**3.2 Dry wrap dressings**

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)


Table 4. Outcomes of Studies on Dry Wrap Dressing Occlusion

Geraldez et al. (1989), in a randomized controlled study of 60 patients with lichen simplex chronicus, observed more infections and other adverse events in patients treated with diflucortolone valerate 0.3% ointment under occlusion as compared those treated without occlusion. Among the patients using dry occlusion, 2 patients (7%) developed pustular lesions surrounding the affected sites, one (3%) had erythema, and one (3%) had hyperpigmentation. None in the control group experienced any side effects. The control group also reported greater improvements in both pruritus and lichenication. The authors noted that the difference in the observed efficacy may be due to poorer absorption of the ointment that tended to adhere to the plastic occlusive material. Furthermore, the adverse events seen in the treatment group may have resulted from the combination of both the ointment vehicle and the nature of the plastic occlusive material that created an overocclusive environment, thereby favoring microbial proliferation and/or contact

Volden et al. (1992) treated 48 patients with chronic, therapy-resistant AD, with once-weekly application of clobetasol propionate lotion under hydrocolloid (Duoderm) occlusive dressings. Of the 48 patients, 44 (92%) had complete resolution of lesions, and 4 (8%) had partial response (defined as >50% clearance). There were also 2 (4%) patients with mild folliculitis. The authors conclude that adverse events were both mild and infrequent.

Gauger et al. (2003) further addressed the concern of skin colonization with *S. aureus* using occlusion therapy for AD. A side-to-side comparative study of 15 patients with generalized or localized AD was performed, in which the flexures of the elbows were covered with silver-coated textiles on one arm and cotton on the other arm for one week. The study found a significant decrease in *S. aureus* colonization on the lesions covered with silver-coated textile just 2 days after initiation of therapy and lasting until the end of the treatment. Additional, a significantly less amount of *S. aureus* was observed on the silver-coated textile sites than the cotton sites at the end of the treatment. Clinical improvement further correlated with the reduction of bacterial colonization. Thus, the silver-coated textile appeared to not only improve active lesions of AD, but also mitigate the potential pro-

Ultimately, DWD occlusion appears to improve disease severity and is perhaps most beneficial in chronic treatment-resistant eczematous lesions. However, there is too little data to determine whether occlusion, in particular DWD occlusion, predisposes skin bacterial growth. But, it seems reasonable to conclude that the addition of antimicrobial topical agents (e.g. antiseptic or silver preparations) to occlusive therapy might be helpful in

In a pilot study of 15 patients, Park et al. (2011) evaluated the efficacy and safety of a hydrogel patch for AD treatment. The hydrogel patch used in this study was composed of an adhesive, thin, flexible, hydrogel layer on an impermeable urethane surface. Unlike hydrocolloid dressings (e.g. Duoderm) with low water content, the hydrogel patch consisted of approximately 50% water. In this 6-week study, patients applied the hydrogel patch over one lesion for 6-8 hours daily and triamcinolone (TAC) 0.1% cream twice daily to another lesion. Erythema, induration, lichenification, excoriation, and total EASI scores significantly improved compared to baseline in both the hydrogel patch and TAC groups.

microbial effects of dry occlusion alone. (Gauger et al. 2003)

countering the potential risk of infection. (Abeck et al. 1999; Gauger 2006)

sensitization. (Geraldez et al. 1989)

(Volden 1992)

**3.3 Hydrogel patch** 

Table 4. Outcomes of Studies on Dry Wrap Dressing Occlusion

Geraldez et al. (1989), in a randomized controlled study of 60 patients with lichen simplex chronicus, observed more infections and other adverse events in patients treated with diflucortolone valerate 0.3% ointment under occlusion as compared those treated without occlusion. Among the patients using dry occlusion, 2 patients (7%) developed pustular lesions surrounding the affected sites, one (3%) had erythema, and one (3%) had hyperpigmentation. None in the control group experienced any side effects. The control group also reported greater improvements in both pruritus and lichenication. The authors noted that the difference in the observed efficacy may be due to poorer absorption of the ointment that tended to adhere to the plastic occlusive material. Furthermore, the adverse events seen in the treatment group may have resulted from the combination of both the ointment vehicle and the nature of the plastic occlusive material that created an overocclusive environment, thereby favoring microbial proliferation and/or contact sensitization. (Geraldez et al. 1989)

Volden et al. (1992) treated 48 patients with chronic, therapy-resistant AD, with once-weekly application of clobetasol propionate lotion under hydrocolloid (Duoderm) occlusive dressings. Of the 48 patients, 44 (92%) had complete resolution of lesions, and 4 (8%) had partial response (defined as >50% clearance). There were also 2 (4%) patients with mild folliculitis. The authors conclude that adverse events were both mild and infrequent. (Volden 1992)

Gauger et al. (2003) further addressed the concern of skin colonization with *S. aureus* using occlusion therapy for AD. A side-to-side comparative study of 15 patients with generalized or localized AD was performed, in which the flexures of the elbows were covered with silver-coated textiles on one arm and cotton on the other arm for one week. The study found a significant decrease in *S. aureus* colonization on the lesions covered with silver-coated textile just 2 days after initiation of therapy and lasting until the end of the treatment. Additional, a significantly less amount of *S. aureus* was observed on the silver-coated textile sites than the cotton sites at the end of the treatment. Clinical improvement further correlated with the reduction of bacterial colonization. Thus, the silver-coated textile appeared to not only improve active lesions of AD, but also mitigate the potential promicrobial effects of dry occlusion alone. (Gauger et al. 2003)

Ultimately, DWD occlusion appears to improve disease severity and is perhaps most beneficial in chronic treatment-resistant eczematous lesions. However, there is too little data to determine whether occlusion, in particular DWD occlusion, predisposes skin bacterial growth. But, it seems reasonable to conclude that the addition of antimicrobial topical agents (e.g. antiseptic or silver preparations) to occlusive therapy might be helpful in countering the potential risk of infection. (Abeck et al. 1999; Gauger 2006)

#### **3.3 Hydrogel patch**

In a pilot study of 15 patients, Park et al. (2011) evaluated the efficacy and safety of a hydrogel patch for AD treatment. The hydrogel patch used in this study was composed of an adhesive, thin, flexible, hydrogel layer on an impermeable urethane surface. Unlike hydrocolloid dressings (e.g. Duoderm) with low water content, the hydrogel patch consisted of approximately 50% water. In this 6-week study, patients applied the hydrogel patch over one lesion for 6-8 hours daily and triamcinolone (TAC) 0.1% cream twice daily to another lesion. Erythema, induration, lichenification, excoriation, and total EASI scores significantly improved compared to baseline in both the hydrogel patch and TAC groups.

adult, who also taking inhaled steroids, developed prolonged suppression of the HPA axis,

As for the effect of occlusive therapy using topical corticosteroids on bone development, McGowan et al. (2003) examined short-term growth and bone turnover in prepubertal children undergoing WWD occlusion for AD. Knemometry, a technique estimating the distance between the heel and knee of the sitting child, was used as a non-invasive measurement of lower leg length, in combination with 24-hour urinary deoxypyridinoline excretion to evaluate bone turnover. Lower leg length and urinary deoxypyridinoline levels for all children remained similar in pre-treatment measurements and during therapy. This suggests that WWD occlusion for a limited duration does not impact growth

Occlusive therapy, in particular WWD occlusion, can be useful as a 'stepped-up' therapy in controlling acute erythrodermic AD or as a second-line therapy for severe and/or refractory disease. There is limited convincing data that WWD occlusion is superior to conventional open application of topical corticosteroids. However, occlusive therapy represents an important alternative to currently available, but often undesirable standard treatment modalities for AD. A few drawbacks of standard therapies include dependency on superpotent topical corticosteroids, frequent and inconvenient sessions of phototherapy, and serious

Based on the studies on occlusive therapy, it appears that the greatest benefits of topical corticosteroids under occlusion is achieved during the first week of therapy. This suggests that if used as 'rescue' therapy for acute flares or intermittently for maintenance, durations of up to 1 week might be adequate (Wolkerstorfer et al. 2000; Pei et al. 2001). Anecdotally, long-term effects are thought to be sustained when WWD occlusion are continued with emollients for 2–4 more weeks to improve skin hydration (Nicol 1987). Variations in protocol regarding duration of WWD occlusion and rewetting procedures possibly contributed to differences observed in efficacy and incidence of infection. It may, therefore, be advisable to limit occlusion to less than 8 hours duration, apply WWD no more than

It is difficult to ascertain the extent to which occlusion may promote bacterial colonization. However, the use of anti-bacterial agents, when applied alone or under occlusion, appears to not only inhibit bacterial colonization, but also reduce disease severity. (Abeck et al. 1999; Brockow et al. 1999; Gauger 2006) Thus, it seems logical that antibacterials, whether topical or systemic, might be a beneficial adjunct to occlusive therapy helping to decrease the potential risk of clinical infection. As such, topical antibacterials in combination with topical corticosteroids under occlusion may be useful when treating small areas of skin for a limited period of time, while systemic antibacterials in combination with topical corticosteroid under occlusion may more be appropriate when treating larger areas of involvement. Yet, the use of antibacterials must be weighed against the potential risk of antimicrobial

More specifically, according to Williams (2000), there are three categories of patients with AD: 1) those with obvious clinical infection, in whom anti-staphylococcal therapy is essential, 2) those with mild disease and a lower density of S. aureus colonization, in whom no evidence supports additional benefit of anti-staphylococcal therapy, and 3) those with fissured or

resistance and contact sensitization. (Williams 2000; Zhai and Maibach 2001)

systemic side effects with oral medications (e.g. nephrotoxicity with cyclosporine use).

in combination with several abdominal striae. (Devillers et al. 2002)

parameters. (McGowan et al. 2003)

**4. Occlusion in clinical practice** 

twice daily, and avoid rewetting procedures.

Improvement in pruritis was observed in both treatment groups, but was only statistically significant in the TAC group. At week 4, there was no significant difference in all subscores between the patch and TAC groups (except pruritus, as stated above). Improvement was maintained after discontinuing treatment for 2 weeks. No adverse events from steroid use occurred. This study appears to demonstrate that instant correction of the dysfunctional skin barrier with the hydrogel patch can improve signs and symptoms of AD comparable to TAC 0.1% cream. Thus, the hydrogel patch may provide a new approach to occlusive therapy without the potential risks of topical corticosteroid use (Park et al. 2011)

#### **3.4 Cutaneous and systemic side effects**

Topical corticosteroid use can cause both cutaneous and systemic side effects, most significantly laboratory adrenal insufficiency. Risk factors include the use of high potency corticosteroids, occlusive or prolonged therapy, and application to thin- or barriercompromised skin lesions. (Levin and Maibach 2002) Occlusive therapy with topical corticosteroids does not appear to be associated with an increased incidence of local noninfectious side effects, such as skin atrophy and striae. This is most likely because nearly all studies have examined limited treatment durations and diluted topical corticosteroids. However, several studies demonstrated either lowering of morning cortisol levels (Hartmann and Lahmann 1977; Goodyear et al. 1991), loss of diurnal cortisol rhythm (Hartmann and Lahmann 1977), or overt laboratory HPA suppression with WWD (Wolkerstorfer et al. 2000; Devillers et al. 2002). Importantly, nearly all cases of decreased cortisol levels proved to be transient, returning to normal ranges within weeks of discontinuing therapy.

Specifically, Goodyear et al. (1991) found that 0900 hour cortisol levels were suppressed immediately after treatment with WWD, but returned to normal 2 weeks following therapy. Following this observation by Goodyear et al. (1991) of a transient lowering of morning cortisol levels (Goodyear et al. 1991), Wolkerstorfer et al. (2000) decided to examine the effects of different corticosteroid dilutions under WWD occlusion on HPA axis supression in children with severe refractory AD. Only 3 out of the 18 children in the first treatment group (i.e. 50% dilution of FP cream) and none of the 5 children in the second treatment group (i.e. 10%, 25% and 50% dilutions of FP cream) demonstrated HPA axis suppression based on 0900 hour serum cortisol measurements following 2 weeks of WWD occlusion. In the third treatment group (i.e. 0%, 5%, 10%, or 25% dilutions of FP cream applied to the whole body), children demonstrated HPA axis suppression based on 0600 hour serum cortisol measurements, which was associated with the absolute amount of applied corticosteroid. To be more specific, a dose–response relationship was observed with an absolute amount of topical corticosteroid applied. Patients using 800 µg m-2 daily (equivalent to 1.6 g FP 0.05% cream) had an approximately 80% improvement, while patients using absolute amounts >957 µg m-2 daily had no greater improvement. Patients using absolute amounts ≤800 µg m-2 daily had no suppression of the HPA axis. This suggests that weaker dilutions of topical corticosteroid may have a lower risk of HPA axis suppression, while still maintaining comparable efficacy to more potent dilutions of topical corticosteroid. (Wolkerstorfer et al. 2000)

Similarly, Devillers et al. (2002) found a significant decrease in early-morning serum cortisol levels following 1-week of inpatient WWD therapy. Transient cortisol levels below the normal range were observed after 4 days in 3 children and after one week in 2 adults. One

Improvement in pruritis was observed in both treatment groups, but was only statistically significant in the TAC group. At week 4, there was no significant difference in all subscores between the patch and TAC groups (except pruritus, as stated above). Improvement was maintained after discontinuing treatment for 2 weeks. No adverse events from steroid use occurred. This study appears to demonstrate that instant correction of the dysfunctional skin barrier with the hydrogel patch can improve signs and symptoms of AD comparable to TAC 0.1% cream. Thus, the hydrogel patch may provide a new approach to occlusive therapy without the potential risks of topical

Topical corticosteroid use can cause both cutaneous and systemic side effects, most significantly laboratory adrenal insufficiency. Risk factors include the use of high potency corticosteroids, occlusive or prolonged therapy, and application to thin- or barriercompromised skin lesions. (Levin and Maibach 2002) Occlusive therapy with topical corticosteroids does not appear to be associated with an increased incidence of local noninfectious side effects, such as skin atrophy and striae. This is most likely because nearly all studies have examined limited treatment durations and diluted topical corticosteroids. However, several studies demonstrated either lowering of morning cortisol levels (Hartmann and Lahmann 1977; Goodyear et al. 1991), loss of diurnal cortisol rhythm (Hartmann and Lahmann 1977), or overt laboratory HPA suppression with WWD (Wolkerstorfer et al. 2000; Devillers et al. 2002). Importantly, nearly all cases of decreased cortisol levels proved to be transient, returning to normal ranges within weeks of

Specifically, Goodyear et al. (1991) found that 0900 hour cortisol levels were suppressed immediately after treatment with WWD, but returned to normal 2 weeks following therapy. Following this observation by Goodyear et al. (1991) of a transient lowering of morning cortisol levels (Goodyear et al. 1991), Wolkerstorfer et al. (2000) decided to examine the effects of different corticosteroid dilutions under WWD occlusion on HPA axis supression in children with severe refractory AD. Only 3 out of the 18 children in the first treatment group (i.e. 50% dilution of FP cream) and none of the 5 children in the second treatment group (i.e. 10%, 25% and 50% dilutions of FP cream) demonstrated HPA axis suppression based on 0900 hour serum cortisol measurements following 2 weeks of WWD occlusion. In the third treatment group (i.e. 0%, 5%, 10%, or 25% dilutions of FP cream applied to the whole body), children demonstrated HPA axis suppression based on 0600 hour serum cortisol measurements, which was associated with the absolute amount of applied corticosteroid. To be more specific, a dose–response relationship was observed with an absolute amount of topical corticosteroid applied. Patients using 800 µg m-2 daily (equivalent to 1.6 g FP 0.05% cream) had an approximately 80% improvement, while patients using absolute amounts >957 µg m-2 daily had no greater improvement. Patients using absolute amounts ≤800 µg m-2 daily had no suppression of the HPA axis. This suggests that weaker dilutions of topical corticosteroid may have a lower risk of HPA axis suppression, while still maintaining comparable efficacy to more potent dilutions of

Similarly, Devillers et al. (2002) found a significant decrease in early-morning serum cortisol levels following 1-week of inpatient WWD therapy. Transient cortisol levels below the normal range were observed after 4 days in 3 children and after one week in 2 adults. One

corticosteroid use (Park et al. 2011)

discontinuing therapy.

**3.4 Cutaneous and systemic side effects** 

topical corticosteroid. (Wolkerstorfer et al. 2000)

adult, who also taking inhaled steroids, developed prolonged suppression of the HPA axis, in combination with several abdominal striae. (Devillers et al. 2002)

As for the effect of occlusive therapy using topical corticosteroids on bone development, McGowan et al. (2003) examined short-term growth and bone turnover in prepubertal children undergoing WWD occlusion for AD. Knemometry, a technique estimating the distance between the heel and knee of the sitting child, was used as a non-invasive measurement of lower leg length, in combination with 24-hour urinary deoxypyridinoline excretion to evaluate bone turnover. Lower leg length and urinary deoxypyridinoline levels for all children remained similar in pre-treatment measurements and during therapy. This suggests that WWD occlusion for a limited duration does not impact growth parameters. (McGowan et al. 2003)
