under WWD occlusion. Participants were divided into 3 treatment groups. The first group consisted of 18 children, who were treated with 50% dilution of fluticasone propionate 0.05% (FP) cream under WWD for 2 weeks. In the second group, 5 children with symmetrically localized AD were treated with different dilutions (10%, 25% and 50%) of FP cream on the left and the right side of the body under WWD for one week and then 10% dilution of FP cream under WWD the following week. In the third group, 8 children were treated with 0% (i.e. only emollient), 5%, 10%, or 25% dilutions of FP cream applied to the entire body under WWD. After just one week of therapy, significant improvement in disease severity was observed, without noticeable differences between 5%, 10%, or 25% dilutions of FP cream under WWD. Less improvement was observed in the second week of therapy. In terms of skin infections, mild-to-moderate folliculitis was reported in a large proportion of the children, with 33% (6/18) children in the first group, 40% (2/5) children in the second group, and 63% (5/8) children in the third group. There was also one case of furunculosis in the third group. Interestingly, generalized folliculitis was noted in both of the children treated with only emollient during the first week. These findings suggests that although WWD occlusion may foster bacterial growth,


#### 274 Atopic Dermatitis – Disease Etiology and Clinical Management Occlusive Therapy in Atopic Dermatitis 275

Table 2. Outcomes of Studies on Wet Wrap Dressing Occlusion (DPD = deoxypyridinoline,

HPA = hypothalamic-pituitary-adrenal, HRQoL = Health Related Quality of Life)


Table 2. Outcomes of Studies on Wet Wrap Dressing Occlusion (DPD = deoxypyridinoline, HPA = hypothalamic-pituitary-adrenal, HRQoL = Health Related Quality of Life)

cheek in a patient without a facial mask, and purulent conjunctivitis in a patient with a facial mask. These complications may be attributed to variations in standard protocal for WWD application, such as prolonged (>8 hours) occlusion and the frequent rewetting procedure.

McGowan et al. (2003) examined the effects of WWD therapy using topical corticosteroids on short-term growth and bone turnover in 8 prepubertal children, ranging from 3-8 years of age. Tubular bandages were applied over 10% or 25% dilutions of beclomethasone dipropionate for 24 hours each day for 2 weeks. After 2 weeks, frequency of tubular bandages was reduced to overnight use for one week and then as required for the remainder of the treatment period. Occlusive dressings were applied for a median duration of 12 weeks (range 2 – 18 weeks). Short-term growth was assessed by measuring lower leg length velocity by knemometry, while bone turnover was assessed by urinary deoxypyridinoline excretion. (McGowan et al. 2003) (See Section 3.4 Cutaneous and Systemic Side Effects for

In randomized control trial, Beattie and Lewis-Jones (2004) compared the use of 1% hydrocortisone under WWD to conventional open therapy in 19 children with moderate, widespread AD. The control group applied 1% hydrocortisone twice daily for 2 weeks, without WWD. In the study group, patients applied 1% hydrocortisone once in the morning for 2 weeks, with WWD twice daily for the first week and then only at night for the second week. Both groups were allowed to apply non-steroidal emollients as often as necessary. Beattie and Lewis Jones (2004) found no difference in clinical improvement between the control group and the study group. The authors, therefore, concluded that conventional open therapy using 1% hydrocortisone and emollients alone appeared to be as effective as using 1% hydrocortisone under WWD for moderate AD. Despite these findings, it is important to note that the use of 1% hydrocortisone is a less potent choice than what is generally used in clinical practice when treating moderate AD. If the authors had evaluated the use of a mid-potency topical corticosteroid under WWD, the degree of improvement between the study and control groups might have been markedly different. In terms of health related quality of life, Beattie and Lewis-Jones (2004) found greater improvements in the non-WWD control group than the WWD group for both the child and the family. Children in the non-WWD control group also reported more sleep than the WWD group, but there was no significant difference for itch between treatment groups. In regards to infections, 2 of the 10 (20%) children in the WWD group experienced folliculitis, one of which had to be withdrawal from the study. There were no reported clinical infections in the

Foelster-Holst et al. (2006) conducted a randomized, controlled study of 24 adults and children with acute episodes of AD. This was left-right comparison study, in which patients had skin lesions symmetrically affecting both arms or legs. One arm or leg was randomly treated with the topical prednicarbat (a medium potency corticosteroid), with WWD using a tubular bandage. The other extremity received topical prednicarbat alone. After 48-72 hours of therapy, both groups showed improvement of the local SCORAD, but the improvement in the WWD group was significantly better. No adverse effects were observed in either

Hindley et al. (2006) carried a randomized, control trial to investigate the efficacy of WWD as compared to conventional topically applied corticosteroids. This 4-week study consisted of a total of 50 children with moderate-to-severe eczema. In the conventional treatment group, patients had emollients applied as needed and 1% hydrocortisone ointment (or more

(Devillers et al. 2002)

further discussion of this study)

non-WWD control group. (Beattie and Lewis-Jones 2004)

treatment group. (Foelster-Holst et al. 2006)

the addition of topical corticosteroids to the treatment regimen appeared to provide some protective benefits. (Wolkerstorfer et al. 2000)

Tang (2000) treated 10 children experiencing a flare of facial eczema with WWD occlusion. Children were initiated on an intermittent treatment regimen involving 10% dilution of mometasone furoate 0.1% cream or ointment under WWD applied for 2-3 hours once daily for a few consecutive days. All parents reported good treatment response. No cutaneous side effects were observed from topical corticosteroid use. (Tang 2000)

Pei et al. (2001) performed a randomized control trial of 40 children with moderate-to-severe AD. Prior to starting the study, all patient were instructed to apply 0.005% flucinolone acetonide cream twice daily for 2 weeks to standardize treatment medications. Patient were then randomized to receive 10% dilution of 0.1% mometasone furoate ointment or 10% dilution of 0.005% fluticasone propionate ointment. These topical agents were applied once a day for 2 weeks without WWD. After this 2-week period of open application, patients were further randomized to receive the same topical agent for 2 more weeks without WWD, or for 2 more weeks under WWD. Only 30 patients (75%) entered into this second phase of the study since their disease severity had failed to improve by more than 50% after the initial 2 weeks of open topical application. In other words, only patients whose disease was refractory to a 2-week period of conventional open therapy continued in the study. Ultimately, there were a total of 27 patients who completed the study. One child receiving fluticasone propionate ointment dropped out of the study because the patient was unable to tolerate WWD. The study found that significantly greater improvements in disease severity and extent in patients using WWD, as compared to controls. These results suggest that WWD may be an effective second-line therapy in children whose disease is refractory to conventional open topical corticosteroids. (Pei et al. 2001)

Schnopp et al. (2002) examined the effect of WWD in a randomized control study of 20 inpatients with exacerbated AD. Children received either a topical corticosteroid preparation (mometasone furoate 0.1%) or a steroid-free preparation (its vehicle) under WWD, applied twice daily for 5 days to the tested area in a left-right study. Disease severity at day 3 and day 5 continuously improved in both groups; however, the mometasone furoate-treated group showed significantly greater irmprovements. *Staphylococcus aureus* bacterial counts initially decreased during the first 3 days of treatment in both groups. At day 5, bacterial counts continued to decrease in the steroid-treated group, but bacterial counts increased in the vehicle-treated group. There were no reported clinical signs of bacterial superinfection in either the steroid or vehicle groups. The study concluded that WWD were useful in treatment of exacerbated AD, with applications of topical corticosteroids showing better efficacy than steroid-free emollients. (Schnopp et al. 2002)

Devillers et al. (2002) evaluated the use of WWD in refractory AD in 12 adults and 14 children. WWD were applied daily and re-wettted every 2-3 hours for 1 week in an inpatient setting. Patients used 5% dilution of FP cream under WWD on affected areas of the face. As for the body, a side-to-side comparison study was performed, in which adults applied 10% and 25% dilutions of FP cream and children applied 5% and 10% dilutions of FP cream. Disease severity improved dramatically during the one week of inpatient therapy. There was no difference in improvement between dilutions applied to each side of the body. Following inpatient therapy, 8 adults and 13 children continued treatment at home with less potent dilutions of FP cream. Exacerbation of AD occurred in 3 adults and 2 children. Infectious complications included localized folliculitis (4 reported cases), secondary impetigo (2 reported cases), localized *Pseudomonas aeruginosa* infection, cellulitis of the left

the addition of topical corticosteroids to the treatment regimen appeared to provide some

Tang (2000) treated 10 children experiencing a flare of facial eczema with WWD occlusion. Children were initiated on an intermittent treatment regimen involving 10% dilution of mometasone furoate 0.1% cream or ointment under WWD applied for 2-3 hours once daily for a few consecutive days. All parents reported good treatment response. No cutaneous

Pei et al. (2001) performed a randomized control trial of 40 children with moderate-to-severe AD. Prior to starting the study, all patient were instructed to apply 0.005% flucinolone acetonide cream twice daily for 2 weeks to standardize treatment medications. Patient were then randomized to receive 10% dilution of 0.1% mometasone furoate ointment or 10% dilution of 0.005% fluticasone propionate ointment. These topical agents were applied once a day for 2 weeks without WWD. After this 2-week period of open application, patients were further randomized to receive the same topical agent for 2 more weeks without WWD, or for 2 more weeks under WWD. Only 30 patients (75%) entered into this second phase of the study since their disease severity had failed to improve by more than 50% after the initial 2 weeks of open topical application. In other words, only patients whose disease was refractory to a 2-week period of conventional open therapy continued in the study. Ultimately, there were a total of 27 patients who completed the study. One child receiving fluticasone propionate ointment dropped out of the study because the patient was unable to tolerate WWD. The study found that significantly greater improvements in disease severity and extent in patients using WWD, as compared to controls. These results suggest that WWD may be an effective second-line therapy in children whose disease is refractory to

Schnopp et al. (2002) examined the effect of WWD in a randomized control study of 20 inpatients with exacerbated AD. Children received either a topical corticosteroid preparation (mometasone furoate 0.1%) or a steroid-free preparation (its vehicle) under WWD, applied twice daily for 5 days to the tested area in a left-right study. Disease severity at day 3 and day 5 continuously improved in both groups; however, the mometasone furoate-treated group showed significantly greater irmprovements. *Staphylococcus aureus* bacterial counts initially decreased during the first 3 days of treatment in both groups. At day 5, bacterial counts continued to decrease in the steroid-treated group, but bacterial counts increased in the vehicle-treated group. There were no reported clinical signs of bacterial superinfection in either the steroid or vehicle groups. The study concluded that WWD were useful in treatment of exacerbated AD, with applications of topical corticosteroids showing better efficacy than steroid-free emollients. (Schnopp et al. 2002) Devillers et al. (2002) evaluated the use of WWD in refractory AD in 12 adults and 14 children. WWD were applied daily and re-wettted every 2-3 hours for 1 week in an inpatient setting. Patients used 5% dilution of FP cream under WWD on affected areas of the face. As for the body, a side-to-side comparison study was performed, in which adults applied 10% and 25% dilutions of FP cream and children applied 5% and 10% dilutions of FP cream. Disease severity improved dramatically during the one week of inpatient therapy. There was no difference in improvement between dilutions applied to each side of the body. Following inpatient therapy, 8 adults and 13 children continued treatment at home with less potent dilutions of FP cream. Exacerbation of AD occurred in 3 adults and 2 children. Infectious complications included localized folliculitis (4 reported cases), secondary impetigo (2 reported cases), localized *Pseudomonas aeruginosa* infection, cellulitis of the left

side effects were observed from topical corticosteroid use. (Tang 2000)

conventional open topical corticosteroids. (Pei et al. 2001)

protective benefits. (Wolkerstorfer et al. 2000)

cheek in a patient without a facial mask, and purulent conjunctivitis in a patient with a facial mask. These complications may be attributed to variations in standard protocal for WWD application, such as prolonged (>8 hours) occlusion and the frequent rewetting procedure. (Devillers et al. 2002)

McGowan et al. (2003) examined the effects of WWD therapy using topical corticosteroids on short-term growth and bone turnover in 8 prepubertal children, ranging from 3-8 years of age. Tubular bandages were applied over 10% or 25% dilutions of beclomethasone dipropionate for 24 hours each day for 2 weeks. After 2 weeks, frequency of tubular bandages was reduced to overnight use for one week and then as required for the remainder of the treatment period. Occlusive dressings were applied for a median duration of 12 weeks (range 2 – 18 weeks). Short-term growth was assessed by measuring lower leg length velocity by knemometry, while bone turnover was assessed by urinary deoxypyridinoline excretion. (McGowan et al. 2003) (See Section 3.4 Cutaneous and Systemic Side Effects for further discussion of this study)

In randomized control trial, Beattie and Lewis-Jones (2004) compared the use of 1% hydrocortisone under WWD to conventional open therapy in 19 children with moderate, widespread AD. The control group applied 1% hydrocortisone twice daily for 2 weeks, without WWD. In the study group, patients applied 1% hydrocortisone once in the morning for 2 weeks, with WWD twice daily for the first week and then only at night for the second week. Both groups were allowed to apply non-steroidal emollients as often as necessary. Beattie and Lewis Jones (2004) found no difference in clinical improvement between the control group and the study group. The authors, therefore, concluded that conventional open therapy using 1% hydrocortisone and emollients alone appeared to be as effective as using 1% hydrocortisone under WWD for moderate AD. Despite these findings, it is important to note that the use of 1% hydrocortisone is a less potent choice than what is generally used in clinical practice when treating moderate AD. If the authors had evaluated the use of a mid-potency topical corticosteroid under WWD, the degree of improvement between the study and control groups might have been markedly different. In terms of health related quality of life, Beattie and Lewis-Jones (2004) found greater improvements in the non-WWD control group than the WWD group for both the child and the family. Children in the non-WWD control group also reported more sleep than the WWD group, but there was no significant difference for itch between treatment groups. In regards to infections, 2 of the 10 (20%) children in the WWD group experienced folliculitis, one of which had to be withdrawal from the study. There were no reported clinical infections in the non-WWD control group. (Beattie and Lewis-Jones 2004)

Foelster-Holst et al. (2006) conducted a randomized, controlled study of 24 adults and children with acute episodes of AD. This was left-right comparison study, in which patients had skin lesions symmetrically affecting both arms or legs. One arm or leg was randomly treated with the topical prednicarbat (a medium potency corticosteroid), with WWD using a tubular bandage. The other extremity received topical prednicarbat alone. After 48-72 hours of therapy, both groups showed improvement of the local SCORAD, but the improvement in the WWD group was significantly better. No adverse effects were observed in either treatment group. (Foelster-Holst et al. 2006)

Hindley et al. (2006) carried a randomized, control trial to investigate the efficacy of WWD as compared to conventional topically applied corticosteroids. This 4-week study consisted of a total of 50 children with moderate-to-severe eczema. In the conventional treatment group, patients had emollients applied as needed and 1% hydrocortisone ointment (or more

(available since 2003). With the introduction of these garments, wet wrapping can be done in 20–25 minutes. Tubifast garments® are available as tights for babies aged 6–24 months, vests for children 6 months through 14 years, and socks and leggings in all sizes. These washable garments are absorbent, holding enough water to remain moist for hours, and are elastic

1. Choose the appropriate width of the tubular bandages and cut these to size to fit the affected body areas (i.e. arms, legs, trunk). Alternatively, Tubifast® garments

2. Apply the appropriate dilution of topical corticosteroids (e.g. fluticasone propionate 0.05% cream, mometasone furoate 0.1% cream) on the involved skin. In general, diluted steroids in emollients of 1:9 are applied to the face of all patients and body of infants, while diluted steroids in emollients of 1:9 or 1:3 are applied on the body of adults. 3. Wet the pieces of tubular bandage in lukewarm water. Alternatively, if Tubifast® garments are used, then the inner garment is moistened using a plant sprayer. 4. Apply the first layer of wet tubular bandages. Connect the arm and leg pieces to the trunk. Apply the facial mask, if necessary. Alternatively, if Tubifast® garments are

5. Apply the second layer of dry tubular bandage. Again, connect the arm and leg pieces to the trunk. Apply the facial mask, if necessary. Alternatively, if Tubifast® garments are used, a second dry Tubifast® garment is placed over the wet one. 6. Re-wet the tubular bandages every 2-3 hours. Alternatively, if Tubifast® garments

8. After 7 days of occlusive therapy, the dilution of topical corticosteroids (e.g. fluticasone propionate 0.05% cream, mometasone furoate 0.1% cream) is applied on

Finally, in a review article, Devillers and Oranje (2006) made the following conclusions regarding WWD occlusion with a grade C of recommendation. 1) WWD using cream or ointment and a double layer of cotton bandages, with a moist first layer and a dry second layer, is an efficacious short-term treatment for children with severe and/or refractory AD.2) The use of WWD with diluted topical corticosteroids is a more efficacious treatment than wet-wrap dressings with emollients only for children with severe and/or refractory AD. 3) The use of WWD with diluted topical corticosteroids is a safe intervention treatment for children with severe and/or refractory AD for up to 14 days, with temporary systemic bioactivity of the corticosteroids as the only reported serious adverse effect. 4) Lowering the absolute amount of applied topical corticosteroid to once daily application and further

DWD occlusion in AD has been less well studied (Table 4). Specifically, Rajka et al. (1981) examined the effect of dry occlusion on skin microbial flora. Occlusion using plastic film was applied to 10 patients with AD. A significant increase in the density of *S. aureus* was observed after 24 hours of dry occlusion. Notably, 2 of the 10 patients had tiny pustules or crusts following dry occlusion. But, there were no reports of AD exacerbation. (Rajka et al. 1981)

and able to conform to the contours of the body. (Page 2005)

used, the inner garment is moistened using a plant spray.

are used, re-wet the inner Tubifast® garment every 2-3 hours.

7. Repeat procedures #1-6 (described above) daily.

the involved skin for 4-7 consecutive days.

dilution can reduce potential risks. (Devillers and Oranje 2006)

Table 3. Protocol for Wet Wrap Dressing occlusion

can be used.

**3.2 Dry wrap dressings** 

potent topical steroids, if necessary) applied twice daily. In the WWD treatment group, patients had wet wraps applied daily for a 24-hour period over 1% hydrocortisone ointment (or more potent topical steroids, if necessary) during the first week, followed by wet wraps applied for a 12- or 24-hour period depending on disease progress for the remaining three weeks. When wet wraps were applied for only a 12-hour period, 1% hydrocortisone and emollients were used during the non-wet wrap period. Both treatment groups demonstrated improvement in overall SCORAD scores; however, there was no significant difference between the conventional and WWD treatment groups. Five out of 23 (22%) children in the WWD treatment group required antibiotics for skin infections, as compared to none of the children in the conventional treatment group. The authors conclude that 4-weeks of maintenance WWD treatment may be associated with more skin infections than conventional treatment. (Hindley et al. 2006) However, it is important to realize that in clinical practice, physicians usually do not use WWD for maintenance therapy of AD over a 4-week duration. Instead, physicians are more likely to use WWD in settings of acute generalized eczematous flares for 3-7 days to induce disease remission. (Williams 2006) Lee et al. (2007) examined the therapeutic efficacy of WWD and the mechanism behind its therapeutic efficacy in treatment of AD. Ten patients with severe AD received WWD (without steroid treatment) for 7–14 days. SCORAD was used to assess AD severity, immediately following the end of treatment and 7 days after termination of treatment. Transepidermal water loss, water content in the corneum, and lipid amount of skin surface were also measured. The SCORAD was significantly reduced after WWD therapy. Additionally, epidermal water content was increased and transepidermal water loss was decreased following WWD therapy; these results were maintained 1 week after terminating therapy. In atopic lesions, increased release of lamellar bodies and restoration of intercellular lipid lamellar structure was observed. The authors speculated that increased secretion of lamellar bodies induced with WWD occlusion may lead to recovery of the abnormal epidermal barrier and clinical improvement in AD. (Lee et al. 2007)

In a clinical study of six children with moderate to severe AD, Hon et al. (2007) tested the efficiacy of WWD occlusion using Tubifast® garments with mometasone furoate 0.1% cream. Short-term use of WWD occlusion over 3 days demonstrated improvement in disease severity based on SCORAD. In addition, a wrist motion monitor was used to measure nocturnal itch, which showed that average scratching activity was significantly reduced by 20–60% on day 3 of treatment. Furthermore, WWD was effective in improving quality of life in these children. (Hon et al. 2007)

Since its introduction by Goodyear et al. (1991) nearly two decades ago, WWD occlusion has been extensively used as a relatively safe and effective treatment modality for children with acute erythrodermic AD and those with severe and/or refractory AD. The most effective topical corticosteroid to be used is still uncertain, but 10% dilutions of potent topical corcorticosteroid are most commonly used. Protocols on adminstration and duration of WWD occlusion can vary between studies. (Oranje et al. 2006) (See Table 3)

Advantages of WWD occlusion include a rapid therapeutic response, reduction in itch and sleep disturbances, and a possible decreased topical corticosteroid use. Disadvantages include high cost, the need for specialized training, increased potential for topical corticosteroid absorption, and increased incidences of folliculitis and other cutaneous infections. (Oranje et al. 2006)

However, the application of WWD has become less time-consuming and more feasible for home use with development of Tubifast® garments manufactured by Medlock Medical®

potent topical steroids, if necessary) applied twice daily. In the WWD treatment group, patients had wet wraps applied daily for a 24-hour period over 1% hydrocortisone ointment (or more potent topical steroids, if necessary) during the first week, followed by wet wraps applied for a 12- or 24-hour period depending on disease progress for the remaining three weeks. When wet wraps were applied for only a 12-hour period, 1% hydrocortisone and emollients were used during the non-wet wrap period. Both treatment groups demonstrated improvement in overall SCORAD scores; however, there was no significant difference between the conventional and WWD treatment groups. Five out of 23 (22%) children in the WWD treatment group required antibiotics for skin infections, as compared to none of the children in the conventional treatment group. The authors conclude that 4-weeks of maintenance WWD treatment may be associated with more skin infections than conventional treatment. (Hindley et al. 2006) However, it is important to realize that in clinical practice, physicians usually do not use WWD for maintenance therapy of AD over a 4-week duration. Instead, physicians are more likely to use WWD in settings of acute generalized eczematous flares for 3-7 days to induce disease remission. (Williams 2006) Lee et al. (2007) examined the therapeutic efficacy of WWD and the mechanism behind its therapeutic efficacy in treatment of AD. Ten patients with severe AD received WWD (without steroid treatment) for 7–14 days. SCORAD was used to assess AD severity, immediately following the end of treatment and 7 days after termination of treatment. Transepidermal water loss, water content in the corneum, and lipid amount of skin surface were also measured. The SCORAD was significantly reduced after WWD therapy. Additionally, epidermal water content was increased and transepidermal water loss was decreased following WWD therapy; these results were maintained 1 week after terminating therapy. In atopic lesions, increased release of lamellar bodies and restoration of intercellular lipid lamellar structure was observed. The authors speculated that increased secretion of lamellar bodies induced with WWD occlusion may lead to recovery of the

abnormal epidermal barrier and clinical improvement in AD. (Lee et al. 2007)

WWD occlusion can vary between studies. (Oranje et al. 2006) (See Table 3)

in these children. (Hon et al. 2007)

infections. (Oranje et al. 2006)

In a clinical study of six children with moderate to severe AD, Hon et al. (2007) tested the efficiacy of WWD occlusion using Tubifast® garments with mometasone furoate 0.1% cream. Short-term use of WWD occlusion over 3 days demonstrated improvement in disease severity based on SCORAD. In addition, a wrist motion monitor was used to measure nocturnal itch, which showed that average scratching activity was significantly reduced by 20–60% on day 3 of treatment. Furthermore, WWD was effective in improving quality of life

Since its introduction by Goodyear et al. (1991) nearly two decades ago, WWD occlusion has been extensively used as a relatively safe and effective treatment modality for children with acute erythrodermic AD and those with severe and/or refractory AD. The most effective topical corticosteroid to be used is still uncertain, but 10% dilutions of potent topical corcorticosteroid are most commonly used. Protocols on adminstration and duration of

Advantages of WWD occlusion include a rapid therapeutic response, reduction in itch and sleep disturbances, and a possible decreased topical corticosteroid use. Disadvantages include high cost, the need for specialized training, increased potential for topical corticosteroid absorption, and increased incidences of folliculitis and other cutaneous

However, the application of WWD has become less time-consuming and more feasible for home use with development of Tubifast® garments manufactured by Medlock Medical® (available since 2003). With the introduction of these garments, wet wrapping can be done in 20–25 minutes. Tubifast garments® are available as tights for babies aged 6–24 months, vests for children 6 months through 14 years, and socks and leggings in all sizes. These washable garments are absorbent, holding enough water to remain moist for hours, and are elastic and able to conform to the contours of the body. (Page 2005)


Table 3. Protocol for Wet Wrap Dressing occlusion

Finally, in a review article, Devillers and Oranje (2006) made the following conclusions regarding WWD occlusion with a grade C of recommendation. 1) WWD using cream or ointment and a double layer of cotton bandages, with a moist first layer and a dry second layer, is an efficacious short-term treatment for children with severe and/or refractory AD.2) The use of WWD with diluted topical corticosteroids is a more efficacious treatment than wet-wrap dressings with emollients only for children with severe and/or refractory AD. 3) The use of WWD with diluted topical corticosteroids is a safe intervention treatment for children with severe and/or refractory AD for up to 14 days, with temporary systemic bioactivity of the corticosteroids as the only reported serious adverse effect. 4) Lowering the absolute amount of applied topical corticosteroid to once daily application and further dilution can reduce potential risks. (Devillers and Oranje 2006)
