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Graves' Immune Reconstitution Inflammatory Syndrome in Childhood

Lookup NU author(s): Dr Akash Sinha, Dr Mario Abinun, Dr Andrew Gennery, Dr Mary Slatter, Dr Timothy Cheetham

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Abstract

Background: The use of hematopoietic stem cell transplantations (HSCTs) as a curative therapy for life-threatening immunodeficiencies has had a profound impact on clinical outcomes. A subset of patients may experience immune reconstitution inflammatory syndrome (IRIS) post-transplant affecting the thyroid gland, but this has received little attention in the pediatric literature. We present the clinical, biochemical, and cytological course of patients with Graves' disease after HSCT in the pediatric population. Patients and Methods: Four children (median age 1.5 years, range 2 months-9 years) underwent HSCT. The conditioning regimen included chemotherapy but not radiotherapy. None of the children or their donors had evidence of thyroid disease pre-HSCT or during the follow-up period. Engraftment was uneventful in all, with stable donor T-cell chimerism, and none had evidence of graft-versus-host disease. Results: Patients developed Graves' disease soon after undergoing HSCT, with a median time interval between HSCT and Graves' disease of 22 months (range 16-28 months). Graves' disease was diagnosed on the basis of clinical and biochemical parameters, including a suppressed thyrotropin, raised free thyroxine, and raised thyrotropin receptor antibodies. Three patients were hypothyroid initially (suggestive of a Th1 profile) before Graves' disease (suggestive of a Th2 profile). In three patients, the clinical picture changed rapidly with hypothyroidism abruptly followed by profound thyroid hormone excess. The onset of Graves' IRIS coincided with a rapid expansion in naive and total CD4. Conclusions: Immunological dysregulation during T-cell engraftment is the most likely mechanism for developing Graves' IRIS after allogenic HSTC. Clinicians need to be aware that HSCT-engendered immune recovery may result in a particularly aggressive form of autoimmune thyroid disease in children with implications for the developing central nervous system. Careful surveillance of thyroid function post-HSCT is essential.


Publication metadata

Author(s): Sinha A, Abinun M, Gennery AR, Barge D, Slatter M, Cheetham T

Publication type: Article

Publication status: Published

Journal: Thyroid

Year: 2013

Volume: 23

Issue: 8

Pages: 1010-1014

Print publication date: 21/08/2013

ISSN (print): 1050-7256

ISSN (electronic): 1557-9077

Publisher: Mary Ann Liebert, Inc. Publishers

URL: http://dx.doi.org/10.1089/thy.2012.0618

DOI: 10.1089/thy.2012.0618


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