Attention has been given to the eruptive occurrence of seborrheic keratosis, senile hemangioma and hypertrichosis in association of malignancies of internal organs. A comprehensive term of eruptive paraneoplastic dermatoses has been proposed. Presented here are cases of eruptive lesions we have experienced in association of malignancies of internal organs including sign of Leser-Trélat (eruptive keratosis), multiple reticulohistiocytosis, hypertrichosis lanuginosa acquisita (eruptive lanugo hair), Crow-Fukase syndrome (eruptive hemangioma) and Bazex’ syndrome (eruptive acrokeratosis) with a review of such cases reported in Japan. Stress has been placed on the dynamic eruptive nature of such lesions as against the static nature of conventional seborrheic keratosis or senile hemangioma.

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“Agricultural chemicals” mean fungicides, insecticides, and other chemicals used for control of fungi, nematodes, mites, insects, rodents and plants which are injurious to crops and other chemicals used for the promotion or depression of physiological functions of crops. In Japan, production, sales, use of agricultural chemicals are regulated mainly by the Agricultural Chemicals Regulation Law, and also by the Poisonous and Deleterious Substances Control Law, the Food Sanitation Law, the Fire Laws, the Labor Safety and Sanitation Law. The development of new agricultural chemicals started after World War II when some organic compounds like DDT, BHC, parathion appeared, and the production of agricultural chemicals were increased year by year until around 1968. However since 1970 the regulation of agricultural chemicals has been accelerated by toxicity or residue problems. As a result, DDT, BHC and parathion disappeared from the market and the production of agricultural chemicals remains flat up until now. Staple agricultural chemicals presently used in Japan are as follows: Insecticides; organophosphaten, carbamates, methomyl, cartap, machine oil, etc., Fungicides; dithiocarbamates, phthalimides, probenazole, isoprothiorane, IBP, etc., Herbicides; paraquat, glyphosate, trifluralin, pyrazolate, CNP, butachlor, benthiocarb, chlomethoxynil, bentazone, pretilachlor, MCP, etc. In 1971, the Agricultural Chemicals Regulation Law was amended, and the strict safety evaluation started. In 1985, the Toxicological Study Guidelines were revised, and toxicological studies have been conducted more thoroughly since then. Recently, since skin toxicity studies have attracted attention considerably, the primary skin irritation studies and the skin sensitization studies are always required for the pesticide registration together with the primary eye irritation studies. Although low toxic agricultural chemicals dominate in market in these days, some people say that, agricultural chemicals poisoning have not decreased so much. It is assumed that the agricultural chemicals are used without much care because of their low toxicity. Therefore, governmental and prefectural authorities and SACI promote the Agricultural Chemicals Hazard Prevention Campaign in order to promote and prevail the instructions for the use of agricultural chemicals. Additionaly, the Ministry of Health and Welfare, in cooperation with other relevant organizations, recently founded the Poisoning Information Center which provides the information necessary for the medical treatment of poisoning.

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The mechanisms governing the incidence of pesticide dermatitis have been considered to lie mainly in primary irritation, contact allergy, and photosensitivity induced by pesticides. Taking these mechanisms into consideration, the authors, based on the characteristics of clinical symptoms, divided patients with pesticide dermatitis into 4 types — chemical burn type, acute dermatitis type, chronic dermatitis type, and solar dermatitis type. 243 patients with pesticide dermatitis visited Saku Central Hospital in 11 years from 1975 through 1985; of them, those with pesticide dermatitis of chemical burn type, of acute dermatitis type, of chronic dematitis type, and of solar dermatitis type were each 10.7%, 52.7%, 25.9% and 10.7%, respectively. Pesticides patch test were carried out for 12 years from 1975 through 1986 at 23 places in the region in Nagano prefecture. The total number of persons tested was 766 and that of pesticides 96. In view of the fact that there are partly those cases of pesticide dermatitis in which the region of rash coincides with the skin part exposed to light and which show symptoms of solar dermatitis, there is a possibility that a pesticide, acting as a photo-sensitizing agent, causes exogeneous photosensitive dermatitis. Therefore, photo-patch test were carried out with 17 pesticides. The subjects of the test were 52 patients of pesticide dermatitis and 26 formers.

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Dermatitis by contact with wild plants, ornamental plants and plant products may occur accidentally, mistakenly, unwisely or by occupation. Today, contact with ornamental plants is the most frequent source of plant dermatitis. The resulting skin reaction may be mechanical injuries, primary irritation or allergic contact dermatitis depending on the kind of plant species. Thirty-three patients with plant contact dermatitis were observed at Medical Institute of Bioregulation Hospital from 1979 to mid 1986. The most common causal plants were Primula obconica, Chrysanthemum, Aloe arborescen Mill, Rhus succedanea and Gingko biloba. In 24-hour closed patch tests using leaves and flowers of Primura obconica, all patients with Primura dermatitis had shown positive reaction. After leaving away Primura obconica, they never suffered from dermatitis. Closed patch tests with aqueous extracts of Chrysanthemum leaves and flowers had shown positive reaction to all patients with Chrysanthemum dermatitis. Patch test reaction with 0.1% and 0.2% helenin was also strongly positive. Four patients with Aloe dermatitis had a primary irritant contact dermatitis, showed negative reaction in closed patch tests. All patients with Rhus succedanea dermatitis gave strongly positive reactions to 0.01% urushiol. Optimal concentration of patch test allergen and diagnostic patch test methodology were discussed.

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About 110 species of mosquitoes are known from Japan. Among them, medically important species have common characteristics that the larvae inhabit water habitats in and/or near the human dwellings and the adult females take blood preferably from man. In west Japan, the most important are Culex pipiens pallens, C. p. quinquefasciatus, C. molestus, C. tritaeniorhynchus, and Aedes albopictus. Effective countermeasures are varied according to the biology of each species. The process of female mosquitoes to find host animals and take blood is rather complicated, and has not been fully understood.

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Female mosquitoes “sting” humans or animals in order to suck the blood and have their eggs matured. First, they thrust their mouth needle (proboscis) into the skin of the victim animal (or human) and inject the salivary fluid and then suck the blood. This saliva causes various skin reactions. At least, two types of skin reactions have been discriminated; the early reaction (erythema and wheal reaction) and the late reaction (papule reaction). Most people show the following lifetime course of the skin reactivity; no reaction—late reaction appears—early reaction appears—late reaction wanes—early reaction wanes—no reaction. It has been speculated that the saliva substances function as the allergens, although the primary toxic stimulation theory has not been positively denied. As to the physicochemical and biological characteristics of the saliva substances, very limited informations are available so far. Several investigations showed that the mosquito saliva contains non-dialyzable peptides which function as the allergens. These studies employed homogenates of the whole mosquito bodies as the analysis materials. However, the mosquito salivary gland is extremely small, usually less than one-thousandth of the whole body, and these homogenate contains too much contaminating materials to analyze the exact nature of the salivary gland substances. This has been in fact the biggest obstruction for these kind of investigations. Recently a new experimental trial was reported in Japan. Namely, salivary glands were separated individually under the stereoscopic microscope observation and then analyzed. Various substances were detected in the salivary gland including histamine, polyamines, esterases and peptides. Although this study itself gave only a preliminary information as to the nature of the salivary gland substances, their sample preparation method of individual salivary gland dissection would be obviously the method of choice for further studies of the mosquito sting allergens.

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Mosquito bites are classified into 4 clinical types of urticaria type, prurigo type, hypersensitivity type and fatal type. Urticaria and prurigo type are very common, but hypersensitivity and fatal type are moderately rare. Twenty-seven patients with mosquito hypersensitivity have been reported in Japan. Fatal cases were 11 out of 27 patients. The cause of death was malignant histiocytosis in 9 patients, intracranial hemorrhage and unknown malignancy in each one. In this presentation, 2 patients with mild type of mosquito bites and 3 patients with mosquito hypersensitivity were reported. The histologic appearance of the skin lesions of mosquito hypersensitivity corresponded to Arthus type vasculitis. A 18-year-old woman with mosquito hypersensitivity died of renal insufficiency, and histologic examinations after autopsy revealed the infiltration of histiocytic tumor cells in the liver, spleen and kidney. A 23-year-old woman with past episodes of mosquito hypersensitivity had ulcerated lesion on the right leg, histologically diagnosed as malignant histiocytosis. She died after 7 months in spite of various treatments.

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Clinical and histological studies were done on three patients (7-month-old girl, 1-year and 4-month old boy, 8-year-old boy) with total albinism. In cases of total albinism, it has been considered that the skin and hair were white and that no pigmentation occurred during the life span. Ophthalmological examination, photo test of skin, tyrosinase activity test of the hair bulb, dopa test and electron micoscope examination of the skin were done. Tyrosinase activity of the hair bulb was considered to be most useful for diagnosing the tyrosinase type of albinism. One child was diagnosed as being tyrosinase-negative type and the other two were the positive type. Due to the photosensitivity of the skin and eyes, the three patients had to be protected from ultraviolet rays by the use of ointment and eye glasses. The patient with the tyrosinase-negative type could not open her eyes in the presence of sun light. The hair and iris in the two of the tyrosinase-positive type have attained color, but the eyes should be protected, at best during childhood.

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A 68-year-old female farmer (case 1) had an ulcerated lesion on the right footpad and numerous, smaller satellite lesions developed on the same extremity. She had rheumatoid arthritis and has been on oral steroid therapy for 25 years. In case 2, a relatively defined erythematous lesion was present on the dorsal surface of the right hand of a 78-year-old male farmer. The patient was treated with a variety of topical antibiotic ointments. The lesions resembled mycetoma and contact dermatitis in case 1 and in case 2, respectively. The histopathological finding showed mixed cell granuloma and the isolated organisms were identified as Sporothrix schenckii.

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A 3-year and 11-month-old girl has noted erythema with band-like depression on the skin surface of the left side forehead since the beginning of 1979. She was examined for the eruption with simple application of Hirudoid ointment, which showed no effect. On July 2nd, 1979, she consulted with our department because of gradual sclerotic change of the skin with hyperpigmentation over the left side frontal region and forehead. Physical examination disclosed sclerotic and atrophic skin of a linear line or a «coup de sabre» with hyperpigmentation extending from the left side occipital region to upper lip. Laboratory investigation including complete blood cell count, CRP, ASO titer, protein electrophoresis, serum calcium, serum phosphate and carcitonine were within normal limits except for high titer of PTH (0.7ng/ml). Histopathologic examination of a skin biopsy specimen of the forehead showed dermal thickenning of closely packed and hyalinized collagen bundles and focal accumulation of mononuclear cell infiltrate around the follicles, sweat gland and fatty tissues. CT scanning view on the height of -13 A showed a small accumulation feature in the choroid plexus of the left ventricle, which was suspected as calcification because of 72-l02 number by the computal analysing. She was treated once a week 64 times in total by the low-frequency electrical acupunctual method in the period of one year and 5 months. Low frequency electrical stimulations had been given between Indou (midportion between bilateral elbows) and the far egde of longer axis of linear scleroderma lesion for 20-30 minutes since 11th treatment time. As the result of the treatment, improvement of cutaneous sclerosis, hyperpigmentation and perilesional alopecia was obtained.

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Radioimmunoassay was used to measure serum levels of neuron-specific enolase (NSE) in 20 patients with a melanoma, mostly stage IV. Immunohistochemical studies on NSE were done on the resected tissues. In the case of no metastatic foci or with metastatic lesions limited to the skin or regional lymph nodes, serum NSE levels were normal limits (less than 15 ng/ml). However, serum NSE levels increased in 11 of 15 patients with widespread metastasis and the range of serum NSE varied from 17.0 to 261.1 ng/ml (mean value: 54.4 ng/ml). The serum NSE level did not always correlate to the serum level of lactic dehydrogenase (LDH). Immunohistochemical studies showed that 3 of 8 primary tumors and 10 of 14 metastatic tumors were positive for NSE. The positivity for immunoreactive NSE in the metastatic tumors was higher than that in primary tumors. The clinical value of serum NSE levels in melanoma patients is the subject of ongoing study.

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Morphologic events associated with immunologic rejection by strain 13 guinea pigs of dinitrophenylated epidermal cells (DNP-EC) were studied, light microscopically. The DNP-EC injection site in the skin of normal animals exhibited clusters of EC with a moderate amount of inflammatory infiltrate composed of neutrophils and mononuclear cells throughout the dermis. Marked proliferation of EC was observed in skin lesions obtained 3 days after the intradermal injection. The EC contained keratohyaline granules. In case of the 5 day site, central keratinization of the proliferated EC had occurred and cysts were evident. Typical delayed-type skin reactions associated with EC necrosis and extensive inflammatory infiltrate including increase in the number of basophilic leukocytes was elicited 7 days after the injection. The implantation of haptenated epidermal cells is considered to be a useful approach when attempting to analyse histologically the course of contact sensitivity from sensitization phase to elicitation.

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To clarify which type of immunoglobulin is involved in the humoral immunological reaction in dermal inflammation, ABC stain with anti-IgG, A, M, D, E antibodies was used for specimens from secondary syphilis (SS) (7 cases) and chronic inflammatory disorders (CID); eg, inflammatory epidermoid cyst (3 cases), ingrown nail (2 cases), dermatitis papillaris capillitii (2 cases), basal cell epithelioma (2 cases), solar keratosis (3 cases). In general, IgG positive cells accounted for 85.5% of the immunoglobulin positive cells, thereby indicating that IgG may play a main role in the humoral immunity in these lesions. The polulation of IgM and IgA positive cells differed between SS and CID. In CID lesions IgA positive cells were more frequently observed than the IgM positive cells, but not in SS lesions.

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Topical application of Solbase (a mixture of polyethylene glycol 400 & 4000) plus occlusion improved the eruptions of 2 patients with Darier’s disease. To determine the mechanism of action, the effect of polyethelene glycol 400 on the rat epidermal DNA synthesis was investigated using autoradiography and doing ¹⁴C-thymidine incorporation studies. Seven days’ topical application of polyethylene glycol 400 activated epidermal DNA synthesis nearly double the value seen in the control. This therapy should be considered for patients with Darier’s disease and especially for whom retinoids cannot be prescribed.

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Seventy-five cases of metastatic skin cancers, collected from 15 institutions in West Japan were studied. Frequent primary tumors were carcinoma of the lung (31%) and the stomach (20%). Metastatic lesions of lung cancer were common on the neck, face and scalp. The anterior part of the abdomen was the most common metastatic site of stomach cancer. The average interval between the appearance of the skin lesion and the detection of the primary cancer was 20 months. Of 23 with lung cancer and 15 with stomach cancer, cutaneous metastasis preceded documentation of the primary tumor in 10 with lung cancer and 4 with stomach cancer. Three of these 4 cases were cases of signet ring cell carcinoma. The average life span after the development of cutaneous metastasis was 11 months and in 13 with lung cancer, it was 4.7 months. The average intervals between appearance of skin lesions and death of 3 patients with squamous cell carcinoma of lung was 0.8 months.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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