{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:01Z","timestamp":1789448581821,"version":"build-2803163510"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Panniculitis in adolescents often poses a diagnostic challenge for physicians. We report an adolescent girl presenting with recurrent steroid-responsive lymphocytic septal panniculitis, genital ulcer, and constitutional symptoms, later complicated by macrophage activation syndrome and steatohepatitis. Extensive evaluation excluded infectious, autoimmune, and malignant causes. Histopathology revealed septal panniculitis without vasculitis or atypical lymphoid cells. Whole-exome sequencing identified a heterozygous\n PSMB9<\/jats:italic>\n variant (c.595A&gt;G; p.Thr199Ala) and a homozygous\n HAVCR2<\/jats:italic>\n variant (c.290T&gt;C; p.Ile97Thr); the latter has not been reported in a homozygous state in existing genomic databases and is predicted to be deleterious. The coexistence of panniculitis, haemophagocytic lymphohistiocytosis (HLH)-like manifestations, and histologically lymphocytic rather than neutrophilic infiltrates suggests a distinct panniculitis\u2013HLH overlap syndrome associated with the\n HAVCR2<\/jats:italic>\n mutation, which does not fit within the subcutaneous panniculitis-like T-cell lymphoma spectrum. A potential contribution (gene dosage effect) from the heterozygous\n PSMB9<\/jats:italic>\n mutation was uncertain, as parental testing was not feasible. The patient achieved sustained remission on corticosteroids and tacrolimus. This case broadens the phenotypic spectrum of\n HAVCR2<\/jats:italic>\n -associated immune dysregulation and documents a novel homozygous\n HAVCR2<\/jats:italic>\n variant (p.Ile97Thr), underscoring the importance of comprehensive genetic evaluation in patients with unexplained recurrent panniculitis.\n <\/jats:p>","DOI":"10.3389\/fimmu.2026.1906895","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:27:20Z","timestamp":1789446440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Reconciling genomic ambiguity with clinical certainty in refractory panniculitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Sayan","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Rabindranath Tagore International Institute of Cardiac Sciences (RTIICS)","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat K.","family":"Sahu","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George\u2019s Medical University","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhish M.","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George\u2019s Medical University","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urmila","family":"Dhakad","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George\u2019s Medical University","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneet","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George\u2019s Medical University","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/dermatopathology8030037","article-title":"Panniculitis in children","volume":"8","author":"Moulonguet","year":"2021","journal-title":"Dermatopathology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/0115733971254702231020060633","article-title":"Panniculitis: a cardinal sign of autoinflammation","volume":"20","author":"Borges","year":"2024","journal-title":"Curr Rheumatol Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/j.1442-200x.2006.02169.x","article-title":"Panniculitis in childhood and adolescence","volume":"48","author":"Moraes","year":"2006","journal-title":"Pediatr Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B5","article-title":"Recommendation for individualizing evidence weights: Recalibration of PM2 to supporting strength","volume-title":"Clinical Genome Resource","year":"2020"},{"key":"B6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1053\/j.semdp.2016.11.009","article-title":"Cutaneous lymphomas with a panniculitic presentation","volume":"34","author":"Willemze","year":"2017","journal-title":"Semin Diagn Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.282419","article-title":"Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis","volume":"108","author":"Moonla","year":"2023","journal-title":"Haematologica"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-087288","article-title":"Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases","volume":"111","author":"Willemze","year":"2008","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0251-4","article-title":"Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome","volume":"50","author":"Gayden","year":"2018","journal-title":"Nat Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2024.06.006","article-title":"Different mutational profiles of subcutaneous panniculitis-like T-cell lymphoma and lupus panniculitis: an additional case series","volume":"116","author":"Machan","year":"2025","journal-title":"Actas Dermo-Sifiliograficas"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004562","article-title":"Genetic profiles of subcutaneous panniculitis-like T-cell lymphoma and clinicopathological impact of HAVCR2 mutations","volume":"5","author":"Koh","year":"2021","journal-title":"Blood Adv"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906895\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:27:21Z","timestamp":1789446441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906895\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":11,"alternative-id":["10.3389\/fimmu.2026.1906895"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1906895","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1906895"}}