The magic of treating atopic dermatitis has not changed — have the correct diagnosis, offer thorough patient and family education, and use the best available, appropriate medicines. We still employ the standard treatments, including occlusives and moisturizers, irritant and allergen avoidance, topical and systemic corticosteroids, antibiotics, antihistamines and, rarely, ultraviolet light therapy. However, within the last couple of years, we’ve been able to add new treatments to our armamentarium. The FDA approved tacrolimus ointment (Protopic 0.03% and 0.1%) in February 2001 for moderate to severe atopic dermatitis. Pimecrolimus cream (Elidel 1%) received approval in March 2002 for mild to moderate disease. Both are approved for use in children aged 2 years and older. The introduction of these agents represents the most important advance in the therapy of atopic dermatitis since the advent of topical corticosteroids in the early 1950s. How one fits these new therapies into their clinical armamentarium can vary based on disease severity and distribution, age of patient, cost considerations, and preference and experience of the prescriber. Reviewed here are several clinical cases depicting successful outcomes achieved using the new topical immunomodulators in combination with mid-potent topical corticosteroids (cortisone strength class 4 or 5). Derived from macrolide antibiotics, these new non-steroidal immunomodulators are cell-selective inflammatory cytokine inhibitors that act primarily by inhibiting T lymphocyte activation via the calcineurin pathway. Because topical steroids also modify the skin’s immune system, these newer agents should be more accurately referred to as topical calcineurin inhibitors (or TCIs). Are New Treatments Needed? Topical steroids have long been the cornerstone of therapy. A 2000 comprehensive review article affirmed that topical steroids are justified as first-line treatment in “all” patients with eczema.1 While known to be helpful, topical steroids have potential side effects and therefore require close monitoring by patients and prescribers. Several studies highlight why safer topical treatments are welcomed. Charman’s survey in 2000 found that greater than 70% of patient responders were concerned about topical steroid side effects, and nearly 24% admitted to noncompliance due to safety concerns.2 Also, contact allergies to topical steroids are increasingly recognized,3 and steroid insensitivity may be a factor in recalcitrant atopic dermatitis.4 Despite these concerns, the use topical steroids will not fade away. This point was emphasized by a panel of highly regarded dermatologists in a Skin and Aging June 2003 supplement — “The Best of Both Worlds: The role of mid-potency topical corticosteroids in the treatment of atopic dermatitis with topical immunomodulators.” Amy Paller, M.D., states in that document: “There’s a phobia that is largely unjustified in the use of topical steroids. Unless topical corticosteroids are used inappropriately, you’re unlikely to have much trouble.” While trained dermatologists and their staff can properly monitor and educate their patients about these issues, an effective, low-to-mid potent corticosteroid combined with the newer steroid-free TCIs could dramatically reduce concerns of cutaneous atrophy, telangiectasia formation, dyspigmentation, steroid-induced acne, and the rare systemic steroid absorption risks of hypothalamic-pituitary-adrenal (HPA) axis suppression, growth retardation, and cataract and glaucoma formation. Combination Topical Therapy As with use of multiple, simultaneous agents to treat acne and psoriasis, many dermatologist agree that combination treatments for atopic dermatitis will be the standard of care in the near future. Since the launch of the first calcineurin inhibitor, dermatology prescribers have experimented with varying regimens of concomitant therapy. We have learned that patients using TCIs as monotherapy will periodically flare, necessitating the use of steroids to cool down the breakthrough. Torok, HM, et al. did a 21-day study with 57 patients with atopic dermatitis and found that initial combined therapy with tacrolimus and hydrocortisone butyrate 0.1% (Class 5) was statistically superior in erythema, induration and excoriation to either agent used alone.5 Our experience reveals several advantages to combination therapy. • First, steroids have a quicker onset of relief and therefore reduce the potential side effect of (transient) burning and stinging reported by patients in the first 1 to 2 weeks of TCI use. • Second, moderate to severe cases resolve more quickly and completely. • Third, patients can discontinue the use of steroids when an acceptable improvement has been met and continue with TCI treatment — therefore, decreasing the need to wait for a follow-up appointment to be switched to a TCI if only a steroid was prescribed on the initial visit. The strategy is to get the patient to clear quickly with concomitant TCI and topical corticosteroid use and then shift to TCI only for the purpose of maintenance therapy. The challenge for practitioners is that we don’t yet know the best evidence-based combination regimen of therapy, but such studies should become available. The following six cases depict some of the successful uses of combination topical treatments we’ve had with our patients after treatment anywhere from 10 to 30 days. We hope you find the information presented here beneficial to your own patients. Case #1 16-year-old male with history of atopic dermatitis since age 3 Pimecrolimus (Elidel Cream) b.i.d. was started along with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The photo at right is that patient at a 1-month follow-up visit. Case #2 Severe atopic dermatitis on bilateral cheeks of a 14-month-old female Treatment was started with pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for only the first 10 days. After 10 days, the topical steroid was discontinued and treatment continued with pimecrolimus b.i.d. After 20 days, this is the patient at a follow-up visit depicted at right. Case #3 Atopic dermatitis in popliteal fossa, 15-year-old male Treatment was started with tacrolimus (Protopic Ointment) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. At top is the patient’s condition depicted before treatment. On the bottom is the patient at a follow-up visit after 10 days. Case #4 Atopic dermatitis, right knee of 13-year-old male This patient was prescribed tacrolimus (Protopic Ointment) b.i.d. in combination with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The patient’s atopic dermatitis resolved in 1 month. (At top, before treatment; at bottom, the patient’s condition after 1 month.) Case #5 Paranasal atopic dermatitis in a 27-year-old female with a lifelong history of atopic dermatitis Pimecrolimus (Elidel Cream) q.h.s. was used with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for the first week only. The patient’s condition cleared, as you can see in the photo at right above, which was taken at a 1-month follow-up visit. Case #6 Severe atopic dermatitis on arm of a 14-month-old female This is the same patient pictured in case #2. Pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. were started for only first 10 days. After 10 days, the topical steroid was discontinued and therapy was continued with pimecrolimus b.i.d. After 20 days of combination therapy, this is the patient at a follow-up visit (depicted at right).
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Atopic Dermatitis: Employing a New Treatment Paradigm
The magic of treating atopic dermatitis has not changed — have the correct diagnosis, offer thorough patient and family education, and use the best available, appropriate medicines. We still employ the standard treatments, including occlusives and moisturizers, irritant and allergen avoidance, topical and systemic corticosteroids, antibiotics, antihistamines and, rarely, ultraviolet light therapy. However, within the last couple of years, we’ve been able to add new treatments to our armamentarium. The FDA approved tacrolimus ointment (Protopic 0.03% and 0.1%) in February 2001 for moderate to severe atopic dermatitis. Pimecrolimus cream (Elidel 1%) received approval in March 2002 for mild to moderate disease. Both are approved for use in children aged 2 years and older. The introduction of these agents represents the most important advance in the therapy of atopic dermatitis since the advent of topical corticosteroids in the early 1950s. How one fits these new therapies into their clinical armamentarium can vary based on disease severity and distribution, age of patient, cost considerations, and preference and experience of the prescriber. Reviewed here are several clinical cases depicting successful outcomes achieved using the new topical immunomodulators in combination with mid-potent topical corticosteroids (cortisone strength class 4 or 5). Derived from macrolide antibiotics, these new non-steroidal immunomodulators are cell-selective inflammatory cytokine inhibitors that act primarily by inhibiting T lymphocyte activation via the calcineurin pathway. Because topical steroids also modify the skin’s immune system, these newer agents should be more accurately referred to as topical calcineurin inhibitors (or TCIs). Are New Treatments Needed? Topical steroids have long been the cornerstone of therapy. A 2000 comprehensive review article affirmed that topical steroids are justified as first-line treatment in “all” patients with eczema.1 While known to be helpful, topical steroids have potential side effects and therefore require close monitoring by patients and prescribers. Several studies highlight why safer topical treatments are welcomed. Charman’s survey in 2000 found that greater than 70% of patient responders were concerned about topical steroid side effects, and nearly 24% admitted to noncompliance due to safety concerns.2 Also, contact allergies to topical steroids are increasingly recognized,3 and steroid insensitivity may be a factor in recalcitrant atopic dermatitis.4 Despite these concerns, the use topical steroids will not fade away. This point was emphasized by a panel of highly regarded dermatologists in a Skin and Aging June 2003 supplement — “The Best of Both Worlds: The role of mid-potency topical corticosteroids in the treatment of atopic dermatitis with topical immunomodulators.” Amy Paller, M.D., states in that document: “There’s a phobia that is largely unjustified in the use of topical steroids. Unless topical corticosteroids are used inappropriately, you’re unlikely to have much trouble.” While trained dermatologists and their staff can properly monitor and educate their patients about these issues, an effective, low-to-mid potent corticosteroid combined with the newer steroid-free TCIs could dramatically reduce concerns of cutaneous atrophy, telangiectasia formation, dyspigmentation, steroid-induced acne, and the rare systemic steroid absorption risks of hypothalamic-pituitary-adrenal (HPA) axis suppression, growth retardation, and cataract and glaucoma formation. Combination Topical Therapy As with use of multiple, simultaneous agents to treat acne and psoriasis, many dermatologist agree that combination treatments for atopic dermatitis will be the standard of care in the near future. Since the launch of the first calcineurin inhibitor, dermatology prescribers have experimented with varying regimens of concomitant therapy. We have learned that patients using TCIs as monotherapy will periodically flare, necessitating the use of steroids to cool down the breakthrough. Torok, HM, et al. did a 21-day study with 57 patients with atopic dermatitis and found that initial combined therapy with tacrolimus and hydrocortisone butyrate 0.1% (Class 5) was statistically superior in erythema, induration and excoriation to either agent used alone.5 Our experience reveals several advantages to combination therapy. • First, steroids have a quicker onset of relief and therefore reduce the potential side effect of (transient) burning and stinging reported by patients in the first 1 to 2 weeks of TCI use. • Second, moderate to severe cases resolve more quickly and completely. • Third, patients can discontinue the use of steroids when an acceptable improvement has been met and continue with TCI treatment — therefore, decreasing the need to wait for a follow-up appointment to be switched to a TCI if only a steroid was prescribed on the initial visit. The strategy is to get the patient to clear quickly with concomitant TCI and topical corticosteroid use and then shift to TCI only for the purpose of maintenance therapy. The challenge for practitioners is that we don’t yet know the best evidence-based combination regimen of therapy, but such studies should become available. The following six cases depict some of the successful uses of combination topical treatments we’ve had with our patients after treatment anywhere from 10 to 30 days. We hope you find the information presented here beneficial to your own patients. Case #1 16-year-old male with history of atopic dermatitis since age 3 Pimecrolimus (Elidel Cream) b.i.d. was started along with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The photo at right is that patient at a 1-month follow-up visit. Case #2 Severe atopic dermatitis on bilateral cheeks of a 14-month-old female Treatment was started with pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for only the first 10 days. After 10 days, the topical steroid was discontinued and treatment continued with pimecrolimus b.i.d. After 20 days, this is the patient at a follow-up visit depicted at right. Case #3 Atopic dermatitis in popliteal fossa, 15-year-old male Treatment was started with tacrolimus (Protopic Ointment) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. At top is the patient’s condition depicted before treatment. On the bottom is the patient at a follow-up visit after 10 days. Case #4 Atopic dermatitis, right knee of 13-year-old male This patient was prescribed tacrolimus (Protopic Ointment) b.i.d. in combination with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The patient’s atopic dermatitis resolved in 1 month. (At top, before treatment; at bottom, the patient’s condition after 1 month.) Case #5 Paranasal atopic dermatitis in a 27-year-old female with a lifelong history of atopic dermatitis Pimecrolimus (Elidel Cream) q.h.s. was used with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for the first week only. The patient’s condition cleared, as you can see in the photo at right above, which was taken at a 1-month follow-up visit. Case #6 Severe atopic dermatitis on arm of a 14-month-old female This is the same patient pictured in case #2. Pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. were started for only first 10 days. After 10 days, the topical steroid was discontinued and therapy was continued with pimecrolimus b.i.d. After 20 days of combination therapy, this is the patient at a follow-up visit (depicted at right).
The magic of treating atopic dermatitis has not changed — have the correct diagnosis, offer thorough patient and family education, and use the best available, appropriate medicines. We still employ the standard treatments, including occlusives and moisturizers, irritant and allergen avoidance, topical and systemic corticosteroids, antibiotics, antihistamines and, rarely, ultraviolet light therapy. However, within the last couple of years, we’ve been able to add new treatments to our armamentarium. The FDA approved tacrolimus ointment (Protopic 0.03% and 0.1%) in February 2001 for moderate to severe atopic dermatitis. Pimecrolimus cream (Elidel 1%) received approval in March 2002 for mild to moderate disease. Both are approved for use in children aged 2 years and older. The introduction of these agents represents the most important advance in the therapy of atopic dermatitis since the advent of topical corticosteroids in the early 1950s. How one fits these new therapies into their clinical armamentarium can vary based on disease severity and distribution, age of patient, cost considerations, and preference and experience of the prescriber. Reviewed here are several clinical cases depicting successful outcomes achieved using the new topical immunomodulators in combination with mid-potent topical corticosteroids (cortisone strength class 4 or 5). Derived from macrolide antibiotics, these new non-steroidal immunomodulators are cell-selective inflammatory cytokine inhibitors that act primarily by inhibiting T lymphocyte activation via the calcineurin pathway. Because topical steroids also modify the skin’s immune system, these newer agents should be more accurately referred to as topical calcineurin inhibitors (or TCIs). Are New Treatments Needed? Topical steroids have long been the cornerstone of therapy. A 2000 comprehensive review article affirmed that topical steroids are justified as first-line treatment in “all” patients with eczema.1 While known to be helpful, topical steroids have potential side effects and therefore require close monitoring by patients and prescribers. Several studies highlight why safer topical treatments are welcomed. Charman’s survey in 2000 found that greater than 70% of patient responders were concerned about topical steroid side effects, and nearly 24% admitted to noncompliance due to safety concerns.2 Also, contact allergies to topical steroids are increasingly recognized,3 and steroid insensitivity may be a factor in recalcitrant atopic dermatitis.4 Despite these concerns, the use topical steroids will not fade away. This point was emphasized by a panel of highly regarded dermatologists in a Skin and Aging June 2003 supplement — “The Best of Both Worlds: The role of mid-potency topical corticosteroids in the treatment of atopic dermatitis with topical immunomodulators.” Amy Paller, M.D., states in that document: “There’s a phobia that is largely unjustified in the use of topical steroids. Unless topical corticosteroids are used inappropriately, you’re unlikely to have much trouble.” While trained dermatologists and their staff can properly monitor and educate their patients about these issues, an effective, low-to-mid potent corticosteroid combined with the newer steroid-free TCIs could dramatically reduce concerns of cutaneous atrophy, telangiectasia formation, dyspigmentation, steroid-induced acne, and the rare systemic steroid absorption risks of hypothalamic-pituitary-adrenal (HPA) axis suppression, growth retardation, and cataract and glaucoma formation. Combination Topical Therapy As with use of multiple, simultaneous agents to treat acne and psoriasis, many dermatologist agree that combination treatments for atopic dermatitis will be the standard of care in the near future. Since the launch of the first calcineurin inhibitor, dermatology prescribers have experimented with varying regimens of concomitant therapy. We have learned that patients using TCIs as monotherapy will periodically flare, necessitating the use of steroids to cool down the breakthrough. Torok, HM, et al. did a 21-day study with 57 patients with atopic dermatitis and found that initial combined therapy with tacrolimus and hydrocortisone butyrate 0.1% (Class 5) was statistically superior in erythema, induration and excoriation to either agent used alone.5 Our experience reveals several advantages to combination therapy. • First, steroids have a quicker onset of relief and therefore reduce the potential side effect of (transient) burning and stinging reported by patients in the first 1 to 2 weeks of TCI use. • Second, moderate to severe cases resolve more quickly and completely. • Third, patients can discontinue the use of steroids when an acceptable improvement has been met and continue with TCI treatment — therefore, decreasing the need to wait for a follow-up appointment to be switched to a TCI if only a steroid was prescribed on the initial visit. The strategy is to get the patient to clear quickly with concomitant TCI and topical corticosteroid use and then shift to TCI only for the purpose of maintenance therapy. The challenge for practitioners is that we don’t yet know the best evidence-based combination regimen of therapy, but such studies should become available. The following six cases depict some of the successful uses of combination topical treatments we’ve had with our patients after treatment anywhere from 10 to 30 days. We hope you find the information presented here beneficial to your own patients. Case #1 16-year-old male with history of atopic dermatitis since age 3 Pimecrolimus (Elidel Cream) b.i.d. was started along with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The photo at right is that patient at a 1-month follow-up visit. Case #2 Severe atopic dermatitis on bilateral cheeks of a 14-month-old female Treatment was started with pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for only the first 10 days. After 10 days, the topical steroid was discontinued and treatment continued with pimecrolimus b.i.d. After 20 days, this is the patient at a follow-up visit depicted at right. Case #3 Atopic dermatitis in popliteal fossa, 15-year-old male Treatment was started with tacrolimus (Protopic Ointment) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. At top is the patient’s condition depicted before treatment. On the bottom is the patient at a follow-up visit after 10 days. Case #4 Atopic dermatitis, right knee of 13-year-old male This patient was prescribed tacrolimus (Protopic Ointment) b.i.d. in combination with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. The patient’s atopic dermatitis resolved in 1 month. (At top, before treatment; at bottom, the patient’s condition after 1 month.) Case #5 Paranasal atopic dermatitis in a 27-year-old female with a lifelong history of atopic dermatitis Pimecrolimus (Elidel Cream) q.h.s. was used with hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. for the first week only. The patient’s condition cleared, as you can see in the photo at right above, which was taken at a 1-month follow-up visit. Case #6 Severe atopic dermatitis on arm of a 14-month-old female This is the same patient pictured in case #2. Pimecrolimus (Elidel Cream) b.i.d. and hydrocortisone butyrate 0.1% (Locoid Lipocream) q.h.s. were started for only first 10 days. After 10 days, the topical steroid was discontinued and therapy was continued with pimecrolimus b.i.d. After 20 days of combination therapy, this is the patient at a follow-up visit (depicted at right).
