ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis.

Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case-control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case-control analysis had described as "probably not associated" and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case-control analysis results, can be considered a reference tool in SJS/TEN.

Epidemiology of acne in the general population: the risk of smoking.

BACKGROUND: Acne is a common skin disorder, but epidemiological data from the general population obtained by examination are scarce. Clinical experience suggests an association between smoking and acne, although confirmatory evidence from appropriate studies is lacking. OBJECTIVES: To determine the prevalence and demographic factors of acne in a general population sample and to investigate the association of smoking and acne on a qualitative and quantitative level. METHODS: In a cross-sectional study, 896 citizens (aged 1--87 years, median 42) of the City of Hamburg were dermatologically examined. The prevalence and severity of acne were recorded and further information on demographic variables, medical history, and alcohol and cigarette consumption were obtained by a standardized interview. RESULTS: According to the clinical examination, acne was present in 26.8% overall, and was more prevalent in men (29.9%) than women (23.7%) (odds ratio, OR 1.37, 95% confidence interval, CI 1.01--1.87). Prevalence followed a significant linear trend over age with peak prevalence between 14 and 29 years (P < 0.001). The reported age at onset was significantly lower in women than men (P = 0.015). According to multiple logistic regression analyses acne prevalence was significantly higher in active smokers (40.8%, OR 2.04, 95% CI 1.40--2.99) as compared with non-smokers (25.2%). A significant linear relationship between acne prevalence and number of cigarettes smoked daily was obtained (trend test: P < 0.0001). In addition, a significant dose-dependent relationship between acne severity and daily cigarette consumption was shown by linear regression analysis (P = 0.001). CONCLUSIONS: Smoking is a clinically important contributory factor to acne prevalence and severity.

[Allergy diagnosis for general practice. Proper testing!]. / Allergiediagnostik für die Praxis. So testen Sie richtig!

The aim of allergy testing is to establish unequivocally the (possible) allergenic nature of the condition, and also to identify the triggering allergen(s). The diagnostic work-up of allergic diseases proceeds in accordance with a stepped schema. The individual steps comprise a history, physical examination, skin tests, in vitro diagnostic procedures and challenge (provocative) testing. With regard to skin tests, the major ones are the prick and scratch test, open and closed patch test and the intracutaneous test. The present article identifies the indications for the various tests, and describes how they are performed, and also discusses the usefulness of the individual in vitro methods and challenges.

Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis.

BACKGROUND: Coronary in-stent restenosis might be triggered by contact allergy to nickel, chromate, or molybdenum ions released from stainless-steel stents. We investigated the association between allergic reactions to stent components and the occurrence of in-stent restenosis. METHODS: Patients with coronary stainless-steel stents who underwent angiography for suspected restenosis were consecutively included in this study. Quantitative coronary angiography for analysis of percentage diameter stenosis was done on 131 patients (mean age 62 years [SD 9]) with 171 stents 6.1 months (2.7) after stent implantation. All patients underwent epicutaneous patch tests (Finn chamber method) for nickel, chromate, molybdenum, manganese, and small 316L stainless-steel plates. Patch tests were assessed by independent dermatologists after 48 h, 72 h, and when necessary 96 h of contact with the potential allergen. FINDINGS: In-stent restenosis (> or =550% diameter stenosis) occurred in 89 patients. All ten patients with positive patch-test results had restenoses (p=0.03). Four male patients had positive reactions to molybdenum, and seven patients (four male, three female) had reactions to nickel. No patient with an allergic reaction to the standard test substances had a positive reaction to the stainless-steel plates. All patients with positive results had recurrent angina pectoris and needed target-vessel revascularisation. INTERPRETATION: Patients with allergic patch-test reactions to nickel and molybdenum had a higher frequency of in-stent restenoses than patients without hypersensitivity. Allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent restenosis.

The excess of atopic eczema in East Germany is related to the intrinsic type.

BACKGROUND: Prevalence data for atopic eczema based on a dermatological examination have not so far been available for East and West Germany. Possible differences in the proportions of extrinsic and intrinsic types of eczema, and how far these could explain differences in the prevalence of eczema, need to be clarified. OBJECTIVES: To compare the prevalence of atopic eczema in pre-school children between different locations in East and West Germany, and over a period of 7 years, at three time points. Additionally, to determine the proportions of intrinsic and extrinsic types of eczema by taking skin prick test reactivity into account. METHODS: Repeated cross-sectional studies in 1991, 1994 and 1997 in 5-6-year-old pre-school children at five different locations in West Germany (n = 2075) and six in East Germany (n = 1926) were carried out. Individuals with eczema were identified by an examination performed by physicians of the Department of Dermatology. In addition, a skin prick test and a standardized questionnaire were used. RESULTS: The overall prevalence of atopic eczema in these children was 10.4%. At all three times of investigation (1991, 17.5% vs. 11.2%; 1994, 12.6% vs. 8.7%; 1997, 11.2% vs. 4.5%) and in the total group (12.9% vs. 8.2%), the prevalence was significantly higher in East than in West Germany. After controlling for influences of sex, parental history of atopic diseases, observer and socio-economic status in multiple logistic regression analyses, these differences remained significant for 1991, 1994 and for the overall group (odds ratio, OR 1.78, 95% confidence interval, CI 1. 43-2.21). Girls (OR 1.56, 95% CI 1.27-1.92) and children whose parents had a higher level of school education (OR 1.17, 95% CI 1. 00-1.37) were affected more frequently. Of all children, 26.6%, and of those with eczema, 41.9% exhibited at least one reaction in the prick test (OR 2.21, 95% CI 1.75-2.80; sensitization in eczema vs. no eczema). Whereas 50.4% of the children with eczema in West Germany were sensitized, only 36.5% of the diseased children in East Germany reacted positively in the prick test (OR 1.77, 95% CI 1.12-2. 79). CONCLUSIONS: These results are in accordance with findings regarding allergic sensitization and hay fever and might indicate that factors other than allergy are responsible for the higher prevalence of atopic eczema in East Germany.

Environmental risk factors for respiratory and skin atopy: results from epidemiological studies in former East and West Germany.

The fall of the Berlin wall in 1989 offered the unique opportunity to compare populations of a similar genetic and geographic background which had been living under quite different environmental exposure conditions for over 40 years. Since 1990 comparative epidemiological studies were performed between various regions in former East and West Germany with yearly questionnaires and 3 years' physical, dermatological, allergological and exposure examination in a total of about 30,000 preschool children. There were striking differences between the various German regions with higher prevalence rates of respiratory atopy (hay fever, asthma) and atopic sensitization (prick test, RAST) in West Germany, while atopic eczema was significantly higher in East Germany (17.5 vs. 11.4% in West Germany). Total serum IgE levels were markedly higher in children in the east of Germany, similarly to the prevalence of parasitic infestation (questionnaire data as well as positive ascaris RAST). In multivariate logistic regression analysis the following factors were significantly associated with atopic eczema: animal contact (odds ratio, OR 2.9), animal furs in the bedroom (OR 2.2), use of gas without ventilation (OR 1.7) and living near road with heavy traffic (OR 1.7). Furthermore, socioeconomic factors measured as parental educational status (university vs. elementary school) were significantly associated (OR 2.3) with atopy. Respiratory tract infections and irritant responses decreased together with decreasing SO2 and suspended particulate air pollution in East Germany from 1991 to 1997. It is concluded that environmental factors from the physical, chemical, biological, and psychological environment (characteristic of a 'modern' or 'western' society) do influence the development of atopic sensitization and disease.

Positive skin tests in late reactions to radiographic contrast media.

In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients.

What makes a child allergic? Analysis of risk factors for allergic sensitization in preschool children from East and West Germany.

Earlier epidemiologic studies within Germany found a higher frequency of allergic sensitization in West Germany. The reasons for that and the role of environmental factors in the process of allergic sensitization are not fully understood. This study aimed to determine the prevalence of positive skin-prick test results 5 years after unification and to investigate risk factors for allergic sensitization in preschool children. A total of 1235 children (5-6 years) from two West and five East German locations were skin-prick tested after the compulsory school entrance examination. Six common aero- (birch, grass, mugwort pollen, cat, HDM, alternaria) and two food allergens (egg, milk) were used and additional information was obtained by questionnaire. Of the tested children 23.3% exhibited at least one positive reaction. The prevalence of sensitization to the single allergens was as follows: grass (14.4%), birch (6.6%), mugwort pollen (4.5%), cat (8.5%), HDM (5.5%), alternaria (4.9%), egg (2.8%), and milk (3.9%). In the crude analysis significantly more children were sensitized in the East German city Magdeburg (40.2%) compared to the West German control region Borken (23.5%) (OR 2.20, CI 1.47-3.29). Dampness and visible molds were reported in 8.8% of all households, but significantly more often for East German apartments (10.3% versus West Germany 1.9%, OR 5.85, CI 2.55-16.53). Dampness and molds were associated with a higher frequency of sensitizations (40.6% versus 27.6% in unaffected homes). After controlling for sex, parental atopy, SES, family size, and smoking during pregnancy, this association remained statistically significant (OR 1.93, CI 1.19-3.12). With regard to single allergens, dampness and visible molds were significantly associated with sensitization to HDM (OR 3.37, CI 1.63-6.96), cat (OR 3.19, CI 1.11-5.74), and mugwort pollen (OR 2.86, CI 1.29-6.35). In addition, family size was inversely and linearly associated with the frequency of sensitization (OR for four, three, and two-person households: 1.10 (0.74-1.63), 1.57 (1.06-2.42), 2.70 (1.39-5.24), respectively, when compared to family size of five or more). Neither parental predisposition for atopic diseases nor parental education level influenced the prick test reactivity. We conclude that in addition to genetic predisposition, environmental factors like indoor climate and probably infectious stimuli (family size) play an important role in the process of allergic sensitization in children.

Evaluating the relevance of aeroallergen sensitization in atopic eczema with the atopy patch test: a randomized, double-blind multicenter study. Atopy Patch Test Study Group.

BACKGROUND: IgE-mediated sensitization of questionable clinical relevance is routinely demonstrated in patients with atopic eczema (AE) by skin prick test or radioallergosorbent test (RAST). We report the results of a randomized, double-blind multicenter study in patients with AE on the relevance and technical aspects of aeroallergen patch testing (atopy patch test, APT). METHODS: Two hundred fifty-three adult patients with AE in remission were tested in 7 study centers on clinically uninvolved, unabraded back skin with 3000 to 10,000 PNU/g of Dermatophagoides pteronyssinus, cat dander, grass, birch, and mugwort pollen allergen extracts in petrolatum. After skin prick and RAST and a detailed history on aeroallergen-induced eczema flares was obtained, reading was done at 48 to 72 hours. RESULTS: Previous eczema flares after contact with specific allergens were reported by 10% (mugwort pollen) to 52% (D pteronyssinus) of patients. The percentage of clear-cut positive APT reactions ranged from 44% with D pteronyssinus to 5% with mugwort. Positive skin prick (36% to 65%) and RAST (49% to 75%) results were more frequent. APT results showed significant concordances with history, skin prick, and RAST for D pteronyssinus, cat dander, and grass pollen (P < .001). Optimal test concentrations were 5000 (grass pollen) and 7000 PNU/g (D pteronyssinus, cat dander). The APT had a higher specificity (69% to 92% depending on allergen) with regard to clinical relevance of an allergen compared with skin prick test (44% to 53%) and RAST (42% to 64%). CONCLUSION: Aeroallergens are able to elicit eczematous skin reactions after epidermal application. The relevance of aeroallergens for AE flares may be evaluated by APT.

Determination of histamine and leukotrienes from basophils in cell supernatants by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method with gradient elution for the separation of the mediator substances histamine and the leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) is described. The detection occurs fluorimetrically after automated precolumn derivatization with o-phthaldialdehyde. All components are chromatographically separable. Because of the different excitation and emission wavelengths, only the most important biological active mediators histamine and LTC4 are determinable in one parallel chromatographic run. The method is examined by linearity and precision tests and is applicable to biological sample matrices like cell supernatants of human basophils enriched by Percoll-density gradient centrifugation and stimulated for mediator release by anti-IgE. The established method is suitable to separate the mediators from other matrix components. The determination limit for histamine is 55.0 micrograms/L and that for LTC4 16.0 micrograms/L, referring to the reference solutions. Therefore, a fast, economical method for the common determination of the most important mediators histamine and LTC4 is established. This method is also suitable for high sample amounts in routine medical analysis.

Determination and characterization of cross-reacting allergens in latex, avocado, banana, and kiwi fruit.

Sera of 11 patients were used to characterize allergens in kiwi fruit, latex, avocado, and banana by SDS-PAGE/immunoblotting and to determine cross-reactions between these allergen extracts in EAST inhibition and immunoblot inhibition. By SDS-PAGE/immunoblotting, allergens with apparent molecular weights of 21, 38, 40, and 42 kDa were visualized in latex extract. In avocado extract, IgE-binding components of 27, 43, 52, 58, 65, 75, and 88 kDa were to be seen, whereas, in banana extract, a 40-kDa protein showed strong IgE binding. Furthermore, allergens of 52, 58, 88, and 94 kDa were detected in the extract of banana. Cross-reactions between these allergen extracts were determined by EAST inhibition. Immunoblot inhibition demonstrated that almost all IgE-reactive bands in nitrocellulose-blotted latex, avocado, and banana extracts and two components of 43 and 67 kDa in kiwi fruit shared common IgE epitopes.

Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial.

BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.

The 'atopy patch test' in evaluating the role of aeroallergens in atopic eczema.

The atopy patch test (APT) is a procedure involving epicutaneous patch tests with allergens known to elicit IgE-mediated reactions and the evaluation of eczematous skin lesions. APT can be performed on normal uninvolved skin without artificial manipulations such as tape stripping or use of irritants. APT has been standardized regarding the use of vehicle and dose response relationships. In several studies, approximately two thirds of patients with atopic eczema (AE) showed positive APT reactions to aeroallergens, most frequently to house dust mite. Positive APT reactions were significantly more frequent in patients with a typical air-exposed eczematous distribution pattern. Using evaporimetry to study transepidermal water loss, allergen-induced disturbance of epidermal barrier functions was found to be significantly more pronounced on APT reactions compared to classical contact allergy patch test sites in the same individual. It has been shown that with APT eczematous skin lesions can be elicited by skin contact with aeroallergens, at least in a subgroup of patients with AE, and thereby, that IgE-mediated allergy does play a role in the etiopathophysiology of this disease. Future studies should help to bring this test into clinical routine in order to establish an equivalent for 'skin provocation' comparable to nasal and bronchial provocation tests in respiratory allergy.

Atopic eczema and other manifestations of atopy: results of a study in East and West Germany.

Within an environmental health study, dermatologic examination of 1273 pre-school-age children (5-7 years old) was carried out in selected areas of East (n = 287) and West (n = 987) Germany in spring 1991. On the basis of comparable genetic background, the influence of a different exposure to air pollutants on the manifestation of atopic diseases was investigated. Halle an der Saale (East Germany) and Duisburg (North/South) as well as Essen (West Germany) were chosen as polluted study areas, whereas the countryside town of Borken (West Germany) served as a control region. Outdoor pollution with particles and SO2 was significantly higher in Halle an der Saale. Of the total study group, 12.9% suffered from atopic eczema at the time of examination. The prevalence was highest in East Germany (17.5%; adjusted odds ratio [OR] 1.39, confidence intervals [GI] 0.77-2.52, compared to Borken). The reported frequencies of hay fever and asthma in the total study population were 2% and 1.3%, respectively, without significant differences between study sites. Some 34.7% of the children showed at least one positive skin prick test reaction; significantly (P < 0.001) higher sensitization rates were obtained in western regions (Essen, Duisburg-South) than in the control region (Borken) and East Germany. Multivariate analysis of the prevalence of atopic eczema showed associations with parental predisposition (OR 1.52, CI 1.03-2.25), sex (for boys, OR 0.63, CI 0.43-0.92), location (Duisburg-South vs Borken OR 0.52, CI 0.30-0.96), month of investigation (May vs April, and March vs February OR 0.55, CI 0.37-0.81), contact with rabbits (for girls, OR 2.90, CI 1.36-6.19), animal fur in bedrooms (2.17, 1.01-4.67), indoor use of gas without hood (1.68, 1.11-2.56), and distance of homes from a busy road (< 50 m 1.71, 1.07-2.73). Nonsignificant associations were observed for history of helminthic infections (OR 1.61, CI 0.98-2.64) and high parental education level (OR 1.83, CI 0.83-4.02). In East and West Germany, atopic eczema seems to follow a course different from that of respiratory allergic diseases and specific sensitization, a fact which underlines the need for a differentiated analysis.