Article

Necrobiotic Xanthogranuloma Without a Monoclonal Gammopathy

Cutis. 2014 December;94(6):293-296

References

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Eighty percent of patients diagnosed with NXG have an associated monoclonal gammopathy and 10% develop multiple myeloma.² Our case presents an unusual variant of NXG due to the absence of a monoclonal gammopathy. Chang et al¹⁰ described a similar case of NXG without a monoclonal gammopathy and hypothesized that periorbital involvement, malignancy, and systemic involvement are the main contributing factors to the morbidity of NXG.

Our patient had mildly elevated IgG SC1, IgG SC3, and IgG SC4 levels. The most substantially elevated subclass was IgG SC4. Elevations of IgG SC4 often are associated with disorders that are allergic or autoimmune in nature, such as pemphigus vulgaris, autoimmune pancreatitis, and inflammatory pseudotumor.¹¹ Our patient denied prior history and lacked manifestations of allergic or autoimmune disorders. A similar case was reported in a 67-year-old man with periorbital NXG and elevated IgG SC4 levels. Singh et al¹² postulated that systemic elevation of IgG SC4 can be associated with NXG of the orbit.

Due to the rarity and uncertain etiology of NXG, there are no definitive first-line therapies.There have been encouraging results with intravenous immunoglobulin,¹³ autologous stem cell transplantation,¹⁴ lenalidomide,¹⁵ melphalan with prednisolone,¹⁶ and chlorambucil with low-dose corticosteroids.¹¹ In 2007, Ho et al¹⁷ identified that CD20 and CD25 were both strongly expressed in tissue specimens of NXG, indicating the possible effectiveness of rituximab and denileukin diftitox, which target CD20 and CD25, respectively. It is unclear how these data pertain to patients without paraproteinemia because the treatment often is directed at the monoclonal gammopathy. These uncertainties are concerning because of the undesirable and often toxic side effects associated with these therapies. Psoralen plus UVA therapy was described as an alternative to cytotoxic drugs and immunosuppressive agents in 1 patient without paraproteinemia.¹⁸

Bullock et al¹⁹ proposed that NXG arises from a foreign body giant cell reaction resulting from circulating immune complexes precipitating in periorbital tissues. Although the relationship between the cutaneous manifestations and a monoclonal gammopathy remains poorly understood, cases of NXG without paraproteinemia challenge this theory. Our case supports the theory that there is no correlation between the histopathologic findings of NXG and the extent of the monoclonal gammopathy.

Conclusion

The etiology and pathogenesis of NXG remain elusive. We strive to attain a more sophisticated understanding of NXG to identify efficacious treatment options. Our case highlights the ambiguous association between the cutaneous lesions of NXG and a monoclonal gammopathy.