Hand-Foot Skin Reaction Secondary to Sunitinib in a Patient With Metastatic Clear Cell Renal Cell Carcinoma.

A man, age 45 years, was diagnosed with intermediate-risk stage IV clear cell renal carcinoma (lung and lymph node metastases). He was prescribed first-line systemic treatment with sunitinib (Sutent) 50 mg per day (each cycle: 4 weeks on, 2 weeks off). Upon day 22 of his second sunitinib cycle, he came to the oncology clinic complaining of difficulty walking due to bilateral sole pain. He described initial tingling sensations, which then became burning and painful, with symmetrical erythema and edema of the soles, without blisters. These turned into painful plaques with yellowish discoloration and hyperkeratosis on pressure-bearing areas. He denied fever or other symptoms. The pain limited his instrumental activities of daily living, but not his self-care activities of daily living. Total body skin examination disclosed hyperkeratotic plaques on the undersurface of the great toes and heels of both feet, predominantly at sites of pressure; no blisters, crusts, ulcers, or fissures were found. No relevant findings were found upon physical examination of his hands, mucosae, and scalp. A diagnosis of grade 2 hand-foot skin reaction (HFSR) was made.

Polymerized-type I collagen induces upregulation of Foxp3-expressing CD4 regulatory T cells and downregulation of IL-17-producing CD4⁺ T cells (Th17) cells in collagen-induced arthritis.

Previous studies showed that polymerized-type I collagen (polymerized collagen) exhibits potent immunoregulatory properties. This work evaluated the effect of intramuscular administration of polymerized collagen in early and established collagen-induced arthritis (CIA) in mice and analyzed changes in Th subsets following therapy. Incidence of CIA was of 100% in mice challenged with type II collagen. Clinimorphometric analysis showed a downregulation of inflammation after administration of all treatments (P < 0.05). Histological analysis showed that the CIA-mice group had extensive bone erosion, pannus and severe focal inflammatory infiltrates. In contrast, there was a remarkable reduction in the severity of arthritis in mice under polymerized collagen, methotrexate or methotrexate/polymerized collagen treatment. Polymerized Collagen but not methotrexate induced tissue joint regeneration. Polymerized Collagen and methotrexate/polymerized collagen but not methotrexate alone induces downregulation of CD4(+)/IL17A(+) T cells and upregulation of Tregs and CD4(+)/IFN-γ(+) T cells. Thus, Polymerized Collagen could be an effective therapeutic agent in early and established rheumatoid arthritis by exerting downregulation of autoimmune inflammation.

Peripheral regulatory cells immunophenotyping in primary Sjögren's syndrome: a cross-sectional study.

INTRODUCTION: IL-10-producing B cells, Foxp3-expressing T cells (Tregs) and the IDO-expressing dendritic cells (pDC) are able to modulate inflammatory processes, to induce immunological tolerance and, in turn, to inhibit the pathogenesis of autoimmune disease. The aim of the study was to characterize and to enumerate peripheral IL-10--producing B cells, Tregs and pDCregs in primary Sjögren's Syndrome (pSS) patients in regard of their clinical and serologic activity. METHODS: Fifty pSS patients and 25 healthy individuals were included in the study. CD19⁺-expressing peripheral B lymphocytes were purified by positive selection. CD19⁺/CD24(hi)/CD38(hi)/IL-10-producing B cells, CD4⁺/CD25(hi)/Foxp3⁺ and CD8⁺/CD28⁺/Foxp3⁺ Tregs, as well as CCR6⁺/CD123⁺/IDO⁺ DCs, were quantitated by flow cytometry. RESULTS: Immature/transitional circulating IgA⁺ IL-10-producing B cells had higher levels in pSS patients versus control group, whereas CD19⁺/CD38(hi)/IgG⁺/IL-10⁺ cells had lower percentage versus control. Indeed CD19⁺/CD24(hi)/CD38(hi)/CD5⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD20⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺, and CD19⁺/CD24(hi)/CD38(hi)/CXCR7⁺/IL-10⁺ cells had higher frequency in clinical inactive pSS patients when compared with control group. Remarkably, only percentages of CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺ and CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺ subsets were increased in pSS serologic inactive versus control group (P < 0.05). The percentage of IDO-expressing pDC cells was higher in pSS patients regardless of their clinical or serologic activity. There were no statistically significant differences in the percentage of CD4⁺/CD25(hi)/Foxp3⁺ Tregs between patient groups versus controls. Nonetheless, a decrease in the frequency of CD8⁺/CD28⁻/Foxp3⁺ Tregs was found in inactive pSS patients versus controls (P < 0.05). CONCLUSIONS: The findings of this exploratory study show that clinical inactive pSS patients have an increased frequency of IL-10--producing B cells and IDO-expressing pDC cells.