Search

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQ) were decided based on the important clinical issues. For document retrieval, key words for published work searches were set for each CQ, and work published from 1980 to the end of September 2014 was searched in PubMed, Cochrane Library and Japana Centra Revuo Medicina databases. The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System technique. A total of 33 CQ were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies., (This article has been co-published with the permission of The Journal of Dermatology, Pediatrics International and Japanese Journal of Radiology. All rights reserved. © 2020 The Authors. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

A multicenter randomized controlled study was conducted to assess the long-term efficacy and safety of cyclosporin A therapy for psoriasis using either a continuous or an intermittent regimen. Initially, both regimens consisted of 3-5 mg/kg/day administration of CyA. Once remission was obtained, CyA dose was maintained between 0.5 and 3 mg/kg/day under the continuous regimen, while under the intermittent regimen, CyA dose was tapered off and, when necessary, topical corticosteroids were used until relapse occurred. Thirty-one patients were followed for at least 48 months (mean follow-up period: 55.9+/-4.6 months): 15 received continuous therapy, and 16 received intermittent therapy. With both regimens, the PASI (Psoriasis Area and Severity Index) score was maintained at 5-12 points throughout the follow-up period. The score was decreased by more than 70% from baseline with both regimens: the responses between them were not significantly different. However, overall control of psoriasis, as assessed from the averaged PASI score, was better in the patients receiving continuous therapy. Although the overall frequency of adverse reactions was similar for the two regimens, cancer occurred in two patients on continuous therapy (gastric cancer and hepatocellular carcinoma in one patient each). We could not, however, definitely attribute the cancers in the two patients to continuous therapy itself. There was a significantly higher incidence of renal impairment in elderly patients receiving either regimen when compared with younger patients. In conclusion, CyA administered to psoriasis patients under both regimens exhibited long-term efficacy and tolerability. Despite a lower overall efficacy, it seems proper to conclude that intermittent therapy is more useful than continuous therapy due to the occurrence of malignancies with continuous therapy. Further investigation is required to determine whether intermittent therapy is really safer than continuous therapy, and, if so, how it should be designed to minimize long-term adverse reactions and achieve overall control comparable to that of continuous CyA therapy.

Tranilast (Rizaben)-induced thrombocytopenia occurring in a 17-year-old man was reported. After withdrawal of the drug, he recovered within a week with oral prednisolone administration. Serological examination revealed no anti-platelet antibody, but platelet-associated IgG (PAIgG) was found. After incubation of peripheral blood of the patient with the drug in vitro, the level of PAIgG was significantly increased. These findings suggest the presence of a drug-dependent anti-platelet IgG in the patient's serum. This is the first report of immune thrombocytopenia caused by Tranilast. Our method for detecting drug-dependent platelet antibody in vitro is safe and useful for diagnosing drug-induced thrombocytopenia.

The expression of intercellular adhesion molecule-1 (ICAM-1) in mouse B16 and human melanoma cell lines was investigated by indirect immunofluorescence using a FACScan analyzer. Mouse B16 melanoma cell lines (B16-F1 and F10) did not express ICAM-1 under ordinary culture conditions. Neither in vitro hyperthermia at 41 degrees C for 3 or 6 hr nor cytokines such as gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) induced ICAM-1 expression in B16 melanoma cell lines. A combination of IFN-gamma with TNF-alpha caused slight induction of ICAM-1 expression in the B16-F10 melanoma cell line. Hyperthermia at 41 degrees C for 3 hr in combination with the cytokines induced a slight expression of ICAM-1 in the B16-F1 melanoma cell line. Hyperthermia at 41 degrees C for 3 hr or 6 hr did not induce de novo ICAM-1 expression but hyperthermia at 43 degrees C for 6 hr caused rather suppression of the expression of ICAM-1 in the three human melanoma cell lines tested. In contrast, they showed a clear increase in the expression of ICAM-1 after treatment with either with IFN-gamma or TNF-alpha, and the expression was further augmented by a combination of the two cytokines. Treatment with cytokines in combination with hyperthermia at 41 degrees C or 43 degrees C for 3 hr did not augment the expression of ICAM-1 over that in cytokine-treated human melanoma cell lines, at normal temperatures. Thus, it is concluded that mouse B16-F1 and F10 melanoma cell lines are different from human melanoma cell lines in terms of induction of ICAM-1 expression by cytokines and/or hyperthermia.

We report a case of Gianotti-Crosti syndrome associated with human herpesvirus-6 (HHV-6) infection. An eight-month-old girl developed monomorphous papules on her cheeks, buttocks, and extremities after the subsidence of exanthema subitum. Viral antibody analysis confirmed primary HHV-6 infection. HHV-6 may be added to the list of causative agents of Gianotti-Crosti syndrome.

Percutaneous injection of absolute ethanol was found to cause rapid destruction of murine and human melanoma nodules. It took only 24-48 hr after the ethanol injection to form ulcers or scars on the lesions. Massive necrosis of murine and human melanoma nests and interstitials and infiltration of mononuclear cells into the demaged tissue were observed histopathologically after ethanol injection. The melanomas recurred approximately 1 week after the destruction of the melanoma nodules by ethanol. Biological response modifiers such as levamisole or interleukin (IL)-2 were effective in preventing the recurrence of murine melanoma after ethanol injection. IL-2 injection caused massive infiltration of NK cells, T cells, and macrophages into the damaged melanoma tissue. The therapeutic modality of a combination of ethanol and IL-2 injections could definitely be useful for the local treatment of human metastatic melanoma, but other modalities such as local hyperthermia or radiation should be considered in combination to attain a permanent cure.

Two cases of metastatic malignant melanoma of the lower limb who were treated successfully with hyperthermic isolated limb perfusion are reported. One patient was infused with cisdiammine (1.1-cyclobutanedicarboxylate) platinum (II) (carboplatin, Paraplatin, Bristol-Myers Squibb Company, New Jersey, USA), and the other was infused with human natural beta-interferon (Feron, Toray, Tokyo, Japan), via the external iliac artery. The first case showed a remarkable suppression of the growth of multiple metastatic melanoma nodules associated with numerous melanophage infiltrations, as shown histopathologically after the operation. The patient's serum level of 5-S-cysteinyl dopa decreased for the two months following the treatment. In the second case, new formation of metastatic melanoma nodules was completely suppressed for up to 12 months following the operation. Analysis of immunological parameters showed that the number of peripheral CD8+ lymphocytes gradually and constantly increased after the operation, while that of CD4+ lymphocytes transiently increased and then returned to the pre-operative level. Natural killer activity transiently decreased to a slight degree 4 days after the operation and then returned to the pre-operative level 21 days after the operation. Side effects, such as nausea, vomiting and leg discomfort, were seen in the patient (Case 1) treated with carboplatin, but were completely reversible. These results suggest that hyperthermic isolated limb perfusion with concomitant infusion of carboplatin or beta-interferon is effective in suppressing the growth of metastatic malignant melanomas of the lower limb.

The role of elevations of serum cytokines in psoriasis is a provocative issue. We report two patients with psoriasis who had episodes of fever, arthritis, and general fatigue. Their symptoms seemed to be associated with increases in serum levels of interleukin (IL)-6, which paralleled the severity of clinical symptoms as well as elevated serum titers of C-reactive protein (CRP) and platelet counts. Since IL-6 is a multipotential cytokine with B-cell activating, T-cell activating, and thrombocytopoietic functions, the symptoms and abnormal laboratory findings in these patients may have been related to their increased serum levels of IL-6. Monitoring the serum level of this cytokine may thus be useful in evaluating the clinical status of patients with psoriatic arthritis.

Differential cell- and immuno-biological properties of two murine melanoma B16 variants, B16-F1 and F10, were investigated. Studies focused on the expression of proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of the expression of ganglioside components after treatment with IL-2. Proto-oncogene c-fos was found to be highly expressed in F10 lines by an in situ hybridization technique and also in F10 lung metastatic nests by immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2 treatment, but successive injections of a combination of LAK cells and IL-2 did cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major component of gangliosides of both F1 and F10 melanomas was GM3. Production of GM3 in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment was continued for 7 days, minor components of gangliosides, such as GM2, GM1, and GD1a, appeared only in F1 melanomas, while the increase of production of GM3 disappeared in both melanomas. These experimental results may provide clues for additional mechanisms which allow these two murine melanoma variants to show different implantation and metastasis rates.

Our experiences of hyperthermic isolated limb perfusion with administration of carboplatin, interferon-beta or a combination of both are reported. Administration of high doses of these reagents was well tolerated by patients with melanoma without severe complications after the treatment. A total of 8 patients underwent this therapeutic modality. Remarkable clinical improvement was seen in the first patient, who was in Stage III at the time of the perfusion. Histopathological findings indicated severe damage to the melanoma cells after the operation. Prophylactic hyperthermic perfusion was performed in 6 other patients with Stage II-III melanoma of the lower limb. None of them have shown any signs of recurrence 1-10 months later. The activities of natural killer cells or T lymphocytes appeared to be increased when the perfusion was carried out with concomitant administration of both carboplatin and interferon-beta. These results suggest that hyperthermic isolated limb perfusion with carboplatin and/or interferon beta administration is effective in patients with advanced stage melanoma.

We observed transient, erythematous skin eruptions in 6 patients during the intravenous administration of interferon (INF)-alpha for chronic active hepatitis C. The eruptions appeared 5 to 14 days (mean: 6.8 days) after initiating its administration. They were localized or disseminated and consisted of edematous, erythematous, and/or papular changes. Vesicles and petechiae also appeared in some cases. The eruptions disappeared in 10 to 14 days, despite the continuance of INF-alpha and without specific treatment. Histological examination obtained from skin eruptions revealed perivascular infiltration of lymphoid cells, the majority which were CD4-positive, of the upper dermis. Edematous changes were present in the papillary dermis. Vascular endothelial cells in the upper dermis expressed both intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), while the epidermal keratinocytes produced neither. These findings suggested a nonallergic mechanism for such eruptions.

The effects of PSK on tumorigenesis in mouse skin were investigated either when mouse skins were initiated by benzo(a)pyrene and promoted by 12-O-tetradecanoyl-phorbol-13-acetate (Group I, two-stage carcinogenesis) or when both initiated and promoted by benzo(a)pyrene (Group II, complete carcinogenesis). Twelve mice in each group were fed chow with or without 0.4% PSK. This concentration of PSK was determined by calculation to give mice enough PSK to exert antitumorigenic activity without cytotoxicity. By the end of the experimental periods (26 weeks), two carcinoma-burdened mice in Group I without PSK were dead, but no carcinomas at all were identified in the mice fed with PSK, although considerable numbers of papillomas developed in both groups. In Group II, carcinomas started to evolve at the 15th week of the experiment regardless of PSK feeding. The number of carcinomas observed in the mice fed with PSK in Group II was statistically significantly lower than that in the mice fed without PSK. Histologically, mild inflammatory infiltrations were seen around the papillomas, and moderate to dense infiltrations, mainly composed of neutrophils, T lymphocytes, and macrophages, were observed in squamous cell carcinomas. There were apparently no significant differences in the number of the infiltrating cells around carcinomas in PSK (+) and PSK (-) groups in both early and fully developed lesions. However, considerable numbers of cells infiltrating into the nests were observed in the early lesions of elicited carcinomas in the mice fed with PSK, while such cells were rarely seen in carcinoma nests in the group without PSK at that stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Three adult T-cell leukemia/lymphoma-derived cell lines, MT-2, MJ, and HUT102, were investigated to determine how they responded to hyperthermia, lymphokine-activated killer (LAK) cells, or a combination of both in vitro. All three cell lines showed a similar sensitivity to LAK cells, but revealed varying degrees of sensitivity to hyperthermia (MT-2 < MJ < HUT102) by 51Cr release assay. Hyperthermia did not cause immediate cell death as determined by the trypan blue exclusion test, but did cause substantial decreases in the numbers of heated cells within 2 days. The density of the cells began to increase thereafter, which was consistent with the results of the experiments labeling the cells with 3H-TdR after hyperthermia. When the cells were heated at 39-43 degrees C for 1-3 hr and then interacted with various LAK cell/ATL cell (E/T) ratios at 37 degrees C for 4 hr, total cytolysis of the cells increased in a synergistic and/or additive manner over that of the cells without hyperthermia. Prolonged incubation of the cells at high temperature did not necessarily cause a large increase in the interaction of LAK cells after hyperthermia. This augmentation of cytolysis by LAK cells after hyperthermia was not seen in normal peripheral lymphocytes. These results suggest that the combination therapy of hyperthermia and LAK cells may be more specific, useful, and effective for treating malignant lymphoma.

Interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and granulocyte/macrophage colony-stimulating factor (GM-CSF) were detected in the culture supernatant after 72 hours incubation with trichophytin in the peripheral blood mononuclear cells (PBMC) obtained from a patient who had a dermatophyte infection. These findings indicate that this patient has peripheral T-lymphocytes that produced IFN-gamma, IL-2 and GM-CSF, which may play roles in the development of delayed-type hypersensitivity (DTH) reaction in the skin.

In a 21-year-old female with severe atopic dermatitis, the secretion of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-gamma) by her peripheral blood mononuclear cells (PBMC) was measured after incubation with/without antigens extracted from Dermatophagoides pteronyssinus (Dp), to which the patient had developed a positive patch-test reaction. Incubation with Dp antigen produced marked secretion of IL-2 and IFN-gamma, but not IL-4. This may suggest that Dp-specific T lymphocytes present in the circulating blood cells are capable of producing IL-2 and IFN-gamma, which may be relevant to the delayed-type allergic reaction occurring in the skin lesion.

Patients with the acquired immunodeficiency syndrome (AIDS) often develop unusual skin complications. We describe a case of a 58-year-old man with AIDS who had a history of multiple transfusions with anti-hemophilic factor A. He developed papulovesicular and lichenified skin lesions on his head, face, neck and the extensor aspects of his extremities accompanied by severe pruritus. Atopic dermatitis was suspected; however, intensive treatment with a potent topical corticosteroid and a systemic antihistamine failed. In addition to the decreased subset of CD4-positive lymphocytes characteristic of AIDS, this patient showed an elevated level of serum IgE particularly specific for Candida albicans, probably because he had a chronic candidial infection of the digestive tract. Oral administration of anti-fungal agents Diflucan and Fungizone produced almost complete relief from the atopic dermatitis-like skin disease within 2 weeks.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.

We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T-lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T-lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors.

During a series of studies on the involvement of house dust mite antigens in 183 cases of atopic dermatitis, we observed an improvement in two patients following the removal of mites from their environment by means of a thorough housecleaning and replacement of the mattress. Both patients manifested the typical clinical skin lesions of atopic dermatitis and had similar laboratory findings. Although the serum IgE concentrations and specific IgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae were each relatively low, the results of patch tests with these antigens were positive. Thus, a regimen aimed at reducing the presence of house dust mites can produce clinical improvement in a subset of patients with atopic dermatitis who show contact hypersensitivity to mite antigens on skin testing, but negative results on IgE (RAST; radioallergosorbent technique) testing.

A 41-year-old woman presented with a painless hard subcutaneous nodule in the right upper eyelid. The lesion was diagnosed clinically as pilomatricoma and removed surgically. Histological examination disclosed a granulomatous lesion composed mainly of mononuclear cells with a foamy appearance and multinucleated giant cells with some admixture of granulocytes, plasma cells, and lymphoid cells. Lipid droplets and dilated ductal structures containing an eosinophilic fibrillar substance were observed in and around the granulomatous lesion. In addition, an intraductal dacryolith was seen near the granulomatous lesion. We finally diagnosed this case as chalazion; the coexisting dacryolithiasis was considered to be involved in the pathogenesis of chalazion.

A 39-year-old man had pseudo-Kaposi sarcoma on his left foot. A biopsy specimen obtained from a cutaneous lesion showed increased numbers of vascular spaces, proliferation of fibroblast-like spindle cells, and deposition of hemosiderin in the dermis. Immunohistochemically, proliferative fibroblast-like spindle cells around the vessels were positive for anti-factor XIIIa antibody. Excessive heat radiation was detected from the skin lesions by thermography.

A review of 872 cases of drug eruption reported in the Japanese dermatological journals from 1984 to 1989 has revealed a growing subset related to treatment with prodrugs, in which the responsible agent may be the metabolite rather than the prodrug itself. This situation is the result of the presence in tissues and fluids of only the metabolite following absorption and degradation of the prodrug. Because of this condition, patients with drug eruptions after prodrug treatment may develop positive patch test and/or lymphocyte stimulation test reactions not only with the introduced prodrug but also with the metabolite produced in vivo and further with other prodrugs which degrade into the same metabolite.

A malignant granular cell tumor (MGCT) appeared on the subungual tissue of the right index finger of a 51-year-old woman. Two years after resection of the tumor, it recurred, and the finger finally had to be amputated. Six months later, she noticed multiple cutaneous nodules on her trunk. Despite chemotherapy and X-ray irradiation, the patient died 18 months after the second operation. Histology of the specimen revealed a proliferation of both polygonal and spindle-shaped cells with large hyperchromatic nuclei and an eosinophilic granular cytoplasm. Peripheral nerves were encompassed by the tumor cells. Immunohistochemically, the tumor cells were positive for S-100 protein and Leu 7 (myelin-associated glycoprotein). These findings support the hypothesis that MGCT cells are of Schwann cell origin.

We report two cases of pilomatrix carcinoma. Wide surgical excision, radiation, and chemotherapy were required for the first patient. The tumor eventually revealed the characteristics of a carcinoma, both clinically and histopathologically, as it recurred. In the second case, although the tumor exhibited the histology of pilomatricoma in the central part of the lesion, there were numerous outgrowing irregular nests of basaloid tumor cells with cellular atypia and frequent mitoses; these are the characteristic features of the pilomatrix carcinoma in its early stages.

In a typical case of Darier's disease, intracytoplasmic desmosomes, gap junctions and many vesicles were observed in the cytoplasm of epidermal keratinocytes. Intracytoplasmic desmosomes were found in the cytoplasm of the excessively keratinized cells, vacuolated cells and acantholytic cells. They were not associated with tonofilaments as much as with ordinal intercellular desmosome-tonofilament complexes, and some of them lacked a central strip and looked similar to the denatured intercellular desmosomes in the morphology of the abnormal keratinocytes of Darier's disease. These intracytoplasmic desmosomes were long and undulating and some of the showed a "tennis racket" image (Caputo). Furthermore, some were combined with the gap junction and the intermediate junction, forming a bounded vesicle in the cytoplasm.

We have carried out in vitro studies of hyperthermic effects on the viability, blastogenesis, and ultrastructural changes of atypical lymphocytes isolated from the peripheral blood of three patients with malignant lymphoma/leukemia. One was lymphocytic lymphoma/leukemia (T-cell origin), and the others were adult T-cell lymphoma/leukemia (both acute and smoldering type). In the cases of adult T-cell lymphoma/leukemia, the peripheral lymphocytes were found to be more sensitive to hyperthermia than those of non-ATL patients in terms of trypan-blue exclusion ability and blastogenesis ability with concanavalin A challenge. When heated under sublethal conditions, lymphocytes of both ATL and non-ATL patients exhibited the following characteristics: production of multilayered nuclear membranes, increase in vesicles (lysosomes), swelling of mitochondria, and cytoplasmic vacuolization.