A case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome-positive acute B-lymphoblastic leukemia.

We report a case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome-positive acute B-lymphoblastic leukemia. The annular appearance may be developed by immunomodulatory effects of blinatumomab.

Multiple Phenotypic Conversion in Malignant Melanoma: Obtainment of Granulocyte Colony-Stimulating Factor-Producing Ability during the Intermission of Nivolumab Therapy.

Malignant melanoma (MM) is one of the most aggressive, recalcitrant, and recurrence-prone skin neoplasms. Its feature is likely to be associated with phenotypic conversion due to tumor heterogeneity. The multidisciplinary assessment, including surgery, drug therapy using anticancer agents and immune checkpoint inhibitors, and radiotherapy, is needed for the treatment of advanced MM. Herein, we report a long-term follow-up MM, in which multiple phenotypic conversion occurred during several treatments. In particular, our case obtained granulocyte colony-stimulating factor-producing ability during the intermission of nivolumab therapy and it was successfully controlled by re-administration of nivolumab. Sharing the case having a varied clinical course is meaningful to increase the knowledge and decision branches for the treatment of melanoma.

Immune-related dermatitis during combined treatment with pembrolizumab and axitinib in a patient with metastatic renal cell\x92carcinoma with stasis dermatitis.

INTRODUCTION: The combination of pembrolizumab and axitinib has recently been approved as a first-line treatment for previously untreated metastatic renal cell carcinoma. However, immune-related adverse events are not well known. CASE PRESENTATION: A 65-year-old male was diagnosed with renal cell carcinoma with metastases to the brain and lungs. The patient had a medical history of stasis dermatitis. During the combined treatment of pembrolizumab and axitinib, blisters appeared on the lower extremities. Skin biopsy revealed septal panniculitis, pustules, and perivascular lymphocytic and neutrophilic infiltration of the skin, and the patient was diagnosed with immune-related dermatitis. The dermatitis improved with oral prednisolone treatment. CONCLUSION: A case of immune-related dermatitis during combinatorial treatment with pembrolizumab and axitinib for renal cell carcinoma has been reported. Preexisting stasis dermatitis may have affected the onset and deterioration of immune-related dermatitis.

Etiological role of cigarette smoking in rheumatoid arthritis: Nasal exposure to cigarette smoke condensate extracts augments the development of collagen-induced arthritis in mice.

Cigarette smoking is a major environmental risk factor for rheumatoid arthritis (RA). However, the experimental bases supporting the etiological role of cigarette smoking in RA have not been fully provided. We have reported that cigarette smoke condensate (CSC), by means of subcutaneous injection into DBA/1J mice with collagen and complete Freund's adjuvant or intraperitoneal injection one day before immunization, augmented the development of arthritis in the mouse model of collagen type II-induced arthritis (CIA). However, these experimental procedures may not be appropriate for cigarette smoking. In this study, we nasally exposed mice to mainstream CSC and found that CSC augmented the induction and development of arthritis and antibody level against collagen. Histological examination confirmed the augmenting effect of CSC. These findings provide experimental bases supporting the etiological role of cigarette smoking in RA.

Cigarette smoke condensate extracts augment collagen-induced arthritis in mice.

Although cigarette smoking is a solid environmental risk factor for rheumatoid arthritis (RA) as revealed by epidemiological studies, the scientific basis has not been provided. Proinflammatory cytokines produced by synoviocytes are implicated in the pathogenesis of RA. As cigarette smoke condensate (CSC) is able to up-regulate the production of proinflammatory cytokines from human fibroblast-like synoviocytes, we studied the effect of CSC on induction of arthritis in the mouse model of collagen type II-induced arthritis (CIA). When mainstream CSC or sidestream CSC was administered into DBA/1J mice at the time of immunization with collagen and complete Freund adjuvant, CSC dose-dependently augmented the induction and clinical development of arthritis at both young and older mice. Peritoneal injected mainstream CSC one day before immunization also exhibited the augmenting effect, suggesting the systemic effect of CSC. These results support the etiological role of cigarette smoking in RA.

Cigarette smoke condensate upregulates the gene and protein expression of proinflammatory cytokines in human fibroblast-like synoviocyte line.

Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which are implicated in the pathogenesis of RA. When human fibroblast-like synoviocytes line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated in both time- and dose-dependent manners. The upregulatory effects of CSC on these cytokines were not significantly inhibited by alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, suggesting that the effects of CSC were independent of AhR. Cycloheximide treatment indicated that the augmenting effect of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression requires de novo protein synthesis. CSC also induced cytokines at protein levels and further augmented the effects of tumor necrosis factor alpha on induction of these cytokines at both mRNA and protein levels. These results support the epidemiological studies indicating a strong association between heavy cigarette smoking and pathogenesis of RA.