Amy S Paller

Northwestern University, Evanston, Illinois, United States

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Publications (274)1414.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric discoid lupus erythematosus (DLE) is rare. The risk of progression to systemic lupus erythematosus (SLE) is uncertain. We sought to determine the risk of progression of pediatric DLE to SLE and to characterize its phenotype. This was a retrospective review of 40 patients with DLE. Six (15%) of 40 patients presented with DLE as a manifestation of concurrent SLE. Of the remaining 34, 9 (26%) eventually met SLE criteria and 15 (44%) developed laboratory abnormalities without meeting SLE criteria. Only 10 (29%) maintained skin-limited disease. The average age at progression to SLE was 11 years, with greatest risk in the first year after DLE diagnosis. Most (89%) patients with SLE met diagnostic criteria with mucocutaneous disease (discoid lesions, malar rash, oral and nasal ulcers, photosensitivity), positive antibodies, and/or cytopenia without developing end-organ damage over 5 years of median follow-up. The study was retrospective. In pediatric patients, DLE carries a significant risk of progression to SLE but may predict a milder phenotype of systemic disease. All patients require careful monitoring for SLE, particularly within the first year of diagnosis. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    Journal of the American Academy of Dermatology 01/2015; · 5.00 Impact Factor
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    ABSTRACT: The National Eczema Association has received increasing numbers of patient inquiries regarding "steroid addiction syndrome," coinciding with the growing presence of social media dedicated to this topic. Although many of the side effects of topical corticosteroids (TCS) are addressed in guidelines, TCS addiction is not. We sought to assess the current evidence regarding addiction/withdrawal. We performed a systematic review of the current literature. Our initial search yielded 294 results with 34 studies meeting inclusion criteria. TCS withdrawal was reported mostly on the face and genital area (99.3%) of women (81.0%) primarily in the setting of long-term inappropriate use of potent TCS. Burning and stinging were the most frequently reported symptoms (65.5%) with erythema being the most common sign (92.3%). TCS withdrawal syndrome can be divided into papulopustular and erythematoedematous subtypes, with the latter presenting with more burning and edema. Low quality of evidence, variability in the extent of data, and the lack of studies with rigorous steroid addiction methodology are limitations. TCS withdrawal is likely a distinct clinical adverse effect of TCS misuse. Patients and providers should be aware of its clinical presentation and risk factors. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    Journal of the American Academy of Dermatology 01/2015; · 5.00 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) is a distressing dermatological disease which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 years ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 years old) and adults with mild-to-moderate AD. The age restriction was emphasised in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 years old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.This article is protected by copyright. All rights reserved.
    Pediatric Allergy and Immunology 01/2015; · 3.38 Impact Factor
  • JAMA The Journal of the American Medical Association 12/2014; 312(24):2676-7. · 30.39 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) is associated with multiple potential risk factors for obesity and high blood pressure (BP), including chronic inflammation, sleep disturbance, and mental health comorbidity. Previous studies found associations between general obesity and AD. However, it is unknown whether AD is associated with central obesity and/or high BP. To determine whether central obesity and high BP are increased in pediatric AD. This case-control study performed in multicenter pediatric dermatology practices in the United States recruited 132 children (age range, 4-17 years) with active moderate to severe AD and 143 healthy controls from April 1, 2009, through December 31, 2012. Diagnosis and severity of AD assessed by a pediatric dermatologist. Body mass index, waist circumference, waist to height ratio, systolic BP, and diastolic BP. Moderate to severe AD was associated with body mass index for age and sex of 97th percentile or greater (logistic regression; odds ratio [OR], 2.64; 95% CI, 1.15-6.06), International Obesity Task Force obesity cutoffs (OR, 2.38; 95% CI, 1.06-5.34), waist circumference in the 85th percentile or greater (OR, 3.92; 95% CI, 1.50-10.26), and waist to height ratio of 0.5 or greater (OR, 2.22; 95% CI, 1.10-4.50). Atopic dermatitis was associated with higher BP for age, sex, and height percentiles (systolic BP: OR, 2.94; 95% CI, 1.04-8.36; diastolic BP: OR, 3.68; 95% CI, 1.19-11.37), particularly a systolic BP in the 90th percentile or higher (OR, 2.06; 95% CI, 1.09-3.90), in multivariate models that controlled for demographics, body mass index and waist circumference percentiles, and history of using prednisone or cyclosporine. Atopic dermatitis was associated with higher systolic BP in Hispanics/Latinos (general linear model; β, .23; 95% CI, .04-.43) and Asians (β, .16; 95% CI, .03-.30). Severe to very severe AD was associated with systolic BP in the 90th percentile or higher (adjusted OR, 3.14; 95% CI, 1.13-8.70). Atopic dermatitis was associated with a family history of hypertension (adjusted OR, 1.88; 95% CI, 1.14-3.10) and type 2 diabetes mellitus (adjusted OR, 1.64; 95% CI, 1.02-2.68) but not obesity or hyperlipidemia. Moderate to severe pediatric AD may be associated with central obesity and increased systolic BP.
    JAMA Dermatology 12/2014; · 4.30 Impact Factor
  • Jonathan I Silverberg, Amy S Paller
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    ABSTRACT: Atopic dermatitis (eczema) is a chronic inflammatory disorder that is associated with other chronic diseases (eg, asthma), major quality-of-life impairment, sleep disturbance, and the use of potent topical and sometimes systemic corticosteroids, all of which might affect growth in childhood and adolescence. However, previous smaller-scale studies found conflicting results. To determine whether eczema is associated with short stature. We used data from 9 US population-based studies, including the National Survey of Children's Health (2003-2004 and 2007-2008), National Health Interview Survey (children's health, 2008-2012; adult health, 2010 and 2012), and National Health and Nutrition Examination Survey (2003-2004 and 2005-2006). Participants included 264 326 children and adolescents and 83 511 adults. History of eczema. Percentiles of height for age and sex in children and height in adults. We constructed multivariate survey linear or logistic regression models for individual studies with Box-Cox transformed or dichotomized height, respectively. Pooled analyses used generalized linear mixed models. Overall, eczema was not associated with significant differences of height (continuous or <5th or <25th percentiles) in any of the studies or in the pooled analyses. We found a significant interaction by age, such that eczema was associated with shorter stature at 12 to 13 but not 14 to 15 or 16 to 17 years of age or in adulthood. Moderate to severe eczema was associated with shorter stature (continuous and <25th percentile). In particular, short stature (<5th percentile) was associated with eczema only when accompanied by an indicator of insufficient sleep (ie, 0 to 3 nights of sufficient sleep per week) (1.3% of children with eczema) but was not associated with asthma, hay fever, or use of prescription medication. The interaction between eczema and insufficient sleep remained significant at 10 to 11 years of age (P = .003) but not at other ages (P > .08 for all). Eczema is not associated with short stature overall. However, a small subset of children and adolescents with severe eczema accompanied by prominent insufficient sleep may have potentially reversible vertical growth impairment.
    JAMA Dermatology 12/2014; · 4.30 Impact Factor
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    ABSTRACT: Pruritus is a common complication in patients with epidermolysis bullosa (EB). There is limited published data about the treatments that individuals with EB use for pruritus. The objective of the current study was to determine quantitatively which treatments individuals with EB have used for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. A questionnaire was developed to evaluate the treatments and therapies used for pruritus in patients of all ages and for all types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (−2 = relieves itch a lot, −1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot) was used to evaluate perceived effectiveness. Patients from seven North American EB centers were invited to participate. Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean = −1.1), topical prescription corticosteroids (mean = −1.0), oils (mean = −0.9), oral hydroxyzine (mean = −0.9), topical diphenhydramine (mean = −0.9), and vaporizing rub (menthol, camphor, eucalyptus) (mean = −0.9). Systemic opioids (mean = 0.3), adherent bandages (mean = 0.3), and bleach baths (mean = 0.2) slightly increased pruritus. Randomized controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in individuals with EB.
    Pediatric Dermatology 12/2014; · 1.52 Impact Factor
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    ABSTRACT: Linear morphea en coup de sabre (ECDS) is a form of localized scleroderma that predominantly affects the pediatric population, with a median age of 10 years at presentation. The existence of neurologic findings in association with ECDS has been well described in the literature. Here we describe 4 patients with ECDS who presented with headaches, which were typical migraines in 3 of the patients. The headaches preceded the onset of cutaneous findings by at least 6 months. Our patients' cases emphasize both the importance of recognizing headaches as a harbinger of ECDS and the necessity of performing thorough cutaneous examination in patients with unexplained headaches or other neurologic disease. Copyright © 2014 by the American Academy of Pediatrics.
    Pediatrics 11/2014; 134(6). · 5.30 Impact Factor
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    ABSTRACT: Genetic investigation of inherited skin disorders has informed understanding of skin self-renewal, differentiation, and barrier function. Erythrokeratodermia variabilis et progressiva (EKVP) is a rare, inherited skin disease characterized by transient figurate patches of erythema, localized or generalized scaling, and frequent palmoplantar keratoderma. By employing exome sequencing, we show that de novo missense mutations in GJA1 (gap junction protein alpha 1) cause EKVP. The severe, progressive skin disease in EKVP subjects with GJA1 mutations is distinct from limited cutaneous findings rarely found in the systemic disorder oculodentodigital dysplasia, also caused by dominant GJA1 mutations. GJA1 encodes connexin 43 (Cx43), the most widely expressed gap junction protein. We show that the GJA1 mutations in EKVP subjects lead to disruption of Cx43 membrane localization, and aggregation within the Golgi. These findings reveal a critical role for Cx43 in epidermal homeostasis, and provide evidence of organ-specific pathobiology resulting from different mutations within GJA1.Journal of Investigative Dermatology accepted article preview online, 14 November 2014. doi:10.1038/jid.2014.485.
    Journal of Investigative Dermatology 11/2014; · 6.37 Impact Factor
  • Amy S Paller, Eugene A Bauer
    Journal of Investigative Dermatology 11/2014; 134(11):2669-70. · 6.37 Impact Factor
  • Journal of Investigative Dermatology 11/2014; 134(11):2671-4. · 6.37 Impact Factor
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    ABSTRACT: Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence.
    Journal of the American Academy of Dermatology 09/2014; · 5.00 Impact Factor
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    ABSTRACT: Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB and factors that contribute to pruritus are unknown. The objective of the current study was to quantitatively identify and to characterize pruritus that EB patients experience using a comprehensive online questionnaire. A questionnaire was developed to evaluate pruritus in all ages and all types of EB. Questions that characterize pruritus were included and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. One hundred forty-six of 216 questionnaires were completed (response rate 68%; 73 male, 73 female; median age 20.0 years). Using a 5-point Likert scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), itchiness was the most bothersome EB complication (mean 3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean 3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Pruritus is common in individuals with EB and can be bothersome. Future studies will need to investigate the most effective treatments given to individuals with EB for pruritus.
    Pediatric Dermatology 09/2014; · 1.52 Impact Factor
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    ABSTRACT: Sleep disturbances are associated with poor health outcomes in adults. However, little is known about the sleep disturbances that occur in adult eczema. We studied the association between adult eczema and sleep disturbance and their impact on overall health and healthcare utilization. We used the 2012 National Health Interview Survey, a cross-sectional, questionnaire of 34,613 adults. Eczema was associated with higher odds of fatigue (odds ratio [95% CI]: 2.97 [2.65-3.34]), regular daytime sleepiness (2.66 [2.34-3.01]) and regular insomnia (2.36 [2.11-2.64]), even after controlling for sleep duration, history of allergic disease, socio-demographics and body mass index. There were significant interactions between eczema and fatigue, sleepiness and insomnia as predictors of poorer overall health status, number of sick days and doctor visits, such that eczema and each of the sleep symptoms was associated with higher odds of poorer outcomes than either eczema or sleep symptoms alone. Latent class analysis was used and identified 5 classes of fatigue, sleep disturbances and allergic disorders. Two classes had high probabilities of eczema; one with high probabilities of asthma, hay fever, food allergy and multiple sleep symptoms; the other with intermediate probability of insomnia alone. Future studies are warranted to better characterize sleep loss in eczema and develop strategies for treatment and prevention.Journal of Investigative Dermatology accepted article preview online, 31 July 2014; doi:10.1038/jid.2014.325.
    Journal of Investigative Dermatology 07/2014; · 6.37 Impact Factor
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    ABSTRACT: Background The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. Methods We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-β, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. Results We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. Conclusions STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; number, NCT00059748 .).
    New England Journal of Medicine 07/2014; · 54.42 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) and ichthyosis vulgaris (IV) are two common disorders of epidermal homeostasis resulting in dry skin. The profilaggrin gene, located on chromosome 1q22, encodes a keratin filament aggregating protein (filaggrin) that is essential to forming the epidermal barrier and maintaining hydration. Null mutations in filaggrin have been found to underlie IV and are common in patients with AD, but the minority of African Americans with AD or IV show these mutations in filaggrin. We have selectively studied African Americans with both AD and IV to maximize the possibility of finding filaggrin null mutations in this population. DNA was collected using buccal swabs from 18 African American children with both AD and IV and 17 African American controls without either of these diseases. Purified genomic DNA was amplified using polymerase chain reaction from three regions of the filaggrin gene, exon 3, including R501X, 2282del4, E2554X, R2447X, 1249insG, R826X, 2767insT, and E2422X. Of the African American children with both AD and IV, 22.2% were heterozygous for filaggrin null mutations. Out of the control group, one carried a null mutation and was later discovered to have a history of asthma. Null mutations found in this population included R501X (n = 1), 2282del4 (n = 2), and R826X (n = 2, including the control patient). Our data demonstrate a prevalence of filaggrin mutations in the African American population that exceeds previously published data, although the overall prevalence is still lower than in other populations. It is likely that factors other than known FLG mutations are involved in African American patients.
    Pediatric Dermatology 06/2014; · 1.52 Impact Factor
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    ABSTRACT: Eruptive xanthomas are cutaneous manifestations of hyperlipidemias in which lipids accumulate in large foam cells within the skin. They classically present as crops of 1- to 4-mm yellow-orange papules and are often associated with extreme hypertriglyceridemia. We describe a 12-year-old boy with autism who was thought to have widespread molluscum contagiosum for a year before dermatologic consultation was obtained. Recognition of eruptive xanthomas led to the discovery of massive hypertriglyceridemia (serum triglycerides 6853 mg/dL) and diabetes mellitus. Through medical intervention, including insulin and fenofibrate therapy, and dietary modification with weight loss, the xanthomas cleared during the subsequent months, and his serum triglyceride levels nearly normalized.
    Pediatrics 06/2014; · 5.30 Impact Factor
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    ABSTRACT: Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
    Journal of the American Academy of Dermatology 05/2014; · 5.00 Impact Factor
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    ABSTRACT: Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.
    Journal of the American Academy of Dermatology 05/2014; · 5.00 Impact Factor
  • JAMA dermatology. 04/2014;

Publication Stats

6k Citations
1,414.58 Total Impact Points


  • 1990–2015
    • Northwestern University
      • • Division of Dermatology
      • • Division of Pediatric Dermatology
      • • Department of Dermatology
      • • Feinberg School of Medicine
      • • Department of Pediatrics
      Evanston, Illinois, United States
    • Rush University Medical Center
      • Department of Dermatology
      Chicago, IL, United States
  • 1989–2015
    • University of Illinois at Chicago
      • • Department of Pediatrics (Peoria)
      • • Department of Dermatology (Chicago)
      Chicago, Illinois, United States
    • Pennsylvania State University
      University Park, Maryland, United States
  • 2012–2013
    • Rady Children's Hospital
      San Diego, California, United States
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
    • University of Michigan
      • Department of Dermatology
      Ann Arbor, MI, United States
    • University of Southern California
      • Department of Dermatology
      Los Angeles, CA, United States
    • Oregon Health and Science University
      • Department of Dermatology
      Portland, Oregon, United States
  • 1996–2013
    • Case Western Reserve University School of Medicine
      • Department of Pediatrics
      Cleveland, Ohio, United States
  • 2011
    • St George Hospital
      Sydney, New South Wales, Australia
  • 2006–2011
    • Boston Children's Hospital
      • Department of Pediatrics
      Boston, Massachusetts, United States
  • 1990–2011
    • Northwestern Memorial Hospital
      • Northwestern Medicine
      Chicago, Illinois, United States
  • 2010
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • Hospital del Niño Jesús
      Madrid, Madrid, Spain
  • 2009
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2008
    • University of Colorado Hospital
      • Department of Pediatrics
      Denver, Colorado, United States
  • 2007
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
    • University of Texas Medical School
      Houston, Texas, United States
  • 2005
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
  • 1993–2005
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 2004
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
  • 2002–2004
    • University of Alabama at Birmingham
      • Department of Dermatology
      Birmingham, AL, United States
    • University of Dundee
      Dundee, Scotland, United Kingdom
    • Our Ladys Childrens Hospital, Crumlin
      Dublin, Leinster, Ireland
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
  • 2003
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2001
    • University of Washington Seattle
      Seattle, Washington, United States
  • 1999
    • Medical College of Wisconsin
      • Department of Dermatology
      Milwaukee, WI, United States
    • Columbia University
      • Department of Dermatology
      New York City, NY, United States
  • 1991–1992
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States