Researchers propose diagnostic criteria for necrobiotic xanthogranuloma

Paraproteinemia and malignancies such as multiple myeloma are the two primary diagnostic criteria proposed for necrobiotic xanthogranuloma, according to a recent report.

Arash Mostaghimi, MD, MPA, MPH, director of the dermatology inpatient service and co-director of the complex medical dermatology fellowship program at Brigham and Women’s Hospital and assistant professor of dermatology at Harvard Medical School, and colleagues described necrobiotic xanthogranuloma (NXG) as “a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders.”

While this condition comes with significant morbidity, clinicians seeking information about it may find only case reports and small trials and have no diagnostic criteria to guide them.

The current analysis was multifaceted. One component was a multicenter cross-sectional study conducted at Brigham and Women’s and Massachusetts General Hospitals and the University of Iowa Hospitals and Clinics between 2000 and 2018 and at the University of Pennsylvania Health System between 2008 and 2018. The data set also included a systemic review of Cochrane, Ovid Embase, PubMed and Web of Science databases. Finally, a consensus exercise was undertaken by eight dermatologists to identify diagnostic criteria for NXG.

Overall, 34 patients with NXG from the multicenter cohort and 201 from the systematic review underwent analysis.

Results showed that paraproteinemia was reported in 82.1% of the cohort, with IgG kappa observed in 50%.

Malignancies occurred in 25.1% of patients. Multiple myeloma, at 14%, was the most commonly reported malignancy.

Paraproteinemia and/or malignancy was reported in 83.8% of patients overall.

Looking closer at the multicenter cohort, paraproteinemia evolved into multiple myeloma over a duration of up to 5.7 years (median = 2.4; range, 0.1 to 5.7 years) after presenting with NXG.

Other findings from the multicenter cohort showed that intravenous immunoglobulin (IVIg) was most likely to yield a treatment response rate, with 100% of nine patients responding. Anti-malarial drugs were effective in four out of five patients (80%), intralesional triamcinolone showed response in six of eight patients (75%), surgery was effective in three of four patients (75%), chemotherapy was effective in eight of 12 patients (67%), and lenalidomide or thalidomide was effective in five of eight patients (63%).

“Our data demonstrated a high rate of response to IVIg, antimalarials and intralesional Kenalog,” Mostaghimi told Healio. “Although these results are promising, the high response rates in the literature are likely overstated due to publication bias.”

In broader terms, some of the factors observed in patients with NXG included papules, plaques and/or nodules that were typically yellow or orange in color, which occurred in 60.4% of patients. These cutaneous lesions were distributed periorbitally in 59.3% of the cohort. In addition, patients with extracutaneous involvement were most likely to experience symptoms in the eye, at 14.5%.

“Our results largely confirm the existing data on the epidemiology and comorbidities of this disease: older patients, with an average age of 62, 82% of whom have an associated paraproteinemia,” Mostaghimi said.

Mostaghimi then outlined the diagnostic criteria proposed by the group. “Clinicians considering a diagnosis of NXG should be familiar with our proposed criteria,” he said. “The two major criteria — both required — are, No. 1, cutaneous papules/plaques or nodules, most often yellow and, No. 2, histology demonstrating palisading granulomas, lymphoplasmacytic infiltrate and zones of necrobiosis. These criteria should be combined with at least one minor criteria, either paraproteinemia or periorbital distribution of cutaneous lesions, to make the diagnosis.”

The researchers defined NXG as a “multisystem disorder” that carries associations with paraproteinemia and malignancy. “The proposed diagnostic criteria may advance clinical research and should be validated,” they wrote. – by Rob Volansky

Disclosures: Mostaghimi reports personal fees from 3Derm and Pfizer, personal fees from and equity in Hims, equity in Lucid, and participation in clinical trials with Aclaris, Concert, Incyte and Lilly, outside the submitted work.