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Subra Kugathasan

Publications and source records attributed to Subra Kugathasan.

26 records · Page 2Linked to original sources
PubMed2004

CARD15 gene mutations and risk for early surgery in pediatric-onset Crohn's disease.

BACKGROUND & AIMS: The risk for Crohn's disease (CD) is determined in part by genetic factors. Three recently described mutations in the CARD15(NOD2) gene have been associated with adult-onset CD. We investigated the effect of CARD15 mutations on disease manifestation, disease progression, and the risk for early surgery in childhood-onset CD. METHODS: Genotyping for 3 CARD15 mutations: R702W, G908R, and 3020insC, was performed in 186 children with CD from a prospective cohort. A transmission-disequilibrium test was used to test for association with CD. Genotype with disease location and behavior was tested with logistic regression analysis. The effect of mutations on surgical outcome was evaluated using a Cox proportional hazard analysis. RESULTS: The mean age at CD diagnosis was 12.4 years. The frequency of allelic mutations observed was 6.6% for R702W, 6% for G908R, and 13.1% for 3020insC. Of Caucasian CD children, 42% had at least one CARD15 mutation. None of the non-Caucasian children with CD had any CARD15 mutation. A significant association was detected for 3020insC (P = .0045). Ileal location (odds ratio, 4.3; P = .003) and stricturing disease (odds ratio, 6.6; P = .0001) was more frequent and the risk for surgery was higher (hazard ratio, 5.8; P < .0001) and surgery occurred earlier (hazard ratio, 2.24) in those children with 3020insC mutation compared with those without 3020insC. CONCLUSIONS: In children with pediatric-onset CD, early development of stricturing behavior leading to surgical resection is influenced by ileal location and 3020insC variant of the CARD15 mutation. Genetic testing may identify children with CD who are at risk for early surgery.

Adolescent↗
PubMed2004

Guidelines for immunizations in patients with inflammatory bowel disease.

During the past 2 decades, medical therapy for Crohn's disease (CD) and ulcerative colitis (UC) has grown to incorporate a variety of immunesuppressing agents. At the same time, basic insights into the aberrant mucosal immune response underlying inflammatory bowel disease (IBD) have expanded dramatically. The interplay of host susceptibility to infection and the safety and efficacy of immunization for vaccine-preventable diseases has been explored in other immune-mediated disease states but only rarely in IBD. The purpose of this review is to formulate best-practice recommendations for immunization in children and adults with IBD by considering the effects of the IBD disease state and its treatments on both the safety and efficacy of immunization. To do so, we first considered the routine recommendations for immunization of children, adults and distinct populations at increased risk for vaccine-preventable disease. Because it was rarely possible to examine direct data on safety and efficacy of immunization in IBD populations, we relied to a large extent upon extrapolation from similar populations and from knowledge of basic mechanisms. The literature suggests that efficacy of immunization may be diminished in some patients whose immune status is compromised by immune suppression. However, except for live agent vaccines, most immunizations may be safely administered to patients with IBD even when immune compromised. Conversely, protection against vaccine-preventable illness may be of even greater benefit to those at risk for morbid or lethal complications of infections because of an immune compromised state. We conclude that for most patients with IBD, recommendations for immunization do not deviate from recommended schedules for the general population.

Adolescent↗
PubMed2003

Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study.

OBJECTIVE: To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN: All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS: The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS: This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn's disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Adolescent↗
PubMed2003

Dermatologic manifestations of Crohn disease in children: response to infliximab.

Dermatologic extraintestinal manifestations of Crohn disease may be refractory to treatment with corticosteroids and immunomodulators. The authors describe four children with Crohn disease with dermatologic manifestations: pyoderma gangrenosum, orofacial involvement, erythema nodosum, and idiopathic lymphedema. These dermatologic conditions were unresponsive to conventional therapy but had rapid and sustained response to the anti-TNF-alpha antibody infliximab. No adverse reactions occurred. Infliximab should be considered for treating the extraintestinal dermatologic manifestations of Crohn disease in children.

Adolescent↗
PubMed2003

Pancreatitis in children.

OBJECTIVES: To determine the incidence, etiology and outcome of pancreatitis at a regional children's hospital. METHODS: Chart review of all patients with pancreatitis seen during a 6 year period at the Children's Hospital of Wisconsin. The diagnosis of pancreatitis required either a serum amylase or lipase >3 times normal or radiographic evidence of pancreatitis. RESULTS: Two hundred fourteen episodes of pancreatitis in 180 patients were documented. The most common etiologies were systemic disease (14%), trauma (14%), drug induced (12%), biliary tract disease (12%), infectious (8%), and idiopathic (8%), which made up 68% of the total cases. Eleven patients died, all from underlying systemic illnesses. The serum amylase and lipase were elevated in 82% and 83% of patients respectively. CONCLUSIONS: Pancreatitis is more common in children than previously thought. Upon careful assessment fewer cases were found to be idiopathic than in previous series. The outcome of pancreatitis depends on co-morbid conditions.

Abdominal Pain↗
PubMed2002

Ureteropelvic junction obstruction: an overlooked cause of cyclic vomiting.

Cyclic vomiting syndrome is an unusual cause of recurrent episodes of repetitive vomiting, particularly in children. Although in only a minority of cases can an underlying cause be found, each patient deserves a thorough evaluation for treatable conditions. We present four cases of cyclic vomiting syndrome caused by ureteropelvic obstruction. Surgical correction was followed by resolution of symptoms in all four patients.

Child↗
PubMed2002

Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction.

OBJECTIVES: Although effective in the treatment of refractory Crohn's disease, episodic retreatment with the antitumor necrosis factor a chimeric monoclonal antibody infliximab (Remicade, Centocor, Malvern, PA) can be associated with severe acute and delayed systemic reactions. METHODS: We analyzed episodic infliximab retreatment over 30 months in 86 adult and pediatric patients receiving 304 infusions to determine factors associated with the development of severe systemic reaction. RESULTS: Overall, 14% of patients experienced severe systemic reactions with episodic infliximab retreatment. There was a significant difference in the rates of severe systemic reaction observed in adults (11/52 [21%]) and pediatric patients (1/34 [3%]) (p < 0.02). Delayed systemic reactions, characterized by arthralgia, fever, and myalgia requiring corticosteroid treatment, were found exclusively in adults (age > 17 yr) and occurred in eight patients treated for luminal Crohn's disease. Acute systemic reactions, characterized by hypotension, mucosal irritability, and laryngospasm requiring epinephrine, diphenhydramine, and/or methylprednisolone treatment, occurred sporadically in three adults and one child, treated for both luminal and fistulizing disease. Second infliximab infusions were associated with two thirds of severe systemic reactions, and a distant second infusion (> or = 20 wk from first infusion) was poorly tolerated relative to earlier retreatment (p < 0.001). Concomitant medications were similar in adults and children. CONCLUSIONS: Episodic infliximab retreatment--specifically, a distant second infusion--is associated with high rates of severe systemic reaction in adults, but not children. We recommend multiple early infusions of infliximab if retreatment is anticipated in adult patients to avoid the development of delayed severe systemic reactions.

Adolescent↗