Pulmonary hemosiderosis with normocomplementemic urticarial vasculitis in a child

urticarial vaculitis especially if normocomplementemic. An eigth year old girl presented with relapsing and remitting chronic and persistent urticarial lesions, conjunctival injection, recurrent cough and hemoptysis. Respiratory findings started at seven years of age. Physical examination revealed diffuse skin lesions mainly settled on the extremites, nonpurulent conjunctival injection, rare ronchi and fine crackles in bilateral lower zones of the lungs. Biopsy of the urticaria like skin lesions demonstrated leukocytoclastic vasculitis. Rheumatological markers were negative. Levels of complement fractions 3 and 4 were normal. Chest x-ray demonstrated diffuse alveolar infiltrative images. High Resolution Computed Tomography of the chest revealed diffuse ground-glass appearance, increased interstitial density. Diagnostic flexible fiberoptic bronchoscopy was performed and bronchoalveolar lavage fluid revealed hemosiderin laden alveolar macrophages. She was started on systemic corticosteroid treatment. During follow up, pulmonary symptoms disappeared, however skin lesions and conjunctival symptoms persisted and exacerbated four times in two years. CT of lungs after two years of treatment revealed rare patchy areas of ground glass appearance in bilateral lower lobes and right upper lobe as well as a few of milimetric pleural nodules. This patient is still followed up under low dose steroids and pulmonary findings regressed but low grade inflammation due to vasculitis is thought to continue as supported by the persistence of tomographic findings in the lungs despite the absence of any symptoms. This case demonstrates association of urticarial vasculitis and pulmonary hemosiderosis in the setting of normocomplementemia

EUROPEAN CYTOKINE NETWORK

Background. Allergic rhinitis (AR) is a disease characterized by IgE-mediated, allergic inflammation of the nasal mucosa. T helper (Th) 2 cells play an important role in the development of IgE-mediated diseases such as AR, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Th1 cytokines (IL-12 and IFN-gamma) are known to suppress this Th2 immune response, aiding the treatment of these diseases. beta-1,3-1,6-glucan (Glucan) is an immunomodulator stimulating particularly the antitumor response. An efficient antitumor stimulation can be achieved through a Th1-mediated immune response. Objective. The aim of this study was to investigate the effects of Glucan on the immunopathogenic processes in the microenvironment to determine if it reverses the Th2-mediated immune response in AR to Th1-mediated response. Methods. 24 Olea europea mono-sensitized patients with AR were randomized into Glucan and placebo groups. The Glucan group consisted of 12 patients who received Glucan treatment for 12 weeks, while the placebo group of 12 patients received placebo during the same period. A nasal provocation test (NPT) with Olea europea was performed at the beginning and end of treatment, and nasal lavage followed the positive NPT. IL-4, IL-5, IFN-gamma and IL-12 levels and the eosinophil count (%) were measured in nasal lavage fluid (NLF) samples. Simultaneously, peripheral blood eosinophil % values were measured. Results. After treatment, IL-4 and IL-5 levels in NLF from the Glucan group were found to have decreased significantly (p = 0.027, p = 0.04; respectively), while IL-12 levels were found to have significantly increased (p = 0.008). However, IFN-gamma levels had not changed. On the other hand, none of the cytokine levels had changed significantly in the placebo group following treatment. Moreover, the percentage of eosinophils in the NLF was found to have decreased significantly after treatment in the Glucan group (p = 0.01), while that of the placebo group did not change. Peripheral blood percentage eosinophil levels had not changed significantly in any group. Conclusion. Th2-originated IL-4 and IL-5 levels responsible for the allergic inflammatory response in the microenvironment of patients with AR, are decreased with Glucan while levels of Th1-originated IL-12 are increased. Moreover, eosinophils, which are important effector cells of the inflammatory response, are decreased in the microenvironment. As a result, Glucan may have a role as an adjunct to standard treatment in patients with AR

JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY

Background: Olive (Olea europaea; O.e.) pollen is a major cause of seasonal respiratory allergy. The O.e. pollination season lasts two months from the beginning of May till the end of June. It was expected that patients with allergic disease from O.e. sensitization were symptomatic only during this period. However, during the last few years, we have observed that the clinical symptoms appear not only during the O.e. pollination season but also during the rest of the year. Objective: The aim of this study was to observe and document symptoms of respiratory allergic diseases in the O.e. sensitized patients during the O.e. pollination season and after it. Methods: One hundred and twenty-seven patients with respiratory allergic disease were enrolled in the study. Allergenic sensitizations were shown by SPT. Finally, patients were split into two groups as monosensitized with O.e. (n=19) and polysensitized (n=108). Patients were assessed by using scores of respiratory allergic disease symptoms and percentage of peak expiratory flow rate values (PEFR %) (only for asthmatic patients) during the O.e. pollination season and after it. Results: Of the patients with O.e. monosensitization, 13 had allergic rhinitis (AR) only while six had allergic asthma (AA) additionally. AR alone and accompanied by AA was present in 84 and 24 polysensitized patients respectively. Eleven patients with O.e. sensitization (57.9 %) and 86 patients with polysensitization (79.6 %) had AR symptoms throughout the year irrespective of the O.e. pollination season. Similarly, three of the O.e. monosensitized and ten of the polysensitized patients with AA had asthmatic symptoms during the O.e. pollination season and also after it. Conclusions: In the patient group sensitive to O.e. along with other pollen extracts, it was possible to observe symptoms outside the pollination season. However, patients with O.e. monosensitization also had symptoms to a great extent outside the season

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Background. Seasonal allergic rhinitis (SAR) is characterized by a helper T (Th)2 cell-mediated immune response at the target site. There is a relative Th1 and/or regulatory T (Treg) cell insufficiency in patients with SAR. It has been demonstrated that there is a change in the balance between these cells after allergen-specific immunotherapy (SIT), which is a curative treatment modality for this disease. However, there are few studies that evaluate the number and function of these cells in the inflammatory area after SIT treatment. Objective. We aimed to investigate the distribution of Th1, Th2 and Treg cells in nasal biopsies and lavage fluid (NLF) specimens from patients with SAR, before and after SIT. Methods. Twenty-four, symptomatic SAR patients sensitized to Olea europeae, were enrolled in the study prior to treatment. Fifteen, non-allergic subjects with nasal septum deviation, who needed surgical treatment, served as the control group. NLF and inferior turbinate biopsies were obtained from both groups during the pollen season. Conventional, subcutaneous SIT with Olea europeae extract was initiated in patients with SAR. One year after the first biopsy, biopsies and NLF specimens were again obtained for reevaluation. All biopsies were evaluated for Th1, Th2 and Treg cell counts by means of their transcription factors (T-bet, GATA-3 and FoxP3) using an immunohistochemical analysis method. Additionally, all NLF specimens were evaluated for the functions of these cells, by means of their specific cytokines, using an ELISA method. Results. When the basal status of those patients with SAR was evaluated based on transcription factors, prior to treatment, Th1 and Treg cells were found to be fewer than in non-allergic controls (p=0.001 for both T-bet and FoxP3). It was demonstrated that numbers of GATA-3-carrying cells, which are a marker for Th2, were not significantly different between the groups (p=0.276), but evaluation of the Th1/Th2 ratio revealed a relative Th2 dominance in patients with SAR prior to treatment. When evaluated on the basis of cytokine levels, it was observed that Th1-originated IFN-gamma was lower in patients with SAR compared to the control group, both before and after treatment (p=0.012 for both comparisons), Th2-originated IL-4 levels were not significantly different between the groups either before or after treatment (p=0.649, p=0.855; respectively). Th2- and Treg cell-originated IL-10 levels were higher in patients with SAR before treatment (p=0.033), but this difference was not statistically signifact following treatment compared with controls (p=0.174). Treg cell-originated TGF-beta levels were slightly lower in patients with SAR compared to the controls, although the difference was not statistically significant (p=0.178, p=0.296; respectively). None of the above mentioned cytokine levels changed significantly as a result of SIT. Conclusion. The results of our study indicate that although clinical findings improve after one year of SIT, this duration may not be sufficient to detect changes in cytokine patterns and transcription factors. Further studies that evaluate outcome over a longer duration of treatment would provide valuable information

ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY

Background: Allergic rhinitis (AR) is an allergic inflammatory disease in which allergen exposure leads to the appearance of symptoms in sensitized individuals because of histamine liberation from nasal mucosal mast cells. Comorbidity of this disease with allergic asthma is common. Therefore, the one airway one disease theory has been put forward. Lower respiratory tract provocation tests with both nonspecific (methacholine) and specific stimulants (allergen) have yielded positive results in nonasthmatic patients with AR. However, not enough research is available to demonstrate whether there is a response in the lower respiratory tract during nasal provocation tests (NPTs) performed to evaluate only nasal airway in these patients. Objectives: To determine if the lower respiratory tract was affected as a result of NPTs with nonspecific and specific stimulants in nonasthmatic patients with AR and to determine the frequency of lower respiratory tract obstruction due to NPT with nonspecific and specific stimulants. Methods: Thirty-six participants were enrolled in the study between November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). Patients underwent 2 sessions of NPT. The first session was performed with nasal methacholine as a nonspecific stimulant, and the second session was performed with nasal Olea europaea extract as a specific stimulant. The control group underwent only nonspecific nasal provocation with methacholine. Basal nasal opening and nasal pressures were evaluated spirometrically by rhinomanometric measurements and basal respiratory function tests in both groups before methacholine nasal provocation. Whether or not nasal provocation was achieved, spirometric measurements were performed in all patients and controls after NPTs. Results: NPTs with methacholine resulted in a similar frequency of nasal provocation in the patient and control groups (P = .63). However, the mean methacholine dose was lower in patients with AR (P = .049). There was a decrease in parameters of asthma, including the ratio of forced expiratory volume in I second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with methacholine in the patient group. However, NPTs with allergen did not cause a change in lower respiratory tract obstruction criteria. Conclusions: Lower respiratory tract obstruction can occur after NPTs with nonspecific stimulants; therefore, tests performed with specific allergens can be regarded as safer

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Background. Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. Objective We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. Methods. Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immumohistochemical analysis methods (HSCORE, MVD and VSD). Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. Conclusion. There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR

ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY

Background: Sexual dysfunction in chronic diseases has recently attracted attention owing to its impact on quality of life (QoL). Allergic rhinoconjunctivitis (ARC) affects QoL, causing limitations in many areas. However, there has not been research on changes in sexual function in patients with ARC. Objective: To report the effect of ARC and its treatment on sexual function in men and women. Methods: Forty-three sexually active patients with seasonal ARC aged 22 to 49 years were included in the study. The control group was composed of 40 healthy individuals aged 22 to 46 years. Conjunctival symptom scores (CSSs) and nasal symptom scores (NSSs) of patients with symptomatic ARC were determined, as were sexual function scores (SFSs) using the Female Sexual Function Index and the International Index of Erectile Function during allergen exposure in the pollination period and after treatment with oral desloratadine, 5 mg/d, for 30 clays. The SFSs were evaluated in the control group. Results: The CSSs and NSSs significantly improved in treated ARC (P < .001). In women, Female Sexual Function Index results in symptomatic ARC were significantly lower than in treated ARC and controls (P = .003). In men, International Index of Erectile Function results in treated ARC (P = .001) and controls (P < .001) were significantly higher than in symptomatic ARC. Furthermore, correlation between improvement in CSSs and NSSs and that of SFSs was determined (P =.007 for women; P =.001 for men). Conclusion: Improvement in sexual function as a variable of QoL may accompany the treatment of symptoms in patients with ARC

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Chronic liver disease and cirrhosis are two of the most important health problems according to current gastroenterology literature. Based on the recent developments in the field of immunology, advanced follow-up and treatment modalities have been introduced for these disorders. Immune defence against viral infections depends on effective cellular immune responses derived mainly from Th1-related cytokines. Th2 type immune responses can inhibit efficient immune function by secretion of several cytokines such as IL-10, TGF-beta1. In this particular study, we determined the serum levels of TGF-beta1, which plays a role in immune suppression and induction of tissue fibrosis. We evaluated the role of TGF-beta1 in the pathogenesis of chronic liver disease and cirrhosis. Fourteen chronic hepatitis B (CHB), 12 chronic hepatitis C (CHC) patients and 21 cirrhotic patients were enrolled in the study. The control group consisted of ten healthy people. Serum TGF-beta1 levels were higher in both cirrhosis and CHC group when compared to those in CHB and control groups (P < 0.05). Although serum TGF-beta1 levels in the cirrhosis group were higher than that in the CHC group, the difference was not statistically significant. In conclusion, elevated TGF-beta1 levels in patients with CHC and cirrhosis may have a role in the pathogenesis and chronicity of these diseases