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Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis
OBJECTIVES: A congenital loss of cytotoxic lymphocyte activity leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis. Until recently, this disease was uniformly associated with infants or very young children, but it appears now that the onset may be delayed...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312240/ https://www.ncbi.nlm.nih.gov/pubmed/34336208 http://dx.doi.org/10.1002/cti2.1320 |
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author | Minson, Adrian Voskoboinik, Ilia Grigg, Andrew |
author_facet | Minson, Adrian Voskoboinik, Ilia Grigg, Andrew |
author_sort | Minson, Adrian |
collection | PubMed |
description | OBJECTIVES: A congenital loss of cytotoxic lymphocyte activity leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis. Until recently, this disease was uniformly associated with infants or very young children, but it appears now that the onset may be delayed for decades. As a result, some adults are being mis‐ or under‐diagnosed because of their ‘atypical’ symptoms that are not recognised as immunodeficiency. The clinical picture and histopathology can overlap with those of haematologic malignancy, further complicating the diagnostic thought process. The spectrum of atypical symptoms is poorly defined, and therefore, it is important to describe these cases and the attendant immunological and cellular changes associated with familial haemophagocytic lymphohistiocytosis, in order to improve diagnosis and prevent unintended consequences of symptomatic therapies. METHODS: A 45‐year‐old patient presented with suspected T‐cell lymphoma and was treated with combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone) supplemented with granulocyte‐colony stimulating factor (G‐CSF). To mobilise stem cells for autologous transplantation, the patient was then treated with high‐dose G‐CSF and rapidly developed haemophagocytic lymphohistiocytosis. Symptoms resolved temporarily with intensive immunosuppression with alemtuzumab and durably with a subsequent allograft. RESULTS: The patient was found to be a carrier of bi‐allelic mutations in the STXBP2 protein that is essential for cytotoxic lymphocyte function, and the initial diagnosis has been revised as familial haemophagocytic lymphohistiocytosis. CONCLUSION: This case highlights the difficulty in distinguishing atypical/late‐onset familial haemophagocytic lymphohistiocytosis from a malignant process as well as a possible exacerbation of the disease with G‐CSF therapy. |
format | Online Article Text |
id | pubmed-8312240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83122402021-07-30 Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis Minson, Adrian Voskoboinik, Ilia Grigg, Andrew Clin Transl Immunology Case Report OBJECTIVES: A congenital loss of cytotoxic lymphocyte activity leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis. Until recently, this disease was uniformly associated with infants or very young children, but it appears now that the onset may be delayed for decades. As a result, some adults are being mis‐ or under‐diagnosed because of their ‘atypical’ symptoms that are not recognised as immunodeficiency. The clinical picture and histopathology can overlap with those of haematologic malignancy, further complicating the diagnostic thought process. The spectrum of atypical symptoms is poorly defined, and therefore, it is important to describe these cases and the attendant immunological and cellular changes associated with familial haemophagocytic lymphohistiocytosis, in order to improve diagnosis and prevent unintended consequences of symptomatic therapies. METHODS: A 45‐year‐old patient presented with suspected T‐cell lymphoma and was treated with combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone) supplemented with granulocyte‐colony stimulating factor (G‐CSF). To mobilise stem cells for autologous transplantation, the patient was then treated with high‐dose G‐CSF and rapidly developed haemophagocytic lymphohistiocytosis. Symptoms resolved temporarily with intensive immunosuppression with alemtuzumab and durably with a subsequent allograft. RESULTS: The patient was found to be a carrier of bi‐allelic mutations in the STXBP2 protein that is essential for cytotoxic lymphocyte function, and the initial diagnosis has been revised as familial haemophagocytic lymphohistiocytosis. CONCLUSION: This case highlights the difficulty in distinguishing atypical/late‐onset familial haemophagocytic lymphohistiocytosis from a malignant process as well as a possible exacerbation of the disease with G‐CSF therapy. John Wiley and Sons Inc. 2021-07-26 /pmc/articles/PMC8312240/ /pubmed/34336208 http://dx.doi.org/10.1002/cti2.1320 Text en © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Case Report Minson, Adrian Voskoboinik, Ilia Grigg, Andrew Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title | Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title_full | Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title_fullStr | Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title_full_unstemmed | Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title_short | Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
title_sort | dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312240/ https://www.ncbi.nlm.nih.gov/pubmed/34336208 http://dx.doi.org/10.1002/cti2.1320 |
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