Occupational dermatoses from exposure to epoxy resin compounds in a ski factory.

Of 22 workers in a ski factory, occupational allergic contact dermatitis was found in 8. 6 were sensitive to epoxy resin compounds, i.e., epoxy resins, hardeners or diluents, 1 to cobalt in glass-fiber reinforcements, and 1 to formaldehyde in a urea-formaldehyde glue and a lacquer. 4 workers had irritant contact dermatitis from epoxy resin compounds, lacquers, sanding dust, or glass-fiber dust. 3 had contact allergy from a new sensitizer, diethyleneglycol diglycidyl ether, in a reactive diluent. Immediate transfer of workers sensitized to epoxy resin from epoxy exposure prevents aggravation of their dermatitis and broadening of the sensitization to epoxy hardeners, diluents and other compounds.

A simplified Boyden chamber assay for neutrophil chemotaxis based on quantitation of myeloperoxidase.

Cell locomotion and chemotaxis are usually assayed by the Boyden chamber technique, in which the response is measured by microscopical counting of the cells migrated into a micropore filter. We report a simplified Boyden chamber method which utilizes myeloperoxidase (MPO) specific to neutrophilic and monocytic leukocytes. The chamber is incubated for a period long enough for the neutrophils to migrate through the first of two superimposed filters. The cells entering the second filter are then lysed and the released MPO activity is quantitated. Random migration, chemokinesis, and chemotaxis measurements of neutrophils were compared by the enzymatic and the conventional cell count methods. There was good agreement between the two methods (0.84 less than r less than 0.98). The intraassay precision of the enzymatic and the cell count methods was equal; the coefficients of variation were 14 and 15%, respectively. The enzymatic method provides a more objective, reliable, and rapid modification of the Boyden chamber assay for analysis of neutrophil chemotaxis.

"Ditrawash"--a novel remover of dithranol (anthralin) for short contact therapy of psoriasis.

A new washable ointment enables rapid and complete removal of surplus dithranol in the short contact therapy of psoriasis. It emulsifies the vehicles and dissolves dithranol into the washwater as fluorescent borate complexes.

Inhibition of soybean lipoxygenase-1 by 10-butyryl substituted 1,8-dihydroxy-9-anthrone (butantrone).

10-Butyryl substituted 1,8-dihydroxyanthrone (butantrone) inhibited soybean lipoxygenase-1 irreversibly and more efficiently than its parent compound 1,8-dihydroxyanthrone (dithranol, anthralin) (IC50 values 0.090 mM and 1.1 mM, respectively). Intact butantrone rather than its hydrolysis product was the primary effector and the 10-butyryl moiety its site specific probe, probably directing the inhibitor to the proximity of the binding site of the lipid substrate/product.

Ambulatory treatment of psoriasis with dithranol sticks--a novel paraffin formulation.

The efficacy and tolerability of a novel stiff dithranol stick (Ditrastick, Orion, Espoo, Finland) were evaluated in an open multicenter trial comprising 121 outpatients with limited psoriasis of the plaque type. Daily treatment was started with 1.5% dithranol sticks and continued in most patients with 3% sticks after 2 weeks. An excellent or good result was obtained in over half of the patients. Early irritation of a rather narrow rim of the skin surrounding the lesions was common, but only about 10% of the patients discontinued the trial due to this side effect. Paraffin-based dithranol sticks thus enable ambulatory treatment of chronic plaque psoriasis in the areas of predilection. Dithranol is stable in this novel preparation for at least 3 years.

Tumor-producing activity of dithranol (anthralin) and two of its 10-acyl analogs in the dorsal skin of female NMRI mice.

The tumor-producing activity of local applications of dithranol, 10-propionyl dithranol and butantrone was studied in 420 female white NMRI mice. An initiation with 20 micrograms of 7,12-dimethyl-benz(alpha)anthracene (DMBA) was followed 2 weeks later by three applications per week of the test compounds in 50 microliters of acetone for 50 weeks. Several control groups receiving only acetone or DMBA and test compounds without DMBA were included. Dithranol and 10-propionyl dithranol caused transient, although serious, skin irritation during the first 2 weeks of the treatment. Hyperplasia was a common finding in the same groups at the end of the treatment. Dithranol (3.5 mM) induced 11 papillomas in 8 mice (26.7%) without DMBA and 29 papillomas in 17 mice (56.7%) with DMBA. 10-Propionyl dithranol was tumorigenic as well: 3.5 mM caused 15 papillomas in 11 mice (36.6%) without DMBA and 28 papillomas in 17 mice (56.7%) with DMBA and 1.5 mM with DMBA caused 7 papillomas in 6 mice (20%). In the butantrone groups, there was only one single papilloma with the 1.5 mM concentration plus DMBA. It is concluded that, in contrast to dithranol and 10-propionyl dithranol, butantrone (3.5 mM) is not tumorigenic in the dorsal murine skin.

Antipsoriatic activity of 10-acyl analogues of dithranol (anthralin). I. Phase I clinical trial of 10-propionyl dithranol and 10-butyryl dithranol (butantrone).

Dithranol, 10-propionyl dithranol and 10-butyryl dithranol were compared as regards their antipsoriatic, staining and irritative properties. They were applied under 12-mm Finnchambers on the lesional skin of 17 psoriasis patients every second day for 20 days. In 9 patients their concentration was equimolar (2 mmol/kg of white petrolatum) corresponding to 0.05% dithranol, and in 8 patients the concentrations were 2, 4, and 8 mmol for dithranol, 10-propionyl dithranol and 10-butyryl dithranol, respectively. Without regard to the concentration, they all produced under occlusion almost equal thinning of the lesions, but when a 2 mmol concentration was used, 10-butyryl dithranol (butantrone) showed least staining and irritation on the treated sites.

Irritation and staining by dithranol (anthralin) and related compounds. V. Short-contact and tape-stripping experiments with dithranol and butantrone.

Dithranol (D) and butantrone (BD) were compared as regards irritation and staining in conditions resembling short-contact therapy. Nine psoriatics were tested with 0.5% D and 0.66% BD using exposures of 20 min and 3 h. Partial removal of the horny layer by 15 tape strippings before and after the exposure resembled the impaired barrier of lesions and posttreatment washing, respectively. Development of erythema and staining, and alterations in blood flow were followed for 7 days. In the unstripped skin, D caused after 20 min exposure within 3 days a faint but defined erythema and increase in blood flow, and within 7 days a brownish hue. Irritation was suppressed by stripping after 20 min exposure. After 3 h contact, irrespective of stripping, much stronger irritation and staining developed. BD caused no staining after 20 min of exposure and little if any erythema. After 3 h contact, it caused only minimal staining and markedly less irritation than equimolar D.

Local sweat stimulation with the skin prick technique.

Intracutaneous injections of cholinergic agonists are usually employed for induction of local sweating. The possibility to apply a less painful skin prick technique as a sweat test was examined. Pricks were made on the forearm skin of 25 young men by puncturing the skin through drops of methacholine (MCH) and control saline solutions with lancets having a point length of 1 mm. The drops were kept on skin for 10 min and were then wiped off. Using an evaporimeter the measurements of water loss (WL) were started 5 min later and continued at 5 min intervals. Sweat loss (SL) was calculated from the difference of rates of evaporative WL recorded at the MCH and saline pricks. Ten, 1, 0.1, and 0.01% solutions of MCH elicited the following average peak evaporative sweat losses: 107.1, 77.5, 32.4 and 5.4 g m-2h-1. Both the degree and duration of the sweat responses were dependent on concentration. The prick technique is well tolerated and may serve for comparative studies of local sweating.

T and B lymphocytes, macrophages and Langerhans' cells during the course of contact allergic and irritant skin reactions in man.

The in situ distribution of lymphocyte subclasses, macrophages and Langerhans' cells was analysed with histochemical (ANAE staining), immunohistochemical (immunoperoxidase) and electron microscopic methods during the course of epicutaneous allergic and irritant skin reactions. Serial biopsies were taken during the first 5-72 hours following the allergen (nickel and chromium) or irritant (non-anoic acid and dithranol) application. Empty and petrolatum-filled Finn chambers were used as controls. No significant differences in the number of mononuclear inflammatory cells or their subclasses were found in the early recognition and elicitation phases of the allergic or irritant-induced reactions. Nor was there any difference in the frequency of lymphocyte-Langerhans' cell contacts, although exocytic cells were most frequent in dithranol reactions.

Irritation and staining by dithranol (anthralin) and related compounds. IV. Visual estimation of erythema compared with contact thermometry and laser Doppler flowmetry.

Irritation and staining caused by equi-irritant doses of dithranol (anthralin) and 10-butyryl dithranol (butantrone) were observed for one week after a single 24-hour exposure under occlusion. The test chambers were applied on the uninvolved dorsal skin of 11 psoriasis patients. The estimates of erythema were made with a refined reading scale, and to test the visual discriminatory power they were compared with objective measurements of contact temperature and blood flow of the skin. A sensitive thermistor and a novel laser Doppler flowmeter were used. On the whole, erythema, contact temperature and superficial blood flow, as interdependent parameters of cutaneous inflammation, all showed a time-dependent statistically significant correlation to the dose of dithranol and 10-butyryl dithranol. The intercorrelations between erythema and blood flow and between erythema and temperature were statistically significant, too. With the doses used, staining of the skin did not hamper the measurement of superficial blood flow, but it did exaggerate visual estimates of erythema at the 4th and 7th day readings.

Irritation and staining by dithranol (anthralin) and related compounds. III. Cumulative irritancy and staining during repeated chamber testing.

Irritation and staining, the side effects of dithranol and related compounds have previously been studied after a single chamber-exposure. To mimic the therapeutic situation, the chamber application was repeated for 3 weeks on the uninvolved back skin of 17 psoriasis patients. In equimolar concentrations corresponding to 0.05% dithranol, dithranol caused markedly more erythema and staining than 10-propionyl dithranol and 10-butyryl dithranol, whereas 10-butyryl dithranol irritated and stained less than 10-propionyl dithranol. To reach the irritation and staining level of dithranol, a 4-fold higher concentration of 10-butyryl dithranol was required. During the first week the irritation culminated, declining later despite repeated applications, possibly because of exhaustion of anthrone-induced inflammatory mediators.

Polymorphic acetylator phenotype and systemic lupus erythematosus.

Out of 69 patients with spontaneous systemic lupus erythematosus (SLE), phenotyped for polymorphic acetylation with sulphadimidine, 52 (75%) were slow acetylators. In the subgroup of SLE patients with chronic biologically false positive seroreactions for syphilis the percentage of slow acetylators was even higher, 88%. In the majority of the slow acetylators the disease had started later and had followed a milder course than in rapid acetylators. Cutaneous reactions suspected to be drug-induced were seen in 19 (17 slow acetylators) during an observation period of 3--7 years. The reactions were mostly of exanthematous or urticarial type but also fixed type of eruption was seen. Provocation tests with the suspected drug were performed in 14 patients. In 5 cases it could be demonstrated that the eruption was caused by the drug. The predominance of slow acetylators among our patients with spontaneous SLE was the same as has been observed in drug-induced SLE. This suggests a similar genetic background.