苯甲酸雌二醇及UVA辐照对体外培养的人皮肤成纤维细胞胶原合成的影响

目的探讨苯甲酸雌二醇对体外培养的人成纤维细胞增殖、胶原合成及其对UVA抑制胶原合成的影响。方法在培养的人成纤维细胞中分别加入不同剂量的苯甲酸雌二醇,继续培养48h,用MTT法测定细胞的增殖情况,同时应用RT-PCR方法检测经不同剂量苯甲酸雌二醇及10J/cm²UVA处理后人成纤维细胞Ⅰ、Ⅲ型前胶原mRNA的表达情况。结果MTT法检测结果显示,苯甲酸雌二醇对体外培养的成纤维细胞增殖无明显促进作用。RT-PCR结果提示,苯甲酸雌二醇处理组两型前胶原的表达水平明显上调(P<0.05),而UVA照射后两型前胶原的表达显著下降,苯甲酸雌二醇可在一定水平对抗其作用(P<0.05)。结论苯甲酸雌二醇对体外培养的成纤维细胞Ⅰ、Ⅲ型前胶原的合成有一定的促进作用,并可对抗紫外线抑制胶原合成的作用。     

Sodium benzoate-induced repeated episodes of acute urticaria/angio-oedema: randomized controlled trial

BACKGROUND: Sodium benzoate (E 211) is widely used to delay yeast spoilage of acidic foods and beverages. Numerous cases of adverse reactions to benzoate have been recorded, but most of the studies that have been conducted lacked proper placebo controls or blinding. OBJECTIVE: The aim of this study is to determine the incidence of intolerance to sodium benzoate among subjects who experienced repeated episodes of acute urticaria/angio-oedema following the ingestion of a meal or a product containing this substance. METHODS: This was a retrospective study based on the analysis of data from patients reported to have experienced episodes of urticaria, with or without angio-oedema, after ingesting meals or products containing sodium benzoate. At the first visit to the outpatients clinic, a careful history was taken. Patients were then given the following diagnostic tests: tests for IgE for common inhalant allergens and food allergens, and a double-blind, placebo-controlled challenge with sodium benzoate. RESULTS: A total of 47 subjects were enrolled in the study; five (11%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (2%) had a reaction after the ingestion of 75 mg of sodium benzoate without an adverse reaction to placebo. CONCLUSION: This study shows that the percentage of repeated episodes of acute urticaria/angio-oedema reactions induced by sodium benzoate is very low (2%). In view of our results, we suggest that when faced with patients who have suffered adverse reactions that could be attributed to sodium benzoate, physicians should also carefully evaluate other possible causes.     

Reactions to aspirin and food additives in patients with chronic urticaria,including the physical urticarias*

In 131 patients with chronic urticaria, including physical urticarias, oral provocation tests were done with aspirin. A total of thirty-one patients showed a reaction on aspirin challenge. Reactions were seen in 35% of patients with idiopathic urticaria, 52% of patients with cholinergic urticaria, and 43% of those with pressure urticaria. The patients with reactions to aspirin were also tested with tartrazine, sodium benzoate, 4-hydroxy benzoic acid, sodium- and phenyl salicylate and the analgesics indomethacin, paracetamol and mefenamic acid. In nineteen of twenty three aspirin sensitive patients, positive reactions to one or more of these substances were observed. Indomethacin and tartrazine had the highest scores. There was no statistically significant correlation between aspirin reactions and the presence of nasal polyposis, sinusitis, asthma or atopy.     

Urticaria induced by preservatives and dye additives in food and drugs

Fifty-two patients with recurrent urticaria or angio-oedema and thirty-three controls have been provoked with five different food dyes and the preservatives sodium benzoate and 4-hydroxy-benzoic acid, as well as aspirin, sulphanilic acid and a placebo. The reaction was judged as positive in thirty-nine patients who developed urticaria within 14 h. Of these, thirty-five reacted to aspirin, twenty-seven to benzoic acid compounds and twenty-seven to azo dyes. The four patients who did not have urticaria after aspirin, reacted with urticaria to benzoic acid compounds, and three of them to azo dyes. No definite pattern for the reaction to the different azo dyes was seen. None had an urticarial reaction from sulphanilic acid, Patent Blue (a non-azo dye) or placebo. The doses of additives used in the provocation tests are easily exceeded in daily life by the consumption of foods and drugs. Recurrences of urticaria could be prevented through the avoidance of food and drugs containing azo dyes and preservatives.     

Contact allergy to balsam of Peru. II. Patch test results in 102 patients with selected balsam of Peru constituents.

BACKGROUND: In Switzerland, Germany, and Austria, allergic reactions to balsam of Peru (BP) have now made it the third most common contact allergen. OBJECTIVE: A series of 20 single BP constituents (including resorcinol monobenzoate), established in 1995, was used for patch tests in patients with a positive reaction to BP in the standard series. MATERIALS AND METHODS: Between 1995 and 1998, 2,273 patients were tested with the standard series, including BP, fragrance mix (FM), and propolis. Patients positive for BP were requested to participate in a further test using the 19 compounds of the BP constituents and resorcin monobenzoate (BP series); 102 patients agreed and were patch tested. The results of the 72-hour reading were used for the evaluation. RESULTS: A total of 93 patients reacted to 1 or more of the BP series compounds. Positive reactions were seen, in decreasing order, to cinnamic alcohol, cinnamic acid, coniferyl benzoate, benzoic acid, cinnamyl cinnamate, eugenol, resorcinol monobenzoate, coniferyl alcohol, and benzyl alcohol. There were no positive reactions to vanillin or ferulic acid. A correlation between skin lesions and frequent consumption of sweets was found in 7 patients with major positive test reactions to coniferyl benzoate and benzyl alcohol. Most of the reactions to eugenol and isoeugenol had less to do with BP itself than with a primary sensitization to fragrances. Although resorcin monobenzoate (RMB) has up to now not been detected in BP, 16 patients reacted distinctly to this compound. Eleven were strong smokers; the remaining ones had contact with plastic materials that have been reported to contain RMB. RMB is used frequently as an antioxidant in synthetic material. When these patients stopped smoking, the skin lesions cleared. However, consumption of sweets caused recurrences. CONCLUSION: The evaluation of reactions to single constituents of BP by testing with the special BP series facilitates understanding how sensitization may be acquired. The allergen may prove to be BP itself or 1 or more of its constituents. Testing for the constituents of this series may provide patients with a more specific allergen diagnosis and may facilitate improved therapy. BP may function as an important indicator for contact allergy to RMB.     

Profuse scabies: kinetic curves of parasitologic cure with an association of benzyl benzoate and sulfiram

BACKGROUND: In vitro exposure to benzyl benzoate (25 p. 100) kills Sarcoptes scabiei within three hours. The aim of our study was to determine in vivo elimination of Sarcopte scabiei with a benzyl benzoate-sulfiram association. METHODS: Medical charts of patients hospitalized for disseminated scabies from 1993 to 1999 were reviewed retrospectively. The diagnosis of scabies was confirmed by microscopic determination. Parasitological examinations were conducted every day or every two days until negative results. Patients were treated by successive applications of benzyl benzoate until parasitological cure. RESULTS: Twenty patients were included in the study. The median delay of parasitological cure was seven days. After 15 days, 95 p. 100 of patients were cured. Two cutaneous side-effects were reported. DISCUSSION: Despite immediate in vitro efficacy, benzyl benzoate action is delayed in vivo. The time of parasitological negativation after one application of benzyl benzoate is unknown. Therefore, it is not currently possible to determine whether our therapeutic regimen was excessive or not.     

Contact allergy to isoeugenol and its derivatives: problems with allergen substitution

A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate in 19, isoeugenyl benzoate in 4, isoeugenyl phenylacetate in 16, isoeugenyl methyl ether in 6 and benzyl isoeugenyl ether in 2 patients. There was a concomitant reaction to isoeugenol in 36/40 of those positive to transisoeugenol, 13/19 of those to isoeugenyl acetate, 3/4 of those to isoeugenyl benzoate and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism of the derivatives. It is more commonly observed with the esters rather than the ethers. Isoeugenyl acetate has been proposed as an alternative to isoeugenol, but there is a high degree of concomitant reactivity with isoeugenol.     

Immediate- and Delayed-Type Contact Hypersensitivity in Children Older than 5 Years With Atopic Dermatitis: A Pilot Study Comparing Different Tests

Abstract: We conducted a prospective open study of immediate- and delayed-type contact hypersensitivity to food and other allergens in 33 children with atoplc dermatitis (AD). The design of the study was exploratory and not randomized. Various methods for detecting immediate-type hypersensitivity were compared. Thirty-three children age 5 to 15 years with persistent AD were initially enrolled, but 3 dropped out. Nine patients had positive reactions to foods in the patch-scratch tests, four had positive reactions in the skin application food test, and five had positive reactions to foods in the prick tests. Positive reactions to foods were observed in only three patients on the delayed-type patch tests. In all tests, but especially the patch-scratch and prick tests, positive reactions to food allergens were observed without clinically related symptoms. None of these tests gave ideal results. Twenty (67%) of the 30 children had positive reactions to inhalants in prick testing. Fourteen showed positive patch-test reactions with the European standard series (True Test). The most positive reactions were to nickel (9 patients), cobalt, and balsam of Peru. Restrictive measures led to evident improvement of AD only in some children. The results of this study illustrate that food allergy plays only a limited rote in patients with AD age 5 to 15 years. We could not conclude which of the tests would predict which children might benefit from dietary manipulation.     

The use of skin testing in the investigation of cutaneous adverse drug reactions

Skin testing with the suspected compound has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (ADRs), but the value and specificity of these tests need to be determined. In this study, 72 patients with presumed drug eruptions (27 maculopapular, 18 urticarial, seven erythrodermic, nine eczematous, four photosensitivity, three fixed drug eruptions, three with pruritus and one with acute generalized exanthematous pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and 30 had intradermal tests (performed on hospitalized patients using a sterile solution of the suspected drug, diluted sequentially) with immediate and delayed readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%, 24% and 67% in patch, prick and intradermal skin tests, respectively. The results of skin tests varied with the drug tested and with the clinical type of cutaneous ADR, as a significantly higher number of positive patch tests was observed in maculopapular rashes than in urticarial reactions ( P =  0.001). This study supports the value of careful sequential drug skin testing in establishing the cause of cutaneous ADR. Guidelines are proposed for performing these tests, and these include the use of appropriate negative control patients to avoid false-positive results.     

Treatment of scabies with permethrin versus lindane and benzyl benzoate

This open clinical study was designed to evaluate and compare the efficacy and side effects of lindane (1% and 0.3%), benzyl benzoate (20% and 10%) and permethrin (5% and 2.5%) after two, three, and one application at bedtime, in the treatment of scabies in 114 adults and 80 children aged between 0 and 5 years. Treatment failures were registered after lindane in 3 adults and 2 children, whereas benzyl benzoate and permethrin cured all patients as assessed after a 3-week follow-up. The number of irritations and post-scabious eczematous reactions was increased after benzyl benzoate treatment. Permethrin proved to be very reliable and exhibited few side effects when applied once at bedtime. Because of the percutaneous absorption and neurotoxicity of lindane, the application of permethrin can be recommended as a useful alternative in premature infants and small children, patients with seizures and neurological complications, in cases of therapeutic failure with lindane the treatment needs to be repeated, in scabies crustosa, as well as in children, pregnant women and nursing mothers.     

The reproducibility of patch tests

There is conflicting evidence regarding the reproducibility of patch testing. Discordant results have been reported in up to 44% of cases. The clinical relevance of these discordant patch tests has not been previously assessed. We studied 383 consecutive patients receiving simultaneous duplicate patch testing on opposite sides of the upper back with 10 allergens from the European standard series. Completely discordant patch tests-a negative test on one side with a positive test on the opposite side-were recorded in 30 (8%) patients. Two patients had discordant tests to two of the allergens; 28 had discordant reactions to one allergen. Completely discordant tests were recorded for nickel in 10 (3%) patients, balsam of Peru in two (0.5%), thiomersal in one (0.3%), cobalt in four (1%), paraphenylenediamine in three (0.8%), fragrance mix in two (0.5%), formaldehyde in four (1%), potassium dichromate in two (0.5%), lanolin in three (0.8%) and Kathon CG in one (0.3%). Of those patients with completely discordant patch tests, the allergen was deemed to be a true positive in 11 (3% of total) cases and of possible relevance in a further three. The allergen was felt to be relevant to the presenting complaint in seven (2% of total) patients.     

The usefulness of skin tests to prove drug hypersensitivity

BACKGROUND: Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility. OBJECTIVES: To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies. METHODS: During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients. RESULTS: Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria. CONCLUSIONS: Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.     

Plants as the cause of contact allergy diagnosed at the Dermatological Clinic, Medical Academy, in Bia?ystok

In patients with allergic changes hospitalized in the years 1984-1988 in the Department a careful history was obtained for detection of correlations between the appearance of skin lesions and contact with plants. In patients with a positive history patch tests were done with a panel of routine allergens and leaves and/or flowers of certain plants. Positive tests with various plants were obtained in 14 cases. In 6 patients reporting contact with primrose positive tests were obtained with flowers and leaves of this plant, four of five tobacco planters tested who had eczematous lesions of the hands, aave also positive results of the test with tobacco leaves, and in three children reporting contact with butter-cup changes were observed resembling dermatitis pratensis bullosa. In one case allergy to parsnip was demonstrated. It is stressed that plants may give rise to contact dermatitis as well as to allergic-toxic changes.     

The treatment of scabies with permethrin in comparison with lindane and benzyl benzoate

This open clinical study was designed to evaluate and compare the efficacy and side-effects of lindane (1% and 0.3%), benzyl benzoate (20% and 10%) and permethrin (5% and 2.5%) after twice-, three times- and once application at bedtime, respectively, in the treatment of scabies in 104 adults and 70 children aged between 0 and 5 years. Treatment failures were registered afer lindane in 3 adults and 2 children, while benzyl benzoate and permethrin cured all patients as assessed after 3 weeks follow-up. The number of irritations and postscabious eccematous reactions was increased after benzyl benzoate. Permethrin revealed to be very reliable and exhibited only a few side-effects when applied once at bedtime. Because of the risk of the percutaneous absorption and neurotoxicity of lindane, the application of permethrin can be recommended as an useful alternative in premature infants and small children, patients with seizures and neurological complications, in cases of treatment failures of lindane with the need to repeat the therapy, in scabies crustosa as well as in children, pregnant woman and nursing mothers.     

Contact dermatitis to palladium: A study of 2,300 patients

In the last few years, several investigators have detected a high prevalence of positive patch test reactions to palladium chloride in nickel-sensitized patients. In the majority of these patients, the positive patch tests to palladium chloride had no clinical relavance. The purpose of this study was to evaluate the prevalence and the clinical relevance of the patch test reactions to palladium in patients undergoing patch tests. Two thousand three hundred consecutive patients with allergic contact dermatitis were patch tested with PdCl₂ (1% petrolatum) between January 1991 and September 1992. A positive reaction to palladium chloride was detected in 171 of the 2,300 patients (7.4%). One hundred sixty-nine of these 171 patients had a concomitant positive reaction to nickel sulfate. In our opinion, the similarity of the external electronic structure of these two elements is not sufficient by itself to justify a wrong immunologic recognition, whereas a stereochemical analysis of the compound of these two metals could better explain the possible mechanism of this cross-reaction.     

Dermatitis as a side-effect of long-term topical treatment with certain beta-blocking agents

Three groups of glaucoma patients, treated topically with various beta-blocking agents, were studied for mucocutaneous side-effects of long-term therapy. In five of eleven patients with ocular and/or periocular dermatitis as an adverse reaction to long-term treatment with metoprolol eye drops a dermatitis, reproducible by patch tests with pure metoprolol 3%, was demonstrable. Histopathological examination of positive patch tests examined in three cases showed a picture compatible with a delayed type of hypersensitivity. Four atenolol treated patients showed adverse reactions, but negative patch tests to atenolol were found. In addition new data are reported in favour of cross-reactivity between certain beta-blocking agents.     

Photosensitivity to piroxicam: absence of cross-reaction with tenoxicam

We studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thimerosal and thiosalicylic acid and 9 of them had positive photopatch tests to piroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to piroxicam. All the patients tested with salicyclic acid were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity.     

Chronic urticaria Investigations with patch and challenge tests

56 patterns with chronic urticaria were patch tested with particular reference to the immediate weal response to a range of materials and this was followed by challenge tests to most of the same substances.
Positive immediate patch tests were commonly seen with balsam of Peru and cinnamon and this appears to be a reaction in many normal subjects.
Positive challenge tests in patients who also had positive immediate patch tests to the same substance occurred in two patients with cinnamon and two patients with cloves. Other substances with a similar action may come to light- in which case the use of immediate patch tests in investigating chronic urticaria is more likely to be of value.
4 patients showed positive immediate patch tests to nickel, one of whom also had a positive 48 h patch test to nickel. 2 other patients had only positive 48 h patch tests lo nickel. However, none of these patients pave a positive challenge lest lo nickel.     

Contact dermatitis from antioxidants

In a search for contact sensitivity to antioxidants we patch tested consecutive patients referred with eczematous dermatitis. Six cases of allergic contact sensitivity to nordihydroguairetic acid (NDGA) were observed. Three had been sensitized by one brand of cream containing 0.1% NDGA, in three patients the source of sensitization could not be traced. In four patients we found positive patch tests to butylated hydroxyanisole and/or to butylated hydroxytoluene. In two cases the positive patch tests were relevant, since both patients remained asymptomatic when antioxidants were avoided in food. They both had acute flares of vesicular eczema on the fingers after oral administration of small amounts. Gallate esters and Vitamin E (d,l-alpha-tocopherol) each gave one unexplained positive patch test. The present data suggest that further search for hidden sensitizers in topical medicaments and cosmetics is warranted. A declaration of all ingredients in industrial products should be placed on the label.     

The usefulness of immunofluorescent tests in pemphigus patients in clinical remission

Direct and indirect immunofluorescent studies (DIF, IIF) were performed on 24 pemphigus vulgaris patients who were in a state of clinical remission. The tests were repeated after an interval of 6 months. All the patients were on maintenance therapy with oral prednisone. The DIF in eight patients showed negative results among whom seven remained negative. Six patients out of 24 showed weakly positive fluorescence and ten patients showed strong positive fluorescence. The IIF was negative in 17 patients and positive in seven patients who also showed positive DIF. During a follow-up period of 20 months, one of eight patients with negative DIF relapsed compared with two of six patients with weak positive DIF and five of 10 patients with strong DIF. Five patients with strong DIF for IgG also had C3, of whom three relapsed, compared with five of 19 patients who were negative for C3. Four of seven patients with positive IIF relapsed compared with four of 17 with negative IIF. It is suggested that repeated DIF tests in pemphigus patients, who are in clinical remission, may serve as an indicator for the immunological activity and be of help in the management of these cases.