August 12, 2014

The presence of H.pylori in cases of chronic idiopathic urticaria

Rashad Feddah
Ibraheem Banihameem
Anwar Farhan
Saeed Al-Ahmari
Fayeh Asiri
Hamad AL Fahaad
Wadha Alfarwan


Correspondence:
Dr. Anwar Farhan, MD 
Consultant dermatologist
King Khalid Hospital, Najran, Saudi Arabia
Tel: (Cell phone) +966 553044333
Email: anwarfarhan@yahoo.com
Abstract
Introduction: Urticaria (or hives) are a kind of skin rash notable for dark red, raised, itchy bumps.Chronic urticaria, defined as urticaria that persists for longer than 6 weeks, it is not a single disease but a reaction pattern that represents cutaneous mast cell degranulation, resulting in extravasation of plasma into the dermis and the patients may not improve or may depend on medication for years to relieve symptoms. chronic urticaria is one of the most common problems facing dermatologists and other specialities. It is the problem which bothers both the patient and the dermatologist. Traditionally, the approach in patients with chronic urticaria (when physical etiology has been excluded) has been to order a panel of laboratory tests to discover an occult medical condition responsible for the skin findings. In many patients, an extensive workup does not discover an etiology. Patients in whom no explanation for his urticaria are said to have chronic idiopathic urticaria. Various infectious agents have been reported as causes of urticaria, including Helicobacter pylori (H. pylori), which is a common worldwide bacterial infection. Its role in inducing allergic conditions, such as chronic urticaria, has been suggested in some reports and ignored in others.

Aim : In our research, we want to look for the prevalence of Helicobacter pylori in the serum of patient who presented with chronic urticaria .The patient has endure treatment and is not cured besides partial treatment causes temporary relive of symptoms. So, it is important to make the right decisions regarding the treatment of chronic urticaria by adding triple therapy for those who are H.pylori positive.

Subjects and Methods: This study is a non controlled , consecutive interventional study involving 60 patients during the period from November 2012 to April 2013 with history of urticarial lesions of > 6 weeks, to search for the possible cause of their chronic urticaria.

Results: Among 60 patients suffering from chronic Urticaria only 40 (66.7%) patients were enrolled in the study with chronic idiopathic urticaria.

25 patients (62.5%) of chronic idiopathic urticaria were infected with H.pylori and 15 patients (37.5%) had negative serology for H.pylori. 80% of patients with positive H.pylori had G.I.T symptoms ,18 patients (72%) were achieved eradication with the first line therapy while 5 patients (20%) required the second line therapy for eradication. In 2 patients (8%) H.pyloripersisted despite two courses of eradication therapy. Response to eradication therapy was evident in 19 patients (76%) in whom H.pylori was eradicated while 4 patients (16%) showed no response despite eradication of H.pylori. Two patients (8%) with persistent H.pylori infection showed no improvement in the urticarial symptoms at the end of study period.

Conclusion: The results of our study strongly suggest that H.pylori should be specifically tested in all patients of CIU, to identify subset of patients who are infected and who could benefit from eradication therapy. H.pylori should be included in the diagnostic work up of all patients with CIU.

Key words : H.pylori, chronic idiopathic urticaria , chronic urticaria




Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis


Published Date December 2013 Volume 2014:8 Pages 1—12

DOI http://dx.doi.org/10.2147/BTT.S35475

Received 16 September 2013, Accepted 11 October 2013, Published 9 December 2013

Filipe Seguro Paula,1 José Delgado Alves1,2

1Immunomediated Systemic Diseases Unit, Department of Medicine 4, Fernando Fonseca Hospital, Amadora, 2Center for the Study of Chronic Diseases, Department of Pharmacology, Faculty of Medical Sciences, Lisbon, Portugal

Abstract: The way rheumatoid arthritis is treated has changed dramatically with the introduction of anti-tumor necrosis factor (anti-TNF) biologics. Nevertheless, many patients still have less than adequate control of their disease activity even with these therapeutic regimens, and current knowledge fails to explain all the data already gathered. There is now a wide range of drugs from different classes of biologic disease-modifying anti-rheumatic drugs available (and soon this number will increase significantly), that provides the opportunity to address each patient as a particular case and thereby optimize medical intervention. Currently available biologics for the treatment of rheumatoid arthritis apart from anti-TNF-based therapies are reviewed, along with an analysis of the new insights they provide into the pathogenesis of the disease and a discussion of future prospects in the area.

Keywords: rheumatoid arthritis, non-anti-tumor necrosis factor, treatment, pathogenesis

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at:http://www.dovepress.com/permissions.php


August 11, 2014

Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome


Yu L1, Xu X, Wang L, Yang Z, Lü H, Qiu Z.

Abstract
BACKGROUND:
Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS.
MATERIAL AND METHODS:
59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ≥ 5 coughs upon exposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy.
RESULTS:
C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) µmol/L vs. 7.8 (3.9, 93.75) µmol/L vs. 31.2 (15.6, 62.5) µmol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum.
CONCLUSIONS:
Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS.


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Natural killer cells from patients with chronic rhinosinusitis have impaired effector functions




Kim JH1, Kim GE, Cho GS, Kwon HJ, Joo CH, Kim HS, Jang YJ.

Abstract

Natural killer (NK) cells are multicompetent lymphocytes of the innate immune system that play a central role in host defense and immune regulation. Although increasing evidence suggests that innate immunity plays a key role in the pathogenesis of chronic rhinosinusitis (CRS), the role of NK cells in CRS has been poorly studied. This study aimed to characterize the peripheral blood NK cells from patients with CRS, and to compare the functions of these cells with those from non-CRS controls. The correlation between NK cell functional activity and prognosis was also assessed. Eighteen CRS patients and 19 healthy non-CRS controls were included. The patients with CRS were classified into two subgroups, namely a treatment-responsive group and recalcitrant group. NK cell degranulation was determined by measuring the cell surface expression of CD107a against 721.221 and K562 cells. Intracytoplasmic cytokine production was determined by flow cytometry. Compared to the controls, the NK cells of CRS group had an impaired ability to degranulate and to produce cytokines such as IFN-γ and TNF-α. The recalcitrant subgroup showed the most severe defects in NK cell effector functions. Moreover, the decreased NK cell functions in patients with CRS were associated with poor prognostic factors such as concomitant asthma and peripheral blood eosinophilia. NK cells, which were originally named for their ability to mediate spontaneous cytotoxicity towards diseased cells including infected cells, may play an important role in regulating the inflammatory process in CRS pathogenesis.


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Vitamin A supplementation and risk of atopy: long-term follow-up of a randomized trial of vitamin A supplementation at six and nine months of age

Research article
Nicholas Kiraly12*Aliu Balde1Ida Marie Lisse1Helle Brander Eriksen13Peter Aaby13and Christine Stabell Benn13
1Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau
2Gastro and Food Allergy, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Rd, Parkville VIC 3052, Australia
3Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, 5 Artillerivej, Copenhagen S DK-2300, Denmark
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BMC Pediatrics 2013, 13:190  doi:10.1186/1471-2431-13-190

The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2431/13/190

Received:21 July 2013
Accepted:15 November 2013
Published:19 November 2013
© 2013 Kiraly et al.; licensee BioMed Central Ltd. 
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The World Health Organization recommends high-dose vitamin A supplementation (VAS) for children above six months of age in low-income countries. VAS has been associated with up-regulation of the Th2 response. We aimed to determine if VAS is associated with atopy in childhood.

Methods

Infants in Guinea-Bissau were randomly allocated VAS or placebo, either at six and nine months of age, or only at nine months of age. At six months of age, children were furthermore randomized to measles vaccine or inactivated polio vaccine. At nine months of age all children received measles vaccine. Children were revisited seven years later and skin prick testing was performed. Atopy was defined as a skin prick reaction ≥3 mm.

Results

40 of 263 children (15%) were atopic. Overall VAS had no significant effect on the risk of atopy (Prevalence Ratio 1.23; 95% CI 0.69-2.18). The Prevalence Ratio was 1.60 (0.66-3.90) for males and 1.00 (0.46-2.15) for females.

Conclusions

There was no significant effect of VAS in infancy on atopy later in childhood. The role of infant VAS in the development of atopy is still unclear.
Keywords: 
Atopy; Immunization; Measles vaccine; Vitamin A supplementation

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Melatonin and atopy: role in atopic dermatitis and asthma


Marseglia L, D'Angelo G, Manti S, Salpietro C, Arrigo T, Barberi I, Reiter RJ, Gitto E.

Abstract
Melatonin may have important immunostimulatory actions in allergic diseases, in addition to its well-known antioxidant and cytoprotective effects in several inflammatory conditions. The activation of the immune system leads to free radical production associated with decreased melatonin levels and depressed antioxidant enzyme activities in several inflammatory diseases. Many skin disorders, including atopic dermatitis, are accompanied by infiltration and activation of mast cells, which release vasoactive and proinflammatory mediators. Experimental data suggest that melatonin inhibits development of atopic eczema and reduces serum total IgE and IL-4. Allergic asthma is a condition characterized by bronchial hyperresponsiveness and the presence of IgE antibodies in response to inhaled allergens; often there is also enhanced total serum IgE levels. Melatonin regulates smooth muscle tone and influences the immune response. Melatonin may, however, act as a pro-inflammatory agent in asthma leading to bronchial constriction. The safety of melatonin as a sleep-inducing agent has been confirmed in asthmatic subjects, but its routine use is not recommended in bronchial asthma. This review summarizes what is known about the role of melatonin as an immunomodulatory agent in asthma and atopic eczema.




Helicobacter pylori immunization and atopic dermatitis in South Italian children





United European Gastroenterol J. Aug 2014; 2(4): 263–267.
PMCID: PMC4114125

Abstract

Background

The epidemiological decrease of Helicobacter pylori (Hp) infection has been recently associated to the increase of several extra-intestinal allergic disorders.

Objective

We investigated the role of specific Hp IgG production in the development of IgE or not IgE mediated food allergy (FA) in children affected by atopic dermatitis (AD).

Methods

From January 2010 to July 2013, 290 South Italian children, aged between 26 and 142 months, were consecutively referred to the Pediatric Clinic of the Pediatric Department at Second University of Naples and were diagnosed as affected by AD. The patients were classified in two groups on the basis of diagnosis of food allergy (88 FA affected and 202 not FA affected) and further divided on the basis of the diagnosis of atopy (63 IgE mediated and 23 not IgE mediated). Hp serum IgG was detected using an enzyme linked immunosorbent assay (ELISA) kit (Wampole® Helicobactor pylori IgG ELISA II, Wampole Laboratories, Cranbury, NJ) and Hp stool antigens using enzyme immunoassay (Premier Platinum HpSa plus, Cincinnati OH).

Results

We found a statistically significant higher prevalence of Hp serology positivity in not FA vs. FA AD-affected children (p = 0.032) and a significant inverse association between FA and Hp immunization (1/OR 0.32 95% CI 0.11–0.95). Further, we identified an absolute prevalence Hp serology positivity in not-IgE-mediated rather than in IgE-mediated FA AD-affected patients (p = 0.0006).

Conclusion

We hypothesize that specific Hp IgG production could protect against the development of both FA and atopy in AD-affected children.
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August 9, 2014

Gum pigmentation: an unusual adverse effect of sublingual immunotherapy


Goh A, Chiang WC, Kang LW, Rao R, Lim HH, Chng CK.

Abstract
Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.

KEYWORDS: Adverse effects; Gingiva; Pigmentation; Sublingual immunotherapy

PMID: 25097854 [PubMed] PMCID: PMC4116043 



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Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: dramatic response to Anakinra


Cattalini M, Meini A, Monari P, Gualdi G, Arisi M, Pelucchi F, Bolognini S, Gattorno M, Calzavara-Pinton PG, Plebani A.

Case presentation

Abstract
BACKGROUND:
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory syndrome characterized by recurrent episodes of fever and localized inflammation. Clinical presentation can be very variable in terms of duration of fever attacks, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of migrating skin rash with myalgia that is sustained by monocytic inflammation.
OBSERVATIONS:
We herein present the case of a family suffering from TRAPS who had been misdiagnosed for a long period of time and whose main symptom was migrating angioedema. Skin biopsy from one of the patients documented a monocytic panniculitis. All the living patients responded dramatically to anakinra treatment.
CONCLUSIONS:
The classic symptom of migratory angioedema with myalgia in TRAPS can be produced by monocytic panniculitis.This manifestation is so characteristic of TRAPS that its occurrence, even in the absence of other manifestations, should prompt genetic analysis. Our patient's condition responded promptly to anakinra treatment.

PMID: 24314780 [PubMed - indexed for MEDLINE] 


Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation



Hiroaki Matsuo, Tomoharu Yokooji, Hironobu Morita, Mina Ooi, Kana Urata, Kaori Ishii, Shunsuke Takahagi, Yuhki Yanase, Takaaki Hiragun, Shoji Mihara and Michihiro Hide

ABSTRACT
Background: Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release.
Methods: The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated.
Results: Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls.
Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

KEY WORDS:
aspirin, basophils, food additives, histamine release, NSAID

Received: 5 January 2013.
Accepted: 7 July 2013.

Allergology International 2013; 62: 503-511
doi:10.2332/allergolint.13-OA-0536

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Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study


Inmaculada Martinez-Saguer, Marco Cicardi, Chiara Suffritti, Eva Rusicke, Emel Aygören-Pürsün, Hildegard Stoll, Tanja Rossmanith, Annette Feussner, Uwe Kalina andWolfhart Kreuz


Background

Hereditary angioedema (HAE) is a rare disease caused by C1-esterase inhibitor (C1-INH) deficiency, characterized by periodic attacks of acute edema affecting subcutaneous (SC) tissues and mucous membranes. Human C1-INH concentrate given intravenously (IV) is effective and safe, but venous access may be difficult. We compared SC and IV administration of human pasteurized C1-INH concentrate with respect to pharmacokinetics, pharmacodynamics, and safety.

Study Design and Methods

This was a prospective, randomized, open-label, crossover study. Twenty-four subjects with mild or moderate HAE were randomly assigned during an attack-free interval to receive 1000 units of human pasteurized C1-INH concentrate IV or SC. Plasma levels of C1-INH activity and antigen, C4 antigen, cleaved high-molecular-weight kininogen (clHK), and C1-INH antibodies were measured.

Results

The mean relative bioavailability of functional C1-INH after SC administration was 39.7%. Maximum C1-INH activity after SC administration occurred within 48 hours and persisted longer than after IV administration. C4 antigen levels increased and clHK levels decreased after IV and SC administration, indicating the pharmacodynamic action of C1-INH. The mean half-life of functional C1-INH was 62 hours after IV administration and 120 hours after SC administration (p = 0.0595). C1-INH concentrate was safe and well tolerated when administered via both routes. As expected, SC administration resulted in a higher incidence of injection site reactions, all of which were mild.

Conclusion

With a relative bioavailability of 39.7%, SC administration of human pasteurized C1-INH yields potentially clinically relevant and sustained plasma levels of C1-INH and is safe and well tolerated.

Risk of sensitization and allergy in Ragweed workers - a pilot study

Short report

Open Access

Oliver BrandtTorsten Zuberbier and Karl-Christian Bergmann
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Allergy, Asthma & Clinical Immunology 2014, 10:42  doi:10.1186/1710-1492-10-42
Published: 8 August 2014

Abstract (provisional)

Background

Due to its high allergenic potential Ambrosia artemisiifolia has become a health threat in many European countries during the last few decades. Hence, several cities and communities initiated ragweed eradication campaigns. In Berlin, Germany, so-called Ambrosia scouts are being assigned the task of finding and eliminating this weed.
We sought to evaluate the potential risk of sensitization and allergy in these individuals.
Findings: In order to assess the risk of sensitization and allergy, we followed-up 20 Ambrosia scouts by skin-prick test with inhalant allergens, immunoserological and pulmonary function tests. Additionally, medical conditions were evaluated by a questionnaire especially designed for this study.
Despite close contact to ragweed over a median duration of 13.8 months, none of the participants became sensitized or allergic to ragweed. One individual developed a clinical non-relevant sensitization towards the taxiconomically-related plant mugwort. A decline in relative FEV1 was most probably due to heavy smoking.

Conclusions

Our surprising findings suggest that intensive contact and exposure to high ragweed pollen concentrations do not necessarily result in sensitization and/ or allergy, meaning that the allergenic potential of this weed might be lower than hitherto expected. However, it is also conceivable that continuous exposure to high allergen levels induced tolerance in the ragweed workers.
Due to the relatively small number of subjects studied, our results might be biased and therefore investigations on larger study groups are needed.

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