Blue Nevus Associated With Acquired Dermal Melanocytosis on the Back.

Dermal melanocytosis includes various congenital and acquired pigmentary disorders characterized by dermal dendritic melanocytes. Blue nevi typically present as papulonodular lesions, whereas other dermal melanocytoses manifest as patches. This report describes a case of a blue nevus associated with acquired dermal melanocytosis on the back of a 46-year-old Japanese woman. The patient presented with a black nodule on a blue-greyish hyperpigmented area on the upper back. Histopathological analysis of the nodule confirmed a common blue nevus, whereas the adjacent hyperpigmented area showed features consistent with acquired dermal melanocytosis. Blue nevi and acquired dermal melanocytoses share a common pathophysiology involving ectopic melanocyte accumulation during embryogenesis. The coexistence of blue nevus and acquired dermal melanocytosis on the back is rare, highlighting the broad spectrum of dermal melanocytosis and the variability of its clinical manifestations. Recognition of such unusual presentations is critical for appropriate diagnosis and management.

Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible.

RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis.

BACKGROUND: Psoriasis, a common inflammatory skin disorder characterized by scaly erythema and plaques, is induced by dysregulation of dendritic cell- and T cell-mediated immune reaction. Receptor-interacting protein kinase 1 (RIPK1) regulates inflammatory signaling in response to stimuli such as TNF-α, TRAIL, and TLRs, resulting in apoptosis, necroptosis and NF-κB activation. However, the physiological relevance in human epidermis remains elusive. OBJECTIVE: In this study, we examined whether RIPK1 is involved in the pathogenesis of psoriasis vulgaris. METHODS: Skin samples of eight patients with psoriasis vulgaris were investigated by western blotting and immunohistochemistry. The functions of RIPK1 in keratinocytes were examined by RT-PCR and ELISA in vitro. TRAIL-neutralization-experiment was employed in an imiquimod-induced murine psoriasis model. RESULTS: In lesional psoriatic epidermis, RIPK1-expression was decreased compared with that in normal epidermis. Cytokines involved in the pathomechanism of psoriasis, such as IL-1ß, IL-17A, IL-22 and TRAIL, reduced RIPK1-expression in normal human epidermal keratinocytes (HEK) in vitro. In addition, RIPK1-knockdown enhanced TRAIL-mediated expression of psoriasis-relating cytokines, such as IL-1ß, IL-6, IL-8, TNF-α, in HEK. Numerous TRAIL-positive cells were detected in the dermis of lesional psoriatic skin, and TRAIL receptors were expressed in psoriatic epidermis and HEK in conventional cultures. Moreover, TRAIL-neutralization in an imiquimod-induced murine psoriasis model remarkably improved skin phenotypes, such as ear thickness, and TNF-α expression in lesional skin. CONCLUSIONS: These results lead us to conclude that RIPK1-downregulation in keratinocytes increases their susceptibility to TRAIL stimulation, and plays a role in the pathogenesis of psoriasis vulgaris.

Prevalence of coronary artery calcification in Japanese patients with psoriasis: A close correlation with bilateral diagonal earlobe creases.

Psoriasis is a multifactorial inflammatory disorder, in which the inflammation affects not only the skin but also the other internal organs, and can induce cardiovascular and cerebrovascular involvements. However, few predictive factors of cardiovascular diseases have been clarified in patients with psoriasis. This study was performed to verify whether diagonal earlobe creases (ELC) can reflect the hidden comorbidities in Japanese psoriatic patients. Prevalence and subtypes of ELC were analyzed in patients with psoriatic and with non-psoriatic skin diseases, and the correlation with coronary artery calcification (CAC) or fatty liver (FL) detected by computed tomography. Prevalence of CAC was approximately twice higher than data of a Japanese resident-based study previously reported. Generally, prevalence of ELC in a psoriatic group and mean age of psoriatic groups accompanied by ELC were higher and younger than those of a non-psoriatic skin disease group, respectively. Statistically significant differences were detected in the mean age of total or male subjects accompanied by bilateral ELC with complete and incomplete length. Bilateralism of ELC was closely correlated with prevalence of CAC and CAC on multiple branches in psoriatic patients (P = 6.6e-6 and odds ratio [OR] = 14.1, P = 0.00884 and OR = 10.7, respectively), but not with that of FL. On the contrary, body mass index of more than 25 was closely correlated with prevalence of FL, but not that of CAC. Comorbidities of psoriatic patients are frequently unnoticed. ELC, an apparatus-related feature, can be a useful predictive factor for hidden coronary artery involvements in psoriatic patients.

Correlation of disease activity and serum level of carcinoembryonic antigen in acquired idiopathic generalized anhidrosis: A case report.

Hypohidrosis and anhidrosis are congenital or acquired conditions which are characterized by inadequate sweating. Acquired idiopathic generalized hypohidrosis/anhidrosis (AIGA) includes idiopathic pure sudomotor failure (IPSF), which has the following distinct features: sudden onset in youth, increased serum immunoglobulin E and responds favorably to systemic corticosteroid. No clinical markers reflecting the disease severity or activity have been established. Here, we report a case of AIGA in a Japanese patient successfully treated with repeated methylprednisolone pulse therapy. In this case, serum carcinoembryonic antigen (CEA) levels increased up to 19.8 ng/mL along with aberrant CEA immunoreactivity of eccrine sweat glands. Interestingly, the serum CEA level normalized as sweating improved with repeated methylprednisolone pulse therapy. Therefore, serum CEA level may serve as a useful clinical marker of hypohidrosis or anhidrosis.

Transplanted bone marrow-derived circulating PDGFRα+ cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft.

Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable genetic blistering skin disease in which the epithelial structure easily separates from the underlying dermis because of genetic loss of functional type VII collagen (Col7) in the cutaneous basement membrane zone. Recent studies have demonstrated that allogeneic bone marrow transplantation (BMT) ameliorates the skin blistering phenotype of RDEB patients by restoring Col7. However, the exact therapeutic mechanism of BMT in RDEB remains unclear. In this study, we investigated the roles of transplanted bone marrow-derived circulating mesenchymal cells in RDEB (Col7-null) mice. In wild-type mice with prior GFP-BMT after lethal irradiation, lineage-negative/GFP-positive (Lin(-)/GFP(+)) cells, including platelet-derived growth factor receptor α-positive (PDGFRα(+)) mesenchymal cells, specifically migrated to skin grafts from RDEB mice and expressed Col7. Vascular endothelial cells and follicular keratinocytes in the deep dermis of the skin grafts expressed SDF-1α, and the bone marrow-derived PDGFRα(+) cells expressed CXCR4 on their surface. Systemic administration of the CXCR4 antagonist AMD3100 markedly decreased the migration of bone marrow-derived PDGFRα(+) cells into the skin graft, resulting in persistent epidermal detachment with massive necrosis and inflammation in the skin graft of RDEB mice; without AMD3100 administration, Col7 was significantly supplemented to ameliorate the pathogenic blistering phenotype. Collectively, these data suggest that the SDF1α/CXCR4 signaling axis induces transplanted bone marrow-derived circulating PDGFRα(+) mesenchymal cells to migrate and supply functional Col7 to regenerate RDEB skin.

PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia.

The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 mo. The source of the epithelial progenitors was the nonhematopoietic, platelet-derived growth factor receptor α-positive (Lin(-)/PDGFRα(+)) bone marrow cell population. Skin grafts release high mobility group box 1 (HMGB1) in vitro and in vivo, which can mobilize the Lin(-)/PDGFRα(+) cells from bone marrow to target the engrafted skin. These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases.

Primary cutaneous anaplastic large cell lymphoma successfully treated with local thermotherapy using pocket hand warmers.

Apart from for cutaneous deep fungal or mycobacterial infections, thermotherapy has been used for various malignant tumors. We report a case of primary cutaneous anaplastic large cell lymphoma, which responded quite well to topical thermotherapy using chemical pocket hand warmers. The treatment resulted in an immediate tumor regression without recurrence. This method is simple and might be a useful tool against solitary cutaneous lymphoma, especially of elderly patients with poor performance status or with various systemic complications.