Infliximab in the treatment of a child with cutaneous granulomas associated with ataxia telangiectasia

Mitra, Angana; Gooi, Jimmy; Darling, Jonathan C.; Newton-Bishop, Julia

doi:10.1016/j.jaad.2010.06.060

Cited by 25 publications

(22 citation statements)

References 6 publications

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“…Nonetheless, high potency topical corticosteroids and cyclosporine A can be used for healing of small superficial ulceration . In addition, more considerable non‐infectious granulomas may respond to fumaric acid esters (FAE), systemic inhibitors of tumor necrosis factor (TNF‐alpha), direct injection of steroids into the site of the granulomatous ulceration, and combination therapy such as topical steroids with concurrent immunoglobulin replacement therapy …”

Section: Associated Complications In A‐t Patientsmentioning

confidence: 99%

Ataxia‐telangiectasia: A review of clinical features and molecular pathology

Amirifar

Ranjouri

Yazdani

et al. 2019

Pediatric Allergy Immunology

138

105

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Ataxia‐telangiectasia (A‐T) is an autosomal recessive primary immunodeficiency (PID) disease that is caused by mutations in ataxia‐telangiectasia mutated (ATM) gene encoding a serine/threonine protein kinase. A‐T patients represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, susceptibility to malignancies, and increased metabolic diseases. This congenital disorder has phenotypic heterogeneity, and the severity of symptoms varies in different patients based on severity of mutations and disease progression. The principal role of nuclear ATM is the coordination of cellular signaling pathways in response to DNA double‐strand breaks, oxidative stress, and cell cycle checkpoint. The pathogenesis of A‐T is not limited to the role of ATM in the DNA damage response (DDR) pathway, and it has other functions mainly in the hematopoietic cells and neurons. ATM adjusts the functions of organelles such as mitochondria and peroxisomes and also regulates angiogenesis and glucose metabolisms. However, ATM has other functions in the cells (especially cell viability) that need further investigations. In this review, we described functions of ATM in the nucleus and cytoplasm, and also its association with some disorder formation such as neurologic, immunologic, vascular, pulmonary, metabolic, and dermatologic complications.

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Section: Associated Complications In A‐t Patientsmentioning

confidence: 99%

Ataxia‐telangiectasia: A review of clinical features and molecular pathology

Amirifar

Ranjouri

Yazdani

et al. 2019

Pediatric Allergy Immunology

138

105

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“…More extensive granulomas may respond to combination therapy (e.g. topical steroids plus IV gamma globulin therapy) [152], systemic inhibitors of tumor necrosis factor (TNF-alpha) [153] or direct injection of steroids into the site of the granulomatous lesions [154]. …”

Section: Introductionmentioning

confidence: 99%

Ataxia telangiectasia: a review

Rothblum-Oviatt

Wright²,

Lefton‐Greif

et al. 2016

Orphanet J Rare Dis

466

488

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Definition of the diseaseAtaxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.EpidemiologyThe world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.Clinical descriptionA-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.EtiologyA-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.DiagnosisThe diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.Differential diagnosisThere are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.Antenatal diagnosisAntenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.Genetic counselingGenetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.Management and prognosisTreatment of the neurologic problems associated wit...

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“…Furthermore, there are several reports on patients presenting with chronic cutaneous granulomas and pulmonary inflammation without apparent underlying infections. [14][15][16][17] Although the immune defects in the adaptive arm of the immune system associated with this disease have been well studied, the effects on the innate immune system remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%