Efficacy and safety of etanercept in psoriasis and psoriatic arthritis in the PRESTA study: analysis in patients from Central and Eastern Europe.

BACKGROUND: Data are limited on the effectiveness of anti-TNF and other biologics on psoriatric arthritis (PsA) in Central and Eastern Europe (CEE). The objective of this analysis was to evaluate the efficacy of etanercept (ETN) in PsA patients from CEE. METHODS: In PRESTA, patients were randomized to receive ETN 50 mg BIW or 50 mg QW for 12 weeks (double-blind phase) and ETN 50 mg QW for 12 additional weeks (open label). In this analysis, only patients from Czech Republic, Hungary, Poland and Serbia were included. The primary efficacy variable was the proportion of subjects achieving a physician global assessment (PGA) of psoriasis status: "clear" or "almost clear" at week 12. RESULTS: In the 307 patients, 54% BIW/QW compared with 40% (QW/QW) (p = .02), achieved "clear"/"almost clear" for PGA of psoriasis at week 12 increasing, to 68% and 60%, respectively (p = .134) by week 24. Mean improvement from baseline in PASI were 59% versus 49% (p = .005) at week 6 and 87% versus 81% (p < .05) at week 24, for the BIW/QW and QW/QW groups, respectively. ETN was well tolerated in both groups over 24 weeks. CONCLUSIONS: Both dose regimens of ETN provided significant improvements in efficacy in PsA treatment and were well tolerated.

Characterization of intrinsic and extrinsic risk factors for celery allergy in immunosenescence.

Recent studies indicated an underestimation of allergies in elderly. In our experimental food allergy model of protein feeding under acid-suppression we aimed to assess whether food allergy can be induced in immunosenescent mice. Furthermore, the impact of gastric digestion on celery allergenicity was evaluated in aged patients. Measurements of serum zinc and iron levels in senescent and adult BALB/c mice for definition of the nutritional status indicated a possible alteration of the immune response in the aged animals due to reduced zinc and iron levels. Feedings of mice with digestion-sensitive celery proteins under physiological gastric conditions induced IgG1 and IgG2a in the aged and preferentially IgG1 in the adult animals. In contrast, incomplete digestion due to acid-suppression rendered celery-specific IgE, positive skin tests and elevated IL-5 levels in both age groups. Also in aged celery allergic patients (mean age 72 years) properly digested celery showed decreased capacity to bind and crosslink IgE as evaluated by skin tests and IgE immunoblot. Thus, in the geriatric murine model, celery allergy was induced only if gastric digestion was hindered. Accordingly, gastric proteolysis decreased in vitro and in vivo IgE-reactivity against celery proteins in aged allergic patients.

Risk assessment in elderly for sensitization to food and respiratory allergens.

For elderly people, epidemiological data are rare for respiratory allergies and completely missing for food allergies. The aim of this study was to examine the prevalence and risk factors for sensitizations in 109 people with a mean age of 77 years, who are living in a geriatric nursing home. The cross-sectional study included a detailed interview, skin prick tests, and serum tests for specific and total IgE, IFN-gamma, and ST2, a marker for Th2-lymphocyte activity. Almost all study subjects (n=101) suffered from co-morbidity, 14 from type I allergy, 25 from gastrointestinal disorders treated with anti-ulcer drugs, 25 were chronic alcoholics and 21 were smokers. The total IgE levels were significantly higher in men (P=0.025), and not affected by smoking or alcohol consumption. Skin prick tests were positive in 41.7% of tested patients. Specific IgE to respiratory allergens was found in 40.4% of all patients and was elevated in men (P=0.013), with a significant correlation to smoking (P=0.029). Specific IgE to food allergens was detected in 24.8%, apparently without connection to the investigated risk factors. However, positive skin prick tests with food allergens could be correlated with chronic alcohol consumption (P=0.036). The intake of anti-ulcer medication was significantly correlated with elevated ST2 levels as an indirect readout for Th2-cell activity (P<0.001). The risk factors for sensitization in elderly to respiratory allergens were chronic damage of respiratory epithelia due to smoking, and for sensitization to food allergens chronic alcohol consumption.

Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.

Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients.

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans.

BACKGROUND: Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible. OBJECTIVE: We have reported that antiulcer drugs promote oral sensitization to digestion-labile food allergens. Because hazelnut proteins were sensitive to gastric digestion in our in vitro assay, we aimed to analyze the effect of antiulcer treatment on oral sensitization to hazelnut proteins. DESIGN: BALB/c mice were fed hazelnut extract with or without antiulcer drugs. In parallel, gastroenterologic patients (n = 153) were screened during antiulcer treatment for specific immunoglobulin (Ig) E to hazelnut and inhalative allergens in vitro and in vivo. RESULTS: Mice fed hazelnut extract in combination with antiulcer drugs formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In the human study population, 5 of 153 (3.3%) patients developed hazelnut-specific IgE, 4 of 5 developed specific skin reactivity, 3 of 5 had a positive result to oral provocation, and 2 of 5 manifested a food allergy to hazelnut after a 3-mo course of antiulcer treatment. Immunoblot testing with recombinant allergens showed that hazelnut, but not Fagales pollen, was the genuine elicitor in mice and humans. CONCLUSION: Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Comparison of chronic autoimmune urticaria with chronic idiopathic urticaria.

BACKGROUND: Chronic urticaria has been described in patients with Helicobacter pylori infection. Despite numerous studies, the correlation between H. pylori infection and chronic urticaria is doubtful. Our study was performed to determine the prevalence of H. pylori infection in autoimmune urticaria and in patients suffering from autoimmune urticaria and autoimmune thyroiditis. METHODS: The authors widely investigated 48 patients. The examinations were extended principally to autologous serum skin test, antithyroid antibodies, and the presence of H. pylori infection as well as detection of antibodies against H. pylori. RESULTS: Out of the 48 patients, 26 were regarded as having autoimmune origin. The prevalence of antithyroid antibodies was different in the two groups of patients with urticaria. There were 11 patients (42.3%) in the autoimmune group compared with three patients (13.6%) in the nonautoimmune group with antithyroid peroxidase antibody (P = 0.03). The difference in the prevalence of H. pylori infection was significant between autoimmune urticaria with and without thyroid autoimmunity (90.9% vs. 46.7%; P = 0.02). Autoimmune thyroiditis was connected with CagA +H. pylori strains, as the H. pylori- specific IgG antibodies revealed significant differences in a prevalence of 120 kDa (P < 0.05). CONCLUSIONS: The authors observed a relationship between autoimmune urticaria and autoimmune thyroiditis. The results strengthen the possibility of cross-reactivity being triggered between CagA plus H. pylori strains and some other organ-specific autoimmune diseases such as autoimmune urticaria and autoimmune thyroiditis. This indicates a possible role of H. pylori in triggering autoimmune urticaria in at least a select group of patients.

Erythema Gyratum Repens an Immunological Paraneoplastic Dermatosis.

The authors present a patient with erythema gyratum repens who had a bronchogenic carcinoma. Autoantibodies and complement at the basement membrane zone of the skin was found which suggest that erythema gyratum repens may have an immunological pathogenesis but the nature of the antigen should be further characterised.