Birch pollen-related foods can cause late eczematous reactions in patients with atopic dermatitis.

BACKGROUND: Previous studies have indicated that in patients with atopic dermatitis (AD) and birch pollen allergy pollen-related foods are able to cause late eczematous response. However, the relevance of AD worsening by ingestion of birch pollen-related foods is still a matter of debate. OBJECTIVE: The purpose of this retrospective study was to determine how frequently birch pollen-related foods induce a deterioration of eczema. Additionally, the diagnostic value of specific IgE (sIgE) determination was evaluated. METHODS: A total of 182 children and adults with AD and suspected birch pollen-related food allergy underwent 261 double-blind placebo-controlled food challenges (DBPCFC). Total and sIgE levels were determined prior to DBPCFC. RESULTS: Sixty-five patients developed allergic reactions (responders) upon DBPCFC with birch pollen-related foods (n = 103 DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined as a median increase of 15.4 severity scoring of atopic dermatitis index points (95% CI 12.4-16.3) from baseline making up 37% of all positive reactions. Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to nonresponders (P < .05). However, patients with late eczematous response could not be differentiated from those with isolated immediate-type reactions by sIgE levels. CONCLUSION: In a subpopulation of patients with AD and birch pollen sensitization, related foods should be considered as a trigger for an aggravation of eczema. As sufficient markers for prediction of late eczematous reactions are still lacking, DBPCFC cannot be replaced in diagnosis of birch pollen-related foods in patients with AD. CLINICAL IMPLICATIONS: In patients with AD and birch pollen allergy, birch pollen-related foods should be considered as a provocation factor for an aggravation of disease signs and symptoms.

In-vitro diagnostic in atopic dermatitis: Options and limitations.

Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis and different exogenous and endogenous trigger factors. One important factor is the sensitization to inhalant and/or food allergens. The detection of total IgE and specific IgE antibodies to inhalant and/or food allergens is one central aspect in diagnosing atopic dermatitis, especially if skin prick tests are not feasible. Many patients are polysensitized, but not all sensitizations are of clinical relevance. The challenge is to identify the sensitizations with clinical relevance and to initiate suitable therapeutic options. In this article we go into detail for the allergens house dust mite, pollen, food, and Malassezia sympodialis. Furthermore, the authors comment on the impact of the detection of specific IgG/IgG4 antibodies in the diagnosis of food allergy in atopic dermatitis. Moreover, new options in the in-vitro diagnostic will be explained briefly and their actual diagnostic significance in patients with atopic dermatitis will be highlighted. These options are the detection of specific IgE antibodies to recombinant allergens and the allergen chip.

[Dermatomycoses due to pets and farm animals : neglected infections?]. / Dermatomykosen durch Haus- und Nutztiere : Vernachlässigte Infektionen?

Dermatomycoses due to contact with pets and livestock frequently affect children and young adults. Zoophilic dermatophytes are the main important causative agents. It has long been known that the often high inflammatory dermatophytoses of the skin and the scalp are caused mostly by Microsporum canis. Due to an absence of an obligation for reporting fungal infections of the skin to the Public Health Office in Germany, an unnoticed but significant change in responsible pathogens has occurred. Today an increasing number of infections due to zoophilic strains of Trichophyton interdigitale (formerly Trichophyton mentagrophytes) and Trichophyton species of Arthroderma benhamiae are found. The latter mentioned dermatophyte is the anamorph species of the teleomorph Arthroderma benhamiae, which originally was isolated in the Far East (Japan). Source of infection of these dermatophytes are small rodents, in particular guinea pigs. These animals are bought in pet shops by the parents of those children who later are affected by the fungal infection. The coincidental purchase of the relevant fungal pathogen is not obvious to the parents. As a consequence, highly contagious dermatophytoses occur, often tinea capitis sometimes with kerion formation. Further dermatophytes should be considered as cause of a zoophilic dermatomycosis. Both Trichophyton verrucosum, the cause of the ringworm in cattle, and Trichophyton erinacei following contact to hedgehogs are worthy of note. Yeasts cannot be ignored as cause of dermatomycosis, especially Malassezia pachydermatis, the only non-lipophilic species within the genus Malassezia, which can be transferred from dog to men. Cryptococcus neoformans also comes from animal sources. The mucous yeast occurs in bird's dropping, and it causes both pulmonary and central nervous system infections, but also primary and secondary cutaneous cryptococcosis in immunocompromised patients (HIV/AIDS) as possible consequence after contact to these animals.

[Food allergy in atopic dermatitis]. / Nahrungsmittelallergie bei atopischer Dermatitis.

Food allergy predominantly affects children rather than adult patients with atopic dermatitis (AD). Early sensitization to foods has been found to be significantly associated with AD. Three different patterns of clinical reactions to food allergens in AD patients exist: i. immediate-type reaction, ii. isolated late-type reaction, iii. combined reaction (i. + ii.). While in children allergens from cow's milk, hen's egg, soy, wheat, fish, peanut or tree nuts are mostly responsible for allergic reactions, birch-pollen related food allergens seem to play a major role in adolescent and adults with AD in Central and Northern Europe. Defects of the epidermal barrier function seem to facilitate the development of sensitization to allergens following epicutaneous exposure. The relevance of defects of the gut barrier as well as genetic characteristics associated with an increased risk for food allergy remain to be further investigated. Numerous studies focus on prevention strategies which include breast-feeding or feeding with hydrolyzed milk substitute formula during the first 4 months of life.

The role of T-cell reactivity towards the autoantigen α-NAC in atopic dermatitis.

BACKGROUND: A subgroup of patients with atopic dermatitis (AD) produces IgE autoantibodies to human proteins which may be present in inflamed skin and perpetuate cutaneous inflammation. OBJECTIVES: In order to investigate mechanisms of 'autoallergy' for AD we studied T-cell responses to the autoallergen Hom s 2, the human transcriptional coactivator α-nascent polypeptide-associated complex (α-NAC). METHODS: Specific proliferation of blood lymphocytes from 30 patients and 12 healthy control individuals was investigated by flow cytometry. The proliferation of skin- and blood-derived T cells was assessed in limiting-dilution assays. T-cell clones (TCC) were generated from peripheral blood and from biopsies of lesional skin of patients with AD and the phenotype and cytokine patterns were determined. RESULTS: α-NAC-specific T-cell responses were detected in patients and control individuals. α-NAC induced a significantly higher proliferation of CCR4+ (compared with CCR4-) and CLA+ (compared with CLA-) T cells from the circulation. Limiting-dilution assays revealed a high proliferation of blood and skin-infiltrating lymphocytes in the presence of α-NAC compared with control cultures. α-NAC-specific TCC generated from lesional skin of AD predominantly produced interferon-γ and some TCC also produced interleukin-17. The cytokine pattern of α-NAC TCC may contribute to keratinocyte apoptosis and eczema formation in AD. CONCLUSIONS: α-NAC-specific TCC can be generated from blood and lesional skin of patients with AD. These TCC produce not only Th2 but also Th1 cytokines which may explain the Th1 phenotype of inflammation in AD.

[Successful symptomatic treatment of epidermodysplasia verruciformis with imiquimod 5% cream]. / Erfolgreiche symptomatische Therapie einer Epidermodysplasia verruciformis mit Imiquimod 5% Creme.

A 19-year-old patient presented with epidermodysplasia verruciformis (EV). In this genodermatosis, pathogenetic factors such as infection by human papilloma viruses as well as sun exposure are considered responsible for the malignant transformation of EV lesions to skin cancer within decades. So far, several therapeutic strategies have been unsatisfactory. In our case HPV 5b was detected and the associated skin lesions were successfully treated with imiquimod 5% cream.

Isolation of alpha-toxin-producing Staphylococcus aureus from the skin of highly sensitized adult patients with severe atopic dermatitis.

BACKGROUND: Staphylococcus aureus (S. aureus) is a well-known trigger factor of atopic dermatitis (AD). Besides staphylococcal superantigens, alpha-toxin may influence cutaneous inflammation via induction of T-cell proliferation and cytokine secretion. OBJECTIVES: To investigate the association between sensitization to inhalant allergens and skin colonization with alpha-toxin-producing S. aureus in AD. PATIENTS AND METHODS: We investigated 127 patients with AD, aged 14-65 years, who were on standard anti-inflammatory and antiseptic treatment before investigation. We evaluated skin colonization, medical history, severity of AD and sensitization to inhalant allergens. RESULTS: Forty-eight of 127 patients were colonized with S. aureus, suffered from more severe AD, had asthma more often and showed higher sensitization levels to inhalant allergens. Thirty of 48 patients with S. aureus skin-colonizing strains produced alpha-toxin and had higher total IgE and specific IgE to birch pollen and timothy grass pollen. CONCLUSIONS: Under topical treatment with antiseptic and anti-inflammatory agents the colonization of lesional skin with S. aureus was clearly lower than commonly found in untreated patients with AD. Colonization with S. aureus was associated with a higher severity of AD, higher degree of sensitization, and a higher frequency of asthma. The proportion of patients whose skin was colonized with alpha-toxin-producing S. aureus was higher than expected from a former study. Cutaneous colonization with alpha-toxin-producing S. aureus was associated with a higher sensitization level to birch pollen allergen in AD. This may point to a higher susceptibility of patients with higher T-helper 2 polarization towards alpha-toxin-producing S. aureus.

European developments in standardisation of sludge physical parameters.

Characterisation is an important step in sludge management as it allows sludge properties to be evaluated and behaviour predicted. This is well recognised by the European Union (EU) countries which consider necessary the development of standardised sludge characterisation methods and procedures because objective and transparent regulations allow sludge management to be properly performed, legal requirements correctly fulfilled, and public confidence built. To this end, the European Committee for Standardization (CEN) established the Technical Committee 308 (TC308) whose scope is the production of Standards for sludge characterisation, and of Guides of good practice. In this field, physical properties are of great importance as they allow the prediction of sludge behaviour when handled and submitted to almost all treatment and utilisation/disposal operations. Activity of CEN/TC308 is developed in three Working Groups (WG) and several Task Groups (TG); in particular, TG3 of WG1 deals with physical parameters. In this paper developments regarding Standards for evaluation of capillary suction time, specific resistance to filtration, compressibility, settleability, thickenability, and calorific value, and Technical Reports dealing with a procedure for laboratory chemical conditioning and with sludge consistency (flowability/solidity) are briefly outlined. The results of relevant inter-laboratory tests for the validation of above standards are summarised.

Sludge characterization: the rôle of physical consistency.

The physical consistency is an important parameter in sewage sludge characterization as it strongly affects almost all treatment, utilization and disposal operations. In addition, in many European Directives a reference to the physical consistency is reported as a characteristic to be evaluated for fulfilling the regulations' requirements. Further, in many analytical methods for sludge, different procedures are indicated depending on whether a sample is liquid or not, is solid or not. Three physical behaviours (liquid, paste-like and solid) can be observed with sludges, so the development of analytical procedures to define the boundary limit between liquid and paste-like behaviours (flowability) and that between solid and paste-like ones (solidity) is of growing interest. Several devices can be used for evaluating the flowability and solidity properties, but often they are costly and difficult to be operated in the field. Tests have been carried out to evaluate the possibility to adopt a simple extrusion procedure for flowability measurements, and a Vicat needle for solidity ones.

Studies on structure-activity relationship of gossypol, gossypol ethers and three naphthaldehydes in the inhibition of spermatozoal metabolism.

Gossypol tetramethyl ether [C30 H24 O2(OCH3)4] and gossypol hexamethyl ether [C30 H24 O2(OCH3)6], which in contrast to gossypol are stable compounds, were tested for their ability to depress fructose degradation in fresh human sperm cells. Both ethers inhibited spermatozoal fructolysis, yet less effectively than did the parent compound. A synthetic compound, O-hydroxylnaphthaldehyde, and two commercially available preparations, 1- and 2-naphthaldehydes, were also tested under the same experimental conditions. These preparations represent about half of the gossypol molecule and possess a reactive aldehyde group in their molecules. Their inhibitory effect on fructose degradation in fresh human sperm cells, however, was considerably smaller than that of gossypol itself. It thus appears that the whole ring structure of gossypol rather than the intact aldehyde group is required for an effective inhibition of spermatozoal energy metabolism.

Effect of gossypol on the motility and metabolism of human spermatozoa.

Gossypol, a polycyclic compound isolated from cotton seeds, had a dose-dependent inhibitory effect on human sperm motility. The drug also inhibited powerfully fructolysis and glycolysis by human spermatozoa. Both lactate and CO2 formation from the 14C-labelled sugars was inhibited, and the prevention of CO2 formation from [1-14C]pyruvate and [2-14C]pyruvate by gossypol indicated a direct effect on the tricarboxylic acid cycle. Repeated washing of the sperm cells after gossypol pretreatment failed to abolish the inhibitory effect on CO2 production. The profound disturbances of the sperm energy metabolism induced by gossypol were also reflected by a striking fall of the sperm ATP content. Gossypol had little effect on glucose utilization by minces of human vaginal mucosa, indicating the specificity of gossypol.

Vaginal contraception with gossypol: a clinical study.

A clinical study concerning the vaginal contraceptive efficacy of gossypol acetic acid was performed. Fifteen women who had undergone tubal sterilization volunteered for the study. The effect of vaginal gossypol-containing gel on spermatozoa was determined by postcoital tests performed in subjects without and after using gossypol gel. After gossypol application, the number of spermatozoa found in cervical mucus was greatly decreased and, in eleven of the fifteen women, all spermatozoa seen were immobilized. In four cases a few poorly motile spermatozoa were seen but they showed no forward progression. We have previously reported that gossypol has an inhibitory effect on herpes simplex virus type 2 in vitro. This anti-viral property of gossypol makes it particularly attractive as a topical barrier contraceptive. The present study shows that gossypol is also promising as a vaginal contraceptive agent in human in vivo experiments.

PIP: 15 women who had undergone tubal sterilization participated in a study of the vaginal contraceptive efficacy of a gel containing gossypol acetic acid. The women were aged 35 on average and had 2-3 children each. Postcoital tests (PCT) were performed 2 weeks before expected menstruation, 1 test after gossypol application, and another after a control application of the vehicle gel without gossypol in the following cycle. The gel was applied about 1 hour before coitus and the PCT was performed about 8 hours later. Gossypol treatment greatly decreased the number of spermatozoa seen in cervical mucus in 13 of 15 test subjects, and all spermatozoa seen were immobilized in 11 of the 15. Poor motility with no forward progress was seen in the other 4 test cases. In control PCTs, 11 of the 15 showed 20 or more spermatozoa per visual field with motility between 20-70%. In 3 of the control PCTs, only 2-15 spermatozoa were seen but the motility was good. The PCTs performed after application of the vehicle gel alone showed 5-30 spermatozoa per visual field and good motility indicating that gel alone had no spermicidal effect. Gossypol gel was well accepted. An in vitro test of the effect of gossypol gel on spermatozoa in cervical mucus demonstrated gradual immobilization within 3-5 minutes. In addition to its antifertility effect, gossypol has antiviral and antigonococcal properties.

Inhibiting herpes simplex virus type 2 infection in human epithelial cells by gossypol, a potent spermicidal and contraceptive agent.

PIP: Gossypol, a male contraceptive, has an antifertility effect of 99.9%. It has also been reported to possess antiviral activities, and to inhibit herpes simplex virus infection in mice. Dorsett and Kerstine found that gossypol inactivated the infectivity of the enveloped virus parainfluenza type 3 and herpes simplex for HEp-2 carcinoma cells but had no effect on the infectivity of the nonenveloped poliovirus. The authors studied the effect of gossypol on infection by herpes simplex virus type 2 (HSV-2), the causative agent of herpes genitalis. In a series of experiments, gossypol and HSV-2 were added sequentially to confluent cultures of human amniotic epithelial cells and observed daily for cytopathic changes. No cytotoxicity was observed. Gossypol exerted a pronounced antiviral effect at 100 mcM; it totally inhibited the infection by 104 plaque-forming units (PFU); 10 mcM inhibited 100 PFU, and even 3 mcM caused some inhibition of HSV. Gossypol's antiviral effect is dose-dependent. The results clearly demonstrate the inhibitory effect of gossypol on HSV-2 infection; the doses used are comparable to or lower than the minimum effective antispermatozoal concentration of gossypol. Studies have reported the lack of toxicity of gossypol on normal cells and tissues, and its inhibiting effect on the growth of gonococci. Further studies should determine whether the antimicrobial effects of gossypol should be considered a favorable side effect in its use as a contraceptive, or whether gossypol has a value as an antiviral agent alone.^ieng

Gossypol, a powerful inhibitor of human spermatozoal metabolism.

PIP: Chinese scientists have reported that Gossypol, a pigment from the cotton plant, exerts a remarkable sperm immobilizing effect in males; clinical trials on more than 4000 healthy men have shown an antifertility effect of 99.9%. Sperm cells were also immobilized in human cervical mucus containing small doses of Gossypol, thus showing that the compound could be used as a topical preparation for women.^ieng