Treatment Options for Atopic Dermatitis—2007 Update

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                                            Treatment Options for Atopic Dermatitis—2007 Update

          a report by
          M i c h a e l P H e f f e r n a n , M D and E l i z a b e t h H o u s h m a n d

          Chief, Division of Dermatology, Wright State University’s Boonshoft School of Medicine

Atopic dermatitis (AD) is a chronic inflammatory                                with relapse after treatment is stopped. Even if the         Michael P Heffernan, MD, is an
                                                                                                                                             associate professor and Chief of the
pruritic skin disease that affects approximately 15% of                         treatment is continued its effectiveness often wears off
                                                                                                                                             Division of Dermatology at Wright
children in industrialized countries. It is the most                            after a variable period, usually around six to 12 months.    State University’s Boonshoft School
common skin disease of young children, but may affect                                                                                        of Medicine in Dayton, Ohio. He is
                                                                                                                                             also the Program Director of the
patients of any age. More than half of the patients with                        Atopiclair™ was US Food and Drug Administration
                                                                                                                                             school’s Dermatology Residency
AD develop asthma and seasonal allergies. Patients with                         (FDA)-approved to relieve the symptoms of AD and             Program and is involved as the
AD have increased transepidermal water loss and xerotic                         irritant contact dermatitis in July 2003. Atopiclair is a    principal investigator for nine
                                                                                                                                             research studies. He has served on
skin.This abnormal barrier contributes to the cutaneous                         hydrophilic cream developed for the management of
                                                                                                                                             numerous task forces and
hyperreactivity which is an essential feature of AD.                            AD; it is a non-steroidal hydrolipidic cream comprised       committees for the American
                                                                                of glycyrrhetinic acid, hyaluronic acid, telmesteine, and    Academy of Dermatology (AAD) and
                                                                                                                                             the Medical Dermatology Society
Therapy for AD should begin with optimal skin care,                             extracts from Vitis vinifera, which have been combined
                                                                                                                                             and has been a member of
addressing the skin barrier defect with regular use of                          with a moisturizing, emollient base. Glycyrrhetinic acid     national and international
emollients and skin hydration, along with the avoidance                         has both anti-inflammatory and antipruritic effects.The      professional societies and
                                                                                                                                             organizations. Among Dr Heffernan’s
of trigger irritants.The severe dryness of the skin is often                    product contains shea butter, and patients with a known
                                                                                                                                             achievements are many honors,
accompanied by intense pruritus and inflammation.                               allergy to nuts or nut oil should exercise caution.          including Teacher of the Year,
Patients should be educated to avoid common irritants                           Atopiclair seems devoid of significant local side effects    Scholars Circle—Dermatology
                                                                                                                                             Foundation, and membership in
and to use agents like soaps and hot water temperatures                         such as irritation and contact dermatitis; burning on
                                                                                                                                             Alpha Omega Alpha. He has been
during showering or bathing with caution.                                       application is rarely reported.                              involved in 77 clinical
                                                                                                                                             pharmacologic studies and has
                                                                                                                                             authored or co-authored more that
Probiotics are orally administered micro-organisms that                         MimyX™ was FDA-approved for the treatment of
                                                                                                                                             40 journal articles and textbooks.
have been used for atopic diseases because they may                             radiation dermatitis, AD and allergic contact dermatitis     Dr Heffernan earned his medical
have anti-inflammatory and anti-allergic properties                             in July 2005. Unlike traditional topical treatments for      degree at the University of
                                                                                                                                             Michigan Medical School in Ann
through promoting helper Th1 cell responses and by                              AD that target the inflammatory pathway, MimyX
                                                                                                                                             Arbor, following that up with an
restoring intestinal permeability and gut flora.                                cream works by restoring the natural components of           internship at the University of
                                                                                the stratum corneum and re-establishing barrier              Michigan Medical Center. He then
                                                                                                                                             performed his residency at the
Lactobacillus spp., Bifidobacterium spp., and Saccharomyces                     function of the outer layers of the epidermis. MimyX
                                                                                                                                             Department of Dermatology at the
spp.—particularly L. casei, L. rhamnosus, L. acidophilus, L.                    cream contains palmitoylethanolamide (PEA), an               Stanford University Medical Center.
plantarum, B. longum, B. bifidum, and S. cerevisiae                             endogenous bioactive fatty acid that is deficient in
boulardii—are the most commonly used probiotics and                             atopic skin. There is evidence that MimyX cream              Elizabeth Houshmand performed her
                                                                                                                                             internal medicine training at
actively researched organisms at the basic level and in                         replenishes PEA levels in atopic skin, restores the
                                                                                                                                             Georgetown University hospital and
clinical trials. However, to date six randomized                                disrupted skin barrier of AD, and promotes skin barrier      is pursuing an interest in
controlled trials have now been performed that, based                           repair. MimyX cream is approved for patients of all ages     dermatology research.
on their data, do not show a clinically useful effect of                        and provides a non-steroidal alternative to treating AD.
probiotics for treating established AD.
                                                                                Topical corticosteroids have been the mainstay of
Chinese medicines have produced impressive responses                            therapy for AD.They reduce inflammation and pruritus
in cases of atopic eczema that have proved resistant to                         by inhibiting the transcriptional activity of several pro-
conventional treatment. However, physicians should                              inflammatory genes. Therapy with these agents should
realize their potential toxicity as well as the uncertainty                     not replace the frequent use of moisturizers. The local
of their ingredients. Although the constituents and                             and systemic effects of topical steroids are well
amounts of plant material may differ in many of these                           recognized. Local effects include skin atrophy, striae,
remedies, placebo controlled trials have been performed                         telangiectasias, hypopigmentation, rosacea, perioral
with a specific formulation. They have shown a                                  dermatitis, and acne. Systemic side effects include
beneficial response in children and adults with atopic                          adrenal suppression, cataracts, glaucoma, and growth
eczema. Nevertheless, the effect is usually temporary,                          retardation in children.

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     Topical corticosteroids are grouped into seven                 years of age, and zafirlukast should not be given to
     potency categories, with class 1 containing the most           children under 12 years of age.
     potent agents and class 7 containing the least. In
     children, only mild to moderately potent steroid               As with TCIs, cyclosporine A inhibits calcineurin-
     preparations should be utilized. Class 1 steroids should       dependent pathways, resulting in reduced levels of pro-
     generally be avoided in children younger than 12 years         inflammatory cytokines such as interleukin (IL)-2 and
     of age. In children with AD, the fingertip unit (FTU)          interferon (IFN). Clinical trials to date have
     is defined as the amount of medication extending               demonstrated cyclosporine as an effective treatment for
     from the tip of the first joint on the palmar aspect of        adult and childhood AD. In children it is especially
     the index finger, and is described as a measure for the        important to note that vaccinations may not be
     application of corticosteroids.                                effective during immunosuppressive therapy.

     Although topical corticosteroids have long been used as        Omalizumab (Xolair®) is a recombinant DNA-
     the mainstay of therapy in AD, the development of              derived humanized immunoglobulin (Ig)G16-kappa
     topical immunomodulators has enabled a steroid free            mono-clonal antibody to human IgE. Omalizumab is
     anti-inflammatory topical treatment. In the US and             approved for the treatment of asthma in patients 12
     Europe, pimecrolimus cream (1%) and tacrolimus                 years and older with serum IgE levels not exceeding
     ointment (0.03%) are approved for the treatment of AD          700IU/ml. The efficacy of omalizumab in patients
     in children aged two or older and in adults.Tacrolimus         with refractory AD and IgE levels far exceeding those
     ointment (0.1%) is only approved for use in adults. Side       of patients with asthma has been reported with mixed
     effects with topical calcineurin inhibitors (TCIs)             results. Acute AD is characterized by a Th2 immune
     include a transient burning sensation of the skin. In a        response (IL-4, IL-5), whereas chronic AD is more
     study comparing the local side effects in children of          encompassed by a Th1 immune profile (IL-2, tumor
     0.03% tacrolimus ointment with 1% pimecrolimus                 necrosis factor alfa (TNF)-α). The Th2 immune
     cream, picrolimus demonstrated better local tolerability.      response in AD is marked by eczematous cutaneous
                                                                    lesions, eosinophilia, and elevated serum IgE levels.
     TCIs are not associated with skin atrophy and were             High-affinity IgE receptors (FceRI) are prominent in
     hailed as a useful alternative in the treatment of sensitive   AD.The significance of this high-affinity receptor for
     areas such as the face. On January 19, 2006 the US FDA         IgE has been demonstrated by studies in which
     announced the approval of updated labeling for both            blockade of the FceRI receptor site by anti-FceRI
     picrolimus (Elidel® cream) and tacrolimus (Protopic®           antibodies results in a paucity of allergen binding.
     ointment).The labeling now includes a boxed warning            FceRI-bound allergen-specific IgE has been
     about possible cancer and a patient medication guide.          unequivocally detected in patients who are allergic.
     The new labeling also identifies these treatments as
     second-line treatments.                                        Omalizumab has warnings for both malignancy and
                                                                    anaphylaxis; however, their incidence appears to be
     TCIs have been compared with topical corticosteroids           remote. Omalizumab only binds free IgE without
     in a limited number of studies. Compared with a low-           crosslinking IgE that is already bound to FceRI
     potency corticosteroid, 0.03% and 0.1% tacrolimus              receptors, minimizing the risk of anaphylaxis. Optimal
     ointments were shown to be more effective in children          candidates with AD are those with severe, refractory
     with moderate to severe AD. Although the optimal               disease in which other systemic therapies were not
     approach has yet to be identified, Picrolimus cream 1%         successful. Omalizumab may provide a safer alternative
     (Elidel) with as-needed pulses of moderate topical             to traditional therapies when treating patients with
     corticosteroids has been proven to be an effective             severe atopy who are persistently unresponsive to other
     treatment regimen. However, both physicians and                therapeutic measures.
     parents of children with AD are hesitant to use TCIs.As
     a result many physicians and patients have discontinued        The treatment of AD with phototherapy is well
     the use of TCIs and have sought alternative, often very        established and represents a standard second-line
     potent interventions, with varying degrees of success.         therapy of choice in adults. In children, UV therapy
                                                                    should be restricted to adolescents greater than 12 years
     The FDA has labeled leukotriene inhibitors such as             of age, except in severe cases.To date, the long-term side
     zileuton, zafirlukast, and montelukast for the                 effects of UV therapy are still unknown. ■
     treatment of asthma. Because asthma and AD have a
     similar pathogenesis, these agents may have a role in          A longer version of this article containing references can be
     the treatment of AD. It should be noted that                   found in the Reference Section on the website supporting this
     montelukast should not be used in children under six           briefing (

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