A case of anti-BP230 antibody-positive bullous pemphigoid receiving DPP-4 inhibitor.

Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disorder. Recently, it has been reported that dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with the development of BP (DPP4i-BP). Patients with DPP4i-BP have autoantibodies (autoAbs) preferentially targeting full-length BP180, but not the BP180NC16a domain. In this report, we described a case of anti-BP230 antibody (Ab)-positive BP receiving DPP4i. A 78-year-old male with a medical history of type 2 diabetes receiving vildagliptin at 100 mg daily for 38 months was referred to our hospital with itching blisters on his body and extremities. Skin biopsy showed subepidermal bulla with eosinophil infiltration. Direct immunofluorescence staining revealed a linear staining pattern with complement C3 and IgG at the subepidermal basement membrane zone. By laboratory testing, autoAbs against BP180NC16a and full-length BP180 were negative by enzyme-linked immunosorbent assay (ELISA); however, anti-BP230 Abs were positive by ELISA (index: 123.91). His HLA genotype was DQB1*04:01 and 05:01. Based on these results, we diagnosed the patient with anti-BP230 Abs-positive BP associated with DPP4i. To the best of our knowledge, this is the first case of DPP4i-BP with only anti-BP230 Abs. Further accumulation of DPP4i-BP cases is needed to clarify the relationship between overall features of DPP4i-BP and anti-BP230 Abs.

Disseminated superficial actinic porokeratosis in a patient undergoing treatment with long-term narrowband ultraviolet B for psoriasis.

Disseminated superficial actinic porokeratosis (DSAP) is a subtype of porokeratosis, thought to be clonal disorder of keratinization. Chronic exposure to ultraviolet (UV) light might be an etiological cause of DSAP, of which frequent sites are sun-exposed areas. We report a case of DSAP that occurred on the trunk of a 79-year-old man with psoriasis treated with narrowband ultraviolet B (NB-UVB) for clearing and maintenance therapies. DSAP has been reported to associate with psoralen and ultraviolet A therapy and broadband UVB, but not NB-UVB. This may be the first case of DSAP after repeated exposure to NB-UVB.

Clinical, dermoscopic, and histopathologic features in a case of infantile hemangioma without proliferation.

Infantile hemangioma precursors or those without a proliferative phase may mimic a port-wine stain. We describe a case of infantile hemangioma precursor, which proved to be Glut-1 positive in biopsy, with the dermoscopic features of red round globular vessels, red comma-like vessels, and red linear vessels. These dermoscopic features should help to distinguish infantile hemangioma precursors or those with an absent or minimal growth phase from a port-wine stain.

Genital Infection as a First Sign of Acute Myeloid Leukemia.

Fournier's gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier's gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy.

Amelanotic vulvar melanoma with intratumor histological heterogeneity.

Amelanotic vulvar melanoma is a rare type of malignant melanoma. This paper describes a case of an asymptomatic ulcerated nodule 20 mm in size. The tumor cells from the nodular lesion showed positive staining immunohistochemically for Melan-A, but negative staining with HMB-45. The cells showed negative reactivity to S-100 except in one region. The melanoma cells in the epidermis were detected in one of the specimens from the excised tumor nodule. The cells in the epidermis showed positive staining for Melan-A and S-100 and partial staining with HMB-45. The tumor was diagnosed as malignant melanoma of the vulva and immunohistochemically shown to have intratumor histological heterogeneity. This case suggests the importance of viewing non-pigmented nodules on the vulva of elderly females as potentially malignant melanoma, and that a combination of immunohistochemical stains may be useful for recognizing the stage of the melanosomes in the melanoma cells.

Adult T-cell leukemia-lymphoma associated with follicular mucinosis.

Follicular mucinosis (alopecia mucinosa) is often associated with malignancies including mycosis fungoides and Sézary syndrome, but not adult T-cell leukemia-lymphoma (ATLL). We report a 49-year-old male patient who had pruritic follicular papules and erythemas clinically, and follicular and perifollicular infiltrates and follicular mucin deposition histopathologically. The patient showed 11% of flower-shaped atypical lymphocytes in blood examination and positive human T-cell leukemia virus type 1 antibody in serology, consistent with the chronic type of ATLL. This case seems to be a very rare association of follicular mucinosis and chronic ATLL, suggesting that malignant T cells may have a feature of folliculotropism as well as epidermotropism.

Pityriasis rubra pilaris with preceding cytomegalovirus infection.

Pityriasis rubra pilaris (PRP) is a papulosquamous disorder comprising 6 clinical types. Some factors - including abnormal vitamin A metabolism, internal malignancies, autoimmune diseases, infection and trauma - are thought to be involved in the etiology. Recently, human immunodeficiency virus (HIV)-associated PRP has been reported to have distinct clinical features, such as nodulocystic acne and lichen spinulosus alongside PRP. We report here the case of a 38-year-old female with onset of classical PRP after a high fever. Virological studies indicated that the patient had primary systemic cytomegalovirus (CMV) infection and not HIV infection. Our case suggested that primary CMV infection might have triggered typical PRP that was clinically different from HIV-associated PRP.

Allergic contact dermatitis caused by sesame oil in a topical Chinese medicine, shi-un-ko.

Topical Chinese medicines are used for skin disorders as traditional medicine in Japan. We describe a case of allergic contact dermatitis from a topical Chinese medicine, shi-un-ko.

New approach to the evaluation of skin color of pigmentary lesions using Skin Tone Color Scale.

Objective methods of measuring skin color are needed to evaluate pigmentary lesions quantitatively. We have developed a new method of measuring skin color using a plastic bar system called the Skin Tone Color Scale based on Munsell's color space system. We have also evaluated the effectiveness of various therapies using this measurement system. Our system was designed to measure skin color in normal skin, pigmentary lesions of solar lentigo, chloasma and ephelides, and postinflammatory pigmentation. Moreover, effectiveness of various therapies for these pigmentary lesions was evaluated. The evaluations made with this system were closely related to physician assessment. This method may be useful in measuring of skin color and evaluating the effectiveness of therapies for pigmentary diseases.

Connective tissue growth factor causes persistent proalpha2(I) collagen gene expression induced by transforming growth factor-beta in a mouse fibrosis model.

Skin fibrotic disorders such as systemic sclerosis (SSc) are characterized by an excessive production of extracellular matrix (ECM) and understood to develop under the influence of certain growth factors. Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that is implicated in various fibrotic disorders and induced in fibroblasts after activation with transforming growth factor-beta (TGF-beta). To better understand the mechanisms of persistent fibrosis seen in SSc, we previously established an animal model of skin fibrosis induced by exogenous application of growth factors. In this model, TGF-beta transiently induced subcutaneous fibrosis and serial injections of CTGF after TGF-beta caused persistent fibrosis. To further define the mechanisms of skin fibrosis induced by TGF-beta and CTGF in vivo, we investigated in this study, the effects of growth factors on the promoter activity of the proalpha2 (I) collagen (COL1A2) gene in skin fibrosis. For this purpose, we utilized transgenic reporter mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial beta-galactosidase gene. Serial injections of CTGF after TGF-beta resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-beta alone on day 8. We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-beta in comparison with the injection of TGF-beta alone. Furthermore, the serial injections recruited mast cells and macrophages. The number of mast cells reached a maximum on day 4 and remained relatively high up to day 8. In contrast to the kinetics of mast cells, the number of macrophages was increased on day 4 and continued to rise during the subsequent consecutive CTGF injections until day 8. These results suggested that CTGF maintains TGF-beta-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts. The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis.

Ultraviolet light exposure suppresses contact hypersensitivity by abrogating endothelial intercellular adhesion molecule-1 up-regulation at the elicitation site.

Hapten sensitization through UV-exposed skin induces systemic immune suppression, which is experimentally demonstrated by inhibition of contact hypersensitivity (CHS). Although this UV-induced effect has been shown to be mediated by inhibition of the afferent phase of the CHS, the UV effects on the efferent (elicitation) phase remain unknown. In this study, UV effects on endothelial ICAM-1 expression at elicitation sites were first examined. Mice were sensitized by hapten application onto UV-exposed back skin, and ears were challenged 5 days later. ICAM-1 up-regulation at nonirradiated elicitation sites following hapten challenge was eliminated by UV exposure on sensitization sites distant from elicitation sites. To assess whether loss of the ICAM-1 up-regulation at elicitation sites contributed to UV-induced immunosuppression, we examined CHS responses in UV-exposed ICAM-1-deficient (ICAM-1(-/-)) mice that genetically lacked the ICAM-1 up-regulation. ICAM-1(-/-) mice exhibited reduced CHS responses without UV exposure, but UV exposure did not further reduce CHS responses in ICAM-1(-/-) mice. Furthermore, ICAM-1 deficiency did not affect the afferent limb, because ICAM-1(-/-) mice had normal generation of hapten-specific suppressor and effector T cells. This UV-induced immunosuppression was associated with a lack of TNF-alpha production after Ag challenge at elicitation sites. Local TNF-alpha injection before elicitation abrogated the UV-induced CHS inhibition with increased endothelial ICAM-1 expression. TNF-alpha production at elicitation sites was down-regulated by IL-10, a possible mediator produced by hapten-specific suppressor T cells that are generated by UV exposure. These results indicate that UV exposure inhibits CHS by abrogating up-regulation of endothelial ICAM-1 expression after Ag challenge at elicitation sites.

Transforming growth factor-beta isoforms differently stimulate proalpha2 (I) collagen gene expression during wound healing process in transgenic mice.

The role of many growth factors and cytokines in the process of wound healing has been intensively investigated in recent two decades. Among them, transforming growth factor-betas (TGF-betas) are well known to have a potent stimulatory effect on collagen synthesis as shown in various in vivo experimental systems. In the present study, we examined the effects of various growth factors on the promoter activity of the proalpha2 (I) collagen gene (COL1A2) during the wound healing process. For this purpose, we utilized transgenic mice harboring the -17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase or a bacterial beta-galactosidase gene. These mice exhibited normal phenotypic expression and the wound healing process was not impaired. Full thickness wounds were made by punch biopsy. We examined the effects of TGF-beta1, -beta2, -beta3, basic fibroblast growth factor, platelet-derived growth factor, and connective tissue growth factor by applying them locally to the open wound every 2 days. Among the growth factors examined, all of the three isoforms of TGF- exhibited a more potent stimulatory effect on COL1A2 promoter activity than did other factors. In addition, while TGF-beta1 and -beta2 significantly increased the number of fibroblasts which were positive for X-Gal staining, TGF-beta3 treatment did not change the number of beta-galactosidase expressing cells. Accumulation of collagen fibers was observed to the same extent in the mice treated with TGF-beta1 and those with TGF-beta3. These findings suggest that TGF-beta1 and -beta3 have similar but not identical regulatory mechanisms of COL1A2 expression, and that their pathophysiological roles in wound healing might be different from each other.