Hymenoptera-induced anaphylaxis: absence of urticaria/angioedema indicates severe anaphylaxis and possibly mastocytosis

Severe anaphylaxis in Hymenoptera venom allergy is associated with a number of risk factors including elevation of baseline serum tryptase (BST), older age, concomitant diseases, and concurrent medications, such as beta-blockers.

This single-center study from Germany included 650 patients fulfilling the criteria for venom immunotherapy.
4 risk factors of severe anaphylaxis were identified:

- elevation of baseline serum tryptase (BST)
- absence of urticaria or angioedema during anaphylaxis
- time interval of less than 5 minutes from sting to onset of symptoms
- senior age

Absence of urticaria/angioedema is an indicator of severe anaphylaxis and possibly mastocytosis, requiring determination of baseline serum tryptase (BST).

References:

Over- and underestimated parameters in severe Hymenoptera venom-induced anaphylaxis: Cardiovascular medication and absence of urticaria/angioedema. Stoevesandt J, Hain J, Kerstan A, Trautmann A. J Allergy Clin Immunol. 2012 May 1. [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/22554708?dopt=Abstract

How to do skin testing for tetracycline allergy?

What are tetracyclines?

Tetracyclines are antimicrobial agents that have been in use since 1948. The chemical structure consists of four tetra- hydrocarbon rings with a “cycl” derivation.

What type of reactions are caused by tetracyclines?

Although classical hypersensitivity reactions are considered much less common than for beta-lactams and other antibiotics, tetracyclines have been implicated in both IgE- and T cell-dependent reactions such as fixed drug eruption, more severe reactions like DiHS and TEN, and reactions involving specific organs such as liver, lungs, and the central nervous system amongst others.

Tetracylcines can induce phototoxic and photoallergic reactions. These are T cell responses directed to photoadducts which originate in the skin. They usually occur after 5 days of drug administration although they may appear within hours and develop progressively spreading over the skin not exposed to ultraviolet radiation. The most common tetracycline involved in these reactions has been minocycline. Death can occur specially in those patients who develop fulminant hepatitis or respiratory failure.

How to diagnose tetracycline allergy?

General principles recommended for in vivo diagnostic tests can be followed for the diagnosis of hypersensitivity reactions to tetracyclines. These consist of:

- SPT/IDT for immediate reactions
- IDT/patch testing for non immediate reactions

For doxycycline, concentrations of 20 mg/mL can be used for SPT. For IDT with doxycline, the maximum non-irritative concentration recommended is one tenth dilution of this (2 mg/mL).

Concentrations above these can induce false positive reactions.

Concentrations for patch testing of 5% w/v or w/w in petrolatum have been recommended. In the photopatch test the drug is applied on the back using an aluminum chamber and 48 hours later irradiation with a UVA lamp is made with a dose of 10 jls/cm2. Photopatch tests with doxycycline in appropriate dilution are useful to confirm photoallergic reactions to this antibiotic.

How to interpret the skin test?

A negative skin test does not rule out IgE-mediated allergy. If the skin test is negative, the abscene of allergy should be confirmed with a graded dose drug challenge.

A positive skin test with a non-irritating concentration suggests the presence of drug-specific IgE.

References:

Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. Mario Sánchez-Borges et al. World Allergy Organization Journal 2013, 6:18.
http://www.waojournal.org/content/6/1/18

General Considerations for Skin Test Procedures in the Diagnosis of Drug Hypersensitivity. Brockow K, et al., Allergy 2012 (January); 57(1):45-51.
http://onlinelibrary.wiley.com/doi/10.1046/j.0105-4538.2001.00001.x-i8/full

Unmet needs for assessment of small airways dysfunction in asthma will hopefully be met by the ongoing ATLANTIS study

An estimated 300 million people suffer from asthma worldwide. Asthma inflammation affects the entire bronchial tree. The small airways, i.e. less than 2 mm diameter, can be affected by inflammation and remodelling. However, their contribution to asthma control and exacerbations has been minimally investigated. Small airways function can be assessed with invasive and non-invasive techniques, including physiological and radiographic testing, in addition to direct and indirect assessments of inflammation. These tests are usually only available in specialised chest clinics. Unfortunately, there is no gold standard tool, or an easy-to-apply measure, available in which to assess small airways dysfunction (SAD). Thus, there is an unmet need to identify SAD easily and correctly across all severities of asthma, and to assess its role in the control of the disease.

The ATLANTIS study ((AssessmenT of smalL Airways involvemeNT In aSthma) aims to:

1) Determine the role of small airways abnormalities in the clinical manifestations of asthma.

2) Evaluate which (combination of) clinical methods best assesses the abnormalities of small airways and large airways dysfunction in asthma and best relates to asthma severity, control and future risk of exacerbations, both cross-sectional and longitudinal.

3) Further develop and validate the small airways dysfunction tool (SADT).

The ATLANTIS study started in 2014 and the first results are expected in 2016. The data gathered could improve our understanding of small airways pathobiology in asthma and provide a database and sample repository to answer future questions.

References: Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. Postma DS et al. Eur Respir J. 2015 Jun;45(6):1534-8. doi: 10.1183/09031936.00214314.
http://erj.ersjournals.com/content/45/6/1534.long
(free full text)

Thiazolidinediones may provide a new anti-inflammatory approach to asthma

Thiazolidinediones are oral diabetes medications that activate peroxisome proliferator-activated receptor gamma and have anti-inflammatory properties. Some studies have found improvements in pulmonary function in asthma patients treated with thiazolidinediones.



PPAR-alpha and -gamma pathways. Image source: Wikipedia, GNU Free Documentation License.

This cohort study included diabetic Veterans with asthma who were taking oral diabetes medications (2,178 patients were on thiazolidinediones). Thiazolidinediones were associated with reductions in risk of asthma exacerbation (OR = 0.79) and oral steroid prescription (OR = 0.73).

Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids.



Animation of thiazolidinediones mechanism of action and peroxisome proliferator-activated receptors (PPARs).

References:

Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study. Seppo T Rinne et al. Allergy, Asthma & Clinical Immunology 2014, 10:34 (free full text) http://www.aacijournal.com/content/10/1/34

Disclaimer: The editor of this website co-authored the first human study of thiazolidinediones in asthma which was cited in the article (Ann Allergy Asthma Immunol 2012, 109(1):75-77)

The microbiome in asthma

The concept of a “common mucosal immune system” relies on cross-talk between mucosal compartments. A balance must be struck that maintains homeostasis between the microbiome and the host. This balance is constantly challenged by a number of factors leading to “dysbiosis”(imbalance) in the microbial community, which is found in asthma. The microbiome (airway or gut) may play a role in the development of specific phenotypes such as allergic or nonallergic asthma and treatment-resistant asthma. Studies of oral or aerosol administration of the microbiota for the treatment and prevention of asthma are in planning stages.


References:

The microbiome in asthma. Yvonne J. Huang et al. JACI, January 2015, Volume 135, Issue 1, Pages 25–30 (free full text).
http://www.jacionline.org/article/S0091-6749(14)01649-2/fulltext
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