Eosinophilic folliculitis in a Caucasian patient: association with toxocariasis?

Sterile eosinophilic folliculitis, a clinical entity first described by Ofuji in 1970, is a rather rare skin disorder, in particular in the non-Asian population. We report the first case of eosinophilic folliculitis associated with toxocariasis in a Caucasian patient. Topical and systemic anti-inflammatory and antiphlogistic therapy along with systemic antihelminthic treatment resulted in complete remission of the skin lesions. In addition, there was a marked decrease of antibodies to Toxocara antigens in the patient's serum following antihelminthic therapy. Given that (I) some cases of eosinophilic folliculitis have been reported which were associated with infestation with metazoan parasites; (2) infestations with the roundworm Toxocara canis are known to induce eosinophilic reactions in some tissues; and (3) therapy-induced remission of eosinophilic folliculitis was accompanied by a decrease of Toxocara-directed antibodies in the patient's serum, we propose that there is an aetiopathogenic link between toxocariasis and eosinophilic folliculitis in this patient.

Upon prolonged allergen exposure IL-4 and IL-4Ralpha knockout mice produce specific IgE leading to anaphylaxis.

BACKGROUND: IL-4 and IL-13 are key regulators in atopic disorders and both signal through the receptor chain IL-4Ralpha. IL-4 and IL-13 are also the only cytokines known to induce class switching to IgE. We sought to compare allergen-specific IgE responses and allergic reactivity of wild-type (wt) mice with IL-4-/- and IL-4Ralpha-/- mice, which lack both IL-4 and IL-13 functions. METHODS: BALB/c wt, IL-4-/- and IL-4Ralpha-/- mice were immunized with ovalbumin intranasally or intraperitoneally and specific antibody titers were measured by ELISA. Bronchoalveolar lavage fluids and lung tissue were analyzed cytologically and histologically. Allergic reactivity was determined by active cutaneous anaphylaxis and anaphylactic shock. RESULTS: wt mice immunized intranasally or intraperitoneally showed high titers of specific IgE 3 and 6 weeks after primary sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon challenge. Intranasal sensitization resulted in airway eosinophilia and goblet cell metaplasia. In contrast, IL-4-/- and IL-4Ralpha-/- mice showed no specific IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous anaphylaxis and anaphylactic shock could be induced as in wt mice, but lung pathology was absent. CONCLUSIONS: We conclude that upon long-term allergen exposure, alternative switch mechanisms independent of IL-4 and IL-4Ralpha may induce IgE but not asthma-like lung pathology. This may be relevant for the development of allergic disease, since long-term allergen exposure is a frequent condition during allergic sensitization.

The impact of the route and frequency of antigen exposure on the IgE response in allergy.

BACKGROUND: Knowledge of the factors which control IgE production is essential in order to understand the pathogenesis of immediate hypersensitivity reactions. We have studied the extent to which the route and frequency of antigen application as well as different antigen amounts may influence IgE synthesis. METHODS: We established sensitisation protocols in BALB/c mice, in which various doses of ovalbumin (Ova) were applied via intranasal, epicutaneous or intraperitoneal routes. Ova-specific antibodies were measured by ELISA. After 6 weeks of sensitisation, anaphylactic shock was measured following intravenous challenge with Ova. In addition, bronchoalveolar lavages were performed in intranasally sensitised mice. RESULTS: We were able to show that the most efficient IgE production was achieved by long-term antigen application via the airways, leading to local allergic airway pathology. The epicutaneous route of antigen application also induced very high IgE titres, while intraperitoneal sensitisation led to significantly lower IgE levels. After intraperitoneal sensitisation, IgE synthesis was best induced by increasing the frequency of antigen application, but not by increasing the amount of antigen. In all groups of mice, Ova-specific IgE antibodies were high enough to induce systemic allergic symptoms leading to anaphylactic shock. The severity of shock correlated with the amount of specific IgE. CONCLUSIONS: Taken together, our results demonstrate that antigen application via the airways or skin induces IgE synthesis more efficiently than via the intraperitoneal route. Few exposures with high-dose antigen are less efficient than multiple exposures with low doses. Our finding that both the route and the frequency of antigen application strongly influence IgE synthesis may help to understand how environmental antigens lead to allergic sensitisation.

An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo.

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.

Mouse macrophage development in the absence of the common gamma chain: defining receptor complexes responsible for IL-4 and IL-13 signaling.

The common gamma chain (gamma c) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed gamma c-deficient mice to define a role for gamma c signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of gamma c- compared to gamma c+ macrophages were observed. We therefore conclude that signaling through the gamma c chain is not essential for the differentiation of mouse macrophages. Although B and T cells require gamma c for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from gamma c- macrophages following stimulation with lipopolysaccharide and interferon-gamma. gamma c- macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor alpha/IL-13R which can function in the absence of gamma c. Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist OY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.

[Reference values in vision development of infants with clinical use of the Teller Acuity Cards]. / Ausgangswerte zur Visusentwicklung von Säuglingen bei klinischer Anwendung der Teller-Acuity-Cards.

BACKGROUND: Using Teller Acuity Cards (TAC) for clinical visual testing, the question arose how our measurements fitted in the different standard tables of the producer's hand-book. In addition, we wanted to investigate how reliable the measurements of newborn and infants were and what the examination success rate under clinical conditions was. METHODS: At the paediatric clinic of the University of Erlangen, we tested the binocular grating acuity of 98 infants up to the age of one year, using the complete set of Teller acuity cards. In addition, 41 of the children underwent a monocular vision test. RESULTS: 1. Theoretical: At first we calculated conversion data for our card set. Using this conversion scale from cy/cm in cy/deg and the corresponding vision equivalent we produced our own standards for the development of grating acuity up to the age of one year. 2. Clinical: In 3-5 min per clinical examination we could determine for 90.8% of the patients a vision equivalent. The reliability of the results was age dependent and was at its best at the age of 5-11 months. The reliability was also very dependent on the duration of the test and the number of test runs. This resulted in a limited card choice for each age group.

A murine interleukin-4 antagonistic mutant protein completely inhibits interleukin-4-induced cell proliferation, differentiation, and signal transduction.

We characterize here a highly efficient antagonist for interleukin-4 (IL-4) in the mouse system. In this double mutant of the murine IL-4 protein, both glutamine 116 and tyrosine 119 were substituted by aspartic acid residues. This variant (QY) bound with similar affinity to the IL-4 receptor alpha subunit as wild type IL-4 without inducing cellular responses. In contrast, QY completely inhibited in a dose-dependent manner the IL-4-induced proliferation of lipopolysaccharide-stimulated murine splenic B-cells, of the murine T cell line CTLL-2, and of the murine pre-B-cell line BA/F3. QY also inhibited the IL-4-stimulated up-regulation of CD23 expression by lipopolysaccharide-stimulated murine splenic B-cells and abolished tyrosine phosphorylation of the transcription factor Stat6 and the tyrosine kinase Jak3 in IL-4-stimulated BA/F3 cells. Selective inhibition of IL-4 may be beneficial in T-helper cell type 2-dominated diseases, like type I hypersensitivity reactions or helminthic infections. The QY mutant could be an attractive tool to study in vivo the therapeutic potential of IL-4 antagonists in mouse systems.