A 39-year-old woman presented with a two-year history of Raynaud's phenomenon and a diagnosis of mixed connective tissue disease (MCTD). She has had multiple subcutaneous nodules on her fingers for one year. At her first visit to our clinic, a total of 12 subcutaneous nodules of up to 3 mm in diameter were observed on the fingers bilaterally. Histological examination of biopsy specimens of the nodules revealed that the nodules were composed of palisading granuloma from the deep dermis to the subcutis, with central necrobiosis and mucin deposition. The final diagnosis was subcutaneous granuloma annulare (GA) in the presence of MCTD. To the best of our knowledge, this is the first case of multiple GA lesions comorbid with MCTD. Because the lesions were distributed only on the fingers, circulatory dysfunction and subsequent tissue damage caused by Raynaud's phenomenon might have been involved in the development of granuloma annulare in this patient.

A man in his 80s had an edematous erythema and induration of the upper and lower extremities 4 months before his visit to our hospital. His medical history included an enlarged prostate, but he was otherwise healthy. His arms, upper back, and legs were symmetrically indurated, and his legs had a peculiar cobblestone appearance. These joints showed normal range of motion. He did not have Raynaud phenomenon or nail-fold capillary abnormalities. Axial T2-weighted post-contrast magnetic resonance imaging revealed abnormal diffuse thickening and enhancement of the fascial planes of the bilateral femoral biceps. Fascial biopsy showed fascial thickening with lymphocyte accumulation. Therefore, he was diagnosed with eosinophilic fasciitis (EF). Prednisolone 40 mg daily was started, but gradually reduced; the serum aldolase level was elevated. We added methotrexate (MTX) 3 months after the start of prednisolone treatment. Subsequently, the skin induration was improved, and the serum aldolase level was reduced; we were able to gradually reduce prednisolone. Currently, the toxicities of MTX are not found. MTX seems to be an effective treatment option for steroid-dependent or steroid-resistant EF.

A 7-year-old girl presented with enlargement of the left labium majus without subjective symptoms. Histological examination of a biopsy specimen revealed proliferation of blood vessels, fibroblasts and collagen fibers. Immunohistochemically, the fibroblasts were positive for estrogen receptor but not progesterone receptor. She was diagnosed with prepubertal unilateral fibrous hyperplasia of the labium majus (PUFH). One year after diagnosis, there was no sign of growth or new lesions without any treatment. PUFH occurs in pre- and early pubertal girls and is characterized by painless, non-tender labial swelling. Only 42 cases of PUFH have been reported in the world so far and PUFH is a rare disease. PUFH is considered to be caused by the sex hormonal response. We report this case along with a literature review.

A 90-year-old woman was admitted to our hospital with a protruding tumor on her left cheek. The dome-shaped, reddish tumor was 2 cm in diameter. Tumor resection with a 1-cm side margin to the depth of the superficial muscular aponeurotic system (SMAS) was performed. Pathological examination revealed that the lesion infiltrated into the deep dermis and actually consisted of two lesions. One lesion consisted of atypical basophilic cells that were negative for CK20 but positive for nervous system tumor markers such as synaptophysin (SYP), chromogranin A (CGA), and CD56, leading to a diagnosis of Merkel cell carcinoma (MCC). The other lesion consisted of atypical squamous cells with eosinophilic cytoplasm and irregularly shaped nuclei, which were positive for CK5/6 but negative for CK20, SYP, CGA, and CD56, leading to a diagnosis of squamous cell carcinoma (SCC). The transitional areas of the two types of lesions were observed. All lesions were negative for Merkel cell polyomavirus (MCPyV) by immunohistochemical analysis. In the present and previously reported cases, MCPyV was negative in 15 of 16 lesions of MCC accompanied by SCC, suggesting that MCPyV is not involved in the carcinogenesis of MCC accompanied by SCC, and the mechanism of pathogenesis may be more complicated than that of MCPyV-positive MCC.

Verrucous carcinoma of the foot is often misdiagnosed by using a partially resected biopsy specimen, because its clinical appearance and pathological features are similar to those of verruca vulgaris. Thus, pathological examination of totally resected tissue is necessary to make a definitive diagnosis. However, it is not easy to perform total resection of large-sized verrucous lesions of the foot, because reconstruction requires skill. We report a case of verrucous carcinoma of the foot with positive immunostainings of both p16 and MIB-1 in the partially resected biopsy specimen, followed by total resection of the lesion. A 69-year-old man with diabetes mellitus was referred to our department because of verrucous hyperkeratosis on the right foot persisting for two years. Histological examination of biopsy specimens showed no dysplastic sign ; however, immunostaining for both p16 and MIB-1 was positive, suggesting malignancy. Total resection of the lesion was performed and a diagnosis of verrucous carcinoma of the foot was made. Since p16 immunostaining is positive in dysplastic or malignant lesion in the uterine cervix and MIB-1 immunostaining is positive in tumor cells with proliferative ability, we performed these immunostainings in this case. As a result, positive staining was found in large parts of the tumor on both p16 and MIB-1 immunostainings, suggesting that a combination of p16 and MIB-1 immunostainings is a useful method of differentiating verrucous carcinoma of the foot from verruca vulgaris or other benign hyperkeratotic lesions of the foot.

A 73-year-old Japanese man presented to our hospital with a four-year history of erythroderma. He had a medical history of mycosis fungoides that was diagnosed by clinicopathologic features. On physical examination, he had diffuse erythroderma and bilateral inguinal lymphadenopathy. Peripheral blood examination showed an increased leukocyte count (21,650/μl) with marked Sézary cells (66%) and high CD4/CD8 ratio. Analysis of clonality by polymerase chain reaction (PCR) revealed the presence of clonal rearrangement both blood and bone marrow. These findings were consistent with secondary Sézary syndrome, T₄N_XM₀B₂ (Stage ⅣA₁). Skin biopsy with immunostaining showed tumor cells that were positive for CCR4. Therefore, he was treated with 1.0 mg/kg of humanized anti-CCR4 monoclonal antibody (mogamulizumab) once a week for 8 weeks. During the treatment, he developed mogamulizumab-induced drug eruption. Therefore, the drug was withdrawn, and he was treated with systemic corticosteroid. After improvement of drug eruption, complete remission in both lymph nodes and blood was noted but not in skin lesions. A complete response was sustained for an additional 7 months but the patient then developed recurrence of peripheral blood lymphocytosis. Since he could not tolerate the usual protocol, mogamulizumab was re-administered at a monthly dose of 1.0 mg/kg for 8 months. Even though we extended the interval dosing, he showed an immediate decrease in circulating Sézary cells and improvement of skin lesions within 6 months after the final administration. He has maintained a partial response for the past 24 months after the treatment. Our case suggests that mogamulizumab has a delayed effect on skin compared with its effects on blood and lymph nodes. Thus, the extended-interval dosing of mogamulizumab appears to be as effective as the recommended dosing, reducing the risk of drug eruption in elderly or indolent cases.

We report a case of widespread erythema in both lower limbs and inguinal region caused by group G Streptococcus in both legs leading to toxic shock-like syndrome (TSLS), for which radical debridements of the lesions were performed and resulted in successful outcome with preservation of limbs. A 57-year-old woman was transported to the emergency unit of our hospital because of fatigue, fever and pain in both thighs with difficulty in walking from the day before the visit. We suspected toxic shock syndrome or TSLS because of redness and swelling accompanied by severe pain in both thighs and shock condition. The antibiotics meropenem and clindamycin were administered to the patient under systemic management in the intensive care unit. On the 3rd hospital day, purpura and blisters appeared around her left thigh and left knee joint. We performed fasciectomy in the thigh and found subcutaneous edema without necrosis. Group G Streptococcus was identified in bacterial cultures of both the subcutaneous tissue and circulating blood, leading to the definitive diagnosis of TSLS. On the 6th hospital day, the erythema spread to her left inguinal region and blisters newly developed in her right knee. Accordingly, we performed surgical debridement in her left inguinal region and both thighs throughout the skin and subcutaneous tissues adjacent to the fascial layers. On the 7th day, since erythema and local heat expanded to her right inguinal region and both lower legs, further debridement was carried out along with intensive administration of antibiotics, ampicillin/sulbactam and clindamycin. Finally, progression of the disease subsided. Starting on the 14th hospital day, six cycles of split-skin grafting onto the ulcers were performed every other week, resulting in reepithelization of all wounds to allow her to be discharged from the hospital in ambulatory condition in six months.

Biologic treatment has dramatically changed the systemic treatment against psoriasis ; however, the transition of oral drugs has not been studied in this biologic era. To elucidate the real-life data of oral systemic treatment of psoriasis in this era, patients who visited our department during the period from January 1, 2010 to March 31, 2016, who were diagnosed as having psoriasis, and who were treated with prescription of cyclosporin, etretinate, or methotrexate were enrolled in this retrospective observational study. The following seven parameters were analyzed : gender, age, type of medicine, duration of treatment, transition to other drugs, combined use of drugs, and presence or absence of transition to molecular targeted drugs. One hundred forty-nine patients were identified. Cyclosporin was the most commonly used medicine (109 cases) in both monotherapy (80 cases) and combination with other systemic drugs. 40.0% of those treated with cyclosporin were shifted to biologics, while the remaining patients were on the same treatment regimen over the long term ; some cases were on cyclosporin for more than 2000 days. Etetinate was administered in 44 cases ; etretinate was administered to mostly elderly patients, and a few patients of reproductive age. The median duration of etretinate use was 255 days, suggesting that it is often used temporarily. Methotrexate was prescribed to 30 patients, and 54.5% of them were switched to biologics, which was the highest rate among the three drugs analyzed. Methotrexate is often used in patients with psoriatic arthritis. In addition, the use of methotrexate.

Emma Guttman-Yassky, MD, PhD, the Sol and Clara Kest professor of dermatology, is vice chair for research at the Department of Dermatology, director of the Center for Excellence in Eczema, and the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York. She earned her MD from Sackler in Tel-Aviv, and a PhD. from Bar-Ilan, Israel. After her Israeli Board certification in dermatology at the Rambam Medical Center at the Technion, Dr. Guttman moved to the U.S. to pursue a postdoctoral fellowship at Laboratory for Investigative Dermatology at The Rockefeller University and a second dermatology residency at Weill-Cornell, NY.