Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.

Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.

Dose-dependent, non-pigmenting fixed drug eruption with eczematous lesions induced by bosutinib: case report.

Bosutinib, widely used as a primary treatment for chronic myeloid leukemia (CML), is known to frequently cause cutaneous drug eruptions. Fixed Drug Eruption (FDE) is common, typically presenting as recurrent lesions that heal with residual hyperpigmentation. Diagnosing FDE, especially Non-Pigmenting Fixed Drug Eruption (NPFDE), is often challenging. A correlation exists between the dosage of certain medications, such as levetiracetam, and the emergence of drug eruptions. This report details a unique case of dose-dependent NPFDE caused by bosutinib. In managing cutaneous drug eruptions, particularly when the causative drug is crucial for treatment, a strategy of tapering the dosage should be considered.

Safety and dose-sparing effect of Japanese encephalitis vaccine administered by microneedle patch in uninfected, healthy adults (MNA-J): a randomised, partly blinded, active-controlled, phase 1 trial.

BACKGROUND: It is unclear whether microneedle vaccinations of Japanese encephalitis virus can induce sufficient neutralising antibodies and reduce the amount of vaccine needed. We aimed to assess the safety and dose-sparing effect of a microneedle vaccine patch against Japanese encephalitis in healthy individuals who are naive to both the vaccine and natural infection. METHODS: The MNA-J study was a randomised, partly blinded, active-controlled, phase 1 clinical trial at Hokkaido University (Sapporo, Japan) that enrolled healthy adults aged 20-34 years with no history of Japanese encephalitis vaccination nor of infection as confirmed by seronegativity. We excluded individuals who had been infected with or vaccinated against Japanese encephalitis. Eligible participants were randomly assigned (1:1:1) to one of three groups to receive inactivated Japanese encephalitis vaccine administered twice, 3 weeks apart, by either 2·5 µg per injection by subcutaneous injection, 0·63 µg per patch by high-dose microneedle array (MNA-25%), or 0·25 µg per patch by low-dose microneedle array (MNA-10%). The randomisation sequence, using stratification by cohort and blocks of six, was computer-generated by a statistician who was unaware of group assignment. After administration, the remaining amount of unadministered vaccine was measured by ELISA and calculated as the delivered amount of vaccine. The primary outcome was the neutralising antibody titre at day 42 after first immunisation. Successful seroconversion was defined as post-vaccination titres of 1·3 (log10) or higher in individuals whose pre-vaccination titres had been less than 1 (log10). This study is registered with the Japan Registry of Clinical Trials (s011190004). FINDINGS: Between Aug 31 and Sept 2, 2019, 39 participants were enrolled and each was randomly assigned to a group (n=13 per group). No serious adverse events were observed. All participants in the microneedle array groups had a localised erythematous reaction. The amount of vaccine delivered by microneedle array to each participant was 0·63-1·15 µg (50-92%) of the full 1·26 µg for the MNA-25% group and 0·25-0·41 µg (51-84%) of the full 0·50 µg for the MNA-10% group. All participants demonstrated seroconversion at day 42, and the mean titres (log10) were 2·55 for MNA-25%, 2·04 for MNA-10%, and 2·08 for subcutaneous injection. INTERPRETATION: A microneedle patch of the Japanese encephalitis vaccine is safe, well tolerated, and immunogenically effective. The dose-sparing effect suggests a significant potential to reduce the amount of immunogens needed. However, improved delivery is needed to make it more tolerable and user friendly. FUNDING: FUJIFILM.

Aldose reductase inhibitor ranirestat significantly improves nerve conduction velocity in diabetic polyneuropathy: A randomized double-blind placebo-controlled study in Japan.

AIMS/INTRODUCTION: Diabetic polyneuropathy is one of the most frequent diabetic complications, and impairs patients' quality of life. We evaluated the efficacy and safety of ranirestat (40 mg/day) in patients with diabetic polyneuropathy. MATERIALS AND METHODS: This was a multicenter, placebo-controlled, randomized double-blind, parallel-group, phase III study in which 557 patients were randomly assigned to either the ranirestat or placebo group and assessed for 52 weeks. The co-primary end-points were the changes in tibial motor nerve conduction velocity and total modified Toronto Clinical Neuropathy Score as a measure of clinical symptoms. RESULTS: There was a significant increase in tibial motor nerve conduction velocity in the ranirestat group compared with the placebo group. The difference between groups in the change at last observation was 0.52 m/s (P = 0.021). Increases in nerve conduction velocity in the ranirestat group were found not only in the tibial motor nerves, but also in the median motor nerves, proximal median sensory nerves and distal median sensory nerves. No significant differences in modified Toronto Clinical Neuropathy Score or safety parameters were found between the two groups. CONCLUSIONS: Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were observed in the ranirestat group during the 52 weeks of treatment.

Portable negative-pressure wound therapy for pyoderma gangrenosum: Report of two cases.

Pyoderma gangrenosum is a chronic non-infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative-pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative-pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative-pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative-pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative-pressure wound therapy systems do.

Two cases of melanomas paradoxically metastasizing to the intestinal tract during nivolumab therapy.

We report two cases of melanomas in patients who developed intestinal metastasis despite other metastatic sites responding to nivolumab and despite the patients having favorable findings such as vitiligo and normal lactate dehydrogenase. The first case is an 85-year-old man who had been administrated nivolumab for lung/cutaneous metastases. After 22 courses of nivolumab therapy, fever and anorexia had appeared and his bodyweight had decreased. An intussusception on the ileocecal valve was revealed by computed tomography, and emergency surgery revealed metastatic lesions on the colon. The second case is an 87-year-old woman treated with nivolumab for lymph node metastases. After 10 courses, laboratory tests had revealed anemia and positive fecal occult blood. Her bodyweight had decreased. Capsule endoscopy showed scattered tumors and clots, indicating metastases of melanoma. The frequency of symptomatic intestinal metastasis of melanoma is very low. Further, intestinal metastasis of melanoma is difficult to detect through routine examinations. Our cases suggest that fecal occult blood test and decreased bodyweight are indications of intestinal metastases.

Modified Dufourmentel flap, easy to design and tailor to the defect.

How to close skin defects is one of the most important considerations for skin surgeons. Rhomboid flaps are used for many types of skin defect. Such flaps, represented by the Limberg and Dufourmentel flaps, are widely used at any region of the body because they are composed of straight lines and are easy to draw. However, these valuable techniques have the disadvantage of being prone to dog-ears at a particular area of the flap. Therefore, our talented predecessors have modified these flaps in order to resolve the problems. The modified flaps they designed were difficult to draw because the modified designs were curvy and along esthetic lines. It is difficult for trainees to draw these flaps. To address this issue, we have developed newly modified rhomboid flaps that are based on the Dufourmentel flap. This flap is different from the Dufourmentel flap in omitting the top half of the diamond above the circle. Thus, the tension on the skin decreases and dog-ears are less likely to occur. In addition, our flaps are geometric and easily drawn even by novices. We believe our flap will be a promising option for closing skin defects at any site.