Treatment of refractory necrobiotic xanthogranulomas with extracorporeal photopheresis and intravenous immunoglobulin.

Necrobiotic xanthogranuloma (NXG) is a disease of fibrotic or telangiectatic granulomatous papules and nodules that can ultimately progress into ulcerated plaques. Although the exact cause of NXG is unknown, it most often occurs in patients with paraproteinemia secondary to a hematologic disease. Consequently, therapy for NXG is targeted at treating the underlying hematologic disease, and subsequent paraproteinemia, with alkylating agents, antimetabolites, radiation, and/or immunosuppressive agents. Cases refractory to these therapies often have poor outcomes. We report the successful treatment of two patients with refractory NXG with two different modalities: extracorporeal photopheresis (ECP) and intravenous immunoglobulin (IVIG). The first case shows a patient without paraproteinemia who had success with ECP and IVIG, and the second is a patient with paraproteinemia treated effectively with IVIG. The beneficial response of our patients to IVIG, as well as ECP, shows that they may be an effective treatment option for refractory NXG.

Nonnecrobiotic necrobiotic xanthogranuloma as an initial manifestation of paraproteinemia and small lymphocytic lymphoma in a patient with Sjögren syndrome.

We report a unique case of periocular nonnecrobiotic necrobiotic xanthogranuloma in a 52-year-old white woman with Sjögren syndrome who was subsequently found to have an immunoglobulin G paraproteinemia and coexisting small lymphocytic lymphoma. Therapy with fludarabine, cytoxan, and rituximab (FCR) resulted in a dramatic resolution of her sicca symptoms and periocular xanthogranulomas. This case further illustrates the association of hematolymphoid disorders with cutaneous xanthogranulomatous disease and the importance of additional appropriate laboratory and radiologic investigation for the accurate diagnosis of an underlying malignancy.

[Diffuse plane normolipemic xanthomatosis and necrobiotic xanthogranuloma associated with monoclonal gammopathy--determining the disease stage with PET-CT and treatment experience. Two case studies and literature review]. / Difuzní plosná normolipemická xantomatóza a nekrobiotický xantogranulom, asociované s monoklonální gamapatií--prínos PET-CT pro stanovení rozsahu nemoci a zkusenosti s lécbou. Popis dvou prípadu a prehled literatury.

UNLABELLED: Monoclonal gammopathy may manifest itself through a range of skin disorders, including plane normolipemic xanthoma and necrobiotic xanthogranuloma. The present paper describes two patients with these cutaneous symptoms. The first has extensive areas of skin affected by flat xanthomas, monoclonal gammopathy with > 10% infiltration of bone marrow with clonal plasmocytes and, according to PET-CT, unclear lymphadenopathy in the retroperitoneal area. The size of this lymphadenopathy (histologically no malignant infiltration and no confirmed infectious aetiology) has not changed significantly over a 4-year follow-up. Repeated PET-CT scans showed decrease in SUV value in this infiltration from 7.5 to 3.8. Four cycles of treatment with a combination of bortezomib, cyclophosphamide and dexamethasone brought neither reduction in monoclonal immunoglobulin nor change to skin morphology. We believe that the abdominal lymphadenopathy is associated with xanthomatosis but have been unable to confirm this unequivocally. The second patient is being followed up for more than 10 years, originally for MGUS, later for asymptomatic multiple myeloma. Last year, painful subcutaneous and cutaneous infiltrates, isolated on an upper limb and more frequent on lower limb, started to occur. These infiltrates are palpable. PET-CT imaging provided an excellent depiction of these infiltrates, showing no pathology on the head, chest and abdomen and no osteolytic foci on the skeleton. CT imaging showed clearly numerous infiltrates in the skin and subcutaneous tissue of lower limbs, particularly both shanks, reaching up to 2 cm in depth. The largest infiltrate, measuring 3.5 by 2 by 10 cm, was identified in the distal dorsal part of the right shank. PET imaging of lower limbs showed distinctly pathological accumulation in all infiltrates described above; the accumulation of glucose in the lower part of the right shank reached 10.0 SUV. CT images of lower limbs showed increased density saturated hypodermis even in the areas where there is no increased accumulation of 18 fluoroglucose. Following 40 Gy irradiation, the size of infiltrate in the radiated area decreased and their soreness ceased. CONCLUSION: PET-CT imaging offered information on extra-cutaneous signs of plane normolipemic xanthomas and provided excellent depiction of the areas of the skin and hypodermis affected by necrobiotic xanthogranuloma. Chemotherapy with cyclophosphamide, bortezomib and dexamethasone brought no reduction in monoclonal immunoglobulin concentration, and no reduction in plane normolipemic xanthomas. Radiotherapy targeted at large foci of xanthogranulomas led to partial regression and ceased infiltrate soreness.

TIMP-1 Mediates Inflammatory and Immune Response to IL-6 in Adult Orbital Xanthogranulomatous Disease.

Purpose: To explore the pathogenesis that TIMP-1 mediated in adult orbital xanthogranulomatous disease (AOXGD), a rare type of non-Langerhans histiocytosis that damages the appearance and quality of life of patientsMethods: We reviewed 22 patients diagnosed with AOXGD based on clinical manifestations and histological analysis, and then investigated the expression of TIMP-1 and IL-6 with q-PCR and IHC in AOXGD tissues and the possible mechanism involved in the induction of TIMP-1 by IL-6.Results: IL-6 and TIMP-1 were significantly increased in AOXGD tissues. IL-6 promoted TIMP-1 production by M1 macrophages by stimulating the phosphorylation of JAK2 and STAT3. Moreover, IL-17 and IFN-γ, the classical markers of Th1 and Th17 cells, were increased in AOXGD.Conclusion: These data implied that the IL6~JAK2/STAT3-TIMP-1 signalling pathway is activated in AOXGD and that adaptive Th1 and Th17 responses are involved in the development of AOXGD.

Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature.

Necrobiotic xanthogranuloma (NXG) was first described in 1980 by Kossard and Winkelmann in an article in which they discussed 8 patients with xanthomatous plaques who were noted to have monoclonal gammopathy, predominantly of the Ig(immunoglobulin)G-κ type.(1) Since then more than 50 patients with this disorder have been described, with approximately 80% of them having an associated monoclonal gammopathy. We describe the first case, to our knowledge, of NXG with associated monoclonal gammopathy treated with thalidomide plus dexamethasone, achieving complete resolution of the skin lesions and sustaining response more than 3 years after treatment.

Orbital necrobiotic xanthogranuloma associated with systemic IgG4 disease.

PURPOSE: The authors describe 2 cases of orbital xanthogranulomatous disease associated with an increase in IgG4-positive plasma cells, and also examine IgG4 in other types of orbital inflammation. METHODS: Immunohistochemistry for total IgG and IgG4 was performed in 18 cases of orbital inflammation, including chronic dacryoadenitis (n=10), necrobiotic xanthogranuloma (n=2), xanthogranuloma (n=1), idiopathic orbital inflammation/pseudotumor (n=4), and fungal infection (n=1). RESULTS: One patient presenting with necrobiotic xanthogranuloma had signs of systemic IgG4 disease. His orbital lesion showed an elevated number of IgG4 positive plasma cells (55%). An orbital xanthogranulomatous lesion in a second patient lacking systemic symptoms also contained a high percentage of IgG4-positive plasma cells (80%). Only 1 case of chronic dacryoadenitis contained prominent IgG4-positive plasma cells (mean 17/hpf). CONCLUSIONS: IgG4-positive plasma cells are relatively rare in nonsclerosing orbital inflammatory lesions. However, systemic disease IgG4 can be associated with necrobiotic xanthogranuloma of the orbit.