Update about Oralair® as a treatment for grass pollen allergic rhinitis.

Sublingual immunotherapy (SLIT) is a well-tolerated, safe, and effective approach to treating allergic rhinitis (AR). Oralair® is a five-grass pollen SLIT tablet containing natural pollen allergens from five of the major grass species responsible for seasonal AR due to grass pollen allergy. Recommended use is in a pre-coseasonal regimen, starting daily treatment approximately 4 months before the start of the pollen season, with treatment then continued daily throughout the season; treatment should continue for 3-5 y. Clinical efficacy and safety of Oralair® in patients with grass pollen-induced AR has been demonstrated in a comprehensive clinical development program of randomized controlled trials. Effectiveness has been substantiated in subsequent observational studies with sustained efficacy following treatment cessation and a favorable level of adherence, quality of life, benefit, and satisfaction for the patients. Supportive evidence for a benefit in reducing the risk or delaying the development of allergic asthma is emerging.

[Adjuvants]. / Adjuvanzien.

It is estimated that only 5% of all patients who can principally benefit from specific immunotherapy (SIT) undergo this treatment. SIT represents the only curative treatment for allergic disorders and efficacy has been demonstrated with various allergens. There is an urgent demand for the development of safe preparations with enhanced efficacy achievable by only a few administrations. Adjuvants are pharmacological or immunological acting molecules modifying the specific immunological response to allergens. In vaccine technology, adjuvants are broadly used to enhance immunogenicity of highly purified antigens with low immune stimulating activity. Adjuvants may target to a retarded allergen release, a modulation of the immune system, or can be used as vector systems to transport allergens and adjuvants effectively to target cells.

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

BACKGROUND: Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. METHODS: Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 µg of allergen or placebo preparation. OUTCOME MEASURES: lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). RESULTS: Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAELobjective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. CONCLUSION: For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance.

Standardization of double blind placebo controlled food challenge with soy within a multicentre trial.

BACKGROUND: Multicentre trials investigating food allergies by double blind placebo controlled food challenges (DBPCFC) need standardized procedures, challenge meals and evaluation criteria. We aimed at developing a standardized approach for identifying patients with birch related soy allergy by means of DBPCFC to soy, including determination of threshold levels, in a multicentre setting. METHODS: Microbiologically stable soy challenge meals were composed of protein isolate with consistent Gly m 4 levels. Patients sensitized to main birch allergen Bet v 1 and concomitant sensitization to its soy homologue Gly m 4 underwent DBPCFC. Outcome was defined according to presence and/or absence of ten objective signs and intensity of eight subjective symptoms as measured by visual analogue scale (VAS). RESULTS: 138 adult subjects (63.8% female, mean age 38 years) underwent DBPCFC. Challenge meals and defined evaluation criteria showed good applicability in all centres involved. 45.7% presented with objective signs and 65.2% with subjective symptoms at soy challenge. Placebo challenge meals elicited non-cardiovascular objective signs in 11.6%. In 82 (59.4%) subjects DBPCFC was judged as positive. 70.7% of DPBCFC+ showed objective signs and 85.4% subjective symptoms at soy challenge. Subjective symptoms to soy challenge meal in DBPCFC+ subjects started at significantly lower dose levels than objective signs (p < 0.001). Median cumulative eliciting doses for first objective signs in DBPCFC+ subjects were 4.7 g [0.7-24.7] and 0.7 g [0.2-4.7] total soy protein for first subjective symptoms (p = 0.01). CONCLUSIONS: We present the hitherto largest group of adults with Bet v 1 and Gly m 4 sensitization being investigated by DBPCFC. In this type of food allergy evaluation of DBPCFC outcome should not only include monitoring of objective signs but also scoring of subjective symptoms. Our data may contribute to standardize DBPCFC in pollen-related food allergy in multicentre settings. TRIAL REGISTRATION: EudraCT: 2009-011737-27.

[Specific immunotherapy]. / Spezifische Immuntherapie.

SCIT (subcutaneous immunotherapy) and SLIT (sublingual immunotherapy) are the only routinely available therapies, which modify allergic diseases sustainably. The ongoing reduction of symptoms and the lower need of symptomatic medication are able to improve the quality of life over a long period of time. However, allergic patients are underprovided due to low use of SIT (specific immunotherapy). After thorough diagnostic workup, the indication has to be checked carefully especially in patients with allergic rhinitis and allergic asthma, to insure that SIT is standard therapy. Allergen extracts are manufacturer-specific preparations, therefore their effects cannot be compared directly, just as SCIT and SLIT efficacy cannot be compared directly. In general, preparations with proven efficacy and safety profile should be preferred. Allergens listed in the TAV (Therapeutic Allergen Regulation) fulfill these requirements. However, it is important to ensure adherence for 3 years of therapy, independent of the route of application. SIT has proven socioeconomic benefit already after a short time of therapy.

[Allergic contact eczema]. / Allergisches Kontaktekzem.

Allergic contact eczema due to type IV reactions are more frequent than irritative eczema in facial skin, particularly in the sensitive periorbital region. Concomitant eczema of different locations is pathognomonic and allows a distinction from seborrhoic dermatitis. Avoidance of allergen exposure is mandatory for an effective treatment; therefore allergological examinations have a very high significance. Patch tests with a wide spectrum of potential allergens have to be included in these tests. Therapeutic regimes include a restrictive use of topical steroids. Substances like calcineurin inhibitors are the first-line therapy in facial atopic dermatitis, in spite of therapeutic effects, they have not yet been approved for other forms of periorbital dermatitis.

[Systemic therapy with anti-infective agents. Principles of rational use of systemic antibiotics in dermatology]. / Systemtherapie mit Antiinfektiva. Grundlagen zum rationalen Einsatz systemischer Antibiotika in der Dermatologie.

BACKGROUND: Antibiotics are frequently prescribed and extremely valuable drugs, because they are curative. However, their often incorrect use is the main reason for the increase of multiresistant pathogens. Inappropriate prescription of broad spectrum antibiotics for skin and soft tissue infections favors the selection and spread of multiresistant bacteria not only in the skin, but also in remote visceral organs (e.g. in the intestines), due to their systemic distribution and effects in the body (so-called collateral damage). For this reason basic knowledge and special prudence when using antibiotics are just as desirable as an awareness of responsibility for the public welfare. AIM: This article intends to convey basic knowledge on the indications and selection of suitable antibiotics as well as on the development of bacterial resistance and it gives recommendations for allergological procedures when patients report alleged drug reactions to antibiotics. RESULTS: Systemic antibiotics for soft tissue infections are indicated when the infection spreads within the tissue so that it is no longer accessible for local antiseptics. In addition to the clinical symptoms, important parameters are high blood sedimentation rates (BSR) and high levels of C-reactive protein (CRP), leukocytosis with neutrophilia and fever (not always present in elderly or immunosuppressed patients). Certain constellations, such as the presence of severe underlying diseases, perfusion disorders or a particular localization (e.g. infection of the face) may necessitate early or parenteral administration. There is no need for systemic administration of antibiotics for uncomplicated wounds without soft tissue infections. Due to their curative effects, the decisive criterion for the use of antibiotics is their sufficient antimicrobial efficacy at the site of infection. An inappropriate administration increases both the selection pressure and costs of treatment and can have fatal consequences in serious situations. In dermatological patients the beta-lactam antibiotics penicillin V, penicillin G and cephalosporins of groups 1 and 2 are the antibiotics most commonly indicated for skin and soft tissue infections. If the patient's history arouses the suspicion of incompatibility to these antibiotics, allergological diagnostics should be carried out in order to avoid as often as possible the alternative use of antibiotics which result in more undesired effects and development of resistance.

Cross-reactive carbohydrate determinants strongly affect the results of the basophil activation test in hymenoptera-venom allergy.

BACKGROUND: In hymenoptera-venom allergy, sera of up to 60% of patients show in vitro reactivity to honeybee venom (HBV) and yellow jacket venom (YJV). This phenomenon is mainly caused by specific IgE (sIgE) against cross-reactive carbohydrate determinants (CCD). Whether or not these antibodies can induce clinical symptoms is a longstanding debate. OBJECTIVE: The aim of this study was to investigate the biological activity of CCD-sIgE and the suitability of the basophil activation test (BAT) in hymenoptera venom-allergic patients having CCD-sIgE. METHODS: The biological activity of CCD-sIgE was analysed by application of native and CCD-depleted YJV and HBV in BAT with the blood of 62 hymenoptera venom-allergic patients and 16 non-allergic controls. According to results of intracutaneous skin tests (IC) with YJV and HBV and the existence of CCD-sIgE, patients were classified into six subgroups. RESULTS: In patients with mono-positive IC and CCD-sIgE, and thus double-positive sIgE, BAT with native venoms was also double positive in up to 67% of the patients. In contrast, BAT with CCD-depleted venoms was positive only with the IC-positive venom. However, activation of basophils with the IC-negative venom was significantly lower compared with the IC-positive one. In IC mono-positive patients without CCD-sIgE, BAT was mono-positive with the IC-positive venom in the native and in the CCD-depleted form. CCD-positive patients with double-positive IC were a heterogeneous group, with the majority of CCD-positive patients also being double positive with the native forms of both venoms but mono-positive with the CCD-depleted ones. CONCLUSIONS: In vitro BAT clearly demonstrates biological activity of CCD-sIgE. However, because most of the patients showed a mono-positive IC and activation of basophils with the IC-negative venom was significantly lower compared with the IC-positive one, the present data suggest that CCD-sIgE is clinically irrelevant in these patients.

Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus.

BACKGROUND: In 2005, a scoring system (CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index) was developed for patients with cutaneous lupus erythematosus (CLE) to assess disease 'activity' and 'damage'. However, the CLASI does not give an accurate assessment of the severity in all disease subtypes. OBJECTIVES: The main objective of this study was to analyse critically the included parameters of the CLASI and to revise the activity and damage score taking into account various clinical features of the different subtypes of CLE. The revised CLASI (RCLASI) was also validated for use in clinical trials. Patients and methods A RCLASI was designed with regard to the anatomical region (i.e. face, chest, arms) and morphological aspects (i.e. erythema, scaling/hyperkeratosis, oedema/infiltration, scarring/atrophy) of skin lesions and evaluated by nine dermatologists who scored 12 patients with different subtypes of CLE to estimate inter- and intrarater reliability. RESULTS: Reliability studies demonstrated an intraclass correlation coefficient (ICC) for an inter-rater reliability of 0.89 for the activity score [95% confidence interval (CI) 0.79-0.96] and of 0.79 for the damage score (95% CI 0.62-0.92). The ICC for intrarater reliability for the activity score was 0.92 (95% CI 0.89-0.95) and the ICC for the damage score was 0.95 (95% CI 0.92-0.98). CONCLUSIONS: In the present study, a RCLASI was developed by experts, and reliability studies supported the validity and applicability of the revised scoring instrument for CLE. Thus, the RCLASI is a valuable instrument in multicentre studies and for the clinical evaluation of activity and damage in different disease subtypes.

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study.

BACKGROUND: Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. METHODS: Patients (7.9-64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG(4) measured. RESULTS: Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8-92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG(4) observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. CONCLUSIONS: Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.

Incremental build-up food challenge--a new diagnostic approach to evaluate pseudoallergic reactions in chronic urticaria: a pilot study: stepwise food challenge in chronic urticaria.

BACKGROUND: The remission rate of patients with chronic urticaria (CU) due to elimination diets varies between 31% and 71%. However, the diagnostic value of subsequent traditional oral provocation tests with food additives in capsules remains unsatisfactory. OBJECTIVES: A newly incremental build-up food challenge (IBUF) for patients with CU was designed and implemented in an open pilot study. Primary endpoint was the percentage of patients developing urticaria during at least one step of IBUF after an initial complete remission due to a pseudoallergen-free elimination diet. METHODS: In total, 153 patients with CU were submitted for 5 weeks to a pseudoallergen-free diet. All patients with remission were included to the 6-week IBUF protocol, containing pseudoallergen-rich foods in a systematic and additive manner. The recurrence and severity of CU was evaluated by urticaria score. Subjective disturbance and quality of life were evaluated by patients' diary, visual analogue scale and quality of life questionnaire (CU-Q2oL). Subsequently, patients were followed up for 3-24 months after IBUF by a telephone interview. RESULTS: A total of 104 patients completed the pseudoallergen-free diet, whereby 51% reported partial, 17% complete and 32% no remission due to the diet. All diet responders showed a decrease in subjective impairment, urticaria and quality of life score (P<0.001 each). Eighty-six percent (12/14) of the patients reaching complete remission, showed a recurrence of urticaria symptoms during the IBUF protocol. Fifty-eight percent (7/12) of these patients still remained free of symptoms due to avoidance of IBUF-identified foods at telephone follow-up. In patients with partial remission to pseudoallergen-free diet, however, IBUF did not provide information about the cause of urticaria symptoms. CONCLUSIONS: The newly developed IBUF protocol seemed to be a promising method for identifying individually incompatible foods in some CU patients. IBUF should be verified by randomized controlled trials to gain additional evidence for its diagnostic value.

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study.

BACKGROUND: Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. METHODS: Patients (7.9-64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG(4) measured. RESULTS: Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8-92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG(4) observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. CONCLUSIONS: Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.

Mathematical modelling of epidemics under specific regard of adenoviral keratoconjunctivitis.

At first ADV is presented as a typical pandemic. The contagiosity of adenovirus is high because of the viability of the virus on inorganic surfaces in medical offices up to 35 days. Outbreaks and epidemics occur 3-30 days after infection, which is mainly contracted from medical facilities. EKC is considered a notifiable condition in most countries, and outbreaks, suspects and infections must be reported. Symptoms like "pink eye", foreign body sensations, photophobia, pain, signs such as follicles, hemorrhages and corneal infiltrates, and vision decrease associated with malaise are frequently observed first in one eye, later involving the fellow eye. Unilateral disease has a high rate of misdiagnosis. Currently no vaccine or virustatic is available, which is effective, cost-efficient and tolerable. Treatment is symptomatic and antiinflammatory. Late scarring may be amenable to phototherapeutic keratectomy. Infection control measures focus on the disinfection of equipment and hands of staff, the handling of infected patients with gloves, spatial separation of infected individuals resp. cohorting of infected patients, use of unit-dose eye solutions, and the chlorination of pools by approved and registered disinfectants and germicides. In connection with this it is shown how to handle the dynamics of infections by mathematical models like cellular automation, systems of differential equations and to visualize periodic effects by Fourier Analysis and to calculate costs by mathematical programming. Using mathematical analysis the percentage of a population needing vaccination to prevent spreading of pandemic can be calculated. It is shown here that especially the method of cellular automation is a simple way to simulate complex epidemiological situations without completely knowing the mathematical details.

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.

[In vitro testing for allergic contact dermatitis]. / In-vitro-Tests zum Nachweis von Kontaktallergien.

Patch testing is the standard method to identify allergic contact dermatitis. Simple, safe and accurate in vitro methods identifying contact allergies would offer both theoretical and practical advantages. Using the lymphocyte transformation test (LTT), allergen-specific lymphocytes central to the pathogenesis of Type IV allergies can be identified. Various studies have assessed the value of LTT in the diagnosis of contact allergies. The current assessment is that the test can be helpful in distinguishing between irritant and allergic reactions. LTT is especially useful in demonstrating drug allergies and can also be employed to prove sensitization to gases or toxic substances. At the present time, it is not an alternative for patch testing in daily practice.