[The fate of 20 sea breams. Mycobacterium marinum infection]. / Das Schicksal von 20 Brassen. Mycobacterium-marinum-Infektion.

Cutaneous infections with Mycobacterium marinum are rare. They also are known as swimming pool or fish tank granulomas. Often the history of contact with contaminated water associated with microtrauma of the upper extremities leads to the correct diagnosis. Since chlorination of swimming pools has become standard, cases of swimming pool granuloma have become rare. Contact with fish tanks now is the most common route of infection. Positive culture of skin biopsy leads to the correct diagnosis. Moxifloxacin in combination with other antibiotics is often effective.

Differential up-regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects.

BACKGROUND: Recent studies suggest that neurotrophins have a pivotal role in neuroimmune interactions. Indeed, in contrast to nonatopic subjects (NA), neurotrophins have been shown to be increased in atopic diseases such as allergic rhinitis (AR) and atopic dermatitis (AD). AIM: The aim of the study was to assess the functional role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and -4 and the expression of pan-neurotrophin receptor (p75(NTR)) and tyrosine kinase (trk)A, -B and -C on peripheral blood eosinophils in AR, AD and NA. METHODS: Peripheral blood eosinophils of patients with AR, AD and NA were purified by CD16 negative selection (purity>98%). Neurotrophin receptor expression was analysed by FACS analysis. Apoptosis test (FACS analysis) and chemotactic index (modified Boyden chamber assay) were assessed after stimulation with BDNF, NT-3/-4 and NGF. RESULTS: The expression of trkA-C and p75(NTR) was significantly higher in AD>AR>NA (P<0.05-0.001). Apoptosis was significantly inhibited by BDNF, NGF, NT-3 in AD (P<0.05-0.001), by NT-3/-4 and NGF in AR (P<0.05-0.01) and by NT-3 (P<0.05-0.01) in NA eosinophils. Chemotaxis was significantly induced by BDNF and NT-3/4 (P<0.01-0.001) in AD peripheral blood eosinophils. CONCLUSION: Neurotrophin receptor expression and neurotrophin functional activity was greatest in AD>AR>NA. AD eosinophils are pre-activated and may therefore better respond to neurotrophins. With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR.

Exotic food allergy: anaphylactic reaction to lychee.

There are very few reports on allergic reactions to lychee fruit in the literature. We describe the case of a 26-year-old man who developed pruritus, generalized urticaria, and severe angioedema of his lips and tongue with dyspnea within 15 minutes after lychee fruit intake. Although we found no lychee-specific immunoglobulin E antibodies, a basophil activation test (BAT) and a cellular antigen stimulation test (CAST) to lychee were both positive, as was a prick-to-prick test with fresh lychee fruit. The patient also suffered from an oral food allergy syndrome to parsley and was sensitized to mugwort but not to latex or profilin. BAT and CAST are helpful tools in the diagnostic workup for exotic food allergy. Mugwort is suggested as the allergen responsible for,the cross-reactivity presented by this patient, as he had no sensitization to latex or profilin.

[Hexadactyly of hand and feet in a patient with basal cell nevus syndrome]. / Hexadaktylie an Hand und Fuss bei einem Patienten mit Basalzellnävussyndrom.

A 35-year-old male patient with hexadactyly on the right hand and both feet presented with multiple basal cell carcinomas of the skin. The results of further investigations led to the diagnosis of basal cell nevus syndrome (BCNS). The basal cell nevus syndrome (Gorlin-Goltz syndrome) characterized by multiple basal cell carcinomas, odontogenic cysts, skeletal abnormalities and associated neoplasms belongs to the group of genodermatoses. Reviewing the current literature we discuss aspects of the pathogenesis of the basal cell nevus syndrome as well as diagnosis criteria and treatment options.

Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs.

BACKGROUND: A role of potential histamine-releasing autoantibodies against the high-affinity IgE receptor on the surface of basophils and mast cells is discussed in the pathogenesis of chronic urticaria. This so-called autoimmune urticaria may be diagnosed by a positive intracutaneous autologous serum skin test, which is found in about 30% of patients with chronic urticaria. OBJECTIVE: Our purpose was, first, to compare the effect of complement-inactivated sera of 20 patients with chronic urticaria and positive autologous serum skin tests, 20 patients with chronic urticaria and negative skin tests, and 20 control subjects without chronic urticaria (10 atopic and 10 nonatopic subjects) and, second, to analyze the effect of anti-inflammatory drugs on the serum activity. METHODS: The following assay systems were used: release of histamine in whole blood samples, surface expression of the activation marker CD63 on basophils, and sulfidoleukotriene de novo production in leukocyte suspensions. Whole blood, basophils, and leukocyte suspensions were obtained from a nonatopic and an atopic donor. RESULTS: Sera of patients with autologous serum skin test positive chronic urticaria resulted not only in significantly increased histamine release compared with skin test-negative chronic urticaria sera but also in a significant higher induction of basophil CD63 surface expression and sulfidoleukotriene de novo production. However, serum activity was neither characteristic for chronic urticaria nor for chronic urticaria with a positive autologous serum skin test. Preincubation with dapsone, chloroquine, and lidocaine dose dependently resulted in a significant reduction of all histamine release, CD63 expression, and sulfidoleukotriene production. In addition, mizolastine was able to inhibit serum-induced sulfidoleukotriene production. CONCLUSION: Further studies investigating the in vivo effect of these drugs will have to clarify their role in the management of the subset of patients with chronic urticaria demonstrating serum-induced inflammatory effects.

Eosinophil apoptosis is mediated by stimulators of cellular oxidative metabolisms and inhibited by antioxidants: involvement of a thiol-sensitive redox regulation in eosinophil cell death.

The mechanisms for induction of eosinophil apoptosis remain uncertain. The role of oxidative stress has not been investigated. The present study was undertaken to determine the role of reactive oxygen species (ROS) and selective antioxidants in eosinophil apoptosis. Eosinophils were cultured with sodium arsenite (SA) known to induce intracellular oxidative metabolites. There was a significant increase in the rate of eosinophil apoptosis with low concentrations of arsenite, whereas high concentrations showed rates of apoptosis similar to control medium. Investigating the role of intracellular oxidants by flow cytometry, we found that while inducing apoptosis, SA more than anti-Fas resulted in a significant dose-dependent production of intracellular H(2)O(2). In contrast, the extracellular release of superoxide decreased after stimulation with SA or anti-Fas as assessed by lucigenin-dependent chemiluminescence. Coincubation experiments demonstrated that arsenite-induced apoptosis can be nearly completely prevented by selective antioxidants such as glutathione (GSH) and N-acetyl-cysteine (NAC), but not dimethyl sulfoxide (DMSO) or taurine (TAUR). Moreover, GSH and NAC significantly reduced eosinophil apoptosis mediated by a monoclonal antibody directed to Fas antigen. Next it was shown that GSH and NAC, but not DMSO or TAUR, were able to significantly delay spontaneous apoptosis in unstimulated eosinophils. Taken together, these data point to an important role of oxygen-dependent mechanisms in the regulation of eosinophil survival and apoptosis. We propose that eosinophil apoptosis may be related to the ability of the cell to maintain an appropriate oxidant-antioxidant balance.

IL-4-induced apoptosis in peripheral blood eosinophils.

BACKGROUND: The regulation of eosinophil survival and apoptosis may play a major role in diseases demonstrating increased numbers of circulating and tissue eosinophils such as allergic reactions. Because few promoters of eosinophil apoptosis have been described so far, the objective of this study was to elucidate the role of endogenous factors on eosinophil survival and apoptosis. METHODS AND RESULTS: Highly purified peripheral blood eosinophils were analyzed in the time course from 24 up to 144 hours in culture. Eosinophil survival was assessed with trypan blue dye exclusion and apoptosis was determined by DNA fragmentation gel analysis and ELISA technique with anti-histone antibodies. We confirmed previous results demonstrating prolonged eosinophil survival and inhibited apoptosis by IL-3, IL-5, and GM-CSF. In contrast, eosinophil apoptosis was significantly enhanced by corticosteroids, particularly dexamethasone and hydrocortisone. However, IL-1beta, IL-8, IL-12, platelet-activating factor, TNF-alpha, and eotaxin had no effect on eosinophil survival or apoptosis when compared with culture medium alone. In contrast, IL-4 at concentrations of 100 U/mL or more inhibited eosinophil survival and induced apoptosis. This effect was time dependent and abrogated by preincubation with neutralizing anti-IL-4 antibodies. However, after 96 hours in coincubation, IL-4 did overcome the survival-prolonging effect of IL-3, IL-5, and GM-CSF. IL-4 did not enhance eosinophil surface expression of APO-1/Fas antigen (CD95). In assessing IL-4-mediated effects on eosinophil function, we found no response by means of the release of eosinophil cationic protein or reactive oxygen species. CONCLUSIONS: Taken together, our data present direct evidence for the presence of functional IL-4 receptors on human eosinophils and indicate that IL-4 may lead to resolution of chronic inflammation by induction of eosinophil apoptosis.

Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria.

BACKGROUND: Chronic urticaria and concurrent angioedema are frustrating problems for both physicians and patients. METHODS: 100 patients with chronic urticaria (mean duration 33.3+/-48.2 months) attending the urticaria consulting hour of our Department of Dermatology within 1 year were carefully analyzed for pathogenesis to avoid extensive unnecessary diagnostic approach in the future. RESULTS: In 43 cases a potential infectious trigger could be identified, 35 were of idiopathic origin, and 15 demonstrated pseudoallergic reactions to acetylsalicylic acid or food additives, 5 had antibodies to thyroid gland, and 2 had malignant diseases. Of patients with foci, 26 had Helicobacter pylori-associated gastritis, 9 chronic tonsillitis or sinusitis, 4 infections with Epstein-Barr virus or cytomegalovirus, 2 dental focal infections and 2 suffered from Yersinia infection. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori-specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3-12 weeks. In contrast, only 50% of untreated H. pylori-seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks. Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%). Moreover, we found H. pylori infection in 2 seronegative subjects demonstrating gastric complaints. CONCLUSIONS: Thus, measurement of H. pylori-specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment with disappearance of long-standing and annoying urticaria symptomatology.

Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis.

The present studies were undertaken to characterize the potential role of eosinophil programmed cell death (PCD) in atopic diseases. Peripheral blood eosinophil PCD was found to be delayed in inhalant allergy (p < 0.05) and delayed to an even greater extent in atopic dermatitis (AD) (p < 0.0001) when compared to nonatopic subjects. There was no difference in the occurrence of PCD between the extrinsic and the intrinsic type of AD, pointing to a secondary role of specific sensitization. Blockade of eosinophil PCD was not responsible for peripheral blood eosinophilia, because we found no obvious relationship of eosinophil survival to blood eosinophil count. Eosinophil supernatants of more patients with AD than of patients with inhalant allergy dose-dependently inhibited PCD in nonatopic eosinophils, and it was shown that this effect was possibly due to autocrine production of granulocyte-macrophage-colony stimulating factor, probably IL-5. Eosinophil expression of CD95 (Fas antigen) did not change over time in culture and was not modulated by cytokines prolonging eosinophil survival. In contrast, IL-3, IL-5, and granulocyte-macrophage-colony stimulating factor caused an upregulated expression of CD69. However, in AD, CD69 on eosinophils was upregulated without the need of exogenous growth factor or factors over time in culture, thus confirming an autocrine production of proeosinophilic cytokines. In conclusion, our data clearly indicate that eosinophil PCD is markedly delayed in the so-called atopic diseases irrespective of allergen sensitization and suggest that this effect is mediated by the autocrine production of growth factors by eosinophils.

Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy.

BACKGROUND: The clinical relevance of gastrointestinal food allergy in adults is largely unknown because the mechanisms are poorly understood and the diagnosis is difficult to confirm. AIMS: To improve the diagnostic means for confirming intestinal food allergy on an objective basis, a new colonoscopic allergen provocation (COLAP) test was developed. PATIENTS: The COLAP test was performed in 70 adult patients with abdominal symptoms suspected to be related to food allergy, and in five healthy volunteers. METHODS: During the COLAP test, the caecal mucosa was challenged endoscopically with three food antigen extracts, a buffer control, and a positive control (histamine). The mucosal weal and flare reaction was registered semiquantitatively 20 minutes after challenge, and tissue biopsy specimens were examined for mast cell and eosinophil activation. RESULTS: No severe systemic anaphylactic reactions were found in response to intestinal challenge. The COLAP test was positive to at least one food antigen in 54 of 70 patients (77%), whereas no reaction in response to antigen was found in healthy volunteers. Antigen induced weal and flare reactions were correlated with intestinal mast cell and eosinophil activation, as well as with patients' history of adverse reactions to food, but not with serum concentrations of total or specific IgE or skin test results. CONCLUSION: The COLAP test may be a useful diagnostic measure in patients with suspected intestinal food allergy and may provide a new tool for the study of underlying mechanisms.

Human HMC-1 mast cells exclusively express the Fc gamma RII subtype of IgG receptor.

Because of their localization at the interface of the internal and external environment mast cells play a crucial role in the immune response and in inflammatory reactions. Effects may be mediated not only by the high-affinity IgE receptor, but also by IgG receptors. Since in rodent mast cells signal transduction via the Fc gamma receptor family has been shown, we analysed the expression of surface receptors for IgG on the human mast cell line HMC-1. It was shown by flow cytometric analysis that HMC-1 constitutively expressed the Fc gamma RII/CD32 subtype whereas Fc gamma RI/CD64 and Fc gamma RIII/CD16 were not expressed. This exclusive expression of the Fc gamma RII subtype of IgG receptor is similar to the expression pattern of basophils, although concerning cell surface molecules HMC-1 rather seem to resemble monocytes. In contrast to monocytes the expression profile on HMC-1 did not change upon stimulation with IL-4, TNF alpha, IFN gamma, PMA or salbutamol. Moreover, the mast cell-activating cytokine SCF and the calcium ionophore A23187 did not modulate the Fc gamma R profile in this study. To assess the importance of the exclusive Fc gamma RIII expression on HMC-1, we investigated whether the production of the cytokine TNF alpha is modulated via Fc gamma RII activation or if an increase in intracellular calcium could be observed. No significant modulation of TNF alpha release or of intracellular free calcium after crosslinking of Fc gamma RII by heat-aggregated IgG or by a second antibody was observed. It remains to be clarified whether this low-affinity subtype for the IgG receptor is involved in antigen-dependent sensitization of human tissue mast cells resulting in secretion of immunoregulatory cytokines. This mechanism may be important for disease states associated with circulating or tissue-bound immune complexes.

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators.

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).