More than fifteen years have passed since the approval of clinical use of tacrolimus ointment for atopic dermatitis. Its efficacy and safety have been demonstrated clearly in many global and domestic short-term and long-term administration trials. Although prolonged external application of steroid causes adverse reactions including cutaneous atrophy, tacrolimus ointment does not cause such adverse reaction. Therefore, tacrolimus has been positioned as a drug that exerts therapeutic effects of external steroid but causes none of its unwanted side-effects. The pathological condition of atopic dermatitis has not been fully understood. However, the genetic, physiological and immunological findings and the therapeutic findings based on the use of new drugs have been accumulating and many scientific advancements have been achieved. With progress in understanding of the pathological condition, the possibility has been suggested that tacrolimus, which was clinically applied originally as an immunosuppressant for control of T cell activation, may control various aspects of the development/pathological condition of atopic dermatitis. In this paper, we summarized the recent findings on tacrolimus including control of itching,inhibition of allergic inflammation and improvement of skin barrier function and addressed the new possibility of treatment of atopic dermatitis with tacrolimus ointment.

A 3-year-old girl was presented with widespread erythemata and red-brown macules on her trunk and extremities. Petechiae were observed within the erythemata. Based on the clinical and histopathological findings, she was diagnosed with Schamberg's disease. In infantile Schamberg's disease, the eruption is often observed on the trunk and the upper extremities as well as the lower extremities. Therefore, it is important to consider the possibility of Schamberg's disease and to perform a biopsy when red-brown patches with petechiae are observed in infancy, regardless of their distribution.

A 6-month-old male developed daily erythema and wheal without apparent itch starting from the day after birth. Antihistamines did not improve his urticaria-like eruptions. Blood tests showed an increase in the number of peripheral blood leukocytes (29570 cells/mm³) and elevated levels of inflammatory markers (CRP : 4. 65 mg/dl ; SAA : 106. 2 μg/ml). In addition, skin biopsy specimens showed the infiltration of neutrophils into the perivascular area and edema in the dermis. Genetic analysis revealed the heterozygous variant of c.1792A＞T (p.Ile598Phe) in the NLRP3 gene, confirming the diagnosis of cryopyrin-associated periodic syndrome (CAPS). The administration of an humanized anti-human IL-1β monoclonal antibody, canakinumab, induced the prompt disappearance of the urticaria-like eruptions and the normalization of inflammatory markers. It is important to consider CAPS as a differential diagnosis of chronic spontaneous urticaria if wheallike eruptions appear and repeat starting from shortly after birth. The genetic analysis of NLRP3 at an early age enables early treatment with canakinumab, which quickly remits symptoms and could improve the long-term prognosis of patients with CAPS.

A 58-year-old woman presented to our hospital with blisters distributed to the oral cavity, trunk, and extremities. The blisters were predominantly distributed in intertriginous areas, such as the axilla. Microscopic examinations revealed subepidermal blister formation. Direct immunofluorescence testing showed the linear deposition of IgG and C3 at the basement membrane zone. Indirect immunofluorescence testing showed IgG reactivity with the dermal side of an artificial blister on 1-mol/l salt-split human skin sections. In an immunoblotting assay using extracts of normal human dermis, the patient's serum reacted with a 290-kd antigen that was identical to type Ⅶ collagen. Based on these findings, the patient was diagnosed with epidermolysis bullosa acquisita (EBA). The patient was initially treated with prednisolone (1 mg/kg/day [60 mg/day]) and the blister formation quickly ceased. However, the blister formation relapsed when the prednisolone was tapered to 40 mg/day. At that time, we started to administer colchicine (1.5 mg/day), which has been shown to be effective in EBA. Thereafter, we were able to gradually taper her dose of prednisolone to 10 mg/day. Colchicine should therefore be considered in the treatment of steroid-resistant EBA.

We report six cases of deep dissecting hematoma. All patients were female with clinical manifestations of dermatoporosis in the extremities. Their mean age was 81. 8 years and two of the patients with long-term systemic corticosteroid therapy were younger than the others. Three patients were prescribed anticoagulant. Deep dissecting hematomas developed at the posterior lower extremities in all cases, with chief complaints of redness and swelling. Deep dissecting hematoma is frequently misdiagnosed as phlegmone because of the similarity of their symptoms. Surgical debridement and skin grafting were chosen in one case, while two cases were treated with negative-pressure wound therapy. Complete healing took one to six months. Physicians should be aware that dermatoporosis is a critical factor predisposing patients to deep dissecting hematoma. Minor trauma may induce extensive bleeding. Preventive measures such as the use of skin-protective clothing are mandatory, especially on the lower extremities of elderly patients.

A 16-year-old man noticed asymptomatic blue-gray patches on his trunk a month before visiting our clinic. The lesion gradually increased in size and number. Clinical examinations were normal and histopathological examination showed melanin deposition in the dermis. The patient was diagnosed as ashy dermatosis based on clinical and pathological findings. The lesion did not respond to 4-month oral ascorbic acid and tranexamic acid therapy. Although there is no established treatment for ashy dermatosis, it was reported that removal of the causative factors improved the symptom when the causes of onset were identified. Therefore, detailed history taking would be important in diagnosing ashy dermatosis.

A 57-year-old man presented with a nodular lesion on his left lower jaw with its 2-year-history of fluctuation in size. No improvement was obtained by local ointment or oral medication therapies. Physical examination showed a slight erythematous, half-spherical, elastic-soft nodule of 10 mm in size on his lower jaw. Histopathological examination revealed an oval bony tissue located in the lower part of the intradermal nevus, suggesting the diagnosis of osteonevus of Nanta. We summarized the reported cases of osteonevus of Nanta in Japan.

A 30-year-old woman visited our hospital with a 3-month history of nail plate deformity of the right thumb. MRI revealed a node measuring 8.7×6.2×4.5 mm on the nail plate of the right thumb ; the node was removed under local anesthesia. It was relatively easy to separate the node from the surrounding tissues, allowing its resection with preservation of the nail matrix. Histopathological examination showed a relatively well-defined nodular lesion lacking connection with the epidermis. The lesion had no capsules, and it extended from the dermis to the subcutaneous tissues. This legion was composed of myxoid stroma and spindle- or asteroid-shaped fibroblast-like cells growing randomly in bundles in the stroma. The tumor cells were positive for vimentin and CD34 on immunostaining. Based on these findings, this patient was diagnosed with superficial acral fibromyxoma. Her postoperative course was favorable, with regeneration of the nail plate ; thus, we successfully minimized postoperative nail plate deformity.

Here we report a case of multiple dermatofibromas (MDF) arising in a patient with systemic lupus erythematosus (SLE) and Sjögren's syndrome. A 40-year-old woman with SLE and Sjögren's syndrome presented with a 5-year history of multiple cutaneous nodules. At the age of 33, she was diagnosed as having SLE and Sjögren's syndrome. Oral prednisolone was initiated and then tacrolimus was added at the age of 35. One month after the first administration of tacrolimus, she noticed a nodule on the chest. Similar nodules then appeared on the chest and limbs, eventually numbering 14 in total. Histologically,the nodule on the chest was composed of a proliferation of collagen bundles and spindle-shaped cells arranged in a storiform pattern in the dermis with reactive epidermal acanthosis, leading to the diagnosis of dermatofibroma. We have reviewed the comorbidity of MDF and internal diseases with special reference to SLE and Sjögren's syndrome.

A 39-year-old woman had been treated with immunotherapy for systemic lupus erythematosus (SLE) and lupus nephritis since 1992, and her condition was stable. In 2001, four small brown nodules appeared on her face and extremities, and they were diagnosed histopathologically as cellular dermatofibromas. In 2008, a subcutaneous nodule appeared on the right cheek and gradually increased in size. Histopathologically, the tumor nest was distributed from the superficial muscle to the fat layer and contained necrotic cells. The tumor was mainly composed of irregular spindle-shaped cells, which may have been fibroblastic in origin. Mitosis and atypia were also seen. The possible diagnoses included nodular fasciitis, atypical fibrous histiocytoma (AFH), and low-grade myofibroblastic sarcoma. Marginal resection of the residual tumor was performed and no recurrence or distant metastasis has occurred for five years. However, new dermatofibromas developed on the dorsum of the night hand and the left forearm. The occurrence of multiple dermatofibromas (MDF) is known to be associated with SLE, but the other contributing risk factors remain unclear. This case was an SLE patient with MDF, and there has been no recurrence after surgery for five years ; therefore, the subcutaneous tumor of the cheek was thought to be AFH on the basis that AFH has been recognized as a subtype of dermatofibroma. As such, this is the first case of AFH arising alongside benign MDF.

A 75-year-old man had developed a rice grain-sized pink nodule on the dorsum of the third finger of his left hand 1 year prior to the initial consultation. As the nodule had gradually increased in size and become a sessile pink mass of 4×3.5×2cm in size, the patient visited our hospital. At the initial consultation, a subcutaneous induration on the left axilla was also palpable, and lymph node metastases were suspected. Histopathologically, the lesion appeared as a nodular lesion within the dermis and resulted in a sheet-like growth of tumor cells, which showed partial continuity with the epidermis. The main constituents of the tumor cells resembled basophilic basilar cells. Clear foamy cells were also found among the tumor cells. The nuclear contour of the tumor cells was irregular and accompanied by chromatin hyperplasia. In addition, numerous mitotic figures were observed. Immunostaining showed positive results for both cytokeratins (AE1/AE3 antibodies) and epithelial membrane antigen. Adipophilin-positive cells were also seen in some areas of the lesion. The patient was diagnosed with sebaceous carcinoma and underwent tumor resection with a 1-cm margin and left axillary lymph node dissection, which revealed the presence of level 1 lymph node metastasis. The occurrence of sebaceous carcinoma on the finger is extremely rare ; hence, we have supported our observations with a literature review.

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of sarcoma that mostly arises in deep soft tissue associated with plexiform neurofibroma in patients with neurofibromatosis type 1 (NF1). Cutaneous MPNST is a rare entity that is predominantly located in the dermis or subcutis and is associated with peripheral nerves in skin or a solitary neurofibroma. Cutaneous MPNST mostly occurs in patients without NF1 and those derived from solitary neurofibromas are rarely reported. Here, we report a case of a 65-year-old woman without NF1 who had a cutaneous MPNST at the excisional site of a nodule on the right chest, which was diagnosed as a solitary neurofibroma and resected 7 years before the first visit. Physical examination revealed a light-brown, slightly elevated, partly erythematous, depressed, and elastically firm subcutaneous tumor measuring about 5 cm in diameter on the right chest. Histopathological examination of the resected tumor showed a hypercellular area composed of hyperchromatic spindle cells with prominent nuclear atypia, frequent mitotic figures with a MIB-1 proliferation marker index of 15％, and a decreased cellular fibrous component, which was irregularly oriented and intermingled in the dermis and subcutis, and invaded at the edge of the fascia. The tumor recurred at the same site 17 months after re-resection and histopathological examination of the recurred tumor, which measured 4.5×3 cm in size,showed a lesser proliferation of spindle cells with diminished nuclear atypia and a MIB-1 index of 5％. While the prognosis of MPNST is generally poor because of a high rate of distant metastasis, that of cutaneous MPNST is not necessarily as bad if early detection and complete resection is achieved. Better prognostic factors of cutaneous MPNST are lesions on areas other than the head and neck, a tumor size of less than 5 cm, and the periphery of the resection area confirmed to be negative for signs of malignancy at check-up after surgery.

We have experienced three cases of sparganosis mansoni, which included a 58-year-old woman, a 68-year-old man, and a 56- year-old man. According to the patients, none of them had consumed undercooked meat of animals such as snakes, frogs,fowl, or wild boars. One of the three patients showed a subcutaneous tumor that was typical of sparganosis mansoni, whereas the other two showed skin eruptions of cutaneous larva migrans, a linear or belt-shaped manifestation of red papules and/or erythema. Histopathological examinations of the skin biopsy specimens from all three cases revealed calcareous corpuscles in the larvae, which were identified as concentric structures that were positively stained by von Kossa staining. Multiple-dot enzyme-linked immunosorbence assay (ELISA) of serum samples showed positive antibodies for Spirometra erinaceieuropaei. All three cases were further diagnosed sparganosis mansoni due to S. erinaceieuropaei using PCR and direct sequence methods. As for treatment, total excision was performed in each case.