An 84-year-old woman was referred to us because of erosions in the oral cavity for 2 months, and blisters on the extremities and trunk for one month. Anti-BP180-NC16a domain antibodies were negative in CLEIA. Histopathology of the blister on the left thigh showed subepidermal bulla. Direct immunouorescence revealed linear depositions of IgG and C3 in the epidermal basement membrane zone. Indirect immunouorescence detected IgG anti-basement membrane zone antibodies in the patient serum, which were positive on the epidermal side in 1M NaCl-split skin. Immunoblotting analysis showed IgG antibodies against BP180 NC16a domain and 120 kDa LAD-1,and IgA antibodies against LAD-1 in the patient sera. Based on these clinical and histopathological ndings, the patient was diagnosed as anti-LAD-1 antibody-positive mucous membrane pemphigoid (MMP) with skin lesions. Cases of anti-LAD-1 antibody-positive MMP were previously reported to have moderate skin manifestations, and about half of cases require treatment similar to high-risk MMP. Treatment was initiated with prednisone 60 mg/day, and mucocutaneous symptoms improved markedly. Anti-BP180 NC16a domain antibodies may be involved in the development of cutaneous lesions of MMP, whereas antibodies against BP180 C-terminal domain and LAD-1 may be involved in the development of mucosal lesions. Cases with anti-BP180 NC16a and anti-LAD-1 antibodies may present on the continuous disease spectrum between MMP and bullous pemphigoid. Skin Research, 22 : 85-91, 2023

A 70-year-old Japanese man with urothelial carcinoma of the right renal pelvis. He was administered enfortumab vedotin ; however, he developed pruritus 9 days after the rst administration and presented with eruption and fever several days later. He was referred to us 14 days after the rst administration of enfortumab vedotin. Physical examination revealed diffuse erythema and bullae on the trunk and extremities, especially in intertriginous areas. Histopathological examination revealed interface dermatitis with widespread epidermal necrosis. Enfortumab vedotin was interrupted and he was treated with topical clobetasol propionate. The lesions resolved within 2 weeks. The lesions recurred several times following enfortumab vedotin readministration ; however, they were resolved on each occasion with topical clobetasol propionate treatment. As the lesions rarely recurred following the addition of prophylactic topical diuprednate, enfortumab vedotin was continued. Enfortumab vedotin is an novel antibody-drug conjugate targeting Nectin-4 that has been approved for the treatment of urothelial carcinoma. Our ndings suggest that enfortumab vedotin causes cutaneous adverse events. Skin Research, 22 : 92-97, 2023

An 81-year-old woman was diagnosed with adult-onset Still’s disease (AOSD). We started treatment with oral steroids and added methotrexate (MTX). After six weeks of treatment, during steroid tapering, she presented to our department with multiple palpable purpura on both lower extremities. Histopathological examination showed ndings of leukocytoclastic vasculitis in the supercial dermis. Immunohistochemistry showed no immunoglobulin or complement deposition and there were no ndings suggestive of collagen disease or systemic vasculitis on blood testing, and there were no signs of worsening of AOSD. We considered the possibility that she developed druginduced vasculitis caused by MTX, but continued administration because it is highly effective in AOSD. The purpura improved with rest and topical steroid application. After discharge from the hospital, she was unable to maintain rest, but only had a slight are-up of purpura. Six weeks after her rst visit to our clinic, she developed sudden fever, rapid expansion, and ulceration of the purpura on both lower legs. We suspected that the drug-induced vasculitis caused by MTX had ared up because the steroid dose was reduced. We discontinued MTX and increased the dose of oral steroids, but there was no improvement. Since the purpura at the time of relapse showed no evidence of vasculitis histopathologically and various culture tests detected Pseudomonas aeruginosa, we diagnosed as ecthyma gangrenosum. Although differentiation of ecthyma gangrenosum for other conditions, such as vasculitis, is difcult, the disease is often seen in immunosuppressed patients. Prompt diagnosis is necessary because appropriate therapeutic intervention is prognostically important. Skin Research, 22 : 98-103, 2023

A 42-year-old woman visited our department for a nodule on her left forearm that had been slowly increasing in size since one year before. Initial ndings revealed a 10 mm diameter, slightly keratinized, dome-shaped, elastic brown nodule. We performed total excision. The mass was spherical in shape and extended from the supercial to the deep dermis, with multiple multinucleated Touton and foreign-body giant cells, and foam cells, similar to those of xanthogranuloma. The deep dermis showed no giant cells, but rather proliferation of cells with spindle-shaped nuclei in a oral pattern. CD68 staining was positive in both areas ; however, in the shallow dermis just below the epidermis, the staining was almost circular, whereas in the deep dermis it was spindle-shaped. Factor XIIIa was clearly positive in the deep dermis ; however, it was attenuated in the shallow dermis areas where only foam-like cells were present. We hypothesized that dermatobroma and xanthogranuloma share a common origin. Skin Research, 22 :104-108, 2023

An 81-year-old woman presented with a tumor on her right lower abdomen, which rst appeared 3 years before. The tumor was asymptomatic ; however, it had been growing and changing to papillomatous appearance gradually. Histopathological testing revealed that it was composed of dense collagen bers with scattered atypical spindle-shaped cells, multinucleated giant cells, and mature adipocytes throughout dermis to subcutaneous tissue. CD34 and p16were positive in immunohistochemistry, and Ki-67 labeling rate was 10%. It had features of both pleomorphic lipoma and pleomorphic broma. Pleomorphic lipoma and pleomorphic broma are both benign neoplasms with good prognosis. Pleomorphic lipoma is classied as a soft tissue tumor, whereas pleomorphic broma is classied as a cutaneous tumor. Differentiation may be difcult because they express varied clinical and pathological patterns. Loss of RB1 gene, a tumor suppressor gene, has been identied recently in both pleomorphic lipoma and pleomorphic broma. We diagnosed the patient as pleomorphic broma. As variants between pleomorphic broma and pleomorphic lipoma may exist, further studies are needed. Skin Research, 22 : 109-113, 2023

Nivolumab had been administered for a 67-year-old man with lung cancer for 25 months. He was referred to us due to erythema and bullae on the entire body for two months. The lesions were diagnosed as bullous pemphigoid with clinical, blood, histopathologic, and direct immunouorescent evaluation. The lesions were resolved by oral corticosteroids. Nivolumab and pembrolizumab are immune checkpoint inhibitors and show high antitumor effects. However, they may induce immune-related adverse events (irAE). We summarized case series of bullous pemphigoid during nivolmab or pembrolizumab treatment in Japan. Our ndings suggest relatively good prognosis in individuals with bullous pemphigoid as irAE. Further accumulation of case series is required. Skin Research, 22 : 114-118, 2023

The patient was a 64-year-old man. He had been treated for psoriasis vulgaris with topical steroids and oral cyclosporine at another hospital for 15 years prior to his initial visit. Three months prior to the initial visit, joint pain in the extremities appeared. He was referred to our hospital with suspected psoriatic arthritis. Erythema with scaling was seen mainly on the trunk and lower extremities. Histopathologically, hyperkeratosis and club-shaped extension of rete ridge were noted. He had arthralgias in his ngers, wrists, ankles, and knees. Blood tests were negative for rheumatoid arthritis. He was diagnosed with psoriatic arthritis. One month after the initial visit,treatment with certolizumab pegol (CZP), a TNF-α inhibitor, was initiated. Six months after the initial visit, skin and joint symptoms improved. When treatment with CZP was discontinued, joint symptoms ared up 5 months later. When treatment with CZP was resumed, skin and joint symptoms improved, but 7 months later, pustular rashes appeared on the palms and soles. Based on the clinical course and histopathological features, we considered a paradoxical reaction (pustular rashes) to TNF-α inhibitors. Treatment with CZP was discontinued and treatment with guselkumab was initiated, and the pustular rashes gradually improved. Psoriasiform or pustular skin rashes may occur during treatment with TNF-α inhibitors, which is called paradoxical reaction. We experienced a case of paradoxical reaction during CZP administration for psoriatic arthritis. Although there are previous reports of paradoxical reactions with CZP, paradoxical reactions are thought to be class effects of TNF-α inhibitors. Our ndings suggest that it is important to consider paradoxical reactions when using TNF-α inhibitors. Skin Research, 22 : 119-125, 2023

A 58-year-old woman (Case 1) was referred to our department after combination treatment with radiotherapy, as the treatment did not provide sufcient therapeutic benet. She was treated with radiotherapy and chemotherapy with carboplatin and etoposide ; however, there was no effect. Her treatment was changed to palliative care. An 87-year-old woman (Case 2) visited our clinic for the treatment of an enlarging mass on the dorsal surface of the right side of her nose, diagnosed as MMC by a previous doctor. We administered avelumab and resected the metastatic lesion on her right cheek, but the tumor subsequently grew. Two months after the initial visit, she was referred to an oncology hospital. She received radiation therapy and chemotherapy with cisplatin and etoposide. However, she died of multiple organ failure. The present cases had advanced unresectable MCC and had an indication for avelumab. However, based on previous reports about response to avelumab, our cases may have had factors that caused resistance to avelumab. Skin Research, 22 : 126-132, 2023

A 71-year-old man with bullous pemphigoid was referred to our hospital. He was receiving treatment with 20 mg of prednisolone ; however, there was no improvement. We increased the dosage of prednisolone to 50 mg (1 mg/kg), but it did not ameliorate his condition. He underwent immunoglobulin therapy, steroid switching from prednisolone to betamethasone, and corticosteroid pulse therapy by methylprednisolone ; however, there was no improvement. We suspected reduced steroid efcacy induced by drug interactions arising from combination use of two CYP3A4 inducers (phenytoin and phenobarbital). We changed phenytoin and phenobarbital to levetiracetam, and his eruption began to improve. In Japan, when we initiate steroid therapy for patients receiving rifampicin, a strong CYP3A4 inducer, we should assume the residual ratio of steroids efcacy to be the reciprocal of the metabolic clearance rate (MCR), and increase the dose by multiplying the normal dose by MCR. However, in the present case, the corticosteroid pulse therapy using a 25-times higher dose of corticosteroids than the standard dose was ineffective. The MCRs of methylprednisolone under the use of phenytoin and phenobarbital are 2.3 and 1.9 respectively ;therefore, the steroid efcacy is supposed to be reduced synergically under the combination use of these drugs. The combination use of the CYP3A4-inducing antiepileptic drugs is relatively common. If patients under multi-CYP3A4-inducing antiepileptic drugs require corticosteroid treatment, it is recommended to increase the dosage of corticosteroids and change antiepileptic drugs in order to sustain steroids efcacy. Skin Research, 22 : 133-138, 2023

A 49-year-old woman with a history of uterine broid presented to our clinic. Multiple red plaques had developed on her chest over the previous three years. Histological study revealed lobular proliferation of vascular endothelial cells without nuclear atypia or mitosis in the lower and middle dermis. The proliferating cells were positive for an erythroblast transformation specicrelated gene, and pericytes were positive for α-smooth muscle actin. A diagnosis of tufted angioma was made. As the lesion gradually increased in size and became painful, the patient was administered low-dose aspirin. The color immediately started to fade, and pain was relieved. Both completely diminished nine months after the initiation of the treatment. The patient took aspirin for 18 months and continued to have no sign of relapse ve months after discontinuation of the medication. Tufted angioma is a benign vascular tumor that predominantly affects children younger than ve years of age ; however, adult-onset cases have also been reported. Spontaneous regression is rare, and treatment with drugs, radiation, and surgical resection have been reported. Although the efcacy of antiplatelet agents varies among reports, low-dose aspirin was effective in the present case. Further research is necessary to conrm predictive factors for treatment response to antiplatelet agents. Skin Research, 22 : 139-144, 2023

A 96-year-old female presented with an erythema on the right lower limb from about 3 years before. She was referred to our department because the erythema did not resolve despite taking topical steroids. On the rst examination, the patient presented with 55×38 mm, oval, welldemarcated erythema with thin scales on her right lower limb. Dermoscopy revealed dotted vessels, glomerular vessels, and thin scales in milky white and milky pink background. Histopathologically, large, bright pagetoid cells with subcircular nuclei in the epidermis were observed and parakeratosis and dyskeratotic cells were partially seen. To differentiate from extramammary Paget’s disease and intraepithelial malignant melanoma, histochemical staining and immunohistochemical staining were performed. Tumor cells showed PAS (＋) (diastase-labile),AE1/AE3 (＋), CK5/6 (＋), and p63 (＋). Alcian blue staining, CK7, GCDFP-15, S-100, and CEA were all negative. Based on these results, we diagnosed the present case as pagetoid Bowen’s disease. Since the patient did not accept tumor resection and was very elderly, we administered imiquimod cream. Topical application of imiquimod lightened the erythema and it showed a tendency to disappear. A second skin biopsy was performed, and histopathological evaluation revealed that the number of pagetoid cells in the epidermis had decreased, and marked lymphocytic inltration was observed in the epidermis and dermis. Among the inltrating lymphocytes, there was a marked increase in CD8-positive cells. Based on the time-course changes in CD8-positive cells before and after application of imiquimod, our ndings suggest that imiquimod had an antitumor effect to Pagetoid Bowen’s disease by activating CD8-positive cells. Skin Research, 22 : 145-151, 2023