{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:18:50Z","timestamp":1792253930787,"version":"4.4.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is not an independent disease but rather a life-threatening clinical syndrome that occurs in many underlying conditions and in all age groups. HLH is the consequence of a severe, uncontrolled hyperinflammatory reaction that in most cases is triggered by an infectious agent. Persistent stimulation of lymphocytes and histiocytes results in hypercytokinemia, leading to the characteristic symptoms of HLH. Genetic defects in familial HLH and in immunodeficiency syndromes associated with albinism affect the transport, processing, and function of cytotoxic granules in natural killer cells and cytotoxic T lymphocytes. This leads to defective killing of target cells and a failure to contract the immune response. The defects are increasingly found also in adolescents and adults. Acquired HLH occurs in autoinflammatory and autoimmune diseases (macrophage activation syndrome) and in patients with iatrogenic immunosuppression or with malignancies, but also in otherwise healthy persons with infections. Treatment of HLH aims at suppressing hypercytokinemia and eliminating the activated and infected cells. In genetic HLH, hematopoietic stem cell transplantation (HSCT) is needed for the correction of the immune defect. Treatment modalities include immunosuppressive, immunomodulatory, and cytostatic drugs; T-cell antibodies; and anticytokine agents. Using immunochemotherapy, familial HLH, which had been invariably fatal, has become a curable disease with more than 50% survivors. Reduced intensity conditioning for HSCT, which is associated with less transplantation-related mortality, will further improve cure rates.<\/jats:p>","DOI":"10.1182\/asheducation-2013.1.605","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T10:51:13Z","timestamp":1386327073000},"page":"605-611","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":273,"title":["Hemophagocytic lymphohistiocytosis: pathogenesis and treatment"],"prefix":"10.1182","volume":"2013","author":[{"given":"Gritta E.","family":"Janka","sequence":"first","affiliation":[{"name":"University Medical Center Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Lehmberg","sequence":"additional","affiliation":[{"name":"University Medical Center Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"12","key":"2019111703430359900_B1","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.3324\/haematol.2010.029389","article-title":"Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases","volume":"95","author":"Rohr","year":"2010","journal-title":"Haematologica"},{"issue":"25","key":"2019111703430359900_B2","doi-asserted-by":"crossref","first-page":"6016","DOI":"10.1182\/blood-2011-12-398958","article-title":"Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5)","volume":"119","author":"Pagel","year":"2012","journal-title":"Blood"},{"issue":"2","key":"2019111703430359900_B3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00431-006-0258-1","article-title":"Familial and acquired hemophagocytic lymphohistiocytosis","volume":"166","author":"Janka","year":"2007","journal-title":"Eur J Pediatr"},{"issue":"6","key":"2019111703430359900_B4","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/ACI.0b013e32834c22f5","article-title":"The expanding spectrum of hemophagocytic lymphohistiocytosis","volume":"11","author":"Filipovich","year":"2011","journal-title":"Curr Opin Allergy Clin Immunol"},{"issue":"3","key":"2019111703430359900_B5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/ar3843","article-title":"Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis","volume":"14","author":"Bode","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"2019111703430359900_B6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev-med-041610-134208","article-title":"Familial and acquired hemophagocytic lymphohistiocytosis","volume":"63","author":"Janka","year":"2012","journal-title":"Annu Rev Med"},{"issue":"22","key":"2019111703430359900_B7","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1182\/blood-2011-07-370148","article-title":"Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH","volume":"118","author":"Zhang","year":"2011","journal-title":"Blood"},{"issue":"3","key":"2019111703430359900_B8","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1172\/JCI116721","article-title":"Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome","volume":"92","author":"Kawaguchi","year":"1993","journal-title":"J Clin Invest"},{"issue":"2","key":"2019111703430359900_B9","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/pbc.22037","article-title":"Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian origin","volume":"53","author":"Beutel","year":"2009","journal-title":"Pediatr Blood Cancer"},{"issue":"10","key":"2019111703430359900_B10","first-page":"1414","article-title":"Haemophagocytic syndrome in rheumatic patients. 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