{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:22:39Z","timestamp":1777861359284,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life\u2010threatening hyperinflammatory conditions with heterogeneous triggers and overlapping clinical phenotypes. Diagnostic uncertainty is particularly challenging in resource\u2010limited settings, where advanced molecular and immunophenotypic investigations are not readily available. A 31\u2010year\u2010old woman presented with recurrent febrile episodes, trilineage cytopenias, hyperferritinemia (peak 16,970\u2009ng\/mL [reference: &lt;\u2009200\u2009ng\/mL]), hypofibrinogenemia, and progressive necrotic panniculitis plaques involving both lower extremities. Histopathological evaluation revealed lobular panniculitis with adipocyte necrosis and absence of vasculitis. While these findings raised strong concern for subcutaneous panniculitis\u2010like T\u2010cell lymphoma (SPTCL), definitive diagnosis was precluded by the absence of immunophenotyping, T\u2010cell receptor clonality studies, and HAVCR2 mutation testing\u2014all unavailable in our setting. The HScore was 216 (&gt;\u200999% probability of HLH\/MAS). A striking feature was the persistent dissociation between markedly elevated ferritin and low C\u2010reactive protein (CRP) values (ratio &lt;\u20090.002), consistent with a non\u2010IL\u20106\u2010dominant, interferon\u2010\u03b3\u2013driven hyperinflammatory state. Based on this phenotype, a sequential treatment strategy combining therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and cyclosporine A (CyA) was implemented without cytotoxic chemotherapy. The patient demonstrated significant clinical and biochemical improvement, with resolution of cytopenias and progressive decline in ferritin. This case highlights the diagnostic overlap between autoimmune panniculitis, SPTCL, and HLH\/MAS, and underscores the importance of phenotype\u2010guided management in complex hyperinflammatory syndromes. It further illustrates that effective treatment can be achieved without cytotoxic therapy in selected patients, even in the absence of definitive molecular diagnosis.<\/jats:p>","DOI":"10.1002\/ccr3.72638","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:51:28Z","timestamp":1777521088000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Adult\n                    <scp>HLH<\/scp>\n                    \/\n                    <scp>MAS<\/scp>\n                    With\n                    <scp>SPTCL<\/scp>\n                    \u2010Like Panniculitis: A Phenotype\u2010Guided, Resource\u2010Adapted Therapeutic Strategy Without Cytotoxic Therapy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9721-6249","authenticated-orcid":false,"given":"Hatem Mousa","family":"Taha","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences An\u2010Najah National University  Nablus Palestine"},{"name":"Department of Internal Medicine Palestine Medical Complex (PMC)  Ramallah Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Marouf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Palestine Medical Complex (PMC)  Ramallah Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled Hatem","family":"Taha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences An\u2010Najah National University  Nablus Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"issue":"9","key":"e_1_2_17_2_1","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1002\/art.38690","article-title":"Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome","volume":"66","author":"Fardet L.","year":"2014","journal-title":"Arthritis & Rhematology"},{"issue":"23","key":"e_1_2_17_3_1","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1182\/blood.2018894618","article-title":"Recommendations for the Management of Hemophagocytic Lymphohistiocytosis in Adults","volume":"133","author":"La Ros\u00e9e P.","year":"2019","journal-title":"Blood"},{"issue":"9927","key":"e_1_2_17_4_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult Haemophagocytic Syndrome","volume":"383","author":"Ramos\u2010Casals M.","year":"2014","journal-title":"Lancet"},{"issue":"3","key":"e_1_2_17_5_1","article-title":"Macrophage Activation Syndrome and Cytokine\u2010Directed Therapies","volume":"36","author":"Schulert G. S.","year":"2022","journal-title":"Best Practice & Research. Clinical Rheumatology"},{"issue":"1","key":"e_1_2_17_6_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/bloodadvances.2018025858","article-title":"Treatment of Refractory Hemophagocytic Lymphohistiocytosis With Emapalumab Despite Severe Concurrent Infections","volume":"3","author":"Lounder D. T.","year":"2019","journal-title":"Blood Advances"},{"issue":"12","key":"e_1_2_17_7_1","doi-asserted-by":"crossref","first-page":"e630","DOI":"10.1016\/S2352-3026(19)30156-5","article-title":"Ruxolitinib in Adult Patients With Secondary Haemophagocytic Lymphohistiocytosis: An Open\u2010Label, Single\u2010Centre, Pilot Trial","volume":"6","author":"Ahmed A.","year":"2019","journal-title":"Lancet Haematology"},{"issue":"19","key":"e_1_2_17_8_1","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1182\/blood-2015-01-551622","article-title":"How I Treat Hemophagocytic Lymphohistiocytosis in the Adult Patient","volume":"125","author":"Schram A. M.","year":"2015","journal-title":"Blood"},{"issue":"5","key":"e_1_2_17_9_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.7453\/gahmj.2013.008","article-title":"The CARE Guidelines: Consensus\u2010Based Clinical Case Reporting Guideline Development","volume":"2","author":"Gagnier J. J.","year":"2013","journal-title":"Global Advances in Health and Medicine"},{"key":"e_1_2_17_10_1","first-page":"341","article-title":"Respiratory Failure and the Hyperferritinemia Syndrome","volume":"25","author":"Karakike E.","year":"2021","journal-title":"Critical Care"},{"issue":"3","key":"e_1_2_17_11_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/pbc.21564","article-title":"The Role of the Initial Bone Marrow Aspirate in the Diagnosis of Hemophagocytic Lymphohistiocytosis","volume":"51","author":"Gupta A.","year":"2008","journal-title":"Pediatric Blood & Cancer"},{"issue":"2","key":"e_1_2_17_12_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH\u20102004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis","volume":"48","author":"Henter J. I.","year":"2007","journal-title":"Pediatric Blood & Cancer"},{"issue":"12","key":"e_1_2_17_13_1","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/s41588-018-0251-4","article-title":"Germline HAVCR2 Mutations Altering TIM\u20103 Characterize Subcutaneous Panniculitis\u2010Like T\u2010Cell Lymphoma With Hemophagocytic Lymphohistiocytosis","volume":"50","author":"Gayden T.","year":"2018","journal-title":"Nature Genetics"},{"issue":"4","key":"e_1_2_17_14_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1182\/bloodadvances.2018028340","article-title":"Frequent Germline Mutations of HAVCR2 in Subcutaneous Panniculitis\u2010Like T\u2010Cell Lymphoma","volume":"3","author":"Polprasert C.","year":"2019","journal-title":"Blood Advances"},{"issue":"21","key":"e_1_2_17_15_1","article-title":"Ruxolitinib for Subcutaneous Panniculitis\u2010Like T\u2010Cell Lymphoma With HAVCR2 Mutation: Targeting Immune Checkpoint\u2013Driven Hyperinflammation","volume":"131","author":"Zhang Q.","year":"2021","journal-title":"Journal of Clinical Investigation"},{"issue":"3","key":"e_1_2_17_16_1","first-page":"e147","article-title":"Therapeutic Plasma Exchange in the Treatment of Secondary Hemophagocytic Lymphohistiocytosis: A Multicentre Study","volume":"23","author":"Demirkol D.","year":"2022","journal-title":"Pediatric Critical Care Medicine"},{"issue":"2","key":"e_1_2_17_17_1","first-page":"139","article-title":"Use of Plasma Exchange in Hemophagocytic Syndromes","volume":"52","author":"Bunte M. 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E.","year":"2008","journal-title":"Pediatric Blood & Cancer"}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.72638","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ccr3.72638","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.72638","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:51:36Z","timestamp":1777521096000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.72638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ccr3.72638"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.72638","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"value":"2050-0904","type":"print"},{"value":"2050-0904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"2025-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72638"}}