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Biomedical subjects

T Werfel

Publications and source records attributed to T Werfel.

At least 19 recordsLinked to original sources
PubMed2006

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.

Adult↗
PubMed2006

[Cutaneous side effects of EGF-receptor inhibition and their management].

The receptor of the epidermal growth factor (EGF-receptor) plays a role in the pathogenesis of many human carcinomas. Recent strategies in anti-tumor therapy target the EGF-receptor, e.g., by the EGF-receptor blocking monoclonal antibody cetuximab or by small molecules inhibiting the tyrosine kinase activity of the EGF-receptor, such as gefitinib and erlotinib. The EGF-receptor is also expressed in normal human skin; in clinical trials with different EGF-receptor inhibitors, cutaneous side effects were common. We report on cutaneous side effects of EGF-receptor blockade, in particular acneiform lesions, xerosis and paronychia, and discuss their management.

Antibodies, Monoclonal↗
PubMed2006

[Hematogenous contact eczema induced by foods].

Oral ingestion or parenteral administration of certain contact allergens may elicit eczematous skin reactions "from inside" in sensitized individuals; this phenomenon has been termed "systemically-induced eczema" or "hematogenous contact eczema". There is a wide range of clinical features from polyetiological dyshidrotic hand and foot eczema to baboon syndrome. The most important contact allergens known to elicit systemically-induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. Diagnosis is based on proof of delayed type hypersensitivity by patch testing and oral challenge. Until more and better data is acquired, special diets (for instance low nickel) should be instituted only in carefully selected patients.

Dermatitis, Contact↗
PubMed2006

[Atopic dermatitis: The hygiene hypothesis: Prevention through helminth infections?].

The prevalence of atopic diseases has steadily increased over the past decades. While genetic predisposition remains an important risk factor, environmental conditions appear to be additional relevant trigger factors, leading to the development of the "hygiene hypothesis". Current data indicates that atopic respiratory diseases seem to occur less frequently following helminth infections. This effect may be due to the induction of anti-inflammatory cytokines during the helminth infection. In contrast, atopic dermatitis seems to represent a separate entity influenced by more than "allergic sensitization". Recent data demonstrate a reduced risk for the development of atopic dermatitis following helminth infections. Further studies are needed to more closely examine the connections between helminth infections and this chronic skin disease, as well as to identify immunologic pathways.

Adolescent↗
PubMed2006

[The educational program for the management of psoriasis vulgaris according to the rules of the Task Force on Dermatological Prevention: current status].

BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease with a substantial impairment of quality of life. Interdisciplinary outpatient educational programs are an innovative supplementary therapy form for the management of this disorder. SUBJECTS AND METHODS: The Task Force on Dermatological Prevention developed a concept for outpatient instruction of psoriasis patients. Five 2-hour classes by dermatologists, psychotherapists/psychologists and dieticians focus on central topics relevant for the patients and the management of the disease. RESULTS: The results presented are based on own experiences with this educational program. The interdisciplinary program is accepted very well and seen as helpful by the concerned. A structure analysis of the effects in a greater number of cases is a current goal. In some areas, health insurance companies are paying for the classes. CONCLUSION: The educational program for the management of psoriasis vulgaris according to the rules of the Task Force on Dermatological Prevention is a supplement of the treatment of patients with this chronic skin disease. Broader implementation in Germany is desirable.

Ambulatory Care↗
PubMed2006

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.

BACKGROUND: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. METHODS: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. RESULTS: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). CONCLUSIONS: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Adolescent↗
PubMed2006

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗
PubMed2005

[Successful treatment of subcorneal pustular type of IgA pemphigus].

IgA pemphigus is a rare autoimmune intraepidermal blistering disease characterized by in vivo bound, and circulating IgA autoantibodies that target cell surface components (cadherins) of epidermal keratinocytes. The average age of onset is approximately 50 years. Histological hallmarks of IgA pemphigus are epidermal acantholysis, subcorneal or intraepidermal pustulosis, and neutrophilic infiltration. The main clinical characteristics are erythematous skin lesions with vesiculopustules, erosions, crusts and desquamation, favoring the trunk, groins, auxiliaries, and proximal extremities. The drug of choice for treating IgA pemphigus is diaminodiphenylsulfone. In this case study, we describe a patient who suffered from IgA pemphigus and responded well to diaminodiphenylsulfone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

[Facial pigmentation following therapy with terbinafine].

A 65-year-old patient presented with grey-brownish maculae localized on the face. He had been treated with oral terbinafine due to onychomycosis, and the first spots manifested after 4 weeks of therapy. Other drugs were not taken by the patient, who was otherwise in a healthy condition. Histology showed melanin localized within macrophages in the upper and lower dermis. Cutaneous side effects are well described in patients treated with terbinafine and usually present as urticaria or eczema. Severe reactions may occur in rare cases. Hyperpigmentation has not yet been described as a consequence of oral terbinafine. Grey hyperpigmentation as it occurred in our patient has been described as a side effect of therapy with minocycline, amiodarone, tricyclic antidepressants, or heavy metals. This case report shows that drug-induced hyperpigmentation should also be considered if the patient takes drugs not known for this kind of side effect.

Administration, Oral↗
PubMed2005

[Evidence-based evaluation of the effect of Type IV Allergies on the reduction of fitness for work. Survey of occupational skin diseases].

Evidence-based guidelines about the distribution of type IV allergens of the European standard series in different professions and its occupational relevance are missing. Based on published data, epidemiological investigations, work related knowledge about industrial processes, and allergen specific properties, recommendations are given about the clinical impact in the working environment for the following allergens: acrylates/methacrylates, epoxy resins, dichromate, cobalt, nickel, formaldehyde, (chlor-)methylisothiazolone, p-phenylendiamine, colophony, thiurame, mercaptobenzothiazole, dithiocarbamate, n-isopropyl-n'-phenyl-p-phenylendiamine, fragrance mix, composite mix, and neomycinsulfate. These recommendations might improve the clearance rate and allergological evaluation of the occupational relevance of different delayed type sensitizations or allergens.

Allergens↗
PubMed2005

Therapy of noninfectious granulomatous skin diseases with fumaric acid esters.

BACKGROUND: Noninfectious granulomatous skin diseases are inflammatory disorders of unknown aetiology which are often recalcitrant to common anti-inflammatory treatment regimens. Recently, in several case reports, fumaric acid esters (FAE) have proved beneficial in granulomatous skin diseases, but studies on a larger collection of consecutive patients have not yet been performed. OBJECTIVES: To investigate the therapeutic efficacy of FAE for the treatment of granulomatous skin diseases. PATIENTS AND METHODS: The therapeutic efficacy and side-effects of FAE were analysed retrospectively in 32 patients with disseminated granuloma annulare (n = 13), annular elastolytic giant cell granuloma (n = 3), sarcoidosis (n = 11), necrobiosis lipoidica (n = 4), or granulomatous cheilitis (n = 1). RESULTS: Three patients discontinued treatment within 4 weeks because of side-effects. Of the remaining 29 patients, 18 patients responded to treatment with FAE. Marked improvement or complete clearance was seen in seven patients. We observed a slight to moderate improvement in 11 patients, and 11 patients did not respond. In patients showing a complete remission, the maximum effect was observed after 8.5 months (SD +/-6 months, range 3-20 months). In two patients with systemic sarcoidosis, the pulmonary changes improved in parallel with the skin. Side-effects were usually mild and resolved spontaneously upon dose reduction or discontinuation of the therapy. CONCLUSIONS: The data presented here indicate that FAE may be considered for the treatment of recalcitrant granulomatous skin disease.

Adolescent↗
PubMed2005

Deficiency in immunoglobulin G2 antibodies against staphylococcal enterotoxin C1 defines a subgroup of patients with atopic dermatitis.

BACKGROUND AND AIM: Atopic dermatitis (AD) is a common chronic inflammatory skin disease often accompanied by cutaneous Staphylococcus aureus colonization and, in this regard, especially complicated by the presence of superantigen-producing strains. Because IgG antibodies comprise an important defence mechanism of the adaptive immune system against bacteria, it was investigated whether AD patients have an abnormal pattern or distribution of superantigen-specific IgG subclass antibodies in association with disease severity and activity. METHODS: Staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin C1 (SEC1) specific IgG antibody subclasses were assessed in n=89 adult AD patients with mild to severe disease activity as determined by the SCORAD score and in n=28 healthy age-matched controls. Results were correlated with the current status of bacterial skin colonization and severity score. RESULTS: Thirty-eight per cent of the AD patients showed a selective deficiency in IgG2 antibodies against SEC1 compared with only 14% in the control group. The absence of these antibodies was found in both currently colonized and non-colonized AD patients and was associated with a severe phenotype (SCORAD more than 40 points in two-thirds of the deficient patients). However, these patients had normal production levels of IgG2 antibodies against pneumococcal capsular polysaccharide (PCP) and SEB, but higher IgG1 and IgG4 titres against SEC1. Except for elevated total IgG1, total IgG subclass levels were normal in this AD subgroup. Yet, peripheral blood mononuclear cells (PBMCs) derived from these patients clearly produced IL-4 and IL-5 upon SEC1 re-stimulation whereas PBMCs from those providing SEC1-specific IgG2 antibodies failed in the production of these cytokines. CONCLUSION: A subgroup of AD patients suffers from a selective deficiency to produce anti-SEC1 IgG2 antibodies. This patient group is characterized by a severe AD phenotype.

Adolescent↗
PubMed2005

Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis.

BACKGROUND: Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. OBJECTIVE: To explore the impact of staphylococcal alpha-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. METHODS: Adult patients with AD were screened for cutaneous colonization with alpha-toxin producing S. aureus. As alpha-toxin may induce necrosis, CD4(+) T cells were incubated with sublytic alpha-toxin concentrations. Proliferation and up-regulation of IFN-gamma on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4(+) T cells was detected with the Electrophoretic Mobility Shift Assay. RESULTS: Thirty-four percent of the patients were colonized with alpha-toxin producing S. aureus and alpha-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic alpha-toxin concentrations induced a marked proliferation of isolated CD4(+) T cells. Microarray analysis indicated that alpha-toxin induced particularly high amounts of IFN-gamma transcripts. Up-regulation of IFN-gamma was confirmed both on the mRNA and the protein level. Stimulation of CD4(+) T cells with alpha-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. CONCLUSION: alpha-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic alpha-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that alpha-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.

Adult↗
PubMed2005

Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.

BACKGROUND: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. METHODS: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticasone propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. RESULTS: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). CONCLUSION: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.

Adult↗
PubMed2004

[Successful treatment of skin and lung sarcoidosis with fumaric acid ester].

A 61-year old female patient with cutaneous sarcoidosis was treated with fumaric acid esters (Fumaderm). After 12 months of therapy, lesions were markedly improved and treatment was discontinued. 18 months later, the cutaneous lesions recurred, angiotensin converting enzyme (ACE) serum levels were increased and a chest X-ray demonstrated pulmonary involvement. Therapy with fumaric acid esters was again started. The skin showed improvement after 2 months and completely cleared within 17 months, within 4 months ACE levels normalized, and within 10 months radiologic changes markedly resolved. This case demonstrates a possible role for fumaric acid esters not only in the treatment of cutaneous but also systemic sarcoidosis.

Dermatologic Agents↗
PubMed2004

Late eczematous reactions to food in children with atopic dermatitis.

BACKGROUND: Food allergy is a common problem in patients with atopic dermatitis (AD), particularly in children. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. OBJECTIVE: To investigate the importance of food for the induction of late eczematous reactions in children with AD and to correlate the clinical outcome to the results of specific IgE determinations and atopy patch tests (APTs). METHODS: One hundred and six double-blind placebo-controlled food challenges (DBPCFCs) to cow's milk, hen's egg, wheat and soy in 64 children with AD (median age 2 years) were analysed retrospectively. Total and food-specific IgE were determined by CAP RAST FEIA and APTs with native foodstuff were performed. The diagnostic values of specific IgE and APT results were calculated. RESULTS: Forty-nine (46%) of the challenges were related to a clinical reaction. An exacerbation of AD (late eczematous reaction) commonly occurred 24 h after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. Forty-five percent of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. The sensitivity of food-specific IgE and the APT was 76% and 70%, respectively. Specific IgE and APT were often false positive, which resulted in low positive predictive values (64% and 45%, respectively). CONCLUSIONS: Late eczematous reactions may often be observed upon food challenge in children with AD. Due to the poor reliability of food-specific IgE and APT results DBPCFCs have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with AD.

Child, Preschool↗