Amy S Paller

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

Are you Amy S Paller?

Claim your profile

Publications (330)1659.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: There are no systemic therapies approved in the United States to treat pediatric psoriasis. Objective: We sought to evaluate long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. Methods: This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. Results: Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (similar to 60%-70%) and 90% improvement in Psoriasis Area and Severity Index score (similar to 30%-40%) and static physician global assessment status clear/almost clear (similar to 40%-50%) were maintained through week 264. Limitations: The number of patients remaining on study at week 264 was small. Conclusion: Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.
    No preview · Article · Feb 2016 · Journal of the American Academy of Dermatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objectives: Children with atopic dermatitis (AD) have a higher risk for development of food allergies. The objective of this study was to examine incidence of food allergy development in infants with AD and the predictive value of food-antigen-specific immunoglobulin E measurements. Methods: This trial examined the long-term safety and efficacy of pimecrolimus cream 1% in >1000 infants (3-18 months) with mild-to-severe AD without a history of food allergy. Food allergy development was followed throughout a 36-month randomized double-blind phase followed by an open-label (OL) phase up to 33 months. Additionally, sIgE for cow's milk, egg white, peanut, wheat, seafood mix, and soybean was measured by ImmunoCAP at baseline, end of the double-blind phase, and end of OL phase. Results: By the end of the OL phase, 15.9% of infants with AD developed at least 1 food allergy; allergy to peanut was most common (6.6%), followed by cow's milk (4.3%) and egg white (3.9%). Seafood, soybean, and wheat allergies were rare. Levels of sIgE for milk, egg, and peanut increased with severity of AD, as determined by Investigator's Global Assessment score. We assigned sIgE decision points for the 6 foods and tested their ability to predict definite food allergy in this population. Positive predictive values for published and newly developed sIgE decision points were low (<0.6 for all values tested). Conclusions: In a large cohort of infants at risk for development of food allergy, sIgE levels were not clinically useful for predicting food allergy development.
    No preview · Article · Dec 2015 · Pediatrics

  • No preview · Article · Dec 2015 · Journal of dermatological science
  • [Show abstract] [Hide abstract]
    ABSTRACT: Disclosure of potential conflict of interest: P. C. Zee owns stock in Teva; has consultant arrangements with Merck, Jazz, Vanda, Philips Respironics, and Pernix; and has received grants from Jazz. F. W. Turek has consultant arrangements with PatientsLikeMe and has received grants from the Department of Defense, the Office of Naval Research, the National Institutes of Health, NASA, Merck, and Vanda Pharmaceuticals. S. H. Sheldon has consultant arrangements with Dymedix and has received payment for lectures from Cadwell Diagnostics. The rest of the authors declare that they have no relevant conflicts of interest.
    No preview · Article · Nov 2015 · Journal of Allergy and Clinical Immunology

  • No preview · Article · Sep 2015 · Pediatric Rheumatology

  • No preview · Article · Sep 2015 · Journal of the European Academy of Dermatology and Venereology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: A subset of atopic dermatitis is associated with increased susceptibility to eczema herpeticum (ADEH+). We previously reported that common single nucleotide polymorphisms (SNPs) in the IFN-γ (IFNG) and IFN-γ receptor 1 (IFNGR1) genes were associated with the ADEH+ phenotype. Objective: We sought to interrogate the role of rare variants in interferon pathway genes for the risk of ADEH+. Methods: We performed targeted sequencing of interferon pathway genes (IFNG, IFNGR1, IFNAR1, and IL12RB1) in 228 European American patients with AD selected according to their eczema herpeticum status, and severity was measured by using the Eczema Area and Severity Index. Replication genotyping was performed in independent samples of 219 European American and 333 African American subjects. Functional investigation of loss-of-function variants was conducted by using site-directed mutagenesis. Results: We identified 494 single nucleotide variants encompassing 105 kb of sequence, including 145 common, 349 (70.6%) rare (minor allele frequency <5%), and 86 (17.4%) novel variants, of which 2.8% were coding synonymous, 93.3% were noncoding (64.6% intronic), and 3.8% were missense. We identified 6 rare IFNGR1 missense variants, including 3 damaging variants (Val14Met [V14M], Val61Ile, and Tyr397Cys [Y397C]) conferring a higher risk for ADEH+ (P = .031). Variants V14M and Y397C were confirmed to be deleterious, leading to partial IFNGR1 deficiency. Seven common IFNGR1 SNPs, along with common protective haplotypes (2-7 SNPs), conferred a reduced risk of ADEH+ (P = .015-.002 and P = .0015-.0004, respectively), and both SNP and haplotype associations were replicated in an independent African American sample (P = .004-.0001 and P = .001-.0001, respectively). Conclusion: Our results provide evidence that both genetic variants in the gene encoding IFNGR1 are implicated in susceptibility to the ADEH+ phenotype.
    No preview · Article · Sep 2015 · The Journal of allergy and clinical immunology

  • No preview · Article · Sep 2015 · Pediatric Rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Given the recent National Institutes of Health proposal for balanced use of male and female cells and animals in preclinical studies, we explored whether sex bias exists in skin research. We surveyed 802 dermatological research articles from 2012 to 2013. No information about the sex of studied cells or animals was provided in 60% of papers. Among keratinocytes of known sex, 70% were male. Few studies compared male versus female cells or animals. Disclosure of sex and comparative studies contribute to our understanding of the biologic basis of sex differences. Addressing sex-specific differences in preclinical research informs subsequent clinical trial design and promotes individualized therapy.Journal of Investigative Dermatology advance online publication, 20 August 2015; doi:10.1038/jid.2015.298.
    No preview · Article · Aug 2015 · Journal of Investigative Dermatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Safe and effective therapies are needed for pediatric patients with psoriasis. The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had moderate-to-severe psoriasis. Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg [≤60 kg], 45 mg [>60-≤100 kg], and 90 mg [>100 kg]) or half-standard dosing (HSD; 0.375 mg/kg [≤60 kg], 22.5 mg [>60-≤100 kg], and 45 mg [>100 kg]) at weeks 0 and 4 and every 12 weeks or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12. Clinical assessments included the proportion of patients achieving a Physician's Global Assessment of cleared/minimal (PGA 0/1), at least 75% improvement in Psoriasis Area and Severity Index (PASI 75), and at least 90% in PASI (PASI 90). Adverse events (AEs) were monitored through week 60. At week 12, 67.6% and 69.4% of patients receiving ustekinumab HSD and SD, respectively, achieved PGA 0/1 versus 5.4% for placebo (P < .001). Significantly greater proportions receiving ustekinumab achieved PASI 75 (HSD, 78.4%; SD, 80.6%; placebo, 10.8%) or PASI 90 (HSD, 54.1%; SD, 61.1%; placebo, 5.4%) at week 12 (P < .001). Through week 12, 56.8% of placebo patients, 51.4% of HSD patients, and 44.4% of SD patients reported at least one AE; through week 60, 81.8% reported AEs. The study was small relative to adult trials. In this patient population (12-17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Aug 2015 · Journal of the American Academy of Dermatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atopic dermatitis affects a substantial number of children, many of whom seek initial treatment from their pediatrician or other primary care provider. Approximately two-thirds of these patients have mild disease and can be adequately managed at the primary care level. However, recent treatment guidelines are written primarily for use by specialists and lack certain elements that would make them more useful to primary care providers. This article evaluates these recent treatment guidelines in terms of evaluation criteria, treatment recommendations, usability, accessibility, and applicability to nonspecialists and integrates them with clinical evidence to present a streamlined severity-based treatment model for the management of a majority of atopic dermatitis cases. Because each patient's situation is unique, individualization of treatment plans is critical as is efficient communication and implementation of the plan with patients and caregivers. Specifically, practical suggestions for individualizing, optimizing, implementing, and communicating treatment plans such as choosing a moisturizer formulation, avoiding common triggers, educating patients/caregivers, providing written treatment plans, and scheduling physician follow-up are provided along with a discussion of available resources for patients/caregivers and providers. Copyright © 2015 by the American Academy of Pediatrics.
    Full-text · Article · Aug 2015 · PEDIATRICS

  • No preview · Article · Aug 2015 · Women s Health
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01). These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jul 2015 · Journal of Allergy and Clinical Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.
    Full-text · Article · Jul 2015 · The American Journal of dermatopathology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Psoriasis is a common chronic immune-mediated inflammatory skin disorder and begins in childhood in almost one-third of the cases. Although children present with the same clinical subtypes of psoriasis seen in adults, lesions may differ in distribution and morphology, and their clinical symptoms at presentation may vary from those reported by adult patients. Nevertheless, diagnosis of psoriasis is primarily based on clinical features. Pediatric psoriasis can have a profound long-term impact on the psychological health of affected children. Additionally, pediatric psoriasis has been associated with certain comorbidities, such as obesity, hypertension, hyperlipidemia, diabetes mellitus and rheumatoid arthritis, making early diagnosis and management essential. As guidelines are lacking and most (systemic) treatments are not approved for use in children, treatment of pediatric psoriasis remains a challenge. A prospective, multicenter, international registry is needed to evaluate these treatments in a standardized manner and ultimately to develop international guidelines on pediatric psoriasis. This article reviews current concepts in pediatric psoriasis including epidemiology, clinical features, diagnosis, the role of topical and systemic agents and the association with other morbidities in childhood.
    Preview · Article · Jun 2015 · Paediatric Drugs
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spherical or nucleic acid (SNA) gold nanoparticle conjugates (13-nm-diameter gold cores functionalized with densely packed and highly oriented nucleic acids) dispersed in Aquaphor have been shown to penetrate the epidermal barrier of both intact mouse and human skin, enter keratinocytes, and efficiently down-regulate gene targets. ganglioside-monosialic acid 3 synthase (GM3S) is a known target that is overexpressed in diabetic mice and responsible for causing insulin resistance and impeding wound healing. GM3S SNAs increase keratinocyte migration and proliferation as well as insulin and insulin-like growth factor-1 (IGF1) receptor activation under both normo- and hyperglycemic conditions. The topical application of GM3S SNAs (50 nM) to splinted 6-mm-diameter full-thickness wounds in diet-induced obese diabetic mice decreases local GM3S expression by >80% at the wound edge through an siRNA pathway and fully heals wounds clinically and histologically within 12 d, whereas control-treated wounds are only 50% closed. Granulation tissue area, vascularity, and IGF1 and EGF receptor phosphorylation are increased in GM3S SNA-treated wounds. These data capitalize on the unique ability of SNAs to naturally penetrate the skin and enter keratinocytes without the need for transfection agents. Moreover, the data further validate GM3 as a mediator of the delayed wound healing in type 2 diabetes and support regional GM3 depletion as a promising therapeutic direction.
    No preview · Article · May 2015 · Proceedings of the National Academy of Sciences

  • No preview · Conference Paper · May 2015
  • Mark A. Seeger · Amy S. Paller
    [Show abstract] [Hide abstract]
    ABSTRACT: Significance: The re-epithelialization of wounded skin requires the rapid and coordinated migration of keratinocytes (KC) into the wound bed. Almost immediately after wounding, cells present at or attracted to the wound site begin to secrete a complex milieu of growth factors. These growth factors exert mitogenic and motogenic effects on KCs, inducing the rapid proliferation and migration of KCs at the wound edge. Recent Advances: New roles for growth factors in KC biology are currently being discovered and investigated. This review will highlight the growth factors, particularly transforming growth factor-α (TGF-α), heparin-binding epidermal growth factor (HB-EGF), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 7 (FGF-7), FGF-10, and hepatocyte growth factor (HGF), which have conclusively been shown to be the most motogenic for KCs. Critical Issues: The cellular and molecular heterogeneity of wounded tissue makes establishing direct relationships between specific growth factors and KC migration difficult in situ. The absence of this complexity in simplified in vitro experimental models of migration makes the clinical relevance of the results obtained from these in vitro studies ambiguous. Future Directions: Deciphering the relationship between growth factors and KC migration is critical for understanding the process of wound healing in normal and disease states. Insights into the basic science of the effects of growth factors on KC migration will hopefully lead to the development of new therapies to treat acute and chronic wounds.
    No preview · Article · Apr 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs. A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear). Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity. Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children. Copyright © 2015 by the American Academy of Pediatrics.
    Full-text · Article · Mar 2015 · PEDIATRICS
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Widespread reversion of genetic disease is rare; however, such events are particularly evident in some skin disorders in which normal clones develop on a background of affected skin. We previously demonstrated that mutations in keratin 10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that is characterized by progressive development of hundreds of normal skin spots via revertant mosaicism. Here, we report on a clinical and histological IWC subtype in which affected subjects have red, scaly skin at birth, experience worsening palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots, beginning at around 20 years of age, that increase in size and number over time. We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC-causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate filament network and mislocalized to the nucleus. As with KRT10 mutations causing IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because reversion is not observed with other disease-causing keratin mutations, the results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in the high frequency of revertant mosaicism in IWC.
    Preview · Article · Mar 2015 · Journal of Clinical Investigation

Publication Stats

9k Citations
1,659.63 Total Impact Points

Institutions

  • 2012-2015
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
    • Oregon Health and Science University
      Portland, Oregon, United States
  • 1990-2015
    • Northwestern University
      • • Department of Pediatrics
      • • Division of Dermatology
      • • Department of Cell and Molecular Biology
      • • Division of Hospital Medicine
      • • Feinberg School of Medicine
      • • Division of Pediatric Dermatology
      Evanston, Illinois, United States
    • Medical University of South Carolina
      • Department of Dermatology
      Charleston, South Carolina, United States
  • 1989-2015
    • University of Illinois at Chicago
      • • Department of Dermatology (Chicago)
      • • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
    • Pennsylvania State University
      • Fusarium Research Center
      University Park, Maryland, United States
  • 1985-2011
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 2009
    • Rush University Medical Center
      • Department of Pediatrics
      Chicago, Illinois, United States
  • 2007
    • University of Texas Medical School
      Houston, Texas, United States
  • 2005-2006
    • University of California, San Diego
      San Diego, California, United States
  • 1992-2006
    • Northwestern Memorial Hospital
      • Northwestern Medicine
      Chicago, Illinois, United States
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2003
    • Columbia University
      • Department of Dermatology
      New York, New York, United States
  • 2002
    • Our Ladys Childrens Hospital, Crumlin
      Dublin, Leinster, Ireland
    • University of Alabama at Birmingham
      • Department of Dermatology
      Birmingham, AL, United States
  • 1996-2002
    • Case Western Reserve University School of Medicine
      • Department of Pediatrics
      Cleveland, Ohio, United States
  • 2001
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 1999
    • Medical College of Wisconsin
      • Department of Dermatology
      Milwaukee, WI, United States
  • 1997
    • Alpert Medical School - Brown University
      Providence, Rhode Island, United States
  • 1995
    • New York Medical College
      New York, New York, United States
  • 1987-1992
    • University of North Carolina at Chapel Hill
      • • Department of Epidemiology
      • • Department of Dermatology
      North Carolina, United States
  • 1986
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States