Treatment of granulomas in patients with ataxia telangiectasia

Background: Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, growth retardation, immunodeficiency, chronic pulmonary disease and chromosomal instability. 
Background: Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, growth retardation, immunodeficiency, chronic pulmonary disease and chromosomal instability. Cutaneous granulomas are a known phenomenon in A-T but extra-dermal manifestation of granulomas at bone and synovia has not been reported so far. The clinical presentation, immunological findings, the long-term course and treatment options of eight patients with severe granulomas will be reported.
Methods: From our cohort of 44 classical A-T patients, eight patients aged 2–11 years (18.2%) presented with granulomas. Immunological features of patients with and without granulomas were compared. Five patients suffered from cutaneous manifestation, in two patients we detected a bone and in one a joint involvement. Patients with significant extra-dermal involvement as well as one patient with massive skin manifestation were treated with TNF inhibitors. The patient with granulomas at his finger joint and elbow was treated with hematopoietic stem cell transplantation (HSCT).
Results: Interestingly, seven of eight patients with granulomas were total IgA deficient, but there were no differences in IgG and IgM levels. All lymphocytes subsets were equally distributed except patients with granuloma had significantly lower naïve CD8 cells. In patients without treatment, four of eight showed a slow but significant enlargement of the granuloma. Treatment success with TNF inhibitors was variable. In one patient, treatment with TNF inhibitors led to a total remission for 3 years up to now. In two patients, treatment with TNF inhibitors led to a partial regression of granulomas. Treatment interruptions caused deterioration again.
Conclusions: Granulomas in A-T progress slowly over years and can lead to significant morbidity.Treatment with TNF inhibitors was safe and in part successful in our patients. Interestingly HSCT leads to complete remission, and indicates that aberrant immune function is responsible for granulomas in A-T patients.
At a glance commentary:
Scientific knowledge on the subject: Little is known about the clinical presentation, course and treatment of granulomas in ataxia telangiectasia (A-T). In addition, this is the first report of extra-dermal manifestation of granulomas at bone and synovia in patients with A-T.
What This Study Adds to the Field: Granulomas in A-T progress slowly over years and can lead to significant morbidity. Treatment with TNF inhibitors was safe and in part successful in our patients.
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Metadaten
Author:Sandra Wölke, Eva Maria Valesky, Shahrzad Bakhtiar, Helena Pommerening, Lisa-Marie Pfeffermann, Ralf Schubert, Stefan Zielen
URN:urn:nbn:de:hebis:30:3-476779
DOI:http://dx.doi.org/10.3389/fimmu.2018.02000
ISSN:1664-3224
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=30279689
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Guzide Aksu
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/09/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/10/11
Tag:TNF inhibitors; ataxia telangiectasia; granulomas; granulomatous inflammation; primary immunodeficiency
Volume:9
Issue:Art. 2000
Pagenumber:8
First Page:1
Last Page:8
Note:
Copyright © 2018 Woelke, Valesky, Bakhtiar, Pommerening, Pfeffermann, Schubert and Zielen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS PPN:439098890
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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