Skin prick testing in patients using beta-blockers : a retrospective analysis

Irene N Fung1, Harold L Kim

Abstract
Rationale: The use of beta-blockers is a relative contraindication in allergen skin testing yet there is a paucity of literature on adverse events in this circumstance. We examined a population of skin tested patients on betablockers to look for any adverse effects.

Methods: Charts from 2004-2008 in a single allergy clinic were reviewed for any patients taking a beta-blocker when skin tested. Data was examined for skin test reactivity, type of skin test, concomitant asthma diagnosis, allergens tested, and adverse events.

Results: One hundred and ninety-one patients were taking beta-blockers when skin testing occurred. Seventy-two patients had positive skin tests. No tests resulted in an adverse event.

Conclusions: This data demonstrates the relative safety of administrating of skin prick tests to patients on betablocker treatment. Larger prospective studies are needed to substantiate the findings of this study.

Introduction
Beta antagonists, commonly known as beta-blockers, are a commonly prescribed class of medications. Beta-blockers are used in the treatment of congestive heart failure, coronary heart disease, cardiac arrhythmia, hypertension, tremor, glaucoma, and migraine headache. Importantly, beta-blockers significantly reduce both morbidity and mortality rates in congestive heart failure, in acute coronary syndrome, and post myocardial infarction.

However, beta-blockade may place atopic subjects at an increased risk of an anaphylactic reaction. Case reports suggest that when systemic allergic reactions occur secondary to immunotherapy, drugs, foods, and insects stings, they may be of greater severity in patients taking beta-blockers. Due to the potential of beta-blockers to amplify the effects of anaphylaxis, these drugs are relatively contraindicated during allergy skin testing. The American Academy of Allergy Asthma & Immunology (AAAAI) outlines this in its position statement, stating that Systemic reactions to skin testing are rare. Nevertheless, special precautions, when these are appropriate, should be taken when the patient who needs sensitivity testing for IgE-mediated disease cannot stop treatment with a beta-blocking agent.

However, in our literature review on the topic, no case reports or prospective studies report adverse events in patients on beta-blockers who underwent skin testing. This retrospective study investigates whether there is any increased risk of anaphylaxis in patients who were allergy skin tested while they continued on a beta-blocker medication.

DOWNLOAD COMPLETE PDF HERE

Read More..

The anti-inflammatory effects of levocetirizine - are they clinically relevant or just an interesting additional effect?

Garry M Walsh

Abstract
Levocetirizine, the R-enantiomer of cetirizine dihydrochloride has pharmacodynamically and pharmacokinetically favourable characteristics, including rapid onset of action, high bioavailability, high affinity for and occupancy of the H1-receptor, limited distribution, minimal hepatic metabolism together with minimal untoward effects. Several wellconducted randomised clinical trials have demonstrated the effectiveness of levocetirizine for the treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children. In addition to the treatment for the immediate shortterm manifestations of allergic disease, there appears to be a growing trend for the use of levocetirizine as long-term therapy. In addition to its being a potent antihistamine, levocetirizine has several documented anti-inflammatory effects that are observed at clinically relevant concentrations that may enhance its therapeutic benefit. This review will consider the potential or otherwise of the reported anti-inflammatory effects of levocetirizine to enhance its effectiveness in the treatment of allergic disease.

Introduction
The effects of histamine are exerted through three well defined classical G protein coupled histamine receptor subtypes termed H1R, H2R, and H3R and the more recently described H4R. Histamine signalling through H1R is responsible for the majority of the immediate manifestations of allergic disease. Levocetirizine (Xyzal) is the single R-isomer of the racemic mixture piperazine H1R-antagonist cetirizine dihydrochloride in a once-daily 5mg formulation. The parent compound cetirizine (Zyrtec), a once-daily 10 mg formulation, is also an effective treatment for allergic disease being the most-widely used second-generation antihistamine worldwide. Levocetirizine is a selective, potent, oral histamine H1R antagonist that is licensed in Europe as tablets and oral solution for use in adults and children over 2 years of age for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and chronic idiopathic urticaria.

More recently, levocetirizine tablets under the trade name Xyzal have been approved by the Food and Drug Administration for use in adults and children over 6 years of age in the United States.

Efficacy and safety
Levocetirizine is a potent antihistamine as demonstrated by its ability to inhibit cutaneous histamine-induced itching and the wheal and flare reaction. The histamineinduced wheal and flare model in human skin is a widelyused reproducible and standardized methodology that gives an objective measure of the effectiveness of antihistamines in human subjects, together with any differences in onset and duration of action. The majority of these studies found levocetirizine to be the most potent of the antihistamines tested, including the parent compound cetirizine. Large, well designed controlled clinical trials have demonstrated the efficacy of levocetirizine in adults with allergic rhinitis and chronic idiopathic urticaria, while well conducted studies have demonstrated levocetirizine to be safe and effective in young children with atopic rhinitis or chronic urticaria.
Levocetirizine appears to have significant effects on nasal blockage. The positive effects on nasal congestion are important findings as many antihistamines are ineffective in this regard. Indeed, histamine is not thought to be the primary cause of nasal congestion but a consequence of other mast cell-derived mediators including prostaglandin D2 and leukotrienes acting in concert. The positive effect by levocetirizine on this important symptom of AR is likely due to its additional anti-inflammatory properties (see below).

In terms of its pharmacological profile levocetirizine exhibits rapid absorption and high bioavailability giving a fast onset and long duration of antihistaminic effect. These observed effects are mirrored by calculations of histamine H1 receptor occupancy that show a rapid and long-lasting presence of levocetirizine at its site of action. In terms of safety levocetirizine exhibits a low potential for drug interactions together with a lack of effect on cognition, psychomotor function and the cardiovascular system. Indeed a recent study examined the sedative potential of a comprehensive battery of first, second and newer generation antihistamines (levocetirizine, desloratadine and levocetirizine) by calculating a proportional impairment ratio for each drug based on studies that used standardised objective methodology and psychometric tests. Levocetirizine had the lowest proportional impairment ratio of all the antihistamines reviewed, followed by fexofenadine and desloratadine respectively.

DOWNLOAD COMPLETE PDF HERE

Read More..

Treating rhinitis in the older population: special considerations

Raymond G Slavin

Abstract
Rhinitis in the elderly is a common but often neglected condition. Structural changes in the nose associated with aging, predisposes the elderly to rhinitis. There are a number of specific factors that affect medical treatment of the elderly including polypharmacy, cognitive dysfunction, changes in body composition, impairment of liver and renal function and the cost of medications in the face of limited resources. Rhinitis in the elderly can be placed in several categories and treatment should be appropriate for each condition. The most important aim is to moisten the nasal mucosa since the nose of the elderly is so dry. Great caution should be used in treatment with first generation antihistamines and decongestants. Medications generally well tolerated by the elderly are second generation antihistamines, intra-nasal anti-inflammatory agents, leukotriene modifiers and iprapropium nasal spray.

Rhinitis is a common and bothersome condition in the elderly. Despite its importance, little attention is paid in the general medical literature. In the most recently published highly regarded geriatric text, rhinitis is not included in the index whereas rhinophyma is. The number of Americans older than 65 years of age will increase from 35 million to 86 million by the year 2050. While the exact number of elderly patient with rhinitis is not known, it is believed that 40% of the general population experiences nasal symptoms. It would be safe to say that the many changes that occur in the connective tissue and vasculature of the nose predisposes aging individuals to chronic rhinitis making the percentage of the elderly with nasal symptoms significantly higher than the general population.

The elderly have generalized decrease in body water content and, along with a degeneration of mucous-secreting glands; the effectiveness of the mucociliary system is reduced, resulting in symptoms of nasal stuffiness. In addition, a decrease in nasal blood flow leads to atrophy and drying of the nasal mucous membrane and increased mucous viscosity. Structural changes in the nose with age include atrophy of the collagen fibers and loss of elastic fibers in the dermis. Weakening of the upper and lower nasal cartilage, retraction of the nasal columella, and downward rotation of the nasal tip contribute to an increase in nasal airway resistance.

This article will deal with the special considerations of treating rhinitis in the older population. Appendix 1 lists the specific factors that may affect general medical treatment in the elderly. The elderly patient is frequently being treated for a variety of medical conditions with a number of medications. The more medications that are prescribed the less likely the patient is to comply. Aside from complying with directions for a large number of medications, the elderly patient frequently has cognitive dysfunction with a resultant decrease in memory.

A number of changes in body composition associated with growing older may effect distribution of particular medications. These changes include decrease in muscle mass, fat and body water. Medications metabolized through the liver and kidney may be affected by decrease in function of the organ systems. Finally, many elderly patients have limited financial resources and may simply not be able to afford the cost of the prescribed medications.

DOWNLOAD COMPLETE PDF HERE

Read More..

Introduction of oral vitamin D supplementation and the rise of the allergy pandemic

Matthias Wjst

Abstract
The history of the allergy pandemic is well documented, enabling us to put the vitamin D hypothesis into its historical context. The purpose of this study is to compare the prevalence of rickets, vitamin D supply, and allergy prevalence at 50-year intervals by means of a retrospective analysis of the literature since 1880. English cities in 1880 were characterized by an extremely high rickets prevalence, the beginning of commercial cod liver oil production, and the near absence of any allergic diseases. By 1930 hay fever prevalence had risen to about 3% in English-speaking countries where cod liver oil was preferentially used for the treatment of rickets. In 1980 vitamin D was used nation-wide in all industrialized countries as supplement to industrial baby food, thus eradicating nearly all cases of rickets. At the same time the allergy prevalence reached an all-time high, affecting about 30% of the population.

Time trends are therefore compatible with the vitamin D hypothesis although direct conclusions cannot be drawn. It is interesting, however, to note that there are at least two earlier research papers linking synthesized vitamin D intake and allergy (Reed 1930 and Selye 1962) published prior to the modern vitamin D hypothesis first proposed in 1999.

The vitamin D allergy hypothesis attributes the initial sensitization against allergens during the newborn period to immunological side effects of vitamin D supplements used for rickets prevention. The increasing interest in the vitamin D hypothesis is understandable because all otherhypotheses about the origin of the allergy epidemic have largely failed to provide any clear answers. Moreover, none of the current hypotheses have ever been tested for compatibility with the historical development of the allergy pandemic.

It may therefore be interesting to examine historical data on vitamin D intake and prevalence of allergy. As chosen method, a systematic analysis of articles published in Pubmed since 1950 was combined with a full-text search of all issues of Science and Nature since 1869. Furthermore, current Google book content was searched in addition to a manual search of textbooks for the keywords vitamin D (and chemical analogues) and allergy between 1920 until 1950 (see also acknowledgments).

Allergic manifestations were so rare in 1880 that today they would be considered an "orphan disease". This may reflect a recognition bias in a community that was understandably preoccupied with more pressing, lifethreatening conditions such as cholera, tuberculosis, typhoid and measles. Nevertheless, allergic symptoms were clearly described at that time. The few studies on allergic diseases from the 19th century all rely on a limited number of cases. The British doctor Harrison Blackley wrote in his 1873 book "Hay Fever: Its causes, treatment, and effective prevention": "Even in this country, where the disorder probably had its commencement and where it is still more common than in any other part of Europe, there are medical men to be found who know very little about it; and on the Continent there are still some to be found who have never even heard of the disease". The origins of the disease are vague.

The first formal description of hay fever is usually ascribed to John Bostock, who presented his own case in 1819 to the London Medico-Chirurgical Society. Another description was made in 1859 when the German professor Philipp Phoebus from Giessen published the first large allergy study, which was based on 158 cases. The sample consisted of patients from many hospitals because allergy was such a rare disease. In 1876 the American physician George Beard, a contemporary of Blackley, assembled only 100 patients. At the end of the 19th century, allergy prevalence may therefore be estimated at 0.1% in England, as well as in the United States of America. In continental Europe, it was not until 1906 that the term "Allergie" was introduced by Clemens von Pirquet.

DOWNLOAD COMPLETE PDF HERE

Read More..

The role of Probiotics in allergic diseases

Sonia Michail

Abstract
Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders.

Introduction
Currently, an estimated 20% of the population worldwide is suffering from some form of allergic disorder with a prevalence that continues to rise. For example, the prevalence of childhood asthma in the USA increased by 50% from 1980 to 2000. Atopic diseases involve Th2 responses to allergens. These clinical disorders are characterized by immediate hypersensitivity. Although the exact etiology of allergic diseases remains ambiguous, many investigators have proposed that environmental exposures may be major trigger factors in the development of allergic diseases.

As the rise in prevalence of allergic diseases has been seen mostly in industrialized countries, this led investigators to formulate the hygiene hypothesis in an attempt to explain the basis of the disease. This hypothesis entails that reduced family size and childhood infections have lowered our exposure to microbes, which play a crucial role in the maturation of the host immune system during the first years of life. In addition to environmental factors, the intestinal flora may be a contributor to allergic disease due to its substantial effect on mucosal immunity. Allergic responses are thought to arise if there is absence of microbial exposure while the immune system is still developing. Exposure to microbial flora early in life allows for a change in the Th1/Th2 balance, favoring a Th1 cell response. Several reports suggest that the make-up of intestinal microflora can be different in individuals with allergic disorders and in those who reside in industrialized countries where the prevalence of allergy is higher. For example, children from an industrialized country like Sweden harbor less Lactobacilli and Bifidobacteria (and more Staphylococcus aureus and Clostridia) in their bowels in comparison to children who live in countries like Estonia where allergic disorders are not as common.

The concept that children with allergic disorder harbor a different profile of microflora has been supported by several other studie. Perhaps the most convincing of these is the KOALA study, which examined flora of 957 infants in the Netherlands. The study revealed that C. dificile colonization at one month of age was associated with an increased likelihood of eczema, recurrent wheezing, and atopic dermatitis. E. coli colonization was associated with eczema rather than recurrent wheezing or atopic dermatitis. No association with bifidobacteria colonization, B. fragilis or lactobacilli colonization was observed.

While this concept has been validated in several other studies, there are a few reports that do not show a significant difference in microflora composition. A recent study comparing microflora composition of 324 European infants showed no association between food sensitization or atopic dermatitis and the intestinal bacteria. In general, however, most studies suggest that an association exists.

DOWNLOAD COMPLETE PDF HERE

Read More..