Body mass index, HbA1c and serum C-reactive protein are predictors of secondary failure in infliximab continuance for Japanese psoriasis patients: A hospital-based retrospective case-control study.

Biologics has had a great impact on psoriasis treatment as well as the life of psoriasis patients. Infliximab (IFX), one of the biologics targeting tumor necrosis factor (TNF), is the first of the biologics introduced to Japanese psoriasis patients. Many patients had benefits of IFX from initial applications and sustained remission of skin lesions and arthritis. Some, however, fall into so-called secondary failure, in which patients become less responsive to IFX when the treatment is repeated. The mechanism of secondary failure and the background of patients with secondary failure have not been completely elucidated. To address this issue, we retrospectively evaluated psoriasis patients treated with IFX in our department. In this retrospective, single-center, case-control study based on the clinical record, a total of 34 patients were enrolled. We excluded 7 patients who discontinued IFX because of adverse events of IFX. We divided other 27 patients into two groups; 16 patients who kept using IFX (Continuance group); and 11 patients who switched to other treatments (Discontinuance group). Among various clinical features, body mass index (BMI), HbA1c, and serum CRP level were significantly higher in the Discontinuance group than the Continuance group. The results indicated that these three clinical features of BMI, HbA1c and serum CRP level before treatment are the predictors of successful IFX treatment and suggest that improvement of metabolic conditions contributes to avoiding secondary failure and discontinuance of IFX.

Multifocal BRAF(V600E)-Mutated Melanoma in situ on the Foot.

Melanoma is an aggressive skin cancer that originates from melanocytes, and about one half of melanoma cases possess a BRAF mutation. Together with PD-L1 expression, the BRAF(V600E) mutation is one of the optimal therapeutic targets for the treatment of melanoma. In this report, we describe a case of multifocal melanoma in situ on the foot, which carried the p.V600E mutation in the BRAF gene. Interestingly, the spotted melanoma lesion is demarcated by normal skin, and in all spotted pigmented lesions, there were no signs of dermal invasion of melanoma cells or spontaneous regression. Our case presented atypical clinical features, which might correlate with the local mutations of BRAF gene and the immunological expression of PD-L1.

Psoriasiform Drug Eruption Caused by Abatacept: Immunohistochemical Investigation of STAT Signaling.

Abatacept is a biological immune modifier that is used for the treatment of rheumatoid arthritis. Although psoriasiform drug eruption is reported as one of the cutaneous adverse effects of abatacept, the precise mechanisms are not fully understood. In this report, we describe a 65-year-old Japanese man with psoriasiform drug eruption caused by abatacept. Interestingly, immunohistochemical staining revealed that the epidermal keratinocytes in the basal layer and lower layers of the stratum spinosum were positive for pSTAT3, partially positive for pSTAT1 and negative for pSTAT6, which is similar to conventional psoriasis vulgaris. Our present study suggests that psoriasiform drug eruption caused by abatacept might develop by similar immunological mechanisms as those of psoriasis vulgaris.

Adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis.

Lipodystrophy is a group of metabolic disorders, possibly caused by autoimmune disease. In this report, we describe a case of adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis without a family history. Interestingly, immunohistochemical staining revealed dense infiltration of IL-27-producing cells as well as MMP-7-and MMP-28-expressing cells, both of which have been reported to facilitate the development of autoimmune disease. Our present case might suggest possible mechanisms for acquired partial lipodystrophy.

Successful adalimumab treatment of a psoriasis vulgaris patient with hemodialysis for renal failure: A case report and a review of the previous reports on biologic treatments for psoriasis patients with hemodialysis for renal failure.

The efficacy and safety of biologic treatments have been established in patients with moderate to severe psoriasis, but there are few reports on biologic therapy for patients with psoriasis complicated by end-stage renal failure on hemodialysis (HD). In this report, we demonstrated the efficacy and safety of adalimumab for patients with severe psoriasis on HD. A 46-year-old Japanese man with a 14-year history of psoriasis was referred to our clinic in September 2009. He had developed hypertension and renal failure during a 7-year history of cyclosporin treatment. With the infliximab treatment, he achieved 75% improvement of the Psoriasis Area and Severity Index (PASI) score within 3 months from the PASI of 42.3 before the treatment. However, his renal failure gradually deteriorated, and HD was initiated at 1 year after the introduction of infliximab. Because of hydration during the i.v. injection of infliximab, he developed pulmonary edema with every infliximab treatment after starting HD. We switched to ustekinumab treatment, but his psoriasis was not improved. Then, we switched to adalimumab and achieved a PASI-100 response within 2 months. The patient received adalimumab treatment for more than a year without any adverse effects. In addition to our case, five articles reported cases of psoriasis patients with renal failure on HD who were treated with biologics. The psoriatic lesions were improved by biologics in these cases, and no severe adverse effects on the renal function were reported. Thus, biologics are a reasonable treatment option for patients with severe psoriasis with renal failure on HD.

Merkel Cell Carcinoma Concomitant with Invasive Bowen's Disease: Immunohistochemical Investigation of Tumor-Infiltrating Leukocytes.

Merkel cell carcinoma (MCC) is an aggressive, cutaneous, neuroendocrine carcinoma and, in rare cases, occurs with Bowen's disease (BD). In this report, we describe a case of MCC concurrent with invasive BD and compare the profiles of tumor-infiltrating leukocytes in the lesional skin of MCC and invasive BD. Interestingly, immunohistochemical study revealed significant numbers of CD8+ cells and caspase 3-expressing cells in the same areas of invasive BD and MCC. Our present case suggests that MCC concurrent with invasive BD might have a good prognosis because of the substantial number of CD8+ cells in the tumor.

Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene.

Fatty acids are shown to be important in various skin functions. Fatty acid binding protein (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system. Among the FABP family proteins, epidermal-type FABP (E-FABP) is solely expressed in keratinocyte but its specific role in skin is not yet fully established. We found an elevated expression of E-FABP in regenerative keratinocytes of healing wounds. However, E-FABP null mice showed no marked differences compared to wild type mice in the process of wound closure, in vivo. On the other hand, in keratinocyte culture, E-FABP gene disruption decreased the cell motility, but did not affect the cell proliferation. E-FABP deletion may be compensated for in vivo by the microenvironment comprised of various cells such as fibroblasts and endothelial cells around the wound. Our analyses suggest that the E-FABP elevation may be necessary for the activation of cell motility within regenerative epidermis during wound healing.

Detection of various types of human papillomavirus DNA, mainly belonging to the cutaneous-group, more frequently in normal tissue than in squamous cell carcinomas of the lip.

BACKGROUND: Mucosal high-risk human papillomaviruses (HPVs), such as type 16, are detectable in oral cancers, especially of the oropharynx and tonsils, and there is evidence that they play a pathogenetic role in some cases. However, information is limited about their significance for cancers of the vermilion of the lip. OBJECTIVE: To determine the detection rate, types and localization of HPVs in squamous cell carcinomas (SCCs) of the lip. METHODS: Nested PCR for cutaneous HPVs, including epidermodysplasia verruciformis-related HPV (EV-HPV), and single PCR for mucosal HPVs, were conducted for a total of 27 SCCs and normal samples from 30 individuals. Tyramide-based in situ hybridization (ISH) was also applied. RESULTS: Various types of HPVs were detected, particularly from normal individuals. Among the kinds of the HPV types detected in this study, half were found by PCR using a primer pair, which we newly designed. The prevalence of HPV was 5 out of 27 SCCs (ca. 18%) and 10 out of 30 normal individuals (ca. 33%). They were the entire cutaneous-group except for two, from one SCC and one normal individual. CONCLUSION: On the surface of the normal lip various types of mainly cutaneous-group HPVs may be present, but there does not appear to be any obvious association with SCCs developing in this site.