**7.1.2 Aeroallergen reduction**

Like with food allergens, different aeroallergens such as dust mites, pollen, mold, and animal dander can cause AD exacerbation. This exacerbation can be triggered either by inhalation or direct contact. Fungus and cockroaches have also been suspected (Michel, et al. 2009; Simon-Nobbe, et al. 2008). There have been conflicting studies that show avoidance of aeroallergens, particularly dust mites, reduce disease symptoms. A double-blind, placebo controlled study using dust mite reducing measures in the home proved to improve the symptoms of atopic dermatitis (Tan, et al. 1996). By contrast, there are also trials that show the reduction in aeroallergens have no affect on symptoms of atopic dermatitis (Koopman, et al. 2001; Oosting, et al. 2002). Although the data varies, there is no harm in taking dust mite reducing measures. Aeroallergen reduction techniques that can be used include: using dust mite-proof encasings on pillows, mattresses, and box springs, washing bedding in hot water weekly, removal of bedroom carpet, and decreasing indoor humidity levels with air conditioning (Arlian & Platts-Mills, 2001).

#### **7.1.3 Detergent and chemical avoidance**

Because there is a higher chance of skin irritation in patients with atopic dermatitis, it is important to avoid those products or chemicals that can cause disease exacerbation (Nassif, et al. 1994). Certain soaps, fabric softeners, perfumes, cosmetics, and lotions contain alcohol and other ingredients that can be irritating to the skin of those patients with AD. These products can induce the itch-scratch cycle and worsen symptoms. It is suggested that laundry detergents containing enzymes can also worsen symptoms. A blinded crossover trial of 25 adults looked at the affect on atopic dermatitis symptoms with enzyme-enriched detergent, and a control detergent, which contained no enzymes. Although no diagnostic criteria were described in the trial, the SCORAD index was used to evaluate the patients' severity of symptoms. There was no statistical difference in symptomatic relief between the two groups of patients (Andersen, et al. 1998). However, enzyme-enriched products should be avoided in patients with known hypersensitivity to enzyme proteins.

### **7.1.4 Phototherapy**

256 Atopic Dermatitis – Disease Etiology and Clinical Management

Hen's egg, milk, wheat, soy, peanuts, nuts, and fish are responsible for 90% of the food allergy in patients with atopic dermatitis (Sircherer & Sampson, 1999). Avoiding these foods, and other foods suspected to cause flares may be helpful in reducing disease exacerbation, especially in children. Several studies identified the effects of dietary restriction in children with atopic dermatitis. One of these trials, conducted by Sloper and associates evaluated 78 children with atopic dermatitis. Patients were on a diet, which excluded cow's milk, eggs, and foods known to trigger exacerbations. At the end of the trial, 64 patients experienced an improvement in their atopic dermatitis symptoms (Sloper, et al. 1991). Few studies in this meta-analysis used validated diagnostic criteria, which could have given skewed results. Because there are no precise findings in these studies, foods containing milk, eggs, or other known causes of disease flares should be

Like with food allergens, different aeroallergens such as dust mites, pollen, mold, and animal dander can cause AD exacerbation. This exacerbation can be triggered either by inhalation or direct contact. Fungus and cockroaches have also been suspected (Michel, et al. 2009; Simon-Nobbe, et al. 2008). There have been conflicting studies that show avoidance of aeroallergens, particularly dust mites, reduce disease symptoms. A double-blind, placebo controlled study using dust mite reducing measures in the home proved to improve the symptoms of atopic dermatitis (Tan, et al. 1996). By contrast, there are also trials that show the reduction in aeroallergens have no affect on symptoms of atopic dermatitis (Koopman, et al. 2001; Oosting, et al. 2002). Although the data varies, there is no harm in taking dust mite reducing measures. Aeroallergen reduction techniques that can be used include: using dust mite-proof encasings on pillows, mattresses, and box springs, washing bedding in hot water weekly, removal of bedroom carpet, and decreasing indoor humidity levels with air

Because there is a higher chance of skin irritation in patients with atopic dermatitis, it is important to avoid those products or chemicals that can cause disease exacerbation (Nassif, et al. 1994). Certain soaps, fabric softeners, perfumes, cosmetics, and lotions contain alcohol and other ingredients that can be irritating to the skin of those patients with AD. These products can induce the itch-scratch cycle and worsen symptoms. It is suggested that laundry detergents containing enzymes can also worsen symptoms. A blinded crossover trial of 25 adults looked at the affect on atopic dermatitis symptoms with enzyme-enriched detergent, and a control detergent, which contained no enzymes. Although no diagnostic criteria were described in the trial, the SCORAD index was used to evaluate the patients' severity of symptoms. There was no statistical difference in symptomatic relief between the two groups of patients (Andersen, et al. 1998). However, enzyme-enriched products should be avoided in patients with known hypersensitivity to

**7. Treatment** 

**7.1.1 Dietary restrictions** 

**7.1 Nonphamacological interventions** 

avoided in patients with atopic dermatitis.

conditioning (Arlian & Platts-Mills, 2001).

**7.1.3 Detergent and chemical avoidance** 

enzyme proteins.

**7.1.2 Aeroallergen reduction** 

The use of natural sunlight for the treatment of atopic dermatitis has been shown to be beneficial, but sunburn should be avoided. If sunlight occurs in the presence of high humidity, or heat which triggers sweating, aggravation of symptoms can occur. Ultraviolet (UV) light (UVB, narrowband UVB, and high-intensity UVA) therapy can be useful in adjunct with other treatments options for patients. Topical glucocorticoid therapy, high-dose UVA1 phototherapy, and UVA-UVB phototherapy were compared in patients with atopic dermatitis. This was a randomized, multi-center trial that found significant differences in favor of high-dose UVA1 and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. (Krutmann, et al. 1998). There are also several small trials that look at specific wavelengths of and equipment for UV therapy. Chemophototherapy, psoralen with UVA (PUVA), has also been shown to be effective, but should be limited to those patients with widespread AD. Comparison studies with PUVA are limited. Short-term adverse events of UV phototherapy are mild and include: erythema, pruritis, and pigmentation. Potential long-term adverse effects include: premature skin aging, and cutaneous malignancies (Leung, et al. 2004). UV phototherapy is proven to be an effective method of therapy, because of this it is usually used as a second or third line of treatment.

#### **7.1.5 Psychological approaches**

Patients with atopic dermatitis are shown to have significant issues with anxiety, anger, and emotional stress (Bender 2002). They usually respond to embarrassment, frustration, anxiety, or other upsetting events with increased pruritis and scratching (Kodama, et al. 1999). Although emotional factors do not cause atopic dermatitis, studies show that psychological techniques, such as stress reduction approaches, behavior modifications, and group counseling sessions may reduce the exacerbation of atopic dermatitis, particularly those prone to habitual scratching (Melin, et al. 1986).

#### **7.2 Pharmacological therapies 7.2.1 Nonprescription therapies**

#### **7.2.1.1 Antihistamines**

Oral antihistamines are usually recommended for pruritis. However, a recent study of 16 trials showed no little evidence associated with the relief of pruritis with sedating or nonsedating antihistamines (Klein & Clark, 1999). These observations, however, do not exclude the possibility that individual patients may benefit from antihistamines. Because pruritis can be worse at night, oral histamines have been beneficial at bedtime for their sedative properties in patients experiencing symptoms, and can be used as a short-term adjuvant to topical therapy (Kristal & Klein, 2000). The first generation antihistamines, hydroxyzine, diphenhydramine, and cyproheptadine all have sedative effects, but it is shown hydroxyzine to be more effective than the latter (Denman, 1986; Leung, et al. 1998). Newer generation antihistamines ceterizine, loratadine, and fexofenadine may not be beneficial since they lack the sedating properties of the first generation antihistamines. Topical antihistamines should be avoided to the risk of irritating the skin further (Shelley, et al.

Clinical Management of Atopic Dermatitis 259

Group 1: Super-High Potency Vehicle

Clobetasol propionate 0.05% Cream, gel, foam, ointment, solution

Group 2: High Potency Vehicle

Betamethasone dipropionate augmented 0.05% Gel, lotion, ointment

Desoximetasone 0.25% Cream, gel, ointment

Halcinonide 0.1% Cream, ointment Mometasone furoate 0.1% Ointment Triamcinolone acetonide 0.5% Ointment

Amcinonide 0.1% Cream, lotion Betamethasone dipropionate 0.05% Cream Betamethasone valerate 0.1% Ointment Desoximetasone 0.05% Cream Diflorasone diacetate 0.05% Cream Fluocinonide emollient 0.05% Cream Fluticasone propionate 0.005% Ointment Triamcinolone acetonide 0.1% Ointment Triamcinolone acetonide 0.5% Cream

Betamethasone valerate 0.12% Foam Fluocinolone acetonide 0.025% Ointment Hydrocortisone valerate 0.2% Ointment Mometasone furoate 0.1% Cream, lotion Triamcinolone acetonide 0.1% Cream

Betamethasone dipropionate 0.05% Lotion Betamethasone valerate 0.1% Cream Desonide 0.05% Ointment Fluocinolone acetonide 0.025% Cream Flurandrenolide 0.05% Lotion Fluticasone propionate 0.05% Cream

Table 4. Topical Steroids Preparations

Alclometasone Desonate 0.05% Cream, ointment Fluocinolone acetonide 0.01% Oil, cream,

Desonide 0.01%, 0.05% Cream, gel, foam, lotion

Fluocinonide 0.05% Cream, gel, ointment, solution

Group 3: Medium-High Potency Vehicle

Group 4: Medium Potency Vehicle

Group 5: Medium-Low Potency Vehicle

Group 6: Low Potency Vehicle

Halobetasol propionate 0.05% Cream, ointment

Fluocinonide 0.1% Cream

Amcinonide 0.1% Ointment Betamethasone dipropionate 0.05% augmented Cream Betamethasone dipropionate 0.05% Ointment

Desoximetasone 0.05% Gel Diflorasone diacetate 0.05% Ointment

1996). Common side effects of antihistamines include: sedation, dry mouth, constipation, blurred vision, and dizziness.

#### **7.2.1.2 Coal tar preparations**

Coal tar has been used to treat skin disorders for centuries. Although the exact pharmacologic effects are unknown, it is thought coal tar has antibacterial, antifungal, antipruritic, and keratoplastic effects (Andrew & Moses, 1999; Grupper, 1971; Lavker, et al. 1981). There is a theoretical risk that coal tar being a carcinogen based on observational studies of workers who use tar components in their occupation, however there have been no increase in cancer with clinical use (Callen, et al. 2007). Coal tar preparations have many disadvantages. Their odor, dark staining color, and side effects make them less desirable to patients. Coal tar comes in a variety of formulations, including creams, gels, shampoos, lotions and soaps. Newer formulations make the preparations more tolerable than older versions (Niordson & Stahl, 1985). It is suggested that coal tar be applied at night to avoid the odor and staining of daytime clothing. Adverse effects associated with coal tar preparations include burning, stinging, folliculitis, and photosensitization (Kristal & Klein, 2000).

#### **7.2.1.3 Emollients**

Xerosis contributes to microfissures and cracks which can introduce microbes and allergens under the skin. This usually becomes exacerbated in the cold, dry winder months. Because AD is characterized by a decrease in skin barrier function, moisturizing and skin protection play an important role in the disease. Emollients have long been used for this. Although emollients have not been found to improve atopic dermatitis directly, they are a vital source of skin hydration and protection for these patients. The moisturizing aids are available in the forms of lotions, creams, and ointments, and are usually used in conjunction with corticosteroids. Formulations that contain certain dyes, alcohols, or fragrances can exacerbate atopic dermatitis and should be avoided. Because lotions are less viscous than the other formulations, they contain more water, which can cause an evaporative effect causing further skin drying. Ointments may interfere with appropriate sweat removal and result in sweat retention dermatitis. Emollients are better at maintaining skin hydration when applied after the patient soaks in a lukewarm bath.

### **7.2.2 Prescription therapies**

#### **7.2.2.1 Topical preparations**

#### *7.2.2.1.1 Topical corticosteroids*

Topical corticosteroids have been a standard for treatment of atopic dermatitis and other skin disorders for years. Clinicians who are not familiar with topical corticosteroids can be challenged when providing care, due to the various strengths and formulations in which these medications are available. The decision to use a more or less potent corticosteroids depends on the severity of the dermatitis, location of the lesions, and the type of skin involved. Based on their vasoconstrictor assays, there are six potentcies of topical corticosteroids that are available though prescription, please refer to Table 4. Potency of topical corticosteroids depends on the concentration of the medication, but also the delivery vehicle. For example, betamethasone valerate ointment is considered more potent than a foam or cream containing the same medication. In general, the lowest potency that will control symptoms should be used. Low potency corticosteroids are recommended for the

1996). Common side effects of antihistamines include: sedation, dry mouth, constipation,

Coal tar has been used to treat skin disorders for centuries. Although the exact pharmacologic effects are unknown, it is thought coal tar has antibacterial, antifungal, antipruritic, and keratoplastic effects (Andrew & Moses, 1999; Grupper, 1971; Lavker, et al. 1981). There is a theoretical risk that coal tar being a carcinogen based on observational studies of workers who use tar components in their occupation, however there have been no increase in cancer with clinical use (Callen, et al. 2007). Coal tar preparations have many disadvantages. Their odor, dark staining color, and side effects make them less desirable to patients. Coal tar comes in a variety of formulations, including creams, gels, shampoos, lotions and soaps. Newer formulations make the preparations more tolerable than older versions (Niordson & Stahl, 1985). It is suggested that coal tar be applied at night to avoid the odor and staining of daytime clothing. Adverse effects associated with coal tar preparations include burning, stinging,

Xerosis contributes to microfissures and cracks which can introduce microbes and allergens under the skin. This usually becomes exacerbated in the cold, dry winder months. Because AD is characterized by a decrease in skin barrier function, moisturizing and skin protection play an important role in the disease. Emollients have long been used for this. Although emollients have not been found to improve atopic dermatitis directly, they are a vital source of skin hydration and protection for these patients. The moisturizing aids are available in the forms of lotions, creams, and ointments, and are usually used in conjunction with corticosteroids. Formulations that contain certain dyes, alcohols, or fragrances can exacerbate atopic dermatitis and should be avoided. Because lotions are less viscous than the other formulations, they contain more water, which can cause an evaporative effect causing further skin drying. Ointments may interfere with appropriate sweat removal and result in sweat retention dermatitis. Emollients are better at maintaining skin hydration

Topical corticosteroids have been a standard for treatment of atopic dermatitis and other skin disorders for years. Clinicians who are not familiar with topical corticosteroids can be challenged when providing care, due to the various strengths and formulations in which these medications are available. The decision to use a more or less potent corticosteroids depends on the severity of the dermatitis, location of the lesions, and the type of skin involved. Based on their vasoconstrictor assays, there are six potentcies of topical corticosteroids that are available though prescription, please refer to Table 4. Potency of topical corticosteroids depends on the concentration of the medication, but also the delivery vehicle. For example, betamethasone valerate ointment is considered more potent than a foam or cream containing the same medication. In general, the lowest potency that will control symptoms should be used. Low potency corticosteroids are recommended for the

blurred vision, and dizziness. **7.2.1.2 Coal tar preparations** 

**7.2.1.3 Emollients** 

**7.2.2 Prescription therapies 7.2.2.1 Topical preparations**  *7.2.2.1.1 Topical corticosteroids* 

folliculitis, and photosensitization (Kristal & Klein, 2000).

when applied after the patient soaks in a lukewarm bath.


Table 4. Topical Steroids Preparations

Clinical Management of Atopic Dermatitis 261

short term use (two years for pimecrolimus and 4 years for tacrolimus) and have been shown to have favorable outcomes, but have been advised that they be used in accordance to their guidelines due to the potential cancer risk. Long term studies for these drugs are still needed.

There are those individuals in which topical steroid use does not result in complete remission. As result, systemic immunosuppressant along with novel therapeutic options are warranted for severe refractory cases to provide increase in therapeutic options with effective remission rates and limited adverse effects. These subsets of patients should be referred to a specialist (i.e., dermatologist or allergist) for further evaluation. Severe atopic dermatitis may be described as the presence of widespread skin lesions or physically and/or emotionally disabling disease that significantly compromises a patient's quality of life. The

Systemic corticosteroids are not recommended for chronic or maintenance treatment of atopic dermatitis due to many common side effects associated with their use and possible rebound flaring upon discontinuation (Akdis et al, 2006). Typical side effects include; osteoporosis, cataracts, growth suppression, and poor wound healing. A short course of systemic corticosteroids with taper is recommended to abort an acute flare-up. Recommended dosing with prednisone is 40 to 60 mg daily for three to four days followed

Cyclosporine has proven beneficial in attenuating exacerbations in adults and children with severe atopic dermatitis. It also may be used for intermittent chronic not just short-term therapy. Cyclosporine is classified as a calcineurin inhibitor, which blocks T cell activation. A dose of 5mg/kg/day divided every 12 hours has been evaluated. Monitoring of trough levels, renal, and hepatic function is essential. A taper by 1mg/kg/day every one to three months is recommended. (Sowden et al, 1991; Brazelli et al, 2002). Common side effects associated with cyclosporine include increased risk of infection, malignancy, nephrotoxicity,

Interferon-gamma (IFN-gamma) works by suppressing T helper cell activity along with other immunomodulatory effects (Schmitt 2007). Interferon-gamma (IFN-gamma) has shown varying results in the treatment of severe atopic dermatitis although a couple of trials have shown a reduction in symptoms and body surface involvement (Hanifin et al 1993). Side effects that may occur include granulocytopenia, fever/chills, myalgias, headache, and

Several biological therapies have been studied for severe atopic dermatitis and only a few have shown benefit in small subset of patients. Further studies are necessary before any of these medications can be routinely recommended. Some of the biological therapies that have been evaluated are Omalizumab, Rituximab, Infliximab, Etanercept, Alefacept, and

Antimetabolites azathioprine and methotrexate have shown usefulness in severe atopic dermatitis. Azathioprine is an antagonist of purine metabolism that inhibits T cell

following will describe available systemic therapies for atopic dermatitis.

by 20 to 30 mg daily for three to four days can be beneficial.

**7.2.2.2 Systemic immunosuppressants** 

*7.2.2.2.1 Corticosteroids* 

*7.2.2.2.2 Cyclosporine* 

hypertension, and seizures.

Mepolizumab (Graves et al 2007).

*7.2.2.2.4 Antimetabolites, azathiaprine, and methotrexate* 

*7.2.2.2.3 Interferons* 

inject site pain.

face, eyelids, genitalia, and sensitive areas, as well as on young children and infants (Leung & Barber, 2003). More potent corticosteroids are used on other areas of the body in adults and children over 12 years of age.

The dosing application of topical corticosteroids is important in the management of the disease, but there are limited trials on the optimal dose. Potent topical corticosteroids should be used for the shortest duration of time and an emollient used in combination during flareups to prevent steroid-related side effects (Akdis, et al. 2006). Corticosteroids should be applied once to twice a day; frequent use does not improve efficacy and increases the risk of side effects (Bleehen, et al 1995; Leung & Barber, 2003). The risk of adverse reactions depends on the drug potency, skin integrity, and length of treatment (Fleischer, 1999). It is the clinician's responsibility to balance the need for a potent corticosteroid with the potential for adverse reactions. Adverse effects of topical corticosteroids can be local or systemic. The latter, which occurs rarely, include adrenal suppression, Cushing's syndrome, cataracts, and glaucoma (Correale, et al. 1999; Ruiz-Maldonado, et al. 1982; Stoppoloni, et al. 1983). Local adverse reactions include skin atrophy, contact dermatitis related to the vehicle, depigmentation, rosacea, steroid acne, and folliculitis (Correale, et al. 1999; Fleischer, 1999; Raimer, 2000). Treatment with topical corticosteroids can also reduce the colonization of S. Aureas, which may trigger exacerbations (Lipozencic & Wolf, 2007).

#### *7.2.2.1.2 Topical calcineurin inhibitors*

Pimecrolimus and tacrolimus are topical immunosuppresants that selectively inhibit the activation of T cells by inhibiting calcineurin, an enzyme required for the transcription of certain genes that code for specific inflammatory cytokines (Bornhovd, et al. 2002; Grassberger, et al. 2009). These are not recommended as first-line therapy or for mild atopic dermatitis. Pimecrolimus cream 1% and Tacrolimus ointment 0.03% are recommended for second-line therapy for mild to moderate AD in non-immunocompromised patients over two years old who have not been successful with other topical treatments.

Short-term (up to four years) treatment with Tacrolimus has been shown safe and effective in children older than two years of age. In a 12-week randomized, vehicle-controlled, double blind, multicenter study of 351 children, 2 to 15 years of age, with moderate to severe atopic dermatitis, tacrolimus ointment (0.03% and 0.1% concentrations) was safe and significantly more efficacious than the vehicle (Paller, et al. 2001). Studies also show that the calcineurin inhibitors are more effective that topical cortical steroids. In a multicenter, randomized, double-blind, parallel-group comparison of tacrolimus ointment 0.03% and 0.1% with hydrocortisone acetate ointment 1% involved 560 children 2 to 15 years of age (Reitamo, et al. 2002). Both concentrations of tacrolimus were significantly more effective than hydrocortisone acetate.

Pimecrolimus has also shown similar results to tacrolimus. Two identically designed, multicenter, randomized, controlled trials compared pimecrolimus cream 1% with vehicle in 403 children 2 to 17 years of age. Both groups received treatment twice daily for 6 weeks. Results showed significant alleviation of symptoms and signs with pimecrolimus compared with the vehicle (Van Leent, et al. 1998.)

Adverse effects of these two agents are similar. The most common adverse reactions are mild to moderate transient burning, stinging, itching, and erythema at the application site, which tends to resolve after the first few days of treatment (Bekersky, et al. 2001; Kang, et al. 2001; Paller, et al. 2001; Reitamo, et al. 2002; Soter, et al. 2001). They are, however, contraindicated in pregnant or breast feeding women. These agents have been studied for

face, eyelids, genitalia, and sensitive areas, as well as on young children and infants (Leung & Barber, 2003). More potent corticosteroids are used on other areas of the body in adults

The dosing application of topical corticosteroids is important in the management of the disease, but there are limited trials on the optimal dose. Potent topical corticosteroids should be used for the shortest duration of time and an emollient used in combination during flareups to prevent steroid-related side effects (Akdis, et al. 2006). Corticosteroids should be applied once to twice a day; frequent use does not improve efficacy and increases the risk of side effects (Bleehen, et al 1995; Leung & Barber, 2003). The risk of adverse reactions depends on the drug potency, skin integrity, and length of treatment (Fleischer, 1999). It is the clinician's responsibility to balance the need for a potent corticosteroid with the potential for adverse reactions. Adverse effects of topical corticosteroids can be local or systemic. The latter, which occurs rarely, include adrenal suppression, Cushing's syndrome, cataracts, and glaucoma (Correale, et al. 1999; Ruiz-Maldonado, et al. 1982; Stoppoloni, et al. 1983). Local adverse reactions include skin atrophy, contact dermatitis related to the vehicle, depigmentation, rosacea, steroid acne, and folliculitis (Correale, et al. 1999; Fleischer, 1999; Raimer, 2000). Treatment with topical corticosteroids can also reduce the colonization of S.

Pimecrolimus and tacrolimus are topical immunosuppresants that selectively inhibit the activation of T cells by inhibiting calcineurin, an enzyme required for the transcription of certain genes that code for specific inflammatory cytokines (Bornhovd, et al. 2002; Grassberger, et al. 2009). These are not recommended as first-line therapy or for mild atopic dermatitis. Pimecrolimus cream 1% and Tacrolimus ointment 0.03% are recommended for second-line therapy for mild to moderate AD in non-immunocompromised patients over

Short-term (up to four years) treatment with Tacrolimus has been shown safe and effective in children older than two years of age. In a 12-week randomized, vehicle-controlled, double blind, multicenter study of 351 children, 2 to 15 years of age, with moderate to severe atopic dermatitis, tacrolimus ointment (0.03% and 0.1% concentrations) was safe and significantly more efficacious than the vehicle (Paller, et al. 2001). Studies also show that the calcineurin inhibitors are more effective that topical cortical steroids. In a multicenter, randomized, double-blind, parallel-group comparison of tacrolimus ointment 0.03% and 0.1% with hydrocortisone acetate ointment 1% involved 560 children 2 to 15 years of age (Reitamo, et al. 2002). Both concentrations of tacrolimus were significantly more effective than

Pimecrolimus has also shown similar results to tacrolimus. Two identically designed, multicenter, randomized, controlled trials compared pimecrolimus cream 1% with vehicle in 403 children 2 to 17 years of age. Both groups received treatment twice daily for 6 weeks. Results showed significant alleviation of symptoms and signs with pimecrolimus compared

Adverse effects of these two agents are similar. The most common adverse reactions are mild to moderate transient burning, stinging, itching, and erythema at the application site, which tends to resolve after the first few days of treatment (Bekersky, et al. 2001; Kang, et al. 2001; Paller, et al. 2001; Reitamo, et al. 2002; Soter, et al. 2001). They are, however, contraindicated in pregnant or breast feeding women. These agents have been studied for

Aureas, which may trigger exacerbations (Lipozencic & Wolf, 2007).

two years old who have not been successful with other topical treatments.

and children over 12 years of age.

*7.2.2.1.2 Topical calcineurin inhibitors* 

hydrocortisone acetate.

with the vehicle (Van Leent, et al. 1998.)

short term use (two years for pimecrolimus and 4 years for tacrolimus) and have been shown to have favorable outcomes, but have been advised that they be used in accordance to their guidelines due to the potential cancer risk. Long term studies for these drugs are still needed.

### **7.2.2.2 Systemic immunosuppressants**

There are those individuals in which topical steroid use does not result in complete remission. As result, systemic immunosuppressant along with novel therapeutic options are warranted for severe refractory cases to provide increase in therapeutic options with effective remission rates and limited adverse effects. These subsets of patients should be referred to a specialist (i.e., dermatologist or allergist) for further evaluation. Severe atopic dermatitis may be described as the presence of widespread skin lesions or physically and/or emotionally disabling disease that significantly compromises a patient's quality of life. The following will describe available systemic therapies for atopic dermatitis.
