Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters.

BACKGROUND: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. OBJECTIVE: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. METHODS: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. RESULTS: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 10(10)/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. CONCLUSIONS: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization.

Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status.

BACKGROUND: Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys-LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts. METHODS: Urinary Cys-LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys-LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme-linked immunoassay (ELISA). RESULTS: Mean clinical score during the exacerbation was 64.3 +/- 3.1 and during remission 22.4 +/- 4 (P < 0.01). Cys-LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 +/- 20.8 vs 123.2 +/- 9.9 pg/mg creatinine; P < 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 +/- 8.7 vs 123.2 +/- 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation Cys-LTs levels were significantly correlated with the clinical status (rS = 0.73, P < 0.01) and with eosinophil counts (r = 0.86; P < 0.01) but not with the duration of the disease, age of patients, or IgE levels. CONCLUSIONS: Our results point to enhanced biosynthesis of Cys-LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys-LTs. A strong correlation between Cys-LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.

[Selected parameters of the cellular and humoral immunity in atopic dermatitis. Relationship to the severity of the disease]. / Charakterystyka wybranych parametrów odpornosci komórkowej i humoralnej u chorych na atopowe zapalenie skóry. Zwiazek z zaawansowaniem klinicznym choroby.

UNLABELLED: Despite the great progress, our understanding of the pathogenesis of atopic dermatitis (AD) is still incomplete. In particular, the clinical importance of various changes of the immune system parameters is unclear. Accordingly we have undertaken the study to compare selected parameters of cellular and humoral immunity between AD subjects (n = 26) and healthy controls (n = 10). These parameters included immunoglobulin levels (IgE in particular), neutrophil respiratory, oxygen burst, peripheral blood lymphocyte phenotype and response to mitogens. We also analysed the relationship between these parameters and clinical severity of skin lesions. RESULTS: Mean total immunoglobulin E levels were very significantly increased in the AD group (1563 +/- 459 vs 35.5 +/- 12.1 IU/ml; p = 0.001). Simultaneously total serum IgE levels varied extensively between individual subjects with AD and were significantly correlated to clinical severity of the disease (Rs = 0.44; p = 0.02). Atopic dermatitis was also associated with the increase in the number of CD4+ and simultaneous decrease in the CD8+ lymphocytes causing statistically significant difference in CD4:CD8 ratio compared to the control group. We also observed changes of proliferation indices to phytohaemagglutinin (decrease) and increase of responses to anti CD3 mAb (OKT-3) and staphylococcal enterotoxin B. None of these immune parameters however, appeared to be statistically correlated to clinical status. CONCLUSIONS: We find that atopic dermatitis is associated with significant changes of several important indices of cellular and humoral immunity including increased IgE levels and altered peripheral lymphocyte proliferation capacity and phenotype. Change of total IgE levels appears to be the most important from clinical point of view.

[Bronchial asthma--a chronic inflammatory disorder]. / Astma oskrzelowa--przewlekla choroba zapalna.

Inflammation is a major process in the pathogenesis of bronchial asthma. Pivotal role in the induction of the inflammation in atopic subjects is played by mast cells and eosinophils and their mediators. Lymphocytes T and macrophages modulate this process. Although the pathogenesis of asthma in non-atopic subjects is not totally clear the inflammation has similar course as in asthma with IgE overproduction. Current research emphasise e.g. the role of adhesion molecules, bronchial epithelial cells and nitric oxide in the pathogenesis of asthma. Selectin E, ICAM-1, VCAM-1 take part in the migration of inflammatory cells in the asthmatic lung. Expression of these molecules is included by IL-1, TNF-alpha, and IL-4. Inflammation leads to the bronchial epithelial damage and release of proinflammatory cytokines, which augment the above process. The epithelial damage causes exposure of nerve endings, which can lead to the activation of axon reflexes. The concentration of NO in the exhaled air of asthmatics is much higher than in healthy subjects. It may be produced by inflammatory cells and may augment the inflammation as well as cause bronchial hyperresponsiveness. The better understanding of inflammatory patterns of bronchial asthma has major influence on the therapeutic approach. Inhaled anti-inflammatory drugs are of the first choice in pharmacotherapy of even mild forms of asthma.

The effect of prostacyclin on asthma precipitated by aspirin.

Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin inhibits generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in 9 known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes have been overestimated in this type of asthma. Idiosyncrasy to aspirin, which affects 5-10% of adult asthmatics, was thought several decades to be of allergic background, while in fact numerous and extensive immunological studies ruled out typical IgE--mediated allergic mechanisms for aspirin--induced asthma. In 1974, at the Department of Allergy and Clinical Immunology in Cracow, a novel hypothesis was put forward. If stated that in sensitive patients, precipitation of asthmatic attacks by aspirin and by certain nonsteroidal antiinflammatory drugs (NSAID) results from inhibition of specific enzyme in the bronchi, cyclooxygenase, leading to an imbalance of prostanoids in the respiratory tract. Over the years which followed evidence has been accumulated which strongly support this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of effect of i.v. prostacyclin on aspirin-induced asthma.

Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin impedes generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in nine known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes has been overestimated in this type of asthma.

Aspirin sensitive asthma and arachidonic acid transformation.

Inhibition by nonsteroidal antiinflammatory drugs of cyclooxygenase appears to be the basic mechanism operating in aspirin-sensitive asthma. Evidence in favor of this theory is presented. We also discuss biochemical consequences of blockade of cyclooxygenase for clinical symptomatology, prevention and treatment of aspirin-sensitive asthma.

Hydrocortisone and airflow impairment in aspirin-induced asthma.

We studied the effects of intravenous injection of hydrocortisone, as compared to its solvent, in 31 patients with aspirin-induced asthma. Mean FEV1 fell significantly 5 minutes after an intravenous bolus of 300 mg of hydrocortisone, but not after the solvent, and returned to the initial values 1 hour later. Only three of 31 patients displayed at this time clinical signs of increased impairment of airflow that resolved spontaneously. Neither in these three patients nor in another patient known already to respond with bronchoconstriction to 30 to 50 mg of hydrocortisone did intravenous injections of 20 mg of methylprednisolone, 4 mg of dexamethasone, or 4 mg of betamethasone produce any signs of bronchial obstruction. In the whole group of patients, mean FEV1 increased significantly 3 to 5 hours after hydrocortisone injection. It is hypothesized that hydrocortisone might induce early bronchoconstriction in patients with aspirin-induced asthma through its inhibitory effects on prostanoid biosynthesis. Use of intravenous steroids other than hydrocortisone is advisable in patients with aspirin-induced asthma.

Idiosyncrasy to pyrazolone drugs.

Studies carried out in 68 patients with idiosyncratic reactions to noramidopyrine and/or aminophenazone led to distinction of two different groups. In the first group: 1) noramidopyrine, aminophenazone, phenylbutazone and sulfinpyrazone as well as several other inhibitors of cyclooxygenase, including aspirin, precipitated bronchoconstriction; 2) skin tests with pyrazolone drugs were virtually negative; 3) all patients had chronic asthma. In the second group: 1) noramidopyrine and aminophenazone induced anaphylactic shock and/or urticaria; 2) skin tests with these drugs were highly positive; 3) phenylbutazone, sulfinpyrazone and several other cyclooxygenase inhibitors, including aspirin, could be taken with impunity; 4) chronic bronchial asthma was present in only one-fourth of the patients. We suggest that the pathogenic mechanisms responsible for the idiosyncratic reactions involve inhibition of cyclooxygenase in the first group, and allergic reactions in the second group. Distinction of these two groups is of clinical importance since in individual patients it gives insight into the safe administration of pyrazolone and aspirin-like drugs.

Inhibition by ketotifen of idiosyncratic reactions to aspirin.

Ketotifen administered prior to aspirin offered protection against bronchoconstriction in 13 of 14 patients with aspirin-sensitive asthma. In four other subjects, suffering from urticaria/angioedema following ingestion of aspirin-like drugs, pretreatment with ketotifen resulted in total prevention of the adverse reactions. These results support the suggestion of a common pathogenetic mechanism operating in two distinct clinical patterns of idiosyncrasy to aspirin and other cyclo-oxygenase inhibitors. They also indicate that ketotifen might find application in treatment of adverse reactions to aspirin.