[Sunlight and malignant melanoma].
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Biomedical subjects
Publications and source records attributed to B Przybilla.
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Several nonsteroid antiinflammatory drugs (e.g., benoxaprofen, carprofen, and piroxicam) are known to induce photosensitivity reactions, but this has not yet been documented for ibuprofen. We observed a photosensitivity reaction in a patient treated with an oral ibuprofen preparation. This patient had a lowered minimal erythema dose for UVA but not for UVB after oral administration of ibuprofen. Results of a photopatch test with the drug were negative. In vitro UVA irradiation of human erythrocytes in the presence of ibuprofen caused ultraviolet dose-dependent phototoxic hemolysis.
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beta-Casomorphine-7, a naturally occurring product of cow's milk with opiate-like activity, was studied for possible direct histamine liberation activities in humans. It was found to cause concentration-dependent in vitro histamine release from peripheral leukocytes of healthy adult volunteers. Intradermal injection of beta-casomorphine-7 induced a wheal and flare reaction in the skin similar to histamine or codeine. Oral pretreatment with the H1 antagonist terfenadine significantly inhibited the skin responses to beta-casomorphine-7. The intradermal injection of an opiate receptor antagonist, naloxone, inhibited in vitro histamine release and skin reactions only in a 100-fold excess over beta-casomorphine-7. These findings suggest that beta-casomorphine-7 can be regarded as a noncytotoxic, direct histamine releaser in humans. The clinical relevance of these findings deserves further studies.
A 54-year-old Caucasian male suffering from psoriasis had been treated in 1978 and 1980 with PUVA (cumulative UVA dose 492.5 J/cm2) and from 1980 to 1989 with UVB (cumulative UVB dose 264.5 J/cm2). Other occasional treatment had comprised the topical administration of glucocorticosteroids, dithranol or tar. In 1989, on the upper part of the patient's back a newly developed pigmented skin lesion was excised under the clinical diagnosis of a pigmented, dysplastic nevus. Histological examination revealed a superficial spreading malignant melanoma (0.4 mm thick, Clark level II). In this case, exposure to high cumulative doses of therapeutic UV irradiation might have played an etiological role for the development of malignant melanoma.
A 31-year-old black man was examined for evaluation of a suspected occupational disease. Three years earlier he had been suffering from acute mercury intoxication during work in a mercury recycling factory. Skin symptoms then had been a lichenoid drug eruption, patchy alopecia and stomatitis, which had all disappeared rapidly after systemic glucocorticosteroid treatment. The examination revealed positive patch test reactions to metallic mercury and inorganic mercury compounds, an elevated titre of serum antinuclear antibodies and normal IgE levels. The induction of antinuclear antibodies by mercury has been shown in animal experiments. It can be hypothesized that this patient, who may have had an increased individual susceptibility, became allergic to mercury by the mercury intoxication.
Olaquindox is an oral anti-bacterial agent used as an additive to animal food. It is known to cause photosensitization in pig breeders, probably due to a photoallergic mechanism. Also, olaquindox was found to be phototoxic in animal experiments. We have evaluated the phototoxic properties of olaquindox in vitro with a photohemolysis test using different light sources. Irradiation with a source rich in ultraviolet A (UVA) and, to a lesser degree, with a lamp emitting mainly visible light induced photohemolysis, which depended on the concentration of olaquindox and the radiation dose. Exposure to radiation rich in UVB caused no olaquindox-dependent hemolysis. The absorption spectrum of olaquindox changed prominently after irradiation, indicating photodegradation of the compound.
Loss of earning capacity caused by skin diseases frequently has to be assessed by accredited dermatological experts. Assessments must take account of the appropriate legal situation in each case. Each case needs to be carefully and individually evaluated; tabulated estimations can only be used as a basis.
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The aim of this study was to compare the efficacy and safety of a monomethoxypolyethylene glycol (mPEG) modified grass pollen mix allergen preparation (mPEG-gm) and a partly purified grass pollen mix allergen preparation (gm) in hyposensitization (HS), evaluating both products at two dose levels. Thirty adult patients with allergic rhinoconjunctivitis were allocated into two treatment groups based on their sensitivity to conjunctival provocation tests (CPT). Treatment was given in a double-blind manner. The starting dose was 20 BU and was approximately doubled weekly up to 20,000 BU the first year and 120,000 BU the second year. Skin testing and CPT were performed before treatment and at each dose level. All patients reached 20,000 BU the first year. Twenty-five patients continued the second year. Twenty-one of those reached 120,000 BU (9/12 on mPEG-gm and 12/13 on gm). The frequency of general side effects was reduced by about 50% with the mPEG grass mix compared with native grass mix. A significant improvement in the conjunctival sensitivity was found in both treatment groups the second year (120,000 BU) but not the first year (20,000 BU). Seventy-eight percent of the patients in the gm group and 50% in the mPEG-gm group improved by CPT (not statistically significant). The skin sensitivity was reduced after 1 year at low dose in 69% of the gm-treated patients and 33% of the mPEG treated patients. After the second year at high dose levels, the skin sensitivity decreased in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
We report on a 54-year-old patient with an 11-year history of Arndt-Gottron scleromyxoedema. We found typical lichenoid papules, diffuse skin thickening and skin hardening. Clinical and laboratory investigations revealed a monoclonal gammopathy of the IgG1 type, normal histology of the bone marrow and normal urine. Therefore, a diagnosis of monoclonal gammopathy of undetermined significance was recorded. Phimosis and stenosis of the urethra were the only other pathologic findings. Systemic treatment with chlorambucil and PUVA had little beneficial effect on the skin thickening after 9 months.
A cooperative photopatch test study was conducted by 45 dermatologic centers in Austria, Germany, and Switzerland. Results obtained from 1985 to 1990 are presented. A standard photopatch test tray of 32 substances was applied to the back of patients with suspected photosensivity. After applications for 24 hours, test sites were irradiated with 10 joules/cm2UVA. Unirradiated controls were included. Readings were performed immediately and 24, 48, and 72 hours after irradiation; responses were qualitatively graded on a 4-point scale. All data were stored and processed by a computer. With computer-assisted analysis of reaction patterns photoallergic reactions were identified and distinguished from phototoxic reactions. Data of 1129 patients were evaluated. Among a total of 2859 positive test reactions in 870 patients, 2041 in 778 patients were found to be photoinduced and 818 in 413 patients were contact reactions; 108 reactions in 83 patients were classified as photoallergic. Nonsteroidal anti-inflammatory drugs, disinfectants, sunscreens, phenothiazines, and fragrances caused most often photoallergic reactions. Many unspecific phototoxic reactions were induced by tiaprofenic acid, promethazine, carprofen, chlorpromazine, fenticolar, wood balsam of Peru, and perfumes. Despite the distinction between photoallergic and phototoxic responses, many test reactions lacked relevance for the patients' dermatoses.
12-hydroxyeicosatetraenoic acid (12-HETE), the main eicosanoid in skin, is assumed to have both pathophysiologic effects in inflammatory skin diseases such as psoriasis and atopic eczema and a physiologic role in the biology of cutaneous reparative processes. Because 12-HETE exerts its effects via specific high-affinity epidermal receptors, and ultraviolet-B (UV-B) is capable of modulating various cell-surface molecules, the effects of single and repeated UV-B irradiations on the 12(S)-HETE binding sites in a human epidermal cell line, SCL-II, were studied. UV-B (100-300 J/m2) induced a large decrease in 12(S)-HETE binding in a dose-dependent manner. The inhibition occurred after a latency period of 6 h, reached its maximum at 18 h and slowly declined thereafter. A single UV-B dose of 300 J/m2 or repeated irradiation with 50 J/m2 of UV-B resulted in a 70% decrease in the number of binding sites (Bmax), whereas receptor affinity remained unaffected. The modulation of epidermal 12-HETE receptors by UV-B may partly explain the therapeutic effects of UV-B, but possibly also contribute to photodamage to skin.
Allergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long-standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self-injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy.
In general, specific immunotherapy with hymenoptera venoms can be considered as safe, but occasionally there are patients who cannot reach the maintenance dose due to repeated systemic reactions (RSR) or who suffer from RSR during maintenance therapy. In a multicenter retrospective study comprising seven departments in Germany, Austria and Switzerland 23 patients with RSR were reported from approximately 3000 patients treated with hymenoptera venoms (bee and wasp venom to approximately equivalent frequency). From these, 22 were allergic to bee venom and only one to vespid venom. In general the clinical symptoms of RSR were milder than the initial reaction. But 4/23 (18%) exhibited cardiovascular reactions up to full shock. Neither anamnestic details, reactivity in skin tests or in vitro tests revealed a special pattern of patients with RSR. In some patients, however, an extremely high reactivity in the skin test was found and may indicate the possibility of further RSR.
In a total of 525 patients with hypersensitivity reactions to hymenoptera stings diagnostic parameters of hymenoptera venom (HV) allergy (severity of reactions, skin test threshold and RAST for bee and vespid venoms) were investigated for their relationship to the following indicators of atopy: positive history of atopic diseases, elevated (less than or equal to 100 kU/l) total serum IgE and positive prick test reactions to common inhalant allergens (CIA) (grass pollen, cat epithelium, house dust mite). There was a conclusive history of atopic disease in 25%, a total serum IgE greater than or equal to 100 kU/l in 48%, and at least one positive reaction to CIA in 53%. Total IgE greater than or equal to 100 kU/l correlated with a higher frequency of RAST classes greater than or equal to 2 (P less than 0.01) and with less severe reactions to hymenoptera stings (P less than 0.05). In the presence of at least one positive reaction to CIA, there were more frequently skin test thresholds less than or equal to 10 micrograms/ml (P less than 0.05) and RAST classes greater than or equal to 2 (P less than 0.01) for HV than in CIA prick test negative individuals. There was no significant, relationship between the other pairs of parameters evaluated. Thus, reactivity to HV in diagnostic tests is increased in the presence of certain indicators of atopy. This has to be considered in the interpretation of skin test and RAST results obtained with HV.