Johannes Huss-Marp

Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy

BACKGROUND Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by persistent blood eosinophilia > or =1.5 x 10(9)/L, absence of a secondary cause, and evidence of eosinophil-associated pathology. With the exception of a recent multicenter trial of mepolizumab (anti-IL-5 mAb), published therapeutic experience has been restricted to case reports and small case series. OBJECTIVE The purpose of the study was to collect and summarize baseline demographic, clinical, and laboratory characteristics in a large, diverse cohort of patients with HES and to review responses to treatment with conventional and novel therapies. METHODS Clinical and laboratory data from 188 patients with HES, seen between January 2001 and December 2006 at 11 institutions in the United States and Europe, were collected retrospectively by chart review. RESULTS Eighteen of 161 patients (11%) tested were Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) mutation-positive, and 29 of 168 patients tested (17%) had a demonstrable aberrant or clonal T-cell population. Corticosteroid monotherapy induced complete or partial responses at 1 month in 85% (120/141) of patients with most remaining on maintenance doses (median, 10 mg prednisone equivalent daily for 2 months to 20 years). Hydroxyurea and IFN-alpha (used in 64 and 46 patients, respectively) were also effective, but their use was limited by toxicity. Imatinib (used in 68 patients) was more effective in patients with the FIP1L1-PDGFRA mutation (88%) than in those without (23%; P < .001). CONCLUSION This study, the largest clinical analysis of patients with HES to date, not only provides useful information for clinicians but also should stimulate prospective trials to optimize treatment of HES.

Secretion of proinflammatory eicosanoid-like substances precedes allergen release from pollen grains in the initiation of allergic sensitization.

It is commonly believed that allergic sensitization starts when an allergen contacts the surface of an antigen-presenting cell in mucosal or skin epithelia. Most studies dealing with this aspect use allergen extracts as stimulus. Under natural exposure conditions, however, the bioavailability of allergen depends on allergen liberation from internal binding sites within the allergen carrier, e.g. pollen grains. In comparing total protein and major allergen release from timothy grass (Phleum pratense L.) pollen freshly collected on rural meadows or near high-traffic roads, there was a striking difference between the pollen, with higher allergen release rates from rural meadow pollen grains. Thus, allergen release does not explain the higher prevalence rates of atopic sensitization and disease observed in many epidemiological studies in children exposed to automobile exhaust. Therefore, other possible effectors from pollen grains were investigated. Pollen grains incubated in protein- free buffer were found to secrete significant amounts of eicosanoid-like substances, namely leukotriene (LT) B4-like and prostaglandin E2-like substances, in a pH-, time- and temperature-dependent fashion. The highest values of eicosanoid secretion were found in birch, grass and mugwort pollen, while pine (Pinus sylvestris L.) pollen showed only marginal eicosanoid-like secretion. Additionally, the release of these substances was significantly higher from pollen which had been collected near roads with heavy traffic, indicating a stronger proinflammatory activity of these pollen grains. In order to investigate the effects of air pollutants, native pollen grains were exposed in a dose- and time-dependent fashion in a fluidized bed reactor to traffic-related pollutants, e.g. volatile organic compounds (toluene, m-xylene), leading again to a significant increase in the secretion of LTB4-like immunoreactivity, in contrast to exposure with sulfur dioxide. This finding opens a new dimension of understanding of the early events in allergic sensitization, indicating that proinflammatory effects of the allergen carrier, e.g. the pollen grain itself, can lead to activation of the mucosal membrane. These findings might help to also explain the higher prevalence rates of pollen allergy in areas with high automobile exhaust emissions. Furthermore, the allergenic ‘potency’ of various allergens has to be redefined at the allergen carrier level with regard to different stages of allergen and mediator release prior to the contact with the host’s immune system.

Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema – a blinded, randomized, placebo‐controlled, crossover trial

To cite this article: Pfab F, Huss‐Marp J, Gatti A, Fuqin J, Athanasiadis GI, Irnich D, Raap U, Schober W, Behrendt H, Ring J, Darsow U. Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema – a blinded, randomized, placebo‐controlled, crossover trial. Allergy 2010; 65: 903–910.

Influence of short-term exposure to airborne Der p 1 and volatile organic compounds on skin barrier function and dermal blood flow in patients with atopic eczema and healthy individuals.

Background Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available.

Year-to-Year Variation in Release of Bet v 1 Allergen from Birch Pollen: Evidence for Geographical Differences between West and South Germany

Background: The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. Objective: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. Methods: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. Results: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). Conclusions: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably.

Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis – a patient‐ and examiner‐blinded, randomized, placebo‐controlled, crossover trial

Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner‐blinded, randomized, placebo‐controlled, crossover trial.

The course of eczema in children aged 5–7 years and its relation to atopy: differences between boys and girls

Background  The role of atopy in the pathophysiology of eczema is still under debate. The concept and analyses of the nonatopic and atopic subtypes of eczema have gained increasing interest in recent studies. The course of these subtypes and differences between boys and girls have not been investigated so far.

Temperature modulated histamine-itch in lesional and nonlesional skin in atopic eczema - a combined psychophysical and neuroimaging study

Background: Itch is the major symptom of many allergic diseases; yet it is still difficult to measure objectively. The aim of this study was to use an evaluated itch stimulus model in lesional (LS) and nonlesional (NLS) atopic eczema (AE) skin and to characterize cerebral responses using functional magnetic resonance imaging (fMRI).

Effect of Acupuncture on Allergen-Induced Basophil Activation in Patients with Atopic Eczema:A Pilot Trial

OBJECTIVE AND METHODS The crucial symptom of atopic eczema is itch. Acupuncture has been shown to exhibit a significant effect on experimental itch; however, studies focusing on clinical itch in atopic eczema and corresponding mechanisms are lacking. The study design was a unicenter, single-blinded (observer), prospective, randomized clinical pilot trial with an additional experimental part. In 10 patients with atopic eczema, we investigated the effect of acupuncture treatment (n = 5) compared to no treatment (n = 5) on itch intensity and in vitro basophil CD63 expression upon allergen stimulation (house dust mite and timothy grass pollen) in a pilot trial. RESULTS Mean itch intensity in a visual analog scale was rated significantly lower in the acupuncture group (-25% ± 26% [day 15-day 0]; -24% ± 31% [day 33-day 0]) than in the control group (15% ± 6% [day 15-day 0]; 29% ± 9% [day 33-day 0]). From day 0 (before treatment) to day 15 (after 5 acupuncture treatments) as well as day 33 (after 10 acupuncture treatments), the acupuncture group showed less CD63 positive basophils than the control group regarding stimulation with house dust mite and grass pollen allergen at various concentrations (5 ng/mL, 1 ng/mL, 0.5 ng/mL, or 0.25 ng/mL). CONCLUSIONS Our results show a reduction of itch intensity and of in vitro allergen-induced basophil activation in patients with atopic eczema after acupuncture treatment. Reducing basophil activation can be a further tool in investigating the mechanisms of action of acupuncture in immunoglobulin E-mediated allergy. Due to the limited number of patients included in our pilot trial, further studies are needed to strengthen the hypothesis.

Pollen grains induce a rapid and biphasic eczematous immune response in atopic eczema patients

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6–96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-γ in the late phase. The NPT was continuously dominated by IFN-γ. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase.