Gum pigmentation: an unusual adverse effect of sublingual immunotherapy

Asia Pac Allergy. 2014 Jul;4(3):177-9. doi: 10.5415/apallergy.2014.4.3.177. Epub 2014 Jul 29.

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] 

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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

Transfusion Volume 54, Issue 6, pages 1552–1561, June 2014

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.

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

Short report

Oliver Brandt, Torsten 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.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Clearing the Air - Asthma and Indoor Air Exposures

Institute of Medicine (US) Committee on the Assessment of Asthma and Indoor Air.

Washington (DC): National Academies Press (US); 2000.

ISBN-10: 0-309-06496-1

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Since about 1980, asthma prevalence and asthma-related hospitalizations and deaths have increased substantially, especially among children. Of particular concern is the high mortality rate among African Americans with asthma.

Recent studies have suggested that indoor exposures--to dust mites, cockroaches, mold, pet dander, tobacco smoke, and other biological and chemical pollutants--may influence the disease course of asthma. To ensure an appropriate response, public health and education officials have sought a science-based assessment of asthma and its relationship to indoor air exposures.

Clearing the Air meets this need. This book examines how indoor pollutants contribute to asthma-- its causation, prevalence, triggering, and severity. The committee discusses asthma among the general population and in sensitive subpopulations including children, low-income individuals, and urban residents. Based on the most current findings, the book also evaluates the scientific basis for mitigating the effects of indoor air pollutants implicated in asthma. The committee identifies priorities for public health policy, public education outreach, preventive intervention, and further research.

Contents

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• THE NATIONAL ACADEMIES
• COMMITTEE ON THE ASSESSMENT OF ASTHMA AND INDOOR AIR
• PREFACE
• ACKNOWLEDGMENTS
• EXECUTIVE SUMMARY
• 1. MAJOR ISSUES IN UNDERSTANDING ASTHMA
  • ORIGIN OF THE STUDY
  • SUMMARY OF THE INDOOR ALLERGENS REPORT
  • DEFINITIONS OF ASTHMA
  • CLINICAL PRESENTATION OF ASTHMA
  • RISK FACTORS FOR ASTHMA
  • TRENDS IN THE PREVALENCE OF ASTHMA
  • MECHANISMS OF ASTHMA
  • EVALUATING THE EFFECTIVENESS OF INTERVENTIONS TO REDUCE ASTHMA
  • REFERENCES
• 2. METHODOLOGICAL CONSIDERATIONS IN EVALUATING THE EVIDENCE
  • EVALUATING THE EVIDENCE
  • SUMMARIZING CONCLUSIONS REGARDING THE EVIDENCE
  • ASSESSING EXPOSURES TO AGENTS IN INDOOR AIR
  • OTHER CONSIDERATIONS
  • REFERENCES
• 3. PATTERNS OF ASTHMA MORBIDITY AND MORTALITY
  • THE BURDEN OF ASTHMA
  • MORTALITY
  • UTILIZATION OF HEALTH CARE SERVICES
  • PREVALENCE
  • SEVERITY
  • TRENDS IN RISK FACTORS
  • TWIN, ADOPTION, AND MIGRANT STUDIES
  • SOCIOECONOMIC STATUS VERSUS RACE OR ETHNICITY
  • ASTHMA RATES IN GERMANY—A NATURAL EXPERIMENT
  • REFLECTIONS ON THE TRENDS
  • REFERENCES
• 4. PATHOPHYSIOLOGICAL BASIS OF ASTHMA
  • AIRWAY INFLAMMATION IN ASTHMA
  • THE AIRWAY SMOOTH MUSCLE IN ASTHMA
  • THE GENETICS OF ASTHMA
  • CONCLUSION
  • REFERENCES
• 5. INDOOR BIOLOGIC EXPOSURES
  • ANIMALS
  • COCKROACH
  • HOUSE DUST MITES
  • ENDOTOXINS
  • FUNGI
  • INFECTIOUS AGENTS
  • HOUSEPLANTS
  • POLLEN
  • REFERENCES
• 6. INDOOR CHEMICAL EXPOSURES
  • NITROGEN DIOXIDE
  • PESTICIDES
  • VOLATILE ORGANIC COMPOUNDS
  • FORMALDEHYDE
  • FRAGRANCES
  • PLASTICIZERS
  • OTHER CHEMICAL EXPOSURES IN THE INDOOR ENVIRONMENT
  • REFERENCES
• 7. EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE
  • DEFINITION OF ENVIRONMENTAL TOBACCO SMOKE (ETS)
  • FACTORS CONTROLLING EXPOSURE TO ETS
  • EVIDENCE OF A RELATIONSHIP BETWEEN ETS AND ASTHMA
  • CONCLUSIONS REGARDING THE HEALTH IMPACTS OF ETS WITH RESPECT TO ASTHMA
  • EVIDENCE REGARDING MEANS OF SOURCE MITIGATION OR PREVENTION
  • CONCLUSIONS REGARDING ETS SOURCE CONTROL OR MITIGATION: FEASIBILITY AND BENEFITS
  • RESEARCH NEEDS
  • REFERENCES
• 8. INDOOR DAMPNESS AND ASTHMA
  • INDOOR WATER SOURCES AND REMOVAL PROCESSES
  • INDOOR DAMPNESS AND RESPIRATORY DISEASE
  • DAMPNESS CONTROL
  • RESEARCH NEEDS
  • REFERENCES
• 9. ASTHMA AND NONRESIDENTIAL INDOOR ENVIRONMENTS
  • BUILDING-RELATED ASTHMA
  • STUDIES OF SCHOOLS
  • CONCLUSION
  • RESEARCH NEEDS
  • REFERENCES
• 10. IMPACT OF VENTILATION AND AIR CLEANING ON ASTHMA
  • THEORETICAL BACKGROUND
  • BUILDING VENTILATION
  • PARTICLE AIR CLEANING: INTRODUCTION AND REVIEW OF CONVENTIONAL PRACTICE
  • REFERENCES
• 11. SUMMARY OF RESEARCH RECOMMENDATIONS AND OVERALL CONCLUSIONS
  • PATHOPHYSIOLOGIC BASIS OF ASTHMA
  • ANIMAL ALLERGENS
  • COCKROACH
  • HOUSE DUST MITES
  • ENDOTOXIN
  • FUNGI
  • INFECTIOUS AGENTS
  • PLANTS
  • NITROGEN DIOXIDE (NO2)
  • PESTICIDES
  • PLASTICIZERS
  • VOLATILE ORGANIC COMPOUNDS
  • FRAGRANCES
  • ENVIRONMENTAL TOBACCO SMOKE (ETS)
  • INDOOR DAMPNESS, MOISTURE PROBLEMS, AND MOISTURE CONTROL
  • NONRESIDENTIAL INDOOR ENVIRONMENTS
  • VENTILATION
  • AIR CLEANING
  • OVERALL CONCLUSIONS
• APPENDIX A THEORETICAL CONSIDERATIONS RELEVANT TO THE INFLUENCE OF VENTILATION AND AIR CLEANING ON EXPOSURES TO INDOOR-GENERATED POLLUTANTS
• APPENDIX B WORKSHOP SUMMARIES
• APPENDIX C COMMITTEE AND STAFF BIOGRAPHIES

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  • PDF version of this title (7.5M)
  Support for this study was provided by the U.S. Environmental Protection Agency (contract no. X825863-01-3). The views presented in the book are those of the Institute of Medicine Committee on the Assessment of Asthma and Indoor Air and are not necessarily those of the funding organization.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

Copyright 2000 by the National Academy of Sciences. All rights reserved.

Bookshelf ID: NBK224477PMID: 25077220

Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis

BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g4643 (Published 05 August 2014)Cite this as: BMJ 2014;349:g4643

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1. 1. 
      
2. 
   
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   A Roy, senior scientist1, 
3. M Eisenhut, consultant paediatrician2, 
4. R J Harris, statistician1, 
5. L C Rodrigues, professor of epidemiology3, 
6. S Sridhar, research associate4, 
7. S Habermann, junior doctor2, 
8. L Snell, junior doctor2, 
9. P Mangtani, senior lecturer3, 
10. I Adetifa, paediatrician and medical epidemiologist5, 
11. A Lalvani, professor of infectious disease4, 
12. I Abubakar, professor of infectious disease epidemiology16

Author affiliations

1. Correspondence to: I Abubakar i.abubakar@ucl.ac.uk

• Accepted 11 July 2014

Abstract

Objectives To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.

Design Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts.

Setting Community congregate settings and households.

Inclusion criteria Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays.

Data extraction Study results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis.

Results The primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77).

Conclusions BCG protects against M tuberculosis infection as well as progression from infection to disease.

Trial registration PROSPERO registration No CRD42011001698 (www.crd.york.ac.uk/prospero/).

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