The mainstay therapeutics for the management for atopic dermatitis have not changed significantly over the last 50 years. These consist of traditional emollients such as petrolatum and various forms of topical steroids for flare-ups of acute disease. For mild atopic dermatitis, these therapies are largely sufficient; however, moderate and severe atopic dermatitis require a multi-faceted, more contemporary approach. The following column will focus on adjunctive therapies for the advanced management of atopic dermatitis.
I will highlight six therapeutic interventions that I use for my patients that will help you optimize the condition of your toughest atopic patients.
1. Difficult Itch: First-Line Approach
Atopic dermatitis is proverbially known as the “itch that rashes.” This is due in large part to the requirement of pruritus as a necessary criterion for the diagnosis of atopic dermatitis. In a recent review of atopic dermatitis by Eichenfield et al, pruritus is a requisite feature and an alternative diagnosis should be considered for a rash that does not itch.1
Itching is so prominent in atopic dermatitis, it is often the single most impactful feature on an atopic’s quality of life (See image above). Sleep patterns are severely affected by atopic itch, disrupting up to 3 hours of normal EEG patterns compared to unaffected controls.
Children who have atopic dermatitis are also two to three times as likely to exhibit scratching and restlessness compared with children who don’t have atopic dermatitis.
Benjamin et al found an average of 46 minutes of nighttime scratching among patients who had atopic dermatitis.2
The result of this kind of sleep interruption can result in severe daytime somnolence, mood disorders, and it also has a marked effects on a child’s growth, skeletal formation, and endocrinologic development.3,4,5
The entry-level therapy for itch in atopic dermatitis is diphenhydramine (Benadryl) given before bed to mitigate nighttime itching. A majority of children referred to my office have been placed on this evening anti-histaminergic therapy at a dose of 1 mg to 2 mg/kg. This therapy is aimed at H1 receptors found in the CNS and has a mixed soporific and anti-pruritic effect.
While effective in some cases, the substitution of hydroxyzine (Atarax) at 1 mg to 2 mg/kg qhs can make a notable difference, given its more potent effects on H1 receptors in C-fiber nociceptive neurons.6 Similar to diphenhydramine, hydroxizine can cause marked somnolence and is recommended primarily for nighttime use.
Unfortunately, non-sedating anti-histamines such as fexofenadine (Allegra) and cetirizine (Zyrtec) are of limited benefit for the itch associated with atopic dermatitis, despite their widespread both as a.m. and p.m. medications.
A meta-analysis of trials evaluating non-sedating anti-histamines over the last 30 years concluded zero benefit of these agents in atopic dermatitis.7
2. Difficult Itch: Second-Line Approach
For the rare patients who fail to respond to classic anti-histamines, I will often introduce oral doxepin.
Although not FDA-approved for use in children, this tricyclic antidepressant can be very effective for night-time itching because of its marked effects on H1 receptors.8
The low dosage employed for itch (1 mg/kg, up to 10 mg/day) is far lower than that required for anti-depressive effects.
3. Emollients
At every visit, we ask our patients to apply moisturizers within 5 minutes of bathing while the skin is still damp. The timing of this application has been a long-standing institution, although no large-scale trials exist for its support.
Current research suggests that the timing of after-bath application may have a less critical effect on evaporative water loss than previously thought.9
However, the use of emollients to prevent and treat flares of atopic dermatitis is incontrovertible. Emollients help by improving the dermis’s immune milieu, which helps lead to better barrier function; they also prevent outside allergens from triggering T cells.
There is great controversy surrounding the “best” emollient for children with eczema. Historically, the gold standard has been thick petrolatum-based emollients. These inert agents are occlusive by design and manage to trap moisture by physically blocking evaporative water loss. While effective, they are very impractical for adolescents and in warmer climates because of their greasy, sticky feel. Moreover, petrolatum ointments are oil-based and may stain clothes and bed sheets.
A new class of ceramide-dominant emollients have emerged over recent years and shown remarkable efficacy in clinical trials for retaining dermal water and improving clinical outcomes in children with atopic dermatitis. (See Figure 2 above.)
Chamlin et al showed improvements in transepidermal water loss and corneal layer hydration when a ceramide-dominant cream was used continuously over 3 weeks.10
In contrast to the inert role of petrolatum to merely cover the epidermis like a raincoat, ceramides intercalate among corneocytes and restore barrier function from within.11
Ceramides are lipids crucial to the epidermis’ barrier function and are grossly deficient in children with atopic dermatitis. Replenishing these lipids has a bold and durable effect on dermal hydration.
4. Wrap Therapy
Wrap therapy is an under-utilized technique that may help clinicians optimize their topical management of localized flares in atopic dermatitis. In most cases, a patient will respond to conventional therapy, but will have a few “stubborn” areas (such as the flexural regions) that fail to improve. (See Figure 3.)
The term wrap therapy means different things to different dermatologists, but my method entails using a flexible bandage (i.e., kerlex) to cover treated skin at night.
After bathing, a topical steroid is applied to damp skin followed by two layers (wet then dry) of the loose-fitting bandage.
This technique serves three important purposes:
1. improved steroid penetration into the dermis for a heightened anti-inflammatory impact
2. decreased evaporative water loss secondary to non-exposed skin
3. decreased ability to scratch affected area and effect additional cytokine release.
A medium- to high-potency steroid should be used for notable efficacy and the treatment should be targeted for less than 2 weeks.12
When used in this fashion, wrap therapy has been proven safe in children, without marked effects on the adrenal axis. I use this therapy often in my own practice – it can be exceptionally helpful for localized, recalcitrant disease.
5. Bleach Baths
The relationship between bacteria and the immunopathogenesis of atopic dermatitis is complex and poorly understood. Children with atopic dermatitis are heavily colonized with staphylococcus, and the extent of this colonization correlates directly with disease activity.13
Clinically, those patients with active impetiginization are more challenging to both treat and clear of their eczema. (See Figure 4.) Bacteria may stimulate dermatitis through several methods, most notably through a super-antigen effect.
Children with atopic dermatitis exhibit specific staphylococcal antibodies (IgE) not present in normal controls. These antibodies readily form complexes with bacteria and stimulate the release of inflammatory cytokines from circulating T cells. Interestingly, the quantity of this IgE antibody also correlates directly with eczema severity.14
Clinicians must make microbial control a priority if we are to successfully optimize our patients’ treatment. Too often, areas of disease such as the one shown here are left to “smolder,” as therapy is directed to inflammation only, without addressing underlying infection that can drive dermatitis.
Acute infection should be addressed with either oral or topical antibiotics depending upon infection severity. I use cefdinir and mupirocin, respectively, as my first-line agents; however, any antimicrobial with adequate Gram-positive coverage will suffice.
Bacterial colonization is a nefarious problem without clinical appearance on clinical exam. In those patients who suffer from chronic, relapsing infection, I institute weekly bleach baths to keep colonization counts low and prevent re-infection.
During the last few minutes of the child’s bath — remember, bathing should be quick to begin with! — a half-cup full of household bleach is introduced into the tub, taking care not to directly contact mucous membranes. This preparation is dilute enough not to sting excoriated skin, yet potent enough to effectively decrease bacterial colonization.
To my knowledge, bleach baths have never been formally evaluated in atopic dermatitis, but have proven quite helpful in reducing bacterial transmission rates in third-world nations. There is additional support for this practice among patients who suffer from epidermolysis bullosa.
6. Systemic Therapies
A complete discussion on the myriad of systemic agents is beyond the scope of this article; however, a few systemic therapies will be highlighted here for use when topical therapy has failed.
These agents are not to be used indiscriminately, as the risk of adverse events is obviously far greater with systemic versus our more common topical preparations.
When appropriately employed, these therapies can ameliorate disease in your toughest patient. I reserve them for children who suffer from repeated complications (i.e., infection), whose family has good disease insight, and with whom I have confidence in compliance. Compliance in these instances is crucial.
Systemic immunosuppressives should rarely, if ever, be used first-line for atopic dermatitis.
Ultraviolet B (UVB) therapy is an exceptional systemic option, both for its safety and efficacy profile. Light treatment works through its potent T lymphocyte and Staphylococcus aureus suppressive effects as well as its ability to induce inhibitory cytokines (TNF, IL-10).
While relatively slow to start — children will sometimes need several weeks of therapy before a palpable effect is observed — UVB also has a nice remissive effect after treatment has ended.
Like many systemic treatments in children, there is a conspicuous paucity of long-term data to assess carcinogenicity after short-term UVB treatment for atopic dermatitis. However, the exposure from a targeted UVB session is comparable to a few minutes of full-spectrum ambient solar exposure. Studies vary, but roughly 70% of children will experience good or excellent clearance with >10 UVB treatments.15
Cyclosporine (Neoral) is a potent immunosuppressive used chiefly by our transplant medicine colleagues to prevent transport organ rejection. This agent works by blocking the creation of the inflammatory cytokine, interleukin-2, within T cells. Cyclosporine can be enormously helpful for the short-term, rapid control of severe atopic dermatitis and is safe for use in children when used for no more than 1 to 2 years.
After 2 years of use, a slow, but fairly predictable, deterioration of kidney function will result. Various electrolytes must be monitored regularly, but approximately 90% of patients will exhibit good clearance within a few weeks of initiation.16 Remission rates are highly variable, so clinicians should have a longer-term, “Plan B” in mind before instituting this therapy.
Mycophenolate mofetil (Celcept) is my favorite cyclosporine “segueway” because of its excellent safety and efficacy profile. This is not a “rescue” medication with a relatively slow onset of action, therefore, I will usually taper cyclosporine gradually as I begin Celcept.
By inhibiting DNA synthesis, this agent (like cyclosporine) has a powerful effect on cytokine formation and release.
Efficacy rates vary widely among clinical trials; however, I have found Celcept very effective with clearance rates tipping 90%. A typical patient course with this medication may run 3 months with an occasional sustained remission over 5 months.
While there is some reassuring data to support the safety of this agent in children for other, non-eczematous conditions, long-term data is lacking. A complete blood cell count should be checked regularly as this agent may have myelosuppressive effects.
Optimizing Care in Your Toughest Cases
In my practice, standard therapy for atopic dermatitis includes topical steroids for flare-ups and topical immunomodulators (such as pimecrolimus [Elidel] and tacrolimus [Protopic]) for maintenance.
This regimen works well in a large majority of our patients who suffer from eczema. Together with a maintenance plan that includes frequent emollient use and allergen avoidance, most of our patients do quite well.
The above discussion has focused on techniques and therapies for optimizing care in your toughest patients. When “pretty good” isn’t good enough, because a persistent plaque remains or a child still can’t sleep through the night, these tactics can be quite helpful to optimize your patient’s overall clinical picture.
The mainstay therapeutics for the management for atopic dermatitis have not changed significantly over the last 50 years. These consist of traditional emollients such as petrolatum and various forms of topical steroids for flare-ups of acute disease. For mild atopic dermatitis, these therapies are largely sufficient; however, moderate and severe atopic dermatitis require a multi-faceted, more contemporary approach. The following column will focus on adjunctive therapies for the advanced management of atopic dermatitis.
I will highlight six therapeutic interventions that I use for my patients that will help you optimize the condition of your toughest atopic patients.
1. Difficult Itch: First-Line Approach
Atopic dermatitis is proverbially known as the “itch that rashes.” This is due in large part to the requirement of pruritus as a necessary criterion for the diagnosis of atopic dermatitis. In a recent review of atopic dermatitis by Eichenfield et al, pruritus is a requisite feature and an alternative diagnosis should be considered for a rash that does not itch.1
Itching is so prominent in atopic dermatitis, it is often the single most impactful feature on an atopic’s quality of life (See image above). Sleep patterns are severely affected by atopic itch, disrupting up to 3 hours of normal EEG patterns compared to unaffected controls.
Children who have atopic dermatitis are also two to three times as likely to exhibit scratching and restlessness compared with children who don’t have atopic dermatitis.
Benjamin et al found an average of 46 minutes of nighttime scratching among patients who had atopic dermatitis.2
The result of this kind of sleep interruption can result in severe daytime somnolence, mood disorders, and it also has a marked effects on a child’s growth, skeletal formation, and endocrinologic development.3,4,5
The entry-level therapy for itch in atopic dermatitis is diphenhydramine (Benadryl) given before bed to mitigate nighttime itching. A majority of children referred to my office have been placed on this evening anti-histaminergic therapy at a dose of 1 mg to 2 mg/kg. This therapy is aimed at H1 receptors found in the CNS and has a mixed soporific and anti-pruritic effect.
While effective in some cases, the substitution of hydroxyzine (Atarax) at 1 mg to 2 mg/kg qhs can make a notable difference, given its more potent effects on H1 receptors in C-fiber nociceptive neurons.6 Similar to diphenhydramine, hydroxizine can cause marked somnolence and is recommended primarily for nighttime use.
Unfortunately, non-sedating anti-histamines such as fexofenadine (Allegra) and cetirizine (Zyrtec) are of limited benefit for the itch associated with atopic dermatitis, despite their widespread both as a.m. and p.m. medications.
A meta-analysis of trials evaluating non-sedating anti-histamines over the last 30 years concluded zero benefit of these agents in atopic dermatitis.7
2. Difficult Itch: Second-Line Approach
For the rare patients who fail to respond to classic anti-histamines, I will often introduce oral doxepin.
Although not FDA-approved for use in children, this tricyclic antidepressant can be very effective for night-time itching because of its marked effects on H1 receptors.8
The low dosage employed for itch (1 mg/kg, up to 10 mg/day) is far lower than that required for anti-depressive effects.
3. Emollients
At every visit, we ask our patients to apply moisturizers within 5 minutes of bathing while the skin is still damp. The timing of this application has been a long-standing institution, although no large-scale trials exist for its support.
Current research suggests that the timing of after-bath application may have a less critical effect on evaporative water loss than previously thought.9
However, the use of emollients to prevent and treat flares of atopic dermatitis is incontrovertible. Emollients help by improving the dermis’s immune milieu, which helps lead to better barrier function; they also prevent outside allergens from triggering T cells.
There is great controversy surrounding the “best” emollient for children with eczema. Historically, the gold standard has been thick petrolatum-based emollients. These inert agents are occlusive by design and manage to trap moisture by physically blocking evaporative water loss. While effective, they are very impractical for adolescents and in warmer climates because of their greasy, sticky feel. Moreover, petrolatum ointments are oil-based and may stain clothes and bed sheets.
A new class of ceramide-dominant emollients have emerged over recent years and shown remarkable efficacy in clinical trials for retaining dermal water and improving clinical outcomes in children with atopic dermatitis. (See Figure 2 above.)
Chamlin et al showed improvements in transepidermal water loss and corneal layer hydration when a ceramide-dominant cream was used continuously over 3 weeks.10
In contrast to the inert role of petrolatum to merely cover the epidermis like a raincoat, ceramides intercalate among corneocytes and restore barrier function from within.11
Ceramides are lipids crucial to the epidermis’ barrier function and are grossly deficient in children with atopic dermatitis. Replenishing these lipids has a bold and durable effect on dermal hydration.
4. Wrap Therapy
Wrap therapy is an under-utilized technique that may help clinicians optimize their topical management of localized flares in atopic dermatitis. In most cases, a patient will respond to conventional therapy, but will have a few “stubborn” areas (such as the flexural regions) that fail to improve. (See Figure 3.)
The term wrap therapy means different things to different dermatologists, but my method entails using a flexible bandage (i.e., kerlex) to cover treated skin at night.
After bathing, a topical steroid is applied to damp skin followed by two layers (wet then dry) of the loose-fitting bandage.
This technique serves three important purposes:
1. improved steroid penetration into the dermis for a heightened anti-inflammatory impact
2. decreased evaporative water loss secondary to non-exposed skin
3. decreased ability to scratch affected area and effect additional cytokine release.
A medium- to high-potency steroid should be used for notable efficacy and the treatment should be targeted for less than 2 weeks.12
When used in this fashion, wrap therapy has been proven safe in children, without marked effects on the adrenal axis. I use this therapy often in my own practice – it can be exceptionally helpful for localized, recalcitrant disease.
5. Bleach Baths
The relationship between bacteria and the immunopathogenesis of atopic dermatitis is complex and poorly understood. Children with atopic dermatitis are heavily colonized with staphylococcus, and the extent of this colonization correlates directly with disease activity.13
Clinically, those patients with active impetiginization are more challenging to both treat and clear of their eczema. (See Figure 4.) Bacteria may stimulate dermatitis through several methods, most notably through a super-antigen effect.
Children with atopic dermatitis exhibit specific staphylococcal antibodies (IgE) not present in normal controls. These antibodies readily form complexes with bacteria and stimulate the release of inflammatory cytokines from circulating T cells. Interestingly, the quantity of this IgE antibody also correlates directly with eczema severity.14
Clinicians must make microbial control a priority if we are to successfully optimize our patients’ treatment. Too often, areas of disease such as the one shown here are left to “smolder,” as therapy is directed to inflammation only, without addressing underlying infection that can drive dermatitis.
Acute infection should be addressed with either oral or topical antibiotics depending upon infection severity. I use cefdinir and mupirocin, respectively, as my first-line agents; however, any antimicrobial with adequate Gram-positive coverage will suffice.
Bacterial colonization is a nefarious problem without clinical appearance on clinical exam. In those patients who suffer from chronic, relapsing infection, I institute weekly bleach baths to keep colonization counts low and prevent re-infection.
During the last few minutes of the child’s bath — remember, bathing should be quick to begin with! — a half-cup full of household bleach is introduced into the tub, taking care not to directly contact mucous membranes. This preparation is dilute enough not to sting excoriated skin, yet potent enough to effectively decrease bacterial colonization.
To my knowledge, bleach baths have never been formally evaluated in atopic dermatitis, but have proven quite helpful in reducing bacterial transmission rates in third-world nations. There is additional support for this practice among patients who suffer from epidermolysis bullosa.
6. Systemic Therapies
A complete discussion on the myriad of systemic agents is beyond the scope of this article; however, a few systemic therapies will be highlighted here for use when topical therapy has failed.
These agents are not to be used indiscriminately, as the risk of adverse events is obviously far greater with systemic versus our more common topical preparations.
When appropriately employed, these therapies can ameliorate disease in your toughest patient. I reserve them for children who suffer from repeated complications (i.e., infection), whose family has good disease insight, and with whom I have confidence in compliance. Compliance in these instances is crucial.
Systemic immunosuppressives should rarely, if ever, be used first-line for atopic dermatitis.
Ultraviolet B (UVB) therapy is an exceptional systemic option, both for its safety and efficacy profile. Light treatment works through its potent T lymphocyte and Staphylococcus aureus suppressive effects as well as its ability to induce inhibitory cytokines (TNF, IL-10).
While relatively slow to start — children will sometimes need several weeks of therapy before a palpable effect is observed — UVB also has a nice remissive effect after treatment has ended.
Like many systemic treatments in children, there is a conspicuous paucity of long-term data to assess carcinogenicity after short-term UVB treatment for atopic dermatitis. However, the exposure from a targeted UVB session is comparable to a few minutes of full-spectrum ambient solar exposure. Studies vary, but roughly 70% of children will experience good or excellent clearance with >10 UVB treatments.15
Cyclosporine (Neoral) is a potent immunosuppressive used chiefly by our transplant medicine colleagues to prevent transport organ rejection. This agent works by blocking the creation of the inflammatory cytokine, interleukin-2, within T cells. Cyclosporine can be enormously helpful for the short-term, rapid control of severe atopic dermatitis and is safe for use in children when used for no more than 1 to 2 years.
After 2 years of use, a slow, but fairly predictable, deterioration of kidney function will result. Various electrolytes must be monitored regularly, but approximately 90% of patients will exhibit good clearance within a few weeks of initiation.16 Remission rates are highly variable, so clinicians should have a longer-term, “Plan B” in mind before instituting this therapy.
Mycophenolate mofetil (Celcept) is my favorite cyclosporine “segueway” because of its excellent safety and efficacy profile. This is not a “rescue” medication with a relatively slow onset of action, therefore, I will usually taper cyclosporine gradually as I begin Celcept.
By inhibiting DNA synthesis, this agent (like cyclosporine) has a powerful effect on cytokine formation and release.
Efficacy rates vary widely among clinical trials; however, I have found Celcept very effective with clearance rates tipping 90%. A typical patient course with this medication may run 3 months with an occasional sustained remission over 5 months.
While there is some reassuring data to support the safety of this agent in children for other, non-eczematous conditions, long-term data is lacking. A complete blood cell count should be checked regularly as this agent may have myelosuppressive effects.
Optimizing Care in Your Toughest Cases
In my practice, standard therapy for atopic dermatitis includes topical steroids for flare-ups and topical immunomodulators (such as pimecrolimus [Elidel] and tacrolimus [Protopic]) for maintenance.
This regimen works well in a large majority of our patients who suffer from eczema. Together with a maintenance plan that includes frequent emollient use and allergen avoidance, most of our patients do quite well.
The above discussion has focused on techniques and therapies for optimizing care in your toughest patients. When “pretty good” isn’t good enough, because a persistent plaque remains or a child still can’t sleep through the night, these tactics can be quite helpful to optimize your patient’s overall clinical picture.
The mainstay therapeutics for the management for atopic dermatitis have not changed significantly over the last 50 years. These consist of traditional emollients such as petrolatum and various forms of topical steroids for flare-ups of acute disease. For mild atopic dermatitis, these therapies are largely sufficient; however, moderate and severe atopic dermatitis require a multi-faceted, more contemporary approach. The following column will focus on adjunctive therapies for the advanced management of atopic dermatitis.
I will highlight six therapeutic interventions that I use for my patients that will help you optimize the condition of your toughest atopic patients.
1. Difficult Itch: First-Line Approach
Atopic dermatitis is proverbially known as the “itch that rashes.” This is due in large part to the requirement of pruritus as a necessary criterion for the diagnosis of atopic dermatitis. In a recent review of atopic dermatitis by Eichenfield et al, pruritus is a requisite feature and an alternative diagnosis should be considered for a rash that does not itch.1
Itching is so prominent in atopic dermatitis, it is often the single most impactful feature on an atopic’s quality of life (See image above). Sleep patterns are severely affected by atopic itch, disrupting up to 3 hours of normal EEG patterns compared to unaffected controls.
Children who have atopic dermatitis are also two to three times as likely to exhibit scratching and restlessness compared with children who don’t have atopic dermatitis.
Benjamin et al found an average of 46 minutes of nighttime scratching among patients who had atopic dermatitis.2
The result of this kind of sleep interruption can result in severe daytime somnolence, mood disorders, and it also has a marked effects on a child’s growth, skeletal formation, and endocrinologic development.3,4,5
The entry-level therapy for itch in atopic dermatitis is diphenhydramine (Benadryl) given before bed to mitigate nighttime itching. A majority of children referred to my office have been placed on this evening anti-histaminergic therapy at a dose of 1 mg to 2 mg/kg. This therapy is aimed at H1 receptors found in the CNS and has a mixed soporific and anti-pruritic effect.
While effective in some cases, the substitution of hydroxyzine (Atarax) at 1 mg to 2 mg/kg qhs can make a notable difference, given its more potent effects on H1 receptors in C-fiber nociceptive neurons.6 Similar to diphenhydramine, hydroxizine can cause marked somnolence and is recommended primarily for nighttime use.
Unfortunately, non-sedating anti-histamines such as fexofenadine (Allegra) and cetirizine (Zyrtec) are of limited benefit for the itch associated with atopic dermatitis, despite their widespread both as a.m. and p.m. medications.
A meta-analysis of trials evaluating non-sedating anti-histamines over the last 30 years concluded zero benefit of these agents in atopic dermatitis.7
2. Difficult Itch: Second-Line Approach
For the rare patients who fail to respond to classic anti-histamines, I will often introduce oral doxepin.
Although not FDA-approved for use in children, this tricyclic antidepressant can be very effective for night-time itching because of its marked effects on H1 receptors.8
The low dosage employed for itch (1 mg/kg, up to 10 mg/day) is far lower than that required for anti-depressive effects.
3. Emollients
At every visit, we ask our patients to apply moisturizers within 5 minutes of bathing while the skin is still damp. The timing of this application has been a long-standing institution, although no large-scale trials exist for its support.
Current research suggests that the timing of after-bath application may have a less critical effect on evaporative water loss than previously thought.9
However, the use of emollients to prevent and treat flares of atopic dermatitis is incontrovertible. Emollients help by improving the dermis’s immune milieu, which helps lead to better barrier function; they also prevent outside allergens from triggering T cells.
There is great controversy surrounding the “best” emollient for children with eczema. Historically, the gold standard has been thick petrolatum-based emollients. These inert agents are occlusive by design and manage to trap moisture by physically blocking evaporative water loss. While effective, they are very impractical for adolescents and in warmer climates because of their greasy, sticky feel. Moreover, petrolatum ointments are oil-based and may stain clothes and bed sheets.
A new class of ceramide-dominant emollients have emerged over recent years and shown remarkable efficacy in clinical trials for retaining dermal water and improving clinical outcomes in children with atopic dermatitis. (See Figure 2 above.)
Chamlin et al showed improvements in transepidermal water loss and corneal layer hydration when a ceramide-dominant cream was used continuously over 3 weeks.10
In contrast to the inert role of petrolatum to merely cover the epidermis like a raincoat, ceramides intercalate among corneocytes and restore barrier function from within.11
Ceramides are lipids crucial to the epidermis’ barrier function and are grossly deficient in children with atopic dermatitis. Replenishing these lipids has a bold and durable effect on dermal hydration.
4. Wrap Therapy
Wrap therapy is an under-utilized technique that may help clinicians optimize their topical management of localized flares in atopic dermatitis. In most cases, a patient will respond to conventional therapy, but will have a few “stubborn” areas (such as the flexural regions) that fail to improve. (See Figure 3.)
The term wrap therapy means different things to different dermatologists, but my method entails using a flexible bandage (i.e., kerlex) to cover treated skin at night.
After bathing, a topical steroid is applied to damp skin followed by two layers (wet then dry) of the loose-fitting bandage.
This technique serves three important purposes:
1. improved steroid penetration into the dermis for a heightened anti-inflammatory impact
2. decreased evaporative water loss secondary to non-exposed skin
3. decreased ability to scratch affected area and effect additional cytokine release.
A medium- to high-potency steroid should be used for notable efficacy and the treatment should be targeted for less than 2 weeks.12
When used in this fashion, wrap therapy has been proven safe in children, without marked effects on the adrenal axis. I use this therapy often in my own practice – it can be exceptionally helpful for localized, recalcitrant disease.
5. Bleach Baths
The relationship between bacteria and the immunopathogenesis of atopic dermatitis is complex and poorly understood. Children with atopic dermatitis are heavily colonized with staphylococcus, and the extent of this colonization correlates directly with disease activity.13
Clinically, those patients with active impetiginization are more challenging to both treat and clear of their eczema. (See Figure 4.) Bacteria may stimulate dermatitis through several methods, most notably through a super-antigen effect.
Children with atopic dermatitis exhibit specific staphylococcal antibodies (IgE) not present in normal controls. These antibodies readily form complexes with bacteria and stimulate the release of inflammatory cytokines from circulating T cells. Interestingly, the quantity of this IgE antibody also correlates directly with eczema severity.14
Clinicians must make microbial control a priority if we are to successfully optimize our patients’ treatment. Too often, areas of disease such as the one shown here are left to “smolder,” as therapy is directed to inflammation only, without addressing underlying infection that can drive dermatitis.
Acute infection should be addressed with either oral or topical antibiotics depending upon infection severity. I use cefdinir and mupirocin, respectively, as my first-line agents; however, any antimicrobial with adequate Gram-positive coverage will suffice.
Bacterial colonization is a nefarious problem without clinical appearance on clinical exam. In those patients who suffer from chronic, relapsing infection, I institute weekly bleach baths to keep colonization counts low and prevent re-infection.
During the last few minutes of the child’s bath — remember, bathing should be quick to begin with! — a half-cup full of household bleach is introduced into the tub, taking care not to directly contact mucous membranes. This preparation is dilute enough not to sting excoriated skin, yet potent enough to effectively decrease bacterial colonization.
To my knowledge, bleach baths have never been formally evaluated in atopic dermatitis, but have proven quite helpful in reducing bacterial transmission rates in third-world nations. There is additional support for this practice among patients who suffer from epidermolysis bullosa.
6. Systemic Therapies
A complete discussion on the myriad of systemic agents is beyond the scope of this article; however, a few systemic therapies will be highlighted here for use when topical therapy has failed.
These agents are not to be used indiscriminately, as the risk of adverse events is obviously far greater with systemic versus our more common topical preparations.
When appropriately employed, these therapies can ameliorate disease in your toughest patient. I reserve them for children who suffer from repeated complications (i.e., infection), whose family has good disease insight, and with whom I have confidence in compliance. Compliance in these instances is crucial.
Systemic immunosuppressives should rarely, if ever, be used first-line for atopic dermatitis.
Ultraviolet B (UVB) therapy is an exceptional systemic option, both for its safety and efficacy profile. Light treatment works through its potent T lymphocyte and Staphylococcus aureus suppressive effects as well as its ability to induce inhibitory cytokines (TNF, IL-10).
While relatively slow to start — children will sometimes need several weeks of therapy before a palpable effect is observed — UVB also has a nice remissive effect after treatment has ended.
Like many systemic treatments in children, there is a conspicuous paucity of long-term data to assess carcinogenicity after short-term UVB treatment for atopic dermatitis. However, the exposure from a targeted UVB session is comparable to a few minutes of full-spectrum ambient solar exposure. Studies vary, but roughly 70% of children will experience good or excellent clearance with >10 UVB treatments.15
Cyclosporine (Neoral) is a potent immunosuppressive used chiefly by our transplant medicine colleagues to prevent transport organ rejection. This agent works by blocking the creation of the inflammatory cytokine, interleukin-2, within T cells. Cyclosporine can be enormously helpful for the short-term, rapid control of severe atopic dermatitis and is safe for use in children when used for no more than 1 to 2 years.
After 2 years of use, a slow, but fairly predictable, deterioration of kidney function will result. Various electrolytes must be monitored regularly, but approximately 90% of patients will exhibit good clearance within a few weeks of initiation.16 Remission rates are highly variable, so clinicians should have a longer-term, “Plan B” in mind before instituting this therapy.
Mycophenolate mofetil (Celcept) is my favorite cyclosporine “segueway” because of its excellent safety and efficacy profile. This is not a “rescue” medication with a relatively slow onset of action, therefore, I will usually taper cyclosporine gradually as I begin Celcept.
By inhibiting DNA synthesis, this agent (like cyclosporine) has a powerful effect on cytokine formation and release.
Efficacy rates vary widely among clinical trials; however, I have found Celcept very effective with clearance rates tipping 90%. A typical patient course with this medication may run 3 months with an occasional sustained remission over 5 months.
While there is some reassuring data to support the safety of this agent in children for other, non-eczematous conditions, long-term data is lacking. A complete blood cell count should be checked regularly as this agent may have myelosuppressive effects.
Optimizing Care in Your Toughest Cases
In my practice, standard therapy for atopic dermatitis includes topical steroids for flare-ups and topical immunomodulators (such as pimecrolimus [Elidel] and tacrolimus [Protopic]) for maintenance.
This regimen works well in a large majority of our patients who suffer from eczema. Together with a maintenance plan that includes frequent emollient use and allergen avoidance, most of our patients do quite well.
The above discussion has focused on techniques and therapies for optimizing care in your toughest patients. When “pretty good” isn’t good enough, because a persistent plaque remains or a child still can’t sleep through the night, these tactics can be quite helpful to optimize your patient’s overall clinical picture.
