Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2
Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening, hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated, but ineffective immune response. Case report. We reported a 19-year-old woman presenting with fever, muscle and joi...
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| Format: | Article |
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Military Health Department, Ministry of Defance, Serbia
2017-01-01
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| Series: | Vojnosanitetski Pregled |
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| Online Access: | http://www.doiserbia.nb.rs/img/doi/0042-8450/2017/0042-84501600224M.pdf |
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| author | Marković Olivera Janić Dragana Pavlović Milorad Tukić Ljiljana Janković Srđa Filipović Branka Marisavljević Dragomir |
| author_facet | Marković Olivera Janić Dragana Pavlović Milorad Tukić Ljiljana Janković Srđa Filipović Branka Marisavljević Dragomir |
| author_sort | Marković Olivera |
| collection | DOAJ |
| description | Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening, hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated, but ineffective immune response. Case report. We reported a 19-year-old woman presenting with fever, muscle and joint pain and sore throat. After diagnostic procedures we made the diagnosis of hemophagocytic lymphohistiocytosis (7 of 8 HLH-2004 diagnostic criteria) caused by Ebstein-Barr viral infection and trigerred by the intense physical activity. Genetic analysis showed three different sequence changes in Munc-18-2, two splice acceptor side mutations/changes affecting exon 10 (c.795–4 C > T) and exon 15 (c.1247–10 C > T) and a missense mutation c.1375 C > T; p.Arg 459 Trp. All mutations were in heterozygous state and their significance in pathogensis of HLH is not clear. After treatment with corticosteroids and cyclosporin A complete clinical remission was achieved. Conclusion. The presented case history suggests the possibility that mutations of undetermined clinical significance in a gene associated with primary HLH may underlie some cases of secondary HLH, probably by causing a partial, rather than total or subtotal, impairment of encoded protein function. Our case also suggests that strenuous physical activity (in apparent synergy with viral infection) can trigger HLH. |
| first_indexed | 2024-12-19T05:55:30Z |
| format | Article |
| id | doaj.art-e9018627b5d747e7b6fca63b338810b6 |
| institution | Directory Open Access Journal |
| issn | 0042-8450 2406-0720 |
| language | English |
| last_indexed | 2024-12-19T05:55:30Z |
| publishDate | 2017-01-01 |
| publisher | Military Health Department, Ministry of Defance, Serbia |
| record_format | Article |
| series | Vojnosanitetski Pregled |
| spelling | doaj.art-e9018627b5d747e7b6fca63b338810b62022-12-21T20:33:28ZengMilitary Health Department, Ministry of Defance, SerbiaVojnosanitetski Pregled0042-84502406-07202017-01-0174549449710.2298/VSP150701224M0042-84501600224MHemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2Marković Olivera0Janić Dragana1Pavlović Milorad2Tukić Ljiljana3Janković Srđa4Filipović Branka5Marisavljević Dragomir6Clinical Hospital Center Bežanijska kosa, Belgrade + Faculty of Medicine, BelgradeFaculty of Medicine, Belgrade + University Children’s Hospital, BelgradeFaculty of Medicine, Belgrade + § Clinic of Infectious Diseases, BelgradeMilitary Medical Academy, Clinic of Haematology, Belgrade + ¶ University of Defence, Faculty of Medicine of the Military Medical Academy, BelgradeClinical Hospital Center Bežanijska kosa, Belgrade + University Children’s Hospital, BelgradeClinical Hospital Center Bežanijska kosa, Belgrade + Faculty of Medicine, BelgradeClinical Hospital Center Bežanijska kosa, Belgrade + Faculty of Medicine, BelgradeIntroduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening, hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated, but ineffective immune response. Case report. We reported a 19-year-old woman presenting with fever, muscle and joint pain and sore throat. After diagnostic procedures we made the diagnosis of hemophagocytic lymphohistiocytosis (7 of 8 HLH-2004 diagnostic criteria) caused by Ebstein-Barr viral infection and trigerred by the intense physical activity. Genetic analysis showed three different sequence changes in Munc-18-2, two splice acceptor side mutations/changes affecting exon 10 (c.795–4 C > T) and exon 15 (c.1247–10 C > T) and a missense mutation c.1375 C > T; p.Arg 459 Trp. All mutations were in heterozygous state and their significance in pathogensis of HLH is not clear. After treatment with corticosteroids and cyclosporin A complete clinical remission was achieved. Conclusion. The presented case history suggests the possibility that mutations of undetermined clinical significance in a gene associated with primary HLH may underlie some cases of secondary HLH, probably by causing a partial, rather than total or subtotal, impairment of encoded protein function. Our case also suggests that strenuous physical activity (in apparent synergy with viral infection) can trigger HLH.http://www.doiserbia.nb.rs/img/doi/0042-8450/2017/0042-84501600224M.pdflymphohistocytosis, hemophagocyticinflammationimmunologic factorsphysical exertionebstein-barr virusmutationdiagnosis, differentialdrug therapy |
| spellingShingle | Marković Olivera Janić Dragana Pavlović Milorad Tukić Ljiljana Janković Srđa Filipović Branka Marisavljević Dragomir Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 Vojnosanitetski Pregled lymphohistocytosis, hemophagocytic inflammation immunologic factors physical exertion ebstein-barr virus mutation diagnosis, differential drug therapy |
| title | Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 |
| title_full | Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 |
| title_fullStr | Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 |
| title_full_unstemmed | Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 |
| title_short | Hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in Munc-18-2 |
| title_sort | hemophagocytic syndrome triggered by intense physical activity and viral infection in a young adult female with three heterozygous mutations in munc 18 2 |
| topic | lymphohistocytosis, hemophagocytic inflammation immunologic factors physical exertion ebstein-barr virus mutation diagnosis, differential drug therapy |
| url | http://www.doiserbia.nb.rs/img/doi/0042-8450/2017/0042-84501600224M.pdf |
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