{"doi":"10.1001/jamadermatol.2019.4221","title":"A Multicenter Cross-Sectional Study and Systematic Review of Necrobiotic Xanthogranuloma With Proposed Diagnostic Criteria","abstract":"Importance: Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders. Despite the morbidity of NXG, the literature is limited to case reports and small studies, and diagnostic criteria are lacking. Objective: To evaluate the characteristics of NXG and propose diagnostic criteria. Design, Setting, and Participants: This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women's and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria. Main Outcomes and Measures: Demographic factors, comorbidities, clinical features, and treatment response. Results: Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-κ (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG. Conclusions and Relevance: Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.","journal":"JAMA Dermatology","year":2020,"id":55885,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289584,"name":"Connie S. Zhong","orcid":"0000-0003-1222-360X","position":1,"is_corresponding":false},{"id":289585,"name":"David A. Hashemi","orcid":"0000-0002-4927-3152","position":2,"is_corresponding":false},{"id":289586,"name":"Hovik J. Ashchyan","orcid":"0000-0002-9651-8757","position":3,"is_corresponding":false},{"id":289587,"name":"Zoe Brown‐Joel","orcid":"0000-0001-7768-1439","position":4,"is_corresponding":false},{"id":289588,"name":"Megan H. Noe","orcid":"0000-0001-8481-4711","position":5,"is_corresponding":false},{"id":289589,"name":"Sotonye Imadojemu","orcid":"0000-0001-9049-9690","position":6,"is_corresponding":false},{"id":289590,"name":"Robert G. Micheletti","orcid":"0000-0003-2517-7008","position":7,"is_corresponding":false},{"id":289591,"name":"Ruth Ann Vleugels","orcid":"0000-0001-8446-7115","position":8,"is_corresponding":false},{"id":289592,"name":"Karolyn A. Wanat","orcid":"0000-0001-6262-2559","position":9,"is_corresponding":false},{"id":279869,"name":"Misha Rosenbach","orcid":null,"position":10,"is_corresponding":false},{"id":289593,"name":"Arash Mostaghimi","orcid":"0000-0002-6084-5617","position":11,"is_corresponding":false},{"id":289583,"name":"Caroline A. Nelson","orcid":"0000-0002-0863-6797","position":0,"is_corresponding":true}],"reference_count":212,"raw_metadata":null,"created_at":"2026-07-18T21:05:29.672878Z","pmid":"31940000","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}