Thisreport presentsa 53-year-old woman with neurofibromatosis type 1 (NF-1). She was brought to the emergency room because of sudden onset of abdominal pain. Contrast-enhanced CT on admission showed a superior mesenteric artery aneurysm and intra-abdominal bleeding. Diagnosis of intra-abdominal hemorrhage due to aneurysm rupture was made. During the course of the disease, multiple intra-abdominal hemorrhages occurred, requiring three endovascular treatmentsand two laparotomiesfor partial jejunal resection and pancreaticoduodenectomy. The pathological specimen removed at the time of pancreaticoduodenectomy showed extensive hemorrhage and proliferating neurofibroma cells in the interstitium, including the perivascular area. Major hemorrhage associated with NF-1 vascular lesions is relatively rare, and there have been few reportsfrom the field of dermatology except for those related to diffuse neurofibromas; however,there have been reportsfrom other fields. It is necessary to explain to patients that they should not be unnecessarily anxious, and that they should go to a core hospital where multidisciplinary treatment is available if they require surgery with major invasion. Patients should be transported to a core hospital in case of emergency. Skin Research, 21 : 157-161, 2022

A 70-year-old woman was referred to our hospital with a two-month history of generalized erythematous bullous skin eruptions that were unresponsive to 25 mg/day of oral prednisolone (PSL) and discontinuation of dipeptidyl peptidase-4 (DPP-4) inhibitor, which had been administered for diabetes. She had been diagnosed as having bullous pemphigoid based on a high serum level of antiBP 180 antibody and histopathological findings. During treatment with an increased dose of oral PSL (45 mg/day), bleeding tendency, such as subcutaneous hemorrhage, hemorrhagic bullae, oral submucosal hemorrhage, and black stool, developed. A diagnosis of acquired hemophilia A (AHA) was made from laboratory results as she had normal PT, prolonged APTT, cross-mixing test with an inhibitor pattern, detection of VIII inhibitor, a reduced activity level of factor VIII, and normal von Willebrand activity. Treatments with oral cyclophosphamide and clotting factor concentrates, such as intravenous activated prothrombin complex concentrates (APCC), along with the increased PSL (50 mg/day) seemed to have had little effect on AHA at first ; however, repeated APCC administration improved AHA within five months from the onset of AHA. Both BP and AHA showed no signs of recurrence after 15 months through the course of PSL tapering. Human leukocyte antigen (HLA) typing revealed that she carried HLA-DQB1*03:01, which is known to have an association with DPP-4 inhibitor-related BP. Among AHA, 1.4 to 4.5% of cases are associated with skin disease, and BP is one of the most common complications for AHA. Although our patient developed AHA during systemic PSL therapy and showed treatment-resistance at first, her condition remitted by five months of repeated APCC administration. AHA is rare but can be a fatal complication during the treatment of BP. Early detection of bleeding tendency and appropriate consultation to specialists, such as hematologists, are required. Skin Research, 21 : 162-169, 2022

An 84-year-old man with type 2 diabetes mellitus who had been taking oral dipeptidyl peptidase-4 inhibitor for one year presented with multiple blisters. At the time of his first visit, he had blisters with crusts and erosions on his trunk and left upper arm. Based on clinical course, histopathological examination, and serological studies, he was diagnosed as dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid. His symptoms had improved completely after discontinuation of dipeptidyl peptidase-4 inhibitor, but relapsed shortly after. Anti-BP180NC16a antibody, which was negative at firstvisit, was confirmed to be positive, and systemic administration of glucocorticoid was required. Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid is generally considered to be mild. However, it is necessary to recognize the possibility of severe or refractory disease due to possible epitope spreading after the discontinuation of dipeptidyl peptidase-4 inhibitors. Skin Research, 21 : 170-174, 2022

A 60-year-old man was treated for herpes zoster on his right lower leg by a local physician. Four weeks later, he noticed asymptomatic eruptions on different sites from the herpetic lesions and visited us. Physical examination revealed linearly arranged lesions that were located from the left chest to the left upper arm, from the middle of the lower abdomen to the left side of the abdomen, and from the left thigh to the left lower leg. Each lesion consisted of pink flat papules distributed continuously or discontinuously along Blaschko’s lines. Histopathological findings included exocytosis and individual cell necrosis of the epidermis, liquefaction degeneration of basal layer, and lymphocytic infiltrations in the upper dermis and around the sweat gland in the mid-dermis. Based on the above findings, we made a diagnosis of lichen striatus and administered 0.1% tacrolimus ointment. After 15 weeks, skin lesions had subsided well leaving only mild pigmentation. Blaschko’s lines are thought to represent the migration pathway of ectodermal cells in the process of embryogenesis of skin. According to the conventional view, postzygotic mutation may lead to cutaneous mosaicism, and some immunological responses to these abnormal clones along the Blaschko’s lines may play a role in the pathogenesis of lichen striatus. However, one of the lesions in our case developed along the ventral median line, which corresponds to the junction of multiple Blaschko’s lines but does not belong to any specific keratinocyte clones. Therefore, we would like to propose a hypothesis that lichen striatus initially develops on the junctional area between the adjoining different keratinocytes clones, not on the same clonal area of keratinocytes. This “junction”theory could also explain some other features of lichen striatus. Skin Research, 21 : 175-180, 2022

We report a 71-year-old woman who had white popular lesions on her neck for about 2 years. On first examination, the patient presented with 1-4 mm size, elastic, slightly firm, smooth-surfaced,follicularly non-congruent white papules scattered on the neck. Dermoscopy revealed a cluster of white, unstructured areas with indistinct borders. Histopathologically, coarsening and increase of collagen fiber bundles were observed in the upper and middle dermis. Elastica van Gieson (EVG) staining and Kossa staining showed no evidence of elastic fiber degeneration or calcium deposition. Based on these findings, a diagnosis of white fibrous papulosis of the neck (WFPN) was made. Structural changes in collagen fibers due to physiological aging may be involved in the pathogenesis of this disease. However, physiological aging alone cannot explain the low frequency of WFPN, and factors other than physiological aging, such as genetic predisposition and underlying diseases, should be evaluated in the future. Skin Research, 21 : 181-186, 2022

Case 1 was an 81-year-old man undergoing treatment for the nummular eczema of the lower leg. The day after being administered the first dose of a COVID-19 vaccine, the patient developed generalized pruritus, multiple serous papules, and erythema on the trunk, upper extremities, and palms, as well as worsening of pre-existing eczema on the lower legs. The serum TARC level of the patient was 1,383 pg/mL. After taking oral antihistamines and topical steroids for two weeks, the erythema faded, papules crusted, and serum TARC level normalized. Case 2 was a 22-year-old woman who had been treated with topical steroids for contact dermatitis by poultices on the ankles. On the same day as she received the second dose of COVID-19 vaccine, erythema with pruritus on the dorsum of the feet appeared and gradually expanded to papules and edematous erythema on the face, extremities, and trunk. The serum TARC level of the patient was 2,090 pg/mL. After taking 15 mg/day oral prednisolone and topical steroids for 10 days, overall erythema became hyperpigmented, and the erythema on the dorsum of the hands and fingers persisted for approximately 2 weeks and then became pigmented. Serum TARC level normalized after the skin rash reformed. Case 3 was a 74-year-old woman with a history of asthma. She received SBT/ABPC therapy for acute cholangitis for one week. Ten days after treatment, she received the first COVID-19 vaccination dose. Two days after vaccination, the patient became aware of pruritus on the extremities ipsilateral to the vaccination site, and small erythematous patches appeared all over the body in a disseminated pattern. Her serum TARC level was 3,862 pg/mL. After taking oral antihistamines and topical steroids for 3 weeks, the erythema completely faded, and the serum TARC level normalized. The DLST showed positive by SBT/ABPC, but the result of drug challenge test was negative. There have been no previous case reports of rash with a high TARC level after vaccination. In the future, it is necessary to accumulate patients with a high TARC level by vaccination and analyze the clinical and pathological trends including immunological mechanisms. Skin Research, 21 : 187-193, 2022

We report a case of squamous cell carcinoma (SCC) treated with the quadrivalent human papillomavirus (HPV) vaccine in a 30-year-old woman with long-term immunosuppression. She complained of a growing perianal tumor that had emerged a year before the first visit. Multiple tumors were found in the vulvar, as well as perianal areas. HPV-DNA testing revealed positivity in the lesion. Although the skin biopsy revealed the proliferation of atypical keratinocytes, most of the lesion comprised acanthosis with some infiltrating parts, yielding the definitive diagnosis of HPVassociated SCC. The widespread lesion and enlarged bilateral illio-inguinal lymph nodes hampered wide curative resection because the treatment may cause poor postoperative quality of life. Thus,we proposed chemoradiotherapy as a guideline-based treatment option. However, she was reluctant to undergo chemotherapy because of concerns about side effects such as infertility or alopecia. As intratumoral administration of HPV tetravalent vaccine (Gardasil ^○R ) is reportedly effective at the case report level, we performed intra-lesional vaccination as an alternative. Skin Research, 21 : 194-199, 2022

A 61-year-old man was referred to our hospital because of erosions on his nasal and oral mucosa and blisters on his trunk and extremities. Histopathological examination revealed subepidermal blister formation. Direct immunofluorescence showed linear deposition of IgG and C3 on the basement membrane zone. Indirect immunofluorescence using 1 M NaCl split skin showed the presence of IgG autoantibodies reactive to the dermal side. Western blot analysis using dermal extract showed autoantibody reactive to 290 kDa protein. ELISA showed the presence of autoantibodies for type VII collagen. Therefore, we diagnosed the patient as mucous membrane pemphigoid (MMP) with antibodies against type VII collagen. Although his cutaneous lesions were easily improved by oral prednisolone, mucous lesions were refractory, which finally improved by additional treatment with plasmapheresis, intravenous immunoglobulin, diaminodiphenylsulfone,azathioprine, tetracycline, and niacinamide. We speculate that epitopes of autoantibodies against type VII collagen are different in MMP from those in epidermolysis bullosa acquisita, which mainly show cutaneous lesions. Skin Research, 21 : 200-205, 2022

A 70-year-old man presented with two months history of erythema and erosions on his lower lip that was resistant to treatment with oral antibacterial agents, ointments containing antibacterial agents, antihistamines, and topical steroids. On physical examination, the lesion on his lower lip consisted of erythema, erosions, ulcers, and blood crusts. Histopathologically, infiltration of numerous plasma cells in the dermis was observed. Immunohistochemistry analysis revealed that plasma cells were a mixture of immunoglobulin κ- and λ-chain positive cells. On the basis of these findings, he was diagnosed with plasma cell cheilitis. He was treated with intralesional injection of corticosteroids, and after 16 doses, remission was achieved for more than one year. Plasma cell cheilitis is a relatively rare benign disease and its etiology is still not clear. Recently, several cases of squamous cell carcinoma arising from plasma cell cheilitis have been reported. Therefore, early diagnosis by appropriate skin biopsy, treatment intervention in early stage, and careful monitoring are important. When the lesion is intractable with topical steroids, intralesional injection of corticosteroids should be considered. Skin Research, 21 : 206-211, 2022

A 79-year-old man was diagnosed with prostate cancer three months before his first visit to our department. Contrast-enhanced CT and whole-body magnetic resonance imaging with diffusion weighted imaging revealed prostate cancer with multiple bone and lymph node metastases. One month prior to his first visit to our department, he was started on apalutamide (a combination of calcium carbonate, cholecalciferol, and magnesium carbonate) and denosumab. One week before his first visit to our department, erythema appeared on his lower extremities and gradually spread to his trunk, so he was referred to our department. Considering the possibility of drug eruption caused by apalutamide, we reduced the dose of apalutamide and started oral olopatadine hydrochloride and topical steroids, but the skin rash continued to spread. One week later, we discontinued apalutamide and started 15 mg of oral prednisolone daily. The skin lesions resolved within three weeks without discontinuation of other medications. Apalutamide is a drug that produces a high rate of skin rash and rarely can cause severe drug eruptions such as toxic epidermal necrolysis. The mechanism of apalutamide-induced drug eruption is unknown. Dermatologists must be aware of symptoms of severe cutaneous adverse reactions of patients treated with apalutamide. Skin Research, 21 : 212-218, 2022

Case 1 :A 79-year-old male came to our department because of a small nodule on the right nasal wing. Although the time of onset was unknown, it was noted to gradually increase in size. At the time of initial examination, an erythematous nodule with a central crust of 6 mm in diameter was observed on the right nasal wing. Case 2 :An 83-year-old male who had been aware of a small nodule on the left nasal wing for the past six months, which gradually increased in size, was referred to our department by his family doctor. A black nodule with hemorrhage was observed on the left nasal wing with a diameter of 10 mm. Partial biopsy revealed squamous cell carcinoma in Case 1 and basal cell carcinoma in Case 2, and both were resected under local anesthesia. The resected defect was reconstructed using a composite tissue graft containing cartilage from the auricle. The color tone of the composite tissue graft changed dynamically postoperatively. The color change may be related to its biosorption mechanism. The size of the composite tissue graft in the autopsy case was relatively large compared to other cases reported in the past. In Case 2, the graft showed partial necrosis and general hyperpigmentation ; however, it remained viable. In the present cases, we used a local anesthetic containing epinephrine. Although it is not frequently used as its vasoconstrictive effect may prevent graft implantation, in our cases, its hemostatic effect may have facilitated the surgical operation and allowed the graft to be harvested easily. In addition,chondrocutaneous advancement flap reconstruction is a helpful method because it is possible to reconstruct even relatively large auricular defects, and it is not a complicated procedure. Skin Research, 21 : 219-225, 2022

A 57-year-old man presented to the Dermatology Department with a 6-week history of rash on the lower extremities. His medical history included chronic alcoholic pancreatitis, and he continued to drink. Physical examination revealed hot, dark red erythematous lesions on the lower extremities,with admixed purpura on the left lower thighs. All lesions were tender when pressed. We considered erythema nodosum, vasculitis, and subcutaneous fat necrosis. White cell blood count was 12,390/μL and both the amylase and lipase levels were markedly elevated (to 3,622 and 6,996 U/L, respectively). C-reactive protein level was 3.62 mg/dL, but we did not detect antibodies against PR3- or MPO-ANCA. Histopathology revealed mild dermal periadnexal lymphocytic infiltrations and dense lymphocytic and histiocytic infiltrations into the upper subcutaneous tissue. Degeneration and necrosis of lipid cells (including ghost-like cells) were observed in the lower regions of subcutaneous tissue. We diagnosed subcutaneous fat necrosis based on these findings. Three weeks after the initial visit, the cutaneous lesions disappeared without treatment, and pancreatitis improved. Among similar reported cases, males were slightly more frequently affected than females, and all patients developed a rash on the lower thighs. Over 90% of patients had acute or chronic pancreatitis, or primary pancreatic cancer. In terms of diagnosis, the histopathological findings (particularly the ghost-like cells) were the most important, and hyperlipasemia was more useful than hyperamylasemia. A confirmed diagnosis of subcutaneous fat necrosis prompts early treatment for pancreatitis as skin rash preceded pancreatic disorder in 61.7% of reported cases. Therefore, it is important to consider subcutaneous fat necrosis (which is rare) when a patient presents with symptoms similar to those described above. Skin Research, 21 : 226-230, 2022

A 49-year-old man complained of a pedunculated tumor on his right lower eyelid that had been slowly enlarging for 7 years. The tumor had a size of 25 mm×20 mm. Histopathological findings revealed that the tumor was cord-like with many horn cysts in the dermis. The largest horn cyst contained vellus hairs, and secondary hair follicles radiated from the wall of the cyst. We diagnosed this tumor histopathologically as a trichofolliculoma. Furthermore, neutrophils were observed near the cyst which we considered the primary hair follicles. Significant vascular hyperplasia, dilatation of vessels, and red blood cells were observed in the stroma of the lesion. In these types of tumors,the pedunculated shape is extremely rare. His frequent touching of the tumor caused it to become pedinculated and it increased in size due to the addition of venous stasis and bacterial infection. Skin Research, 21 : 231-234, 2022

The patient was a Japanese 24-year-old male. He presented with a firm tumor on his occipital scalp one year prior to first visit to our hospital. On the firstvisit,a firm, keloid-like protuberant tumor was observed on his occipital scalp. Numerous hairs emerging from common follicular orifices, forming tufted hairs, were also seen in the cicatricial alopecia lesion. Surgical excision of the tumor was performed at the level of superficial fascia with reconstructive surgery by the advancement-rotation flap because local treatments with intralesional corticosteroids failed to reduce the size of the tumor. Histology of lower magnification of the tumor revealed loss of sebaceous glands, and infiltrations of inflammatory cells in the superficial to mid-dermis with interfollicular diffuse dermal fibrosis and preserved lower parts of follicles in the deep dermis to the subcutis. Proliferated, dilated capillary vessels with infiltrate of inflammatory cells and prominent stromal fibrosis, forming granulation tissue, and destruction of follicular epithelium were observed. Based on these findings, the patient was diagnosed as folliculitis keloidalis. The lesion was healed after surgical treatment, and no recurrence was seen. Pathogenesis of the disease and utility of surgical treatments are discussed. Skin Research, 21 : 235-239, 2022

A 48-year-old man, who had medical history of partial gastrectomy and had type 1 diabetes mellitus, chronic pancreatitis, and chronic hepatitis, presented with vesicles, rashes, and edema on both legs after usage of antifungal ointment and steroid ointment. At first, we thought he showed symptoms of contact dermatitis ; however, the patient didn’t respond to treatment for contact dermatitis. Patch test of antifungal ointment and patch test panel^○R were negative. Low level of serum albumin and his comorbidities made us suspect that he had deficiency dermatitis ; thus, we examined his plasma amino acids. We found declines in the levels of various essential and nonessential amino acids and zinc. Histological examination showed parakeratosis, intracellular edema,eosinophilic necrosis of stratum spinosum, and intraepidermal bulla. He was diagnosed as necrolytic migratory erythema. He did not have glucagonoma. Our case was characteristic as the episode and skin symptoms at the first presentation were very similar to contact dermatitis and he showed various skin symptoms through the period of treatment. It is important to survey levels of plasma amino acids and zinc for patients who have had episodes or diseases that may cause deficiency dermatitis. Skin Research, 21 : 240-245, 2022