Effective treatment of different phenotypes of chronic urticaria with omalizumab: Case reports and review of literature.

Despite the excellent efficacy and safety profile of omalizumab in chronic spontaneous urticaria (CSU), there are scarce data concerning its role in the treatment of refractory cases with different phenotypes of urticaria. We describe our experience with the therapy of nine patients with CSU co-existing with delayed pressure urticaria (DPU) or angioedema or both and refractory to treatment with high-dose antihistamines. The first patient, with severe CSU and recurrent angioedema, did not respond well to cyclosporine A or corticosteroids and suffered from numerous side effects of long-term corticosteroid therapy. The second patient presented with severe symptoms of DPU, which first of all prevented any daily activities of the professional routines. Both patients showed a complete remission of urticaria after the first injection of omalizumab. The third patient with CSU and severe DPU had been ineffectively treated for more than 20 years with various medications. Following the administration of omalizumab, the symptoms of CSU subsided but those of DPU intensified, and the drug was withdrawn after two cycles. In another four patients with refractory CSU and angioedema, the symptoms subsided after the first administration of omalizumab, and the patients have been in remission for about 5 weeks. In the remaining two patients, the symptoms did not resolve despite four 300 mg doses of omalizumab. It is important to establish a therapeutic regimen with omalizumab (150-300 mg; every 4-8 weeks) tailored to individual patient's needs and dependent on the type of urticaria; this may minimize unnecessary the medication exposure, adverse drug effects, and healthcare costs.

Chromoblastomycosis as an endemic disease in temperate Europe: first confirmed case and review of the literature.

This study reports a case of a 56-year-old white male, retired coal-miner, diagnosed with chromoblastomycosis lasting 20 years. The infection site was the burnt skin of the back. For many years the patient had not undertaken any treatment believing that the lesion had been a burn scar. A gradual increase in lesion size prompted the patient to start therapy. The diagnosis was made by histopathological examination and mycological culture. Identification of the causative agent at the species level was achieved by sequence analysis of the internal transcribed spacer (ITS) region and D1/D2 domains of the 26S rDNA. To our knowledge, this is the first documented case of chromoblastomycosis caused by Fonsecaea monophora in temperate Europe, outside the endemic area for the disease. This finding is highly significant for understanding the routes of infection of chromoblastomycosis and radically revises the traditional view of the natural ecology of the etiological agents of the disease.

House dust mite sublingual immunotherapy: a double-blind, placebo-controlled study in elderly patients with allergic rhinitis.

BACKGROUND: Immunotherapy in elderly patients is controversial, and there is still no evidence supporting this treatment's safety and efficacy in this population. This study was performed to evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite (HDM) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM. OBJECTIVE: This study sought to assess nasal symptoms during HDM season, reduce medication use and monitor for adverse reactions during immunotherapy. METHODS: One hundred and eleven 60- to 75-year-old patients with allergic rhinitis and a confirmed Dermatophagoides pteronyssinus and Dermatophagoides farinae allergy were included in the study. The patients were individually randomized to active or placebo groups using a double-blind method (NCTO01605760 ClinicalTrials.gov). A total of 51 subjects in the sublingual allergen-specific immunotherapy (SLIT) group (Staloral 300R, Stallergenes, France) and 57 subjects in the placebo group were monitored for 3 years. RESULTS: Forty-seven patients completed 3 years of SLIT, and 48 subjects finished the placebo treatment in the same time period. The total nasal symptom score decreased by 44% in the active group and 6% in the placebo group after 3 years of SLIT. This difference was only significant in the active group (P < 0.05). At the end of therapy, the total medication score of the active group decreased significantly by a maximum of 51% (P < 0.05), whereas the total medication score of the placebo control group showed an insignificant decrease (P = 0.56). There were no systemic adverse reactions during the study. CONCLUSIONS & CLINICAL RELEVANCE: Sublingual allergen-specific immunotherapy in elderly patients with a HDM allergy to D. pteronyssinus and D. farinae generated a significant clinical improvement in the active group compared with the placebo group, particularly during the heating season. This therapy was well tolerated.

Concentration of endothelin in plasma and BALF fluid from asthmatic patients.

The bronchoconstrictive peptide endothelin-1 (ET-1) has been demonstrated in the airway epithelial and endothelial cells. In this study we investigated the pathophysiological significance of endothelin-1 in asthma. We addressed the issue by assessing the concentration of ET-1 in plasma and bronchoalveolar lavage fluid (BALF) in patients with a different intensity of asthma. Twenty one asthmatic patients (11 men,10 women) and 6 healthy control subjects (C) were included in the study. Eleven asthmatic patients were classified as moderate persistent asthma (SA), all of them were atopic, and another 10 were mild persistent asthmatics (AA). Lung function tests were carried out in all patients investigated. The ET-1 concentration was determined by an ELISA method in plasma and BALF. We found that the SA patients had the highest level of ET-1 (SA - 11.4 +/-3.6 fmol/ml; AA - 7.1 +/-2.7 fmol/ml; C - 5.6 +/-1.8 fmol/ml) in BALF. The same concerned the ET-1 level in plasma (SA - 27.8 +/-3.8 fmol/ml; AA - 18.1 +/-4.3 fmol/ml; C - 17.3 +/-3.0 fmol/ml). A positive correlation between the plasma ET-1 level and lung function indices was observed. We conclude that the higher levels of ET-1 in more severe asthma suggest that endothelins may contribute to the pathophysiology of the disease, its severity, and the regulation of bronchial tone.

Immune complexes IgE/IgG in airborne allergy: increase during pollen season.

In the present study we addressed the question of IgE/IgG immune complex serum level in 92 patients with respiratory allergy in relation to their clinical status. Twenty patients with allergy to insect stings and 22 healthy volunteers were also investigated. IgE/IgG immune complexes and IgG anti-IgE antibodies were estimated using double antibody solid-phase immunoassays in IgG serum fractions isolated by protein A affinity chromatography or in fractions obtained by Sephacryl S-300 gel filtration. Three people (14%) from the control group, two patients (10%) with insect allergy and 41 patients (45%) from the group with airborne allergy exhibited an increased serum level of IgE/IgG immune complexes (chi2, p <0.05). IgG anti-IgE serum level was also significantly higher in the examined group of patients with airborne allergy than in the control group. None of the factors analyzed, including the kind of allergic disease, the type of inhalant allergen (pollen or house dust antigens), the severity of allergy judged from the frequency and intensity of symptoms for 1 year preceding blood sampling and the symptoms exhibited during blood sampling, showed a statistically significant relation to the level of IgE/IgG immune complexes or IgG anti-IgE, when the whole group of patients with respiratory allergy was analyzed. A distinct difference between patients investigated during and outside of the pollen season was found in patients with isolated pollen allergy. The latter exhibited an increase of IgE/IgG immune complexes (57% vs. 29%) significantly more often, which indicates the possible involvement of IgE/IgG immune complexes in the pathogenesis of pollen allergy.

[Circulating immune complexes in airborne allergy--a protective role?]. / Krazace kompleksy immunologiczne w alergii wziewnej--rola ochronna?

Circulating immune complexes (KI) were analyzed in 78 patients with airborne allergy and compared to 34 persons of control group. KI were isolated by precipitation with 3% polyethylene glycol. KI-IgG, KI-IgA, KI-IgM were measured by radial immunodiffusion, KI-IgE by an immunofluorometric assay. Staphylococcal Protein A (SpA) binding to KI was measured by ria. Relations between the level of various KI and the diagnosis of allergic disease, the kind of allergen (related also to the exposition) and the symptoms of atopy were evaluated. Serum levels of KI-IgE, KI-SpA, and KI-IgM were distinctly elevated in airborne allergy, with the positive correlation between KI-SpA and KI-IgM. KI-IgE were related to the kind of sensitizing allergen and to the exposition to the pollen allergens. Most distinct differences in KI level were observed not in relation to the kind of disease or of the sensitizing allergen, but in relation to the symptoms and intensiveness of atopy. Patients showing a greater number and intensiveness of symptoms exhibited higher levels of KI-SpA. However, one of the symptoms scored (dyspnea) was connected with the decreased level of KI-SpA in these patients. We interpret the results in favour of the hypothesis of the dual role of KI in airborne allergy. We propose a protective role for KI-Spa, which contain IgG and may bind IgE, thus protecting the target organs of allergy.

[Bronchoconstriction symptoms mimicking bronchial asthma--report of two cases]. / Objawy bronchospastyczne pozorujace astme oskrzelowa--opis dwóch przypadków.

Two patients sent to the clinic with incorrectly diagnosed asthma have been presented. In both cases the bronchospastic symptoms was caused by the obstacle in the airways. The authors concluded that there is a great necessity to conduct the discriminating diagnosis of bronchospastic symptoms.

[Influence of bacterial infection and formalin vapors on the course of ovalbumin induced experimental bronchospastic reaction in guinea pigs]. / Wplyw zakazenia bakteryjnego i par formaliny na przebieg wywolanych doswiadczalnie stanów bronchospastycznych u swinek morskich.

The pathomechanism of the bronchospastic reaction is not fully explained. Ovalbumin induced bronchospastic reaction in guinea pigs is widely accepted as a classical experimental model and was appleid in this study. The bronchoconstriction, bronchial hypersensitivity and humoral immune response were measured after bronchial infection and chemical injury by formalin vapours. The intensity of the bronchospasm was measured by Lundberg index, the haemolytic activity of complement and the level of circulating immune complexes were measured at the beginning and at the end of the experiment. The increase of the bronchospastic reaction and bronchial hypersensitivity was observed bacterial infection and after formalin vapours too. Bronchial infection and chemical irritation of bronchial tree lead to the increase of the circulating immune complexes level and to the decrease of the haemolytic activity of the complement.

[Influence of bacterial infection during ovalbumin induced experimental asthma in guinea pigs]. / Wplyw zakazenia bakteryjnego na przebieg doswiadczalnej astmy indukowanej owalbumina u swinek morskich.

The pathomechanism of bronchial asthma is not fully explained. The immunologic reactions in the bronchial epithelium may be better understood by an experimental approach in laboratory animals. Ovalbumin induced asthma in guinea pigs is widely accepted as an experimental model of bronchial asthma and was applied in this study. The bronchoconstriction, bronchial hypersensitivity and humoral immune response were measured after bronchial infection (intranasal Pseudomonas aeruginosa application). The increase of the bronchospastic reaction and bronchial hypersensitivity was observed after intranasal Pseudomonas aeruginosa application. Bacterial infection lead to the increase of the circulating immune complexes level and to the decrease of the haemolytic activity of the complement in serum.

[Nedocromil in treating chronic bronchial asthma of a moderate course]. / Nedokromil w leczeniu przewleklej astmy oskrzelowej o sredniociezkim przebiegu.

Randomized, double blind, placebo controlled clinical studies aimed at evaluating the efficiency of nedocromil sodium (Tilade) in the form of metered dosimeter aerosol. Studies involved patients with moderate chronic bronchial asthma controlled with beta 2-agonists and theophylline in the form of sustained release preparations. Forty patients completed the studies. All patients were examined clinically (staging of the symptoms and doses of drugs) and spirometrically prior to and after 4 and 8 weeks of the treatment with nedocromil sodium. Statistically significant clinical improvement and spirometric improvement as well in patients treated with nedocromil sodium were noted. It may be concluded that nedocromil sodium is effective and well tolerated adjuvant therapy in the bronchial asthma.

[IgE-containing immune complexes in bronchial asthma]. / Kompleksy immunologiczne zawierajace IgE w astmie oskrzelowej.

Level of circulating immunological complexes and their immunoglobulin content have been determined in 36 asthmatic patients, including 15 patients with atopic asthma and 21 patients with infectious asthma. A technique of staphylococcal protein A binding has shown, that the level of the circulating immunological complexes is increased in patients with infectious bronchial asthma. An amount of IgE in these complexes has been increased in both atopic and infectious bronchial asthma. However, a level of IgE-containing immunological complexes has been higher in the atopic asthma, then that in infectious form of the disease. An increased IgA content in the immunological complexes has been noted in the infectious asthma.

[Circulating immune complexes in hypertrophic cardiomyopathy and ischemic heart disease]. / Krazace kompleksy immunologiczne w kardiomiopatii przerostowej i chorobie niedokrwiennej serca.

In 32 patients (pts) with hypertrophic cardiomyopathy (HC), 20 pts with ischaemic heart disease (IHD) and 30 healthy controls, the levels of circulating immune complexes (CIC), immunoglobulins A, G and M, C3c and C4 components of the complement, as well as haemolytic activity of the complement were measured. CIC were assessed using two different methods: a) precipitation with 3% polyethylene glycol with subsequent spectrophotometric measurement of protein content in the precipitate, and b) binding with J-125 labelled staphylococcal +protein ++ A. Pts with HC showed a statistically significant increase in concentration of IgM and the immune complexes (shown with both methods) together with a decrease in C4 and hemolytic activity of the complement. In addition an analysis carried out for each individual patient showed that in some cases an increase in immune complexes concentration was paralleled by a decrease in IgG, C4 and haemolytic activity of the complement. This may suggest that in these pts activation of the complement through the classical pathway can occur. In pts with IHD an increase in immune complexes concentration was demonstrated by precipitation method only. Immune globulines and complement components were within limits for the control group. This suggests that in IHD the complement system is not engaged. Our findings indicate that in HC mechanisms other than those present in myocardial ischaemia must be engaged in inducing changes in the immune system.

[Migration inhibition test with thyroid membrane antigen in Graves-Basedow disease and nodular goiter]. / Odczyn hamowania migracji z blonowym antygenem tarczycowym w chorbie Graves-Basedowa i w wolu guzkowym.

The evaluation of the migration inhibition test with thyroid membrane antigen was carried out in 20 patients with Graves' disease, 13 patients with neutral nodular goiter and 13 healthy subjects. A significant inhibition of migration by thyroid antigen as compared to the control group was demonstrated only in the patients with Graves' disease (the value of the migration index was 0.57 +/- 0.07). The respective value was 0.79 +/- 0.16 in patients with nodular goiter and 0.85 +/- 0.11 in healthy subjects. The results obtained indicate the practical value of the migration inhibition test in diagnosing the thyroid diseases having an autoimmune background.