Yuichiro Endo

Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life‐threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5 days consecutively, in an open‐label, multicenter, single‐arm study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5 days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side‐effects from the use of IVIG were not observed. IVIG (400 mg/kg per day) administrated for 5 days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.

Idiopathic thrombocytopenic purpura induced by nivolumab in a metastatic melanoma patient with elevated PD-1 expression on B cells

ABSTRACT Nivolumab has shown promising early results in patients with advanced malignancies, including melanoma and lung cancer, with generally manageable side effects. On the other hand, recent studies showed that the immune activation caused by PD-1 blockade might promote severe autoimmune toxicity. Herein, we report a case of idiopathic thrombocytopenic purpura during nivolumab therapy.

Bullous dermatosis associated with IgG antibodies specific for desmocollins

We describe a 53-year-old man with a two-year history of bullous disease. He had also had stage IV gastric cancer for 3 years. He presented with cutaneous erythemas and blisters, showing an annular arrangement. Histopathological examination revealed intraepidermal pustules of eosinophils and neutrophils without apparent acantholysis. Indirect immunofluorescence (IIF) analysis showed IgG anti-keratinocyte cell surface antibodies. The result of IIF on rat bladder was positive. IgG enzyme-linked immunosorbent assays failed to detect antibodies to either anti-desmoglein-1 (Dsg1), Dsg3, or BP180. Immunoblot analysis with normal human epidermal extract revealed IgG reactivity with 120, 110, and 100 kDa species. Immunofluorescence analysis using COS-7 cells that expressed desmocollin (Dsc) 1, 2, and 3 demonstrated that IgG autoantibodies in the patients serum reacted with all Dsc1-3. A heterogeneous autoantibody profile including IgG reactivity against Dsc1-3 implicated association with cancer-related pemphigoid, although the findings did not fulfill the diagnostic criteria of paraneoplastic pemphigus. A review of the literature revealed that rare autoantibodies to Dsc, most of which were IgA class, were detected in 7 reported bullous diseases. In 5 out of 7 cases, they were combined with autoantibodies to bullous pemphigoid or pemphigus vulgaris. This is the first case that has IgG autoantibodies to all Dsc1~3.

Coexistent Skin Lesions of Vitiligo and Psoriasis Vulgaris. Immunohistochemical Analyses for IL- 17A-producing Cells and Regulatory T Cells

Vitiligo vulgaris (VV) and psoriasis vulgaris (PV) are common dermatoses, with a worldwide occurrence of 0.5-1% and 1-3%, respectively. An imbalance between effector T cells and regulatory T cells (Tregs) can result in the pathogenesis of cutaneous immune diseases. In VV, interleukin (IL)-17-producing T-helper (Th) 17 cells are increased in the lesional skin as seen in PV (1). However, the number of Tregs is drastically reduced in the lesional skin of VV, which may allow an activation of effector T cells (2). In PV, an increased number of lesional Tregs was indicated (3, 4). While both lesional Th17 cells and Tregs are increased in PV, the ratio of Th17 cells to Tregs was shown to be inversely correlated with the psoriasis area and severity index (PASI). It has recently been proposed that Tregs readily turn into Th17 cells in PV, which potentially perpetuates the inflammatory process that characterises the disease (5). Herein, we present a case with the coexistent skin lesions of VV and PV with immunohistochemical analyses.

Onychomadesis developed only on the nails having cutaneous lesions of severe hand-foot-mouth disease.

This paper reported a case of onychomadesis which appeared on the nails after heal of cutaneous lesions of hand-foot-mouth disease (HFMD). There were a few reports describing onychomadesis after HFMD; however, the mechanism is still unclear. The present case was prospectively observed, and onychomadesis was found to develop only on the nails having cutaneous lesions of HFMD. We considered that nail dysfunction due to direct inflammation spreading from skin eruptions around nail is one of the causes of onychomadesis linked to HFMD.

Pazopanib: an alternative in taxane-resistant cutaneous angiosarcoma

Cutaneous angiosarcoma (AS) is a rare and aggressive neoplasm. The prognosis is one of the worst among malignant skin tumors, since the overall 5-year survival rate is less than 30% [1]. Treatment includes surgical excision, radiation, chemotherapy and biological therapy, although the efficacy of these treatments is limited. Surgical excision with negative margins combined with chemotherapy is the most successful strategy for improving the prospect for survival [2].Pazopanib is an orally bioavailable [...]

Pemphigoid without mucosal involvement showing autoantibodies against laminin-332 γ2 subunit

receiving monoclonal antibodies such as natalizumab, rituximab or more recently efalizumab in psoriasis. In our case, it is noticeable that the patient did not receive any immunosuppressive therapy prior to the onset of neurological disease, as he received only interferon alfa, a drug which has been reported to show partial efficacy in the treatment of PML. Currently, the treatment strategy in PML is based mainly on immune reconstitution, i.e. highly active antiretroviral therapy in AIDS and immunosuppression reduction whenever possible in cases related to malignancies and immunosuppressive treatments; no currently available treatment has clearly shown efficacy in JCV infection to date. Some recent in vitro results suggest that mefloquine could be an effective therapy. To our knowledge, this is the first reported case of PML in a patient with Sézary syndrome, which raises the need to detect JCV invasion of the central nervous system in patients with CTCL showing unexplained neurological symptoms. It also emphasizes the role of CD4 T-cell responses in the control of intracerebral JCV invasion of the central nervous system, and in the prevention of PML.

Three-dimensional evaluation of subclinical extension of extramammary Paget’s disease: Visualization of histological border and its comparison to clinical border

In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown.

A Case of an Undifferentiated Squamous Cell Carcinoma Arising from an Epidermal Cyst

An epidermal cyst is a common benign subcutaneous tumor and rarely develops malignancy. We report a case of an undifferentiated cutaneous squamous cell carcinoma (SCC) that arose from an epidermal cyst on the left side of the neck. The epidermal cyst had rapidly increased in size and presented cauliflower-like tumor. Histological study revealed undifferentiated squamous cell carcinoma that was arising from the epidermal cyst.

Prognostic Factors in Cutaneous Squamous Cell Carcinoma: Is Patient Delay in Hospital Visit a Predictor of Survival?

The patients delay in the visit to a hospital seems to play an important role in prognosis in invasive cutaneous squamous cell carcinoma (SCC). This report explored prognostic factors of cutaneous SCC focusing on patient delay in hospital visit. Data of 117 Japanese patients who were treated for invasive cutaneous SCC in our facility between 2000 and 2010 were used for analysis. A multivariate Cox proportional-hazard modelling revealed that a pair of TNM stage (hazard ratio, 5.0; 95% CI, 1.8 to 13.9) and poorer histological differentiation (hazard ratio, 3.2; 95% CI, 0.93 to 10.3), and a pair of tumour size (hazard ratio, 1.02; 95% CI, 1.004 to 1.04) and rapid growth (hazard ratio, 8.25; 95% CI, 1.29 to 52.7) were a prognostic factor whereas patient delay in hospital visit was not. However, patient delay in hospital visit was correlated with larger tumour size.