{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T21:59:32Z","timestamp":1777327172252,"version":"3.51.4"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007653","name":"Universit\u00e4tsklinikum Jena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007653","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with <jats:italic>Aspergillus flavus<\/jats:italic>. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary <jats:italic>Aspergillus flavus<\/jats:italic> infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of <jats:italic>Aspergillus flavus<\/jats:italic>, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.<\/jats:p>","DOI":"10.1007\/s15010-023-02149-x","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T13:02:07Z","timestamp":1703250127000},"page":"685-690","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis"],"prefix":"10.1007","volume":"52","author":[{"given":"Micha","family":"Banz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Stallmach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaus","family":"Ga\u00dfler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Christian","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fritzenwanger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Cornely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Kurzai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias W.","family":"Pletz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"2149_CR1","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","volume":"71","author":"J Peter Donnelly","year":"2020","unstructured":"Peter Donnelly J, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71:1367\u201376. https:\/\/doi.org\/10.1093\/cid\/ciz1008.","journal-title":"Clin Infect Dis"},{"key":"2149_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1742-6405-4-9","volume":"4","author":"DM Murdoch","year":"2007","unstructured":"Murdoch DM, Venter WDF, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4:10. https:\/\/doi.org\/10.1186\/1742-6405-4-9.","journal-title":"AIDS Res Ther"},{"key":"2149_CR3","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/nrmicro2712","volume":"10","author":"DL Barber","year":"2012","unstructured":"Barber DL, Andrade BB, Sereti I, Sher A. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012;10:150\u20136. https:\/\/doi.org\/10.1038\/nrmicro2712.","journal-title":"Nat Rev Microbiol"},{"key":"2149_CR4","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1001\/JAMA.282.23.2220","volume":"282","author":"B Ledergerber","year":"1999","unstructured":"Ledergerber B, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA. 1999;282:2220\u20136. https:\/\/doi.org\/10.1001\/JAMA.282.23.2220.","journal-title":"JAMA"},{"key":"2149_CR5","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/jemt.10098","volume":"57","author":"WD Splettstoesser","year":"2002","unstructured":"Splettstoesser WD, Schuff-Werner P. Oxidative stress in phagocytes-\u201cThe Enemy Within.\u201d Microsc Res Tech. 2002;57:441\u201355. https:\/\/doi.org\/10.1002\/jemt.10098.","journal-title":"Microsc Res Tech"},{"key":"2149_CR6","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/cdd.2008.91","volume":"15","author":"K Labb\u00e9","year":"2008","unstructured":"Labb\u00e9 K, Saleh M. Cell death in the host response to infection. Cell Death Differ. 2008;15:1339\u201349. https:\/\/doi.org\/10.1038\/cdd.2008.91.","journal-title":"Cell Death Differ"},{"key":"2149_CR7","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/cncr.22738","volume":"110","author":"MH Miceli","year":"2007","unstructured":"Miceli MH, et al. Immune reconstitution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: proof of principle, description, and clinical and research implications. Cancer. 2007;110:112\u201320. https:\/\/doi.org\/10.1002\/cncr.22738.","journal-title":"Cancer"},{"key":"2149_CR8","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1046\/j.1365-2362.1999.00474.x","volume":"29","author":"G Todeschini","year":"1999","unstructured":"Todeschini G, et al. Invasive aspergillosis in neutropenic patients: Rapid neutrophil recovery is a risk factor for severe pulmonary complications. Eur J Clin Invest. 1999;29:453\u20137. https:\/\/doi.org\/10.1046\/j.1365-2362.1999.00474.x.","journal-title":"Eur J Clin Invest"},{"key":"2149_CR9","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s40588-016-0033-7","volume":"3","author":"CC Chang","year":"2016","unstructured":"Chang CC, French MA. Immune reconstitution inflammatory syndrome in invasive fungal infections: what we know and what we need to know? Curr Clin Microbiol Rep. 2016;3:63\u201370. https:\/\/doi.org\/10.1007\/s40588-016-0033-7.","journal-title":"Curr Clin Microbiol Rep"},{"key":"2149_CR10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3390\/JOF4040139","volume":"4","author":"S Delli\u00e8re","year":"2018","unstructured":"Delli\u00e8re S, et al. Understanding pathogenesis and care challenges of immune reconstitution inflammatory syndrome in fungal infections. J Fungi. 2018;4:139. https:\/\/doi.org\/10.3390\/JOF4040139.","journal-title":"J Fungi"},{"key":"2149_CR11","unstructured":"Study Details | Hepatosplenic CANdidiasis\u202f: PETscan and Immune response analysis | ClinicalTrials.gov\u201c. Zugegriffen: 29. Oktober 2023. [Online]. Verf\u00fcgbar unter: https:\/\/clinicaltrials.gov\/study\/NCT01916057"},{"key":"2149_CR12","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.rmed.2018.06.029","volume":"141","author":"A Kanj","year":"2018","unstructured":"Kanj A, Abdallah N, Soubani AO. The spectrum of pulmonary aspergillosis. Respir Med. 2018;141:121\u201331. https:\/\/doi.org\/10.1016\/j.rmed.2018.06.029.","journal-title":"Respir Med"},{"key":"2149_CR13","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1111\/PED.13064","volume":"58","author":"A Morimoto","year":"2016","unstructured":"Morimoto A, Nakazawa Y, Ishii E. Hemophagocytic lymphohistiocytosis: pathogenesis, diagnosis, and management. Pediatr Int. 2016;58:817\u201325. https:\/\/doi.org\/10.1111\/PED.13064.","journal-title":"Pediatr Int"},{"key":"2149_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/jof5010009","volume":"5","author":"TF Patterson","year":"2019","unstructured":"Patterson TF, Donnelly JP. New concepts in diagnostics for invasive mycoses: Non-culture-based methodologies. J Fungi. 2019;5:9\u201317. https:\/\/doi.org\/10.3390\/jof5010009.","journal-title":"J Fungi"},{"key":"2149_CR15","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1086\/505603","volume":"43","author":"RR Klont","year":"2006","unstructured":"Klont RR, et al. Paradoxical increase in circulating aspergillus antigen during treatment with caspofungin in a patient with pulmonary aspergillosis. Clin Infect Dis. 2006;43:23\u20138.","journal-title":"Clin Infect Dis"},{"key":"2149_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/JOF6040283","volume":"6","author":"T Fontaine","year":"2020","unstructured":"Fontaine T, Latg\u00e9 JP. Galactomannan produced by Aspergillus fumigatus: an update on the structure, biosynthesis and biological functions of an emblematic fungal biomarker. J Fungi. 2020;6:1\u201317. https:\/\/doi.org\/10.3390\/JOF6040283.","journal-title":"J Fungi"},{"key":"2149_CR17","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","volume":"48","author":"JI Henter","year":"2007","unstructured":"Henter JI, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124\u201331. https:\/\/doi.org\/10.1002\/pbc.21039.","journal-title":"Pediatr Blood Cancer"},{"key":"2149_CR18","doi-asserted-by":"publisher","first-page":"e0251216","DOI":"10.1371\/journal.pone.0251216","volume":"16","author":"S Valade","year":"2021","unstructured":"Valade S, et al. Coagulation disorders in patients with severe hemophagocytic lymphohistiocytosis\u201c. PLoS ONE. 2021;16:e0251216. https:\/\/doi.org\/10.1371\/journal.pone.0251216.","journal-title":"PLoS ONE"},{"key":"2149_CR19","doi-asserted-by":"publisher","DOI":"10.7759\/CUREUS.5402","author":"BS Bindra","year":"2019","unstructured":"Bindra BS, de Jesus KGD, Cisneros O, Jorge VM, Kaur H. Hemophagocytic lymphohistiocytosis: management and special consideration in human immunodeficiency virus positive patients with immune reconstitution syndrome. Cureus. 2019. https:\/\/doi.org\/10.7759\/CUREUS.5402.","journal-title":"Cureus"},{"key":"2149_CR20","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/S1473-3099(07)70290-6","volume":"7","author":"NG Rouphael","year":"2007","unstructured":"Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis. 2007;7:814\u201322. https:\/\/doi.org\/10.1016\/S1473-3099(07)70290-6.","journal-title":"Lancet Infect Dis"},{"key":"2149_CR21","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.30908","author":"RS Ali","year":"2022","unstructured":"Ali RS, Sen M, Tan IJ. Pulmonary aspergillosis complicated by hemophagocytic lymphohistiocytosis: a case report and literature review. Cureus. 2022. https:\/\/doi.org\/10.7759\/cureus.30908.","journal-title":"Cureus"}],"container-title":["Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-023-02149-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s15010-023-02149-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-023-02149-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T09:58:54Z","timestamp":1710928734000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s15010-023-02149-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,22]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["2149"],"URL":"https:\/\/doi.org\/10.1007\/s15010-023-02149-x","relation":{},"ISSN":["0300-8126","1439-0973"],"issn-type":[{"value":"0300-8126","type":"print"},{"value":"1439-0973","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,22]]},"assertion":[{"value":"11 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing financial or non-financial interests that could have appeared to influence the work reported in this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Given the patient\u2019s unfortunate passing, obtaining approval was not initially deemed necessary. However, for thoroughness and transparency, the Ethics Committee as well as the Data Protection Committee of the University Clinic of Jena were consulted, and both committees granted approval for submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors obtained informed consent from the patient\u2019s family for the publication of this case report.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors obtained informed consent from the patient\u2019s family for the publication of this case report. Any potentially identifying information has been appropriately anonymized or pseudonymized.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}