Erwin Schöpf

Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Background Toxic epidermal necrolysis and Stevens–Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case–control study to quantify the risks associated with the use of specific drugs. Methods Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens–Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Results Among drugs usually used for short periods, the risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate rel...

A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis.

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intensely pruritic subacute and chronic eczematous plaques, the pathogenesis of which appears to involve a complex interplay of genetic, pharmacological, environmental and psychological factors. Here, Markus Grewe and colleagues propose that the development of skin lesions in AD patients results from sequential activation of T helper 2 (Th2)- and Th1-type cells.

A Short-Term Trial of Tacrolimus Ointment for Atopic Dermatitis

BACKGROUND Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. METHODS We conducted a randomized, doubleblind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate to severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. RESULTS After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51 patients receiving 0.3 percent tacrolimus, and 22.5 percent for the 54 patients receiving vehicle alone (P<0.001). The results for the face and neck were similar. The differences among the three tacrolimus groups were not statistically significant. A sensation of burning at the site of application was the only adverse event that was significantly more frequent with tacrolimus than with vehicle alone (P<0.001). Throughout the study, most patients in all three tacrolimus groups had blood concentrations of tacrolimus below 0.25 ng per milliliter. The highest concentration was 4.9 ng per milliliter, which was reported in the group receiving 0.3 percent tacrolimus. CONCLUSIONS The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.

Lesional expression of interferon-γ in atopic eczema

Abstract Atopic eczema is thought to be caused by skin-infiltrating CD4 T cells of the Th 1 -like and/or Th 2 -like subtype. We assessed expression of the Th 1 -like cytokine, interferon-γ, and the Th 2 -like cytokine, interleukin-4, in lesional atopic skin. Compared with that in normal skin, interferon-γ and interleukin-4 mRNA expression were increased in eczematous skin lesions in 13 and 4 of 15 patients, respectively. After successful therapy of atopic dermatitis, the increased interferon-γ mRNA expression but not the increased interleukin-4 mRNA expression was significantly downregulated. These data indicate that in-situ expression of interferon-γ is linked to the clinical course of atopic dermatitis.

Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990–1992): Structure and results of a population-based registry

The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.

High-dose UVA1 therapy in the treatment of patients with atopic dermatitis

BACKGROUND Besides glucocorticosteroids, there is currently no known effective therapy for patients with acute atopic dermatitis. OBJECTIVE The therapeutic effectiveness of high-dose UVA1 irradiation in the management of patients with acute exacerbation of atopic dermatitis was examined. METHODS Patients in the high-dose UVA1 group (n = 15) were irradiated with 130 joules/cm2 UVA1; the control group (n = 10) was treated with UVA-UVB therapy in a minimal erythema dose-dependent manner (total number of treatments 15). RESULTS High-dose UVA1 irradiation was found to induce a significant clinical improvement of atopic dermatitis (p less than 0.001). In comparison with UVA-UVB therapy, significant differences in favor of high-dose UVA1 were observed (p less than 0.01). High-dose UVA1, but not UVA-UVB treatment, significantly reduced the elevated serum level of eosinophil cationic protein in patients with atopic dermatitis (p less than 0.003). CONCLUSION These studies indicate that high-dose UVA1 irradiation may represent a novel phototherapeutic modality for the treatment of patients with an acute exacerbation of atopic dermatitis.

High-dose UVA1 therapy for atopic dermatitis: Results of a multicenter trial

BACKGROUND The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis

Summary The clinical and histopathological classification of erythema exudativum multiforme major (EEMM), Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are difficult, due to the lack of clear‐cut criteria. Based on a new clinical classification, 149 of 219 (68%) histopathological specimens, from a total of 534 patients with EEMM. SJS and TEN, have been reviewed. A comparison was made with the clinical picture, and any past history of infection or drug intake. All patients had been included in the German Registry of Severe Skin Reactions between April 1990 and December 1993. No differences could be found between the biopsies examined and the total number of histopathological specimens, concerning clinical diagnosis, gender and age. Sections from 28 of 149 specimens were not diagnostic or were too old to be properly evaluated. In nine cases, other diagnoses were proposed. One hundred and eleven of the histological slides with the diagnosis of EEMM (n= 16), SJS (n=34) and TEN (n=61), were classified as epidermal type of erythema multiforme. In these 111 slides, necrotic keratinocytes could be found, ranging from individual cells to confluent epidermal necrosis. The epidermo‐dermal junction showed changes ranging from vacuolar alteration up to subepidermal blisters. The dermal infiltrate was superficial and mostly perivascular. It was sparse in SJS and TEN, and more pronounced in EEMM. Oedema in the papillary dermis was evident occasionally in all clinical groups. In 59 of 111 cases (53%), at least one eosinophil was present in the dermis. In 11 of 111 (10%), more than 10 eosinophils per field could be seen. Eosinophils were less common in the patients with the most severe forms of TEN, in whom there was detachment of more than 30% of the skin surface area. No differences in the history for drug intake, or for infection with Mycoplasma pneumoniae, herpes simplex and other organisms, could be detected between patients with or without eosinophils in their skin sections. This dermatopathological study of patients with EEMM. SJS and TEN indicates that the epidermal type of erythema multiforme is the pathological correlate for these diseases.

Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis.

Atopic dermatitis (AD) is characterized by alterations in cellular and humoral immunity including elevated serum levels of IgE, IL‐2 receptor (IL‐2R) and eosinophil cationic protein (ECP). In order to evaluate the relevance of these serum parameters as indicators of disease activity, the concentrations of IgE, IL‐2R and ECP were measured in serum samples of patients with an acute exacerbation of AD (n=19) on admission to hospital and every 6 days up to discharge, and compared with those from normal non‐atopic controls (n= 15). The severity of the disease in the AD patients was examined using an established clinical scoring system. On admission, AD patients showed significantly elevated serum levels of IgE, IL‐2R and ECP compared with normal controls (P≤0.0001). Clinical improvement was associated with a decrease of both the clinical score (P≤0.001) and serum ECP levels (P≤0.005). No significant changes in serum IgE and serum IL‐2R were observed. In addition, there was a significant correlation between serum ECP and the clinical score (R=0.67, P≤0.001). These data indicate that serum ECP may be a helpful tool for monitoring disease activity in AD.

Measurement of chemiluminescence in freshly drawn human blood

SummaryThe present investigations were undertaken to find out whether chemiluminescence measurements of stimulated granulocytes can be carried out in freshly drawn blood and — because of the ease of the method — be introduced into routine diagnostics.Blood was drawn from the cubital vein of healthy volunteers at various times and under various conditions. Subsequently the zymosan induced and luminol amplified chemiluminescence was recorded and analyzed. It could be demonstrated that variations existed between individuals which can, however, be minimized when photon counts obtained under standard conditions were related to the number of granulocytes present in the blood samples. It could be further demonstrated that also platelets are activated by zymosan as well and that they, contribute to the total chemiluminescence by a share of about 5%. Platelet chemiluminescence can effectively be suppressed by aspirin. Opsonising factors in plasma (presumably antibodies and/or complement) play a decisive role in the intensity and kinetics of blood chemiluminescence. Measurements of zymosan induced chemiluminescence in freshly drawn unfractionated and fractionated blood seem to be especially suited to monitor and analyze deviations and defects of the cellular and humoral defence mechanisms.ZusammenfassungDie vorliegenden Untersuchungen bilden die Grundlage, um die im Prinzip sehr einfache Messung der Chemilumineszenz stimulierter Granulocyten in frisch gewonnenem Vollblut durchzuführen und damit für die einfache Routine-Diagnostik anwendbar zu machen.Gesunden Freiwilligen wurde zu verschiedenen Zeiten und unter verschiedenen Bedingungen kubital Venenblut entnommen und anschließend die durch Zymosan induzierte und durch Luminol verstärkte Chemilumineszenz analysiert. Die Chemilumineszenz-Kurven verschiedener Individuen zeigten Variationen, die jedoch verringert werden, wenn die unter Standardbedingungen gemessenen Photonen auf die Zahl der im Blut vorhandenen Granulocyten bezogen werden. Es zeigte sich ferner, daß Blutplättchen ebenfalls durch Zymosan aktiviert werden und zu etwa 5% an der gesamten Chemilumineszenz beteiligt sind. Die Plättchen-Chemilumineszenz läßt sich indes durch Zusatz von Aspirin nahezu vollständig ausschalten. Von entscheidender Bedeutung für die Intensität und Kinetik der im Vollblut gemessenen Chemilumineszenz ist die Anwesenheit opsonierender Plasma-Faktoren (Antikörper und/oder Komplement).Die Messung der Chemilumineszenz im Vollblut erscheint uns geeignet, sowohl Abweichungen der zellulären wie der humoralen Abwehrfunktionen rasch und einfach zu erkennen.