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JAMA Dermatol. 2020 Jan 15. doi: 10.1001/jamadermatol.2019.4221. [Epub ahead of print]

A Multicenter Cross-Sectional Study and Systematic Review of Necrobiotic Xanthogranuloma With Proposed Diagnostic Criteria.

Author information

1
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
2
Harvard Medical School, Boston, Massachusetts.
3
Perelman School of Medicine, University of Pennsylvania, Philadelphia.
4
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
5
University of Iowa Carver College of Medicine, Iowa City.
6
Perelman School of Medicine at the University of Pennsylvania, Department of Dermatology, Philadelphia.
7
Perelman School of Medicine at the University of Pennsylvania, Department of Medicine, Philadelphia.
8
Department of Dermatology, University of Iowa Carver College of Medicine, Iowa City.

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.

PMID:
31940000
PMCID:
PMC6990734
[Available on 2021-01-15]
DOI:
10.1001/jamadermatol.2019.4221

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