RecentEric J. Yang, BS,a,​ b​ Sahil Developments Sekhon, MD,a​ Isabelle M. Sanchez, MPH,​a,​c Kristen in M. Beck, MD,​a Tina Bhutani, MDa Atopic Dermatitis abstract ∼ Atopic dermatitis (AD) is a bothersome and common skin disease affecting 10.7% of children in the United States. This skin condition significantly decreases quality of life in not only patients, but in their families as well. Pediatricians are often the first physicians to diagnose and manage these patients and thus are relied on by families to answer questions about this disease. AD is complex, multifactorial, and has historically had limited therapeutic options, but the landscape of this disease is now rapidly changing. Pathways contributing to the pathogenesis of this disease are continually being discovered, and new therapies for AD are being developed at an unprecedented rate. With this article, we will review the current guidelines regarding the management of AD, outline updates in the current aDepartment of Dermatology, University of California, San Francisco, San Francisco, California; bChicago Medical understanding of its pathophysiology, and highlight novel developments School, Rosalind Franklin University of Medicine and available for the treatment of this burdensome disease. Science, North Chicago, Illinois; and cCollege of Medicine, University of Illinois at Chicago, Chicago, Illinois

Mr Yang, Dr Sekhon, Ms Sanchez, and Drs Beck and Atopic dermatitis (AD) is a chronic of AD is responsible for its significant Bhutani participated in the drafting and revising ∼ inflammatory skin disease that affects negative impact on quality of life of this manuscript; and all authors approved the 8 final manuscript as submitted and agree to be 10.7% of children in the United (QoL). Patients with AD often present 1 – accountable for all aspects of the work. States and is becoming increasingly with severe pruritus and xerosis, with 2 4 DOI: https://​doi.​org/​10.​1542/​peds.​2018-​1102 prevalent. ‍‍ Pediatricians are variable lesion distribution based on often the first physicians providing age. Young infants up to 2 years of Accepted for publication Jul 24, 2018 ∼ Address correspondence to Eric J. Yang, BS, treatment to patients with5 new-onset age often present with scaly, crusted AD and disease flares,​ and 50% erythematous patches on the scalp, Department of Dermatology, University of California, San Francisco, 515 Spruce St, San Francisco, CA of patients with AD are treated in face, and extensor surfaces, whereas 6 94118. E-mail: [email protected] a primary care setting. Therefore, prepubertal children present with PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, pediatricians play a key role in the erythematous patches in a flexural 9 1098-4275). overall management of patients with distribution. Adolescents and adults Copyright 2018 by the American Academy of AD and should be well informed about typically present with more lichenified © Pediatrics recent developments in the clinical skin changes. 7 FINANCIAL DISCLOSURE: Dr Bhutani is an management of this disease. The progression of AD is investigator for AbbVie, Janssen, Merck, Eli Lilly, Despite its high prevalence, this unpredictable, but the following and Strata Skin Sciences but has no direct financial complex disease has historically been 4 phenotypes have recently been conflicts to report; the other authors have indicated they have no financial relationships relevant to this poorly understood. With this article, we identified: early-onset transient (9.2% article to disclose. provide an update on recent advances of children), early-onset persistent FUNDING: No external funding. in our understanding of the clinical (6.5%), late-onset (4.8%), 10and absent presentation and pathophysiology or infrequent AD (79.5%). Patients POTENTIAL CONFLICT OF INTEREST: Dr Bhutani is an investigator for AbbVie, Janssen, Merck, Eli Lilly, of AD and highlight new therapeutic with AD have alternating periods of and Strata Skin Sciences; the other authors have developments for this disease. exacerbated disease and symptom indicated they have no potential conflicts of interest CLINICAL COURSE resolution. Thus, both the alleviation of to disclose. symptoms and prevention of flares are importantDiagnosis in the management of AD. “ ” To cite: Yang EJ, Sekhon S, Sanchez IM, et al. AD is a bothersome skin condition often Recent Developments in Atopic Dermatitis. Pedi­ referred to as the itch that rashes atrics. 2018;142(4):e20181102 because of the pruritus that patients Patients commonly present during experience. This hallmark symptom acute flares with intense pruritus, Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018:e20181102 STATE-OF-THE-ART REVIEW ARTICLE xerosis, erosions, excoriations, and which contribute to an increased sleep, social functioning, work ill-defined patches of erythema with7,11​ susceptibility of21, developing22​ productivity, and income. a distribution that varies with age. ‍ skin infections. ‍ Because AD has a well-characterized negative AD is clinically diagnosed on the basis of a decreased antimicrobial 40,41​ 23 impact on sleep in children ‍ of history, morphology, distribution peptide expression,​ >75% of 42 Staphylococcus aureus and their families because of of skin lesions, and associated clinical affected children are colonized by 11 debilitating pruritus and the signs. Other important factors , compared Staphylococcus constant care needed for this disease. suggesting a diagnosis of AD include with <25% of healthy children in 24 Children with moderate-to-severe early onset (<2 years of age), atopy, control groups. 11,12​ AD experience more restless sleep, and family history of disease. colonization worsens inflammation 24 increased waking, greater difficulty This diagnosis should be reevaluated and pruritus,​ increasing the risk of Streptococcus pyogenes falling asleep, and increased daytime frequently, particularly in patients colonization and/or superinfection sleepiness compared with healthy not responding to appropriate with , 21 patients; these are behaviors that treatment, to verify the accuracy viruses, or fungi. AD can also worsen with the severity of AD and of this diagnosis and exclude the predispose patients to disseminated 21,43​ with flares. Parents of affected possibility of other conditions, eczema herpeticum and molluscum ∼ – 21 children also experience significant such as scabies, contact dermatitis, contagiosum outbreaks. sleep loss ( 1 3 hours per night) psoriasis, tinea infections, or viral 7,13​ Currently well-known comorbidities while providing overnight care to Comorbiditiesexanthems. ‍ and Complications of AD are mostly atopic, but AD soothe their children42,44​ and help them “ ” may have a broader impact on return to sleep. ‍ The severity of health. Authors of recent studies sleep disruption associated with AD AD is thought to kick off the have shown that patients25, with26​ AD is comparable to that of other chronic atopic march, predisposing patients are more likely be obese ‍ and conditions requiring constant care, to other atopic disorders later 14,15​ have elevated serum cardiovascular27 including autism spectrum disorder, in life. ‍ Patients with AD with risk markers than healthy patients,– ​ mental retardation,45 and seizure early sensitization to foods have an contributing to increased 28 30 disorders. An effective treatment increased risk of developing asthma,16 cardiovascular disease risk. ‍ plan is necessary to minimize the allergic rhinitis, and food allergies. However, severe AD in children and QoL impairment because of poor46 Therefore, early diagnosis and adolescents– has also been associated sleep in both affected47 patients management of AD and its associated with impaired31 34 growth and short and their families. risk factors may reduce the risk of stature. ‍ Patients with AD are also AD affects children during critical developing other allergic 16diseases at an increased risk of developing stages of childhood development, and improve overall QoL. depression, anxiety, attention-deficit/ – causing significant QoL impairment hyperactivity disorder, and conduct AD has been associated with an 35 37 at ages when patients are most disorder,​ ‍ ‍ with risk correlated increased risk of developing17 a peanut 35 vulnerable. Children with AD can with AD disease severity. AD is allergy specifically,​ but previous be severely impacted by fear of not just skin deep, and management 46,48​ clinical practice guidelines on food embarrassment ‍ and constant should be used to address the 49 allergy prevention were constantly anxiety about future flares. Patients comorbidities, in addition to skin changing. Most recently, the Learning with AD are often socially isolated symptoms, associated with this Early About Peanut Allergy trial and bullied because of the fear of systemic disease. 50 revealed that an early introduction of QoL Impairments contagion and stigma,​ leading to peanut-containing foods reduces the poor self-esteem in these young51 risk of developing a peanut allergy and impressionable patients. As in high-risk patients, including18 Although skin disease is often a result, patients with AD often infants with severe AD. Current perceived to be relatively benign, withdraw socially, avoid group consensus guidelines recommend an children with generalized AD activities, or may even skip school46, 52​to introduction of peanut-containing report QoL deficits similar to that of prevent further embarrassment. ‍ foods such as peanut butter or children with other serious chronic Affected patients will often also have peanut puffs as early as 4 months of diseases, including renal disease impaired concentration because of 38,39​ – age to patients with AD19,20​ to reduce this and cystic fibrosis. ‍ Because of sleep loss, antihistamine sedation, risk of future allergy. ‍ the ever-present nature of the itch and irresistible itch, which, combined Children with AD have significant scratch cycle, AD can be extremely with stunted social development ’ cutaneous immune dysregulation burdensome and infringe on all areas and missed school time, may and an impaired skin barrier, of affected patients lives, including decrease scholastic achievement and Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 YANG et al – ultimately 46,diminish49,​ 52​ 54 future career this multifactorial condition have Thus, the progression of AD may not prospects. ‍ ‍‍ been in the understanding of the be as clear-cut as previously thought. immunology of this disease. Additionally, AD is economically Despite major immunologic burdensome, costing the United However, much of the current 55 similarities to AD in adults, pediatric States $5.3 billion in 2004,​ a understanding of AD immunology AD also reveals features that may number that will likely rise with the is based on studies in adults, who be unique to new-onset disease. The rapidly increasing price of topical present different clinically and 56 skin of affected children reveals T-cell corticosteroids (TCSs). In 1 study, have a longer duration of disease predominance as compared with families of affected patients spent than pediatric patients. Given that healthy children and affected adults, 34.8% ($274) of their available the immune system changes with 62 implicating T-cell activation as a key monthly income on AD care, which age,​ findings in adults may not 69 driver of early AD. Additionally, can be a significant financial burden represent the immunologic processes 57 these children exhibit lymphocyte especially for low-income families. occurring in children. Authors of ’ distributions similar to that of healthy Caregivers for patients with AD often recent studies have characterized adults, implying that accelerated miss work to care for their children s immunologic differences in AD 42 63 64 lymphocyte development may play health issues,​ which can contribute observed with age,​ ethnicity,​ 69 65 a role in disease initiation. The to impaired work performance and and disease subtype,​ suggesting lesional skin of affected children also decreased income. It is important that several distinct inflammatory uniquely reveals gene expression for pediatricians to be aware that mechanisms likely contribute to this more similar to psoriatic lesions than the negative impact of AD on the complex, heterogeneous skin disease. that of adult AD or healthy pediatric QoL for patients and their families Significant recent advances have skin, which may have implications is multimodal. Skin symptoms increased our understanding of the 60 for future treatment. Significant represent a small portion of the underlying mechanisms of both adult inroads are being made to understand negative impact of AD, which also and pediatric AD, contributing to the the pathogenesis of both adult and profoundly affects sleep, childhood development of novel therapies for pediatric AD and the overlap and development, and finances. this complex disease. differences between the 2, which may – PATHOPHYSIOLOGY AND AD has historically been described as help guide the development of future, PATHOGENESIS a biphasic T-cell mediated disease, more targeted therapies. in which an initial T helper (Th) 2 Although various additional pathways (Th2) activation drives acute disease, contribute to AD, the Th2 immune The pathogenesis of AD involves a whereas a later Th1 response 66 response remains the main focus of complex interplay of immunologic maintains chronic AD. Authors of AD pathogenesis and therapeutic dysfunction, genetics, environmental recent studies corroborate the role development. Th2 cells are the exposures, and skin barrier disruption. of early Th1 axis suppression in main producers of Th2 cytokines Loss-of-function filaggrin gene this disease, finding low Th1 T-cell 67 interleukin 4 (IL-4), interleukin 5 mutations were implicated early on as levels in acute AD lesions in adults (IL-5), and interleukin 13 (IL-13) in a major predisposing risk factor for and children recently diagnosed 58 63 AD, but type 2 innate lymphoid cells AD,​ suggesting skin barrier defects to with AD. However, chronic AD (ILC2s), found in increased numbers be key drivers of this disease. However, lesions reveal intensification, rather 70 in lesional AD skin,​ have recently– authors of more recent research than withdrawal, of Th2-related 67 been characterized as an additional have found that filaggrin is deficient inflammation. Strong activation 70 72 source of Th2 cytokine release. ‍‍ in most affected adults regardless of of the Th2 and Th22 inflammatory 59 The recent discovery of these cells in genotype but not in patients with responses are observed in the 60 AD may link several abnormalities new-onset AD. Therefore, filaggrin lesional skin of both children and known to occur within AD and may deficiency is not necessary for disease adults with AD, but affected children serve as a target for new therapies in onset but may be a downstream result demonstrate greater induction of the near future. of disease chronicity. Authors of recent the Th17 axis to levels comparable60 findings have also found skin barrier to that of patients with psoriasis. ILC2s express killer cell lectin- like receptor G1, which normally disruption to occur early in life, with Interestingly, the 60nonlesional skin68 increased neonatal transepidermal of young children and adults binds E-cadherin to inhibit ILC2 water loss predicting61 future also already harbors significant proliferation70 and IL-5 and/or IL-13 development of AD. Nevertheless, inflammation with increased Th2 and production. E-cadherin is normally most recent developments with respect Th17 expression, suggesting that AD expressed by epidermal73 cells but to therapeutics and pathogenesis of involves early systemic involvement. is downregulated in AD and Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 3 70 patients with filaggrin deficiency. essential for all patients with AD both for patients with sleep loss secondary

Because barrier dysfunction is a key during flares and for maintenance, to itch91 because of their sedative pathogenic factor for AD, this model because skin barrier disruption in effect. Young patients should be provides a novel barrier-sensing this disease results in xerosis and monitored for paradoxic excitation, mechanism that contributes to the increased82 transepidermal water a sign of antihistamine toxicity that92, 93​ pathogenesis of AD. loss. Adequate moisturization occurs at higher rates in children. ‍ significantly decreases AD 83 Sedating therapies94 should only be Additionally, ILC2s proliferate in symptoms, including84 pruritus and used short-term,​ because long-term response to elevations in thymic lichenification,​ and decreases– the use can be detrimental95,96​ to school stromal lymphopoietin (TSLP), a pro- amount of prescription85 medications87 performance. ‍ inflammatory cytokine produced by needed for treatment. ‍ ‍ In fact, 74 Although their clinical evidence applying moisturizer to neonates 97 epithelial cells in response to stress is conflicting,​ bleach baths are with a family history of AD reduces found at75 increased levels in AD skin recommended for patients with the risk of future development of the lesions. TSLP selectively increases 88,89​ moderate-to-severe AD with signs of disease and should be considered basophil hematopoiesis76 and promotes secondary bacterial infection because for patients at high risk of developing peripheral basophilia. These of their presumed antistaphylococcal – atopic disease. 82 basophils subsequently release IL-4, and antiseptic properties. These causing ILC2s to proliferate77,​78 in an IL-4 Trigger avoidance is also important may also be useful for maintenance dependent manner. ILC2s release to prevent recurrent symptoms or treatment of patients suffering from IL-5 and IL-13, further contributing disease worsening. A careful history recurrent infections to decrease to the upregulated Th2 response should be taken to characterize bacterial colonization and the risk observed in AD. IL-13 also upregulates relationships between suspected of secondary skin infection7,24,​ and98​ to TSLP release by keratinocytes, creating triggers and skin symptoms. Age can improve disease severity. ‍ These a positive feedback loop for the patients should bathe twice weekly in 79 be used to guide the discussion of ∼ worsening of AD. However, the role 0.005% sodium hypochlorite likely triggers (ie, younger children ∼ of ILC2s specifically in AD pathogenesis are more likely to have a food allergy ( 0.5 cups of 6% bleach in a24 full bathtub of water [ 40 gal]) but may is poorly understood and in the than older children, who are more90 early stages of investigation. Further often triggered by aeroallergens). use bleach baths7 daily if they have characterization of the mechanisms Indiscriminate allergy testing without a severe disease. Intranasal mupirocin of AD-related immune dysfunction history that suggests allergic triggers is and sodium hypochlorite cleansers24,99​ may provide additional benefit,​ ‍ will aid the development of future not recommended, because these tests90 therapeutics. have low positive predictive values. but consensus guidelines for these100 MANAGEMENT Skin-prick or specific immunoglobulin have not yet been developed. E testing should only be done when Vigilant skin care and trigger avoidance there is a high clinical suspicion90 of may often be sufficient for patients allergy-induced dermatitis. If patients with mild disease, but patients with AD is often managed successfully are found to have trigger-induced symptoms not adequately managed in the pediatric primary care disease exacerbation, trigger avoidance by these measures require further setting with topical agents, but can greatly decrease90 the frequency and pharmacologic interventions, including recalcitrant disease has been 82 severity of flares. Topicaltopical and Therapies systemic agents. historically difficult to address Acute management of AD is largely because of a lack of approved80 second-line therapies for AD. focused on controlling pruritus, However, great strides have been which is responsible for significant The recommended first-line QoL impairment. Acute flares pharmacologic therapy for AD made recently in the development 81,82,​ 101​ are often managed with topical continues to be TCSs,​ ‍ ‍ of treatments for AD. Basic Management therapies, but oral antihistamines which have proven to be effective

may provide additional91 benefit in for children over several certain situations. Nonsedating decades. However, TCS phobia

The basic management of AD has not antihistamines are not recommended remains102 a significant concern103 for changed significantly in recent years, for routine treatment of AD, patients and providers,​ and still centering around gentle skin but short-term use of first- is a significant source102,104​ of treatment care and the prevention7,81​ of disease generation antihistamines such as nonadherence. ‍ AD persists on exacerbation. ‍ Skin hydration diphenhydramine, in combination average for 6.1 years and can be and liberal use of moisturizers is with topical therapies, may be helpful active well into adulthood for some Downloaded from www.aappublications.org/news by guest on September 25, 2021 4 YANG et al 105,106​ patients,​ ‍ so physicians often fear long-term TCS effects such as skin atrophy, striae development, or systemic effects. This has resulted in an increased use of second-line treatments, such as the topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus,107 in the management of pediatric AD. However, TCIs are associated with increased rates of burning sensations and pruritus and have higher costs, with no additional benefit over TCSs with 101respect to long- term safety or efficacy. Thus, TCSs, when used appropriately, are a safe and effective first-line option82,108​ for the treatment of pediatric AD. ‍

As the underlying mechanisms of AD have become better understood, new topical therapies have been developed for AD, most notably crisaborole. Crisaborole is a topical FIGURE 1 Guide to site-based topical therapies for AD. (Adapted with permission from Bhutani T, Kamangar F, phosphodiesterase-4 (PDE-4) Cordoro KM. Management of pediatric psoriasis. Pediatr Ann. 2012;41[1]:e13.) inhibitor approved in 2016 for the ≥ treatment of mild-to-moderate109 AD for patients 2 years of age. PDE-4 inhibition inhibits intracellular expensive, nonsteroidal alternative to be treated with the least potent TCS cyclic adenosine monophosphate TCSs and TCIs for the management of that is effective, to minimize82 the risk degradation, ultimately decreasing mild-to-moderate adult and pediatric of TCS-related side effects. TCSs pro-inflammatory cytokine release AD (Fig 1). have greater penetration in sensitive via downregulation of the nuclear and occluded areas such as the face, factor kappa-light-chain-enhancer110 Several other topical PDE-4 neck, and skin folds, so lower potency of activated B cells pathway. Two inhibitors have completed phase II or nonsteroidal agents should be phase III trials revealed that nearly studies112,113​ and have revealed efficacy for used in these areas to decrease one-third of patients using twice- AD. ‍ An ointment preparation of ’ the risk of systemic118 corticosteroid daily crisaborole therapy for 28 tofacitinib, a Janus kinase inhibitor, absorption (Fig 1). Long-term days demonstrated Investigator s also significantly improved AD use of high-potency TCSs should be Static Global Assessment of clear severity114 and pruritus in a phase II avoided in pediatric patients, because or almost clear with at least a trial. Other topical agents being of the increased risk of 118atrophy and 2-grade improvement from baseline, investigated for AD include toll-like striae as patients grow. Because significantly moreP than patients receptor antagonists, serotonin AD often persists for years, long-term applying vehicle ointmentP (AD-301: inhibitors, aryl– hydrocarbon maintenance management should 32.8% vs 25.4%; = .038; AD-302:110 receptor agonists,115 117 and leukotriene alternate TCSs with nonsteroidal 31.4% vs 18.0%; < .001). Notably, antagonists. ‍ Clinical trials are agents such as TCIs or crisaborole crisaborole is well110 tolerated by patients currently ongoing to investigate the as appropriate to reduce the risk of in the short-ter111 m and the long-term efficacy and safety of crisaborole for treatment-related side effects. (48 weeks). Application-site burning patients 3 months to 2 years in age and/or stinging was experienced by Another important consideration 110 Topical(NCT03356977). Therapy Considerations 4.4% of patients in the first 4 weeks,111​ in selecting topical therapies is with decreased incidence over time. vehicle choice. Children notoriously ’ A far greater proportion of patients have poor adherence119 to topical experience stinging in the authors Safe usage of topical therapies medications,​ so physicians clinical experience, but crisaborole still requires a careful and deliberate must prescribe treatments their provides a fairly well-tolerated, albeit approach. Patients generally should patients will actually tolerate and Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 5 TABLE 1 Off-label Systemic Therapies for the Treatment of AD in Children Drug Dose Side Effects Monitoring Azathioprine 1–4 mg/kg per d Myelosuppression, nausea, vomiting, Baseline TPMT levels, CBC, CMP hepatotoxicity Cyclosporine 2.5–6 mg/kg Hypertension, renal insufficiency CBC, CMP, Mg2+, uric acid, lipids, blood pressure Dupilumab 2–4 mg/kga Conjunctivitis, injection-site reactions None Methotrexate 0.2–0.7 mg/kg per wk Nausea, ulcerative stomatitis, hepatotoxicity, CBC, CMP myelosuppression Mycophenolate mofetil 20–50 mg/kg daily Nausea, vomiting, abdominal cramping CBC, CMP CBC, complete blood count; CMP, complete metabolic panel; Mg2+, magnesium ion; TPMT, thiopurine methyltransferase. a The dose used in the phase 2a trial is not currently approved for pediatric use.

use. Ointments are considered the the outpatient setting, physicians than patients receiving the placebo most efficacious vehicle because may be hesitant in using them to (Study of Dupilumab Monotherapy of their occlusive nature and are treat patients with pediatric AD. Administered to Adult Patients “ ” With Moderate-to-Severe Atopic well tolerated120 by infants and young Despite these potential side effects, Dermatitis 1 [SOLO1]: 37.9% vs children. However, adolescents the cost of not treating should 125 often dislike the greasy feel and thus be a key consideration in selecting 10.3%; SOLO2: 36.1% vs 8.5%). avoid using ointments during the “ ” Dupilumab use was associated with 118 treatment for patients. AD is often – daytime. Physicians must aim to an increased risk of conjunctivitis thought of as just a skin disease,​ – optimize treatment adherence and but it is also associated with (4% 5% of patients) and injection- may compromise by recommending significant comorbidity and QoL site reactions125 (8% 14%) over the nighttime ointment use while deficits, as discussed previously. placebo. suggesting daytime application of This disease typically affects patients Topical therapies can be combined thinner118 vehicles, such as creams or during critical stages of development, with dupilumab for additional benefit lotions. However, choosing topical and abnormal development may therapies requires a personalized and to treat patients with recalcitrant ultimately cause lifelong impairment. disease. In the phase III trial LIBERTY approach, and vehicle selection should Pediatric providers must be be evaluated on a case-by-case basis. AD CHRONOS, 38.7% of patients Systemic Therapies mindful of these considerations receiving combination therapy with when deciding the optimal course both twice-weekly dupilumab and ≥ of therapy for their patients. TCS achieved an IGA of 0 or 1 at week Because of a historic lack of safe and Fortunately, more targeted biological 16 with a 2-grade improvement therapies are in development for efficacious options, the threshold from baseline, as compared with 126 for considering the initiation of AD that will create more safe and 12.4% of patients using only TCS. effective121 systemic therapies for this systemic therapies121 has traditionally This response with combination been high. UV-B phototherapy disease. therapy persisted through week 52, is a safe and effective treatment, One such biological therapy is with 36.0% of patients receiving without increased skin– cancer risk, dupilumab,IL-4R a humanα monoclonal combination therapy achieving this for patients with AD91,121​ uncontrolled123 immunoglobulin G4 antibody same end point, as compared with by topical agents. ‍ ‍ However, targeting that was approved just 12.5%126 of patients in the control phototherapy can be inconvenient, in 2017 for the treatment of 124 group. Additionally, combination requiring 2 to 3 treatments per week moderate-to-severe AD for adults. therapy with TCS and twice-weekly for several months. Patients deriving Dupilumab inhibitsIL-4Rα IL-4- and IL-13- dupilumab therapy improved minimal benefit from phototherapy mediated inflammatory responses, disease severity in patients not should consider systemic therapy. because the subunit is responding to cyclosporine, with ≥ Traditionally, azathioprine, shared by the receptor complexes 40.2% achieving an IGA of 0 or1 cyclosporine, methotrexate, and for both of these cytokines. Two with a 2-grade improvement at mycophenolate were the only phase III trials revealed that more week 16 as compared with 13.9% on É systemic therapies that were 121 than one-third of patients on TCS alone in the127 phase III LIBERTY efficacious for recalcitrant AD,​ but dupilumab monotherapy every 2 AD CAF trial. Patients receiving ’ these therapies are associated with weeks for 16 weeks demonstrated combination therapy demonstrated potentially serious side effects and Investigator s Global Assessment no increased risk of serious adverse require close monitoring (Table 1). (IGA) of clear or almost clear with events over TCS monotherapy but Because these medications are not at least a 2-grade improvement still yielded an increased risk of frequently used by pediatricians in from baseline, significantly more conjunctivitis and injection-site Downloaded from www.aappublications.org/news by guest on September 25, 2021 6 YANG et al REFERENCES 1. Shaw TE, Currie GP, Koudelka CW, reactions, consistent with the results It is now apparent that AD extends 126,127​ Simpson EL. 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Downloaded from www.aappublications.org/news by guest on September 25, 2021 Recent Developments in Atopic Dermatitis Eric J. Yang, Sahil Sekhon, Isabelle M. Sanchez, Kristen M. Beck and Tina Bhutani Pediatrics originally published online September 28, 2018;

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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