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Amy S Paller

Publications and source records attributed to Amy S Paller.

At least 19 recordsLinked to original sources
PubMed2006

Pityriasis lichenoides in childhood: a retrospective review of 124 patients.

BACKGROUND: Pityriasis lichenoides (PL) occurs in all age groups, although predominantly in younger individuals. OBJECTIVE: We sought to study the clinical features of PL in children followed up at our institution. METHODS: The records of 124 children who were given the diagnosis of PL at our institution between 1993 and 2003 were retrospectively reviewed. RESULTS: PL chronica (PLC) was recorded in 37% of the cases, PL et varioliformis acuta (PLEVA) in 57.3%, and clinical features of both disorders were seen simultaneously in the remaining. The median age of onset was 60 months (range: 6-180 months), although the median age of onset of PLEVA (median: 60 months) was significantly younger than that of PLC (median: 72 months) (P = .03). The age distribution showed peaks at 2 to 3 years (24.8%) and 5 to 7 years (32%). A history of infection or drug intake preceded the skin manifestations in 30% and 11.2% of patients with PLC and PLEVA, respectively. The disease began most commonly during winter (35%) or fall (30%). The median duration was 20 months (range: 3-132 months) in patients with PLC and 18 months (range: 4-108 months) in patients with PLEVA. Involvement was diffuse in 74.2% of the patients, peripheral in 20.2%, and central in the remainder. The disease was recurrent in 77% of the patients (n = 80). Of the patients, 59% had pruritus, whereas 32% reported no symptoms; the remainder had fever, arthralgia, or both. Erythromycin estolate or ethylsuccinate was administered to 79.7% of the affected children; 66.6% of these showed at least a partial response. LIMITATIONS: The analyzed data were collected retrospectively and biopsies were not performed in all patients. CONCLUSIONS: PL is not an uncommon disease in childhood, with age peaks in the preschool and early school-age years. It is usually recurrent, and shows a seasonal variation with onset most often in the fall or winter. In childhood PL, erythromycin is an effective initial treatment choice.

Adolescent↗
PubMed2006

Ganglioside GM3 promotes carcinoma cell proliferation via urokinase plasminogen activator-induced extracellular signal-regulated kinase-independent p70S6 kinase signaling.

Overexpression of NeuAcalpha2-3Galbeta1-4Glcbeta1-Cer (GM3), a major ganglioside of cutaneous tumor cell membranes, inhibits ligand-dependent and ligand-independent activation of the epidermal growth factor (EGF) receptor in normal and neoplastic epithelial cells. This leads to the suppression of Ras/extracellular signal-regulated kinase (ERK) activation and, in the presence of EGF or fibronectin, inhibits cell proliferation. However, some tumor cells show increased levels of GM3, and vaccines that target GM3 can inhibit the growth of neoplastic cells in vivo, especially melanomas. We report that in the presence of urokinase plasminogen activator (uPA), overexpression of GM3 paradoxically increases the proliferation of carcinoma cells by augmenting ERK-independent p70S6 kinase activation. Functional blockade of uPA receptor (uPAR) or inhibition of p70S6 kinase, but not inhibition of Ras/ERK signaling, suppresses this GM3-induced stimulation of cell proliferation. The ERK-independent activation of p70S6 kinase involves phosphorylation at threonine-389, threonine-421/serine-424, and serine-411 sites with intermediate phosphatidylinositol 3 kinase and protein kinase C-zeta activation. These studies implicate gangliosides as enhancers of uPAR-related signaling and suggest that the response to GM3 depends on the local concentration of uPA. Therapeutic modalities that target or supplement gangliosides may require concomitant treatment that suppresses EGFR or uPAR signaling, respectively, to control neoplastic cell proliferation.

Carcinoma, Squamous Cell↗
PubMed2006

The relationship between family medical history and childhood vitiligo.

BACKGROUND: The association between a family history of vitiligo and other autoimmune/endocrine diseases and increased incidence of childhood vitiligo has been described; however, the influence of family history on the clinical characteristics of childhood vitiligo has rarely been investigated. OBJECTIVE: We sought to examine the relationship between family history and the incidence, extent, and course of childhood vitiligo. METHODS: A retrospective chart review and telephone interviews were performed for 137 pediatric patients with vitiligo and 140 control patients (patients with acne, warts, or molluscum contagiosum matched in age, sex, and ethnicity to the study group). Information about the age, sex, ethnicity, age of onset and diagnosis, site of onset, distribution, treatment, course of disease, and family history was obtained. RESULTS: Patients with vitiligo and an extended family history of vitiligo were more likely to have an earlier age of onset of disease than those with a negative family history (odds ratio = 3.70, P = .024). There was no association between family history and site of onset, distribution, or course of disease. LIMITATIONS: A relatively small sample size, recall bias, disease misclassification, and confounding factors are potential limitations of this study. CONCLUSION: Earlier onset of pediatric vitiligo is linked to a family history of vitiligo. Awareness of this association can allow for closer monitoring, earlier detection, and earlier initiation of treatment.

Adolescent↗
PubMed2006

Incontinentia pigmenti in male patients.

BACKGROUND: Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that is typified by distinctive cutaneous findings and often by abnormalities of teeth, hair, nails, eyes, musculoskeletal system, and central nervous system. The gene that is mutated in patients with IP has been mapped to Xq28 and encodes the NF-kappaB essential modulator, NEMO. Female patients with IP show functional mosaicism and cutaneous manifestations follow Blaschko's lines of ectodermal embryologic development. The condition is generally considered to be lethal in utero in male fetuses, suggesting that having some normal gene expression is critical for survival. OBSERVATIONS: We observed 9 boys with IP. All had normal karotypes and no apparent family history of IP. In 8 of these 9 patients, lesions were localized to one extremity at presentation. The diagnosis was confirmed by histopathologic examination that showed eosinophils within intraepidermal, multiloculated vesicles. One of the boys later developed dental and neurologic abnormalities. LIMITATIONS: The case series was small and the workup for these patients from different sites was not uniform. CONCLUSIONS: Male individuals may show cutaneous and noncutaneous features of IP in a limited distribution that allows survival. Postzygotic mutation/somatic mosaicism is the likely mechanism. Given the potential sequelae associated with this condition, continuing follow-up of these patients is recommended.

Diagnosis, Differential↗
PubMed2006

Patient perspectives on the management of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is increasingly common, with a point prevalence of more than 30% in some countries, and is characterized by visible skin lesions and intense itching. OBJECTIVE: The International Study of Life with Atopic Eczema (ISOLATE) is the first large-scale study to assess the effect of AD on the lives of patients and society, how patients and caregivers manage the condition, and how well patients and caregivers currently believe that AD is controlled. METHODS: Two thousand two patients (>13 years) and caregivers of children (2-13 years) with moderate-to-severe AD randomly selected from 8 countries underwent standardized telephone interviews using questions developed in collaboration with national eczema patient groups and physicians. RESULTS: During each year, patients spend, on average, 1 of 3 days in flare. The majority of patients receive prescription topical corticosteroids to treat flares; however, 49% of respondents are concerned about using these agents. On average, patients and caregivers delay initiating treatment for 7 days after onset of a flare. Only 24% of patients and caregivers feel confident they can manage AD flares adequately. Seventy-five percent of caregivers and patients feel that being able to effectively control AD would be the single most important improvement to their or their child's quality of life. The avoidable secondary economic cost of AD is estimated at 2 billion Euro per year across the European Union. CONCLUSION: ISOLATE highlights the need to improve patients' control of AD to reduce the significant effect this condition has on the patient and society. CLINICAL IMPLICATIONS: ISOLATE shows that patients with AD are untreated for half the time they are in flare, and thus there is an urgent need for physicians to ensure that the patients are educated and confident in using medication as prescribed to gain disease control.

Adolescent↗
PubMed2006

Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1.

We report an unusual case of an inherited disorder of the desmosomal protein plakophilin 1, resulting in ectodermal dysplasia-skin fragility syndrome. The affected 6-year-old boy had red skin at birth and subsequently developed skin fragility, progressive plantar keratoderma, nail dystrophy, and alopecia. Skin biopsy revealed widening of intercellular spaces in the epidermis and a reduced number of small, poorly formed desmosomes. Mutation analysis of the plakophilin 1 gene PKP1 revealed a homozygous deletion of C at nucleotide 888 within exon 5. This mutation differs from the PKP1 gene pathology reported in 8 previously published individuals with this rare genodermatosis. However, all cases show similar clinical features, highlighting the importance of functional plakophilin 1 in maintaining desmosomal adhesion in skin, as well as the role of this protein in aspects of ectodermal development.

Child↗
PubMed2006

The acanthosis nigricans form of epidermal nevus.

We observed 4 individuals with the acanthosis nigricans (AN) form of epidermal nevus, with clinical and histopathologic features of AN oriented along Blaschko's lines. Three patients had stable lesions since childhood. One patient concurrently had typical bilateral AN lesions. This condition may represent a mosaic form of AN.

Acanthosis Nigricans↗
PubMed2006

Lipid rafts: membrane triage centers.

Both biochemical and live cell imaging studies suggest the existence of lipid rafts, specialized membrane microdomains that promote interaction among signaling molecules. Although their composition is still poorly understood, these highly dynamic domains are enriched in cholesterol, sphingolipids, and particular groups of proteins. The mechanism(s) by which trafficking into or out of lipid rafts affects signaling remains unclear.

ErbB Receptors↗
PubMed2005

The epidemiology of molluscum contagiosum in children.

Molluscum contagiosum (MC) is a viral disorder of the skin and mucous membranes characterized by discrete single or multiple, flesh-colored papules. Although MC as a clinical entity is well defined and commonly observed, few data regarding its epidemiology in the pediatric population exist. Our purpose was to collect epidemiologic data on children with MC with regard to age, gender, ethnicity, degree of involvement, relation to pre-existing atopic dermatitis (AD), and immune status. A retrospective chart review was conducted. All subjects were seen at 3 tertiary pediatric dermatology referral centers with two of the sites based at a Children's Hospital. A total of 302 patient charts with the Current Procedural Terminology code diagnosis of MC seen over a 6- to 8-month period were reviewed. Approximately 80% of the patients were younger than 8 years old. The majority of patients (63%) had more than 15 lesions. All but one patient were otherwise healthy, as determined by history and clinical examination. Approximately 24% of the patients presented with a history of previous or active coexistent AD. However, children with AD were at risk for an increased number of lesions. These data provide valuable updated information on the demographics and clinical presentation of MC in pediatric patients in the United States. Limitations include that this was a retrospective study with a population limited to tertiary pediatric dermatology referral centers.

Age Distribution↗
PubMed2005

Asymptomatic inflammatory bowel disease presenting with mucocutaneous findings.

Although inflammatory bowel disease (IBD) typically presents with gastrointestinal complaints, mucocutaneous lesions are commonly associated and can precede gastrointestinal symptoms, thereby alerting the clinician to the diagnosis of IBD before the onset of gastrointestinal symptoms. Nine children are reported who had no gastrointestinal symptoms suggestive of IBD but presented with mucocutaneous findings of IBD and were subsequently diagnosed with Crohn's disease or ulcerative colitis based on characteristic features on gastrointestinal endoscopy and/or biopsies. The majority of the patients had oral and perianal lesions. We believe that IBD is a common etiology for persistent oral lesions in the pediatric population. In addition to a good history, children with unexplained oral mucous membrane lesions should have an examination of the rectal and genital mucosa as well as tests for complete blood count, iron levels, sedimentation rate, albumin, and occult blood in the stool with endoscopy and biopsies to rule out IBD if indicated.

Child↗
PubMed2005

Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies.

OBJECTIVE: To compare the efficacy and safety of tacrolimus ointment and pimecrolimus cream in adult and pediatric patients with mild to very severe atopic dermatitis (AD). METHODS: One thousand and sixty-five patients were randomized to treatment in 3 multicenter, randomized, investigator-blinded, 6-week studies. RESULTS: Based on the Eczema Area Severity Index (EASI), tacrolimus ointment was more effective than pimecrolimus cream at the end of the study in adults (54.1% vs. 34.9%, respectively; P < .0001), in children with moderate/severe disease (67.2% vs. 56.4%, respectively; P = .04), in the combined analysis (52.8% vs. 39.1%, respectively; P < .0001), and at week 1 in children with mild disease (39.2% vs. 31.2%, respectively; P = .04). Tacrolimus was also more effective than pimecrolimus based on the Investigator Global AD Assessment (IGADA), improvement in percentage of total body surface area affected, and improvement in itch scores (P < or = .05), with a faster onset of action. There was no significant difference in the incidence of adverse events (AEs), including application site reactions in the 2 studies involving 650 children. Adults treated with tacrolimus experienced a greater number of local application site reactions on day 1; both groups reported a similar incidence of application site reactions thereafter. More pimecrolimus-treated patients than tacrolimus-treated patients withdrew from the studies because of a lack of efficacy (P < or = .03) or adverse events (P = .002; pediatric mild). CONCLUSION: Tacrolimus ointment is more effective and has a faster onset of action than pimecrolimus cream in adults and children with AD; their safety profiles are similar.

Adolescent↗
PubMed2005

Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis.

OBJECTIVE: This study was designed to evaluate the long-term safety and efficacy of 0.1% tacrolimus ointment in adult and pediatric patients with atopic dermatitis (AD). METHODS: A total of 408 adult and 391 pediatric patients with AD who had participated in a previous clinical trial of tacrolimus ointment were enrolled in this long-term, open-label, noncomparative trial. Tacrolimus ointment 0.1% was applied twice daily either intermittently or continuously to the affected areas. Efficacy and safety assessments included percent body surface area affected, Eczema Area and Severity Index score, individual signs of AD, and the incidence of adverse events. RESULTS: A total of 799 patients were evaluated, of whom 300 (37.5%) were followed for more than 3 years (maximum 49 months). Improvements in efficacy parameters were observed within 1 week of treatment and continued for the duration of the study. Common adverse events included skin burning, pruritus, skin infection, skin erythema, flu-like symptoms, and headache. The incidence of adverse events, including cutaneous infections, did not increase with time on study. CONCLUSION: Tacrolimus ointment therapy is a rapidly effective and safe treatment for the management of AD in pediatric and adult patients for up to 4 years.

Adolescent↗
PubMed2005

Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/alphabeta integrin/epidermal growth factor receptor interactions.

The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting alpha(5)beta(1) integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcalpha2-->3Galbeta1-->3GalNAcbeta1-->4(NeuAcalpha2-->8NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-Cer (GT1b) or NeuAcalpha2-->3Galbeta1-->4Glcbeta1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with alpha(5)beta(1) integrin or uPAR/alpha(5)beta(1) integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin alpha(5)beta(1).

Carcinoma, Squamous Cell↗
PubMed2005

Treatment of pachyonychia congenita.

There are currently no specific treatments for pachyonychia congenita (PC). Available treatments generally are directed at specific manifestations of the disorder, and an effective treatment plan must recognize that different patients are more or less troubled by different manifestations of the disease. Treatment for all aspects of PC has been less than completely satisfactory. Very few studies have compared different approaches to treatment, and fewer still have given longitudinal follow-up of efficacy and patient acceptance. This review is essentially a compilation of anecdotes. It was collected from physicians' reports in the literature, from direct communication with physicians currently following patients with PC and from patients who answered a questionnaire on the Pachyonychia Congenita Project web page (http://www.pachyonychia.org/Registry.html).

Darier Disease↗
PubMed2005

The economics of topical immunomodulators for the treatment of atopic dermatitis.

Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease frequently affecting infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5--20% of the paediatric population. First-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of antihistamines and oral antibacterials. Topical corticosteroids improve the lesions of atopic dermatitis; however, concern on the part of physicians and patients regarding adverse effects has led to reluctance to utilise topical corticosteroids early and especially for prolonged periods. Topical immunomodulators (TIMs), including tacrolimus ointment and pimecrolimus cream, were recently introduced for the treatment of atopic dermatitis. Clinical data show that TIMs are effective in atopic dermatitis, yet do not cause the significant adverse effects associated with topical corticosteroids. Questions remain regarding the place of TIMs as a treatment for atopic dermatitis and how to use them most effectively, from both therapeutic and pharmacoeconomic standpoints. Specifically, two major issues remain unresolved: (i) how TIMs measure up to other therapies, especially topical corticosteroids; and (ii) how members of the TIM drug class compare against each other. Previous research has established that atopic dermatitis has a significant impact on quality of life (QOL) and carries a substantial economic burden. Some studies have also measured the utility of various atopic dermatitis disease states. While there is a need for further research, early economic studies provide evidence that TIMs positively affect the QOL of patients and families. In certain patients, TIMs may be cost effective and have an acceptable incremental cost utility compared with topical corticosteroids.Making cost-effectiveness comparisons between tacrolimus and pimecrolimus is challenging because there are limited head-to-head comparative data. Given currently available efficacy data, the results of one study suggest that tacrolimus may be more cost effective than pimecrolimus in paediatric patients with moderate atopic dermatitis. The full economic and QOL benefits of both agents are yet to be completely understood. The studies reviewed herein are the first to delineate the pharmacoeconomic benefits of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs represent an exciting advance in the treatment of atopic dermatitis. Additional research will help determine the proper place of TIMs among the current array of therapeutic options for atopic dermatitis.

Administration, Topical↗
PubMed2004

Tacrolimus ointment promotes repigmentation of vitiligo in children: a review of 57 cases.

BACKGROUND: Vitiligo is an autoimmune disorder characterized by loss of pigmentation. Phototherapy and application of topical corticosteroids are most commonly prescribed. However, these therapies are often not effective and use of corticosteroids on the face may lead to cutaneous atrophy, telangiectasia, and ocular complications. OBJECTIVE: We sought to assess the efficacy of topical tacrolimus ointment in the treatment of pediatric vitiligo. METHODS: A retrospective review was performed of 57 pediatric patients with vitiligo at two clinical sites. Patients were treated with tacrolimus ointment for at least 3 months. Clinical responses were documented during clinic visits, and by pretacrolimus and posttacrolimus photography. RESULTS: At least partial response was noted to tacrolimus ointment on the head and neck in 89%, and on the trunk and extremities in 63% of patients. Facial vitiligo of the segmental type showed the best response rate. Two patients initially experienced burning on application. CONCLUSIONS: Topical tacrolimus ointment is an effective alternative therapy for childhood vitiligo, particularly involving the head and neck.

Adolescent↗