Intradermal skin test sensitivity and specificity were 75% and 90% in clarithromycin allergy
Clarithromycin is one of the frequently prescribed oral macrolidic antibiotics in the pediatric population (the chemical structure is shown on the right). Suspected adverse reactions to clarithromycin have been relatively often described by parents but there is a lack of reliable detection of specific IgE antibodies.
This Italian study investigated the prevalence of a clarithromycin allergy in children using standardized skin tests and oral provocation tests (OPTs).
64 children were referred with a history of a clarithromycin-associated adverse drug reaction. All these children underwent skin tests and OPTs. The nonirritating intradermal skin test concentration for clarithromycin was determined in a control group of 18 children who had tolerated clarithromycin in the previous month. The nonirritating intradermal concentration was 10:2 dilution (0.5 mg/mL).
9 of the 64 children had an immediately positive intradermal response to the 10:2 dilution and only 1 child to the 10:3 dilution (0.05 mg/mL). None had positive skin prick test results or delayed skin responses to intradermal tests. 4 of 64 children (6%) with previously described adverse reactions due to clarithromycin intake had a positive OPT reaction.
When the intradermal skin test was correlated to the OPT results, intradermal test sensitivity and specificity were 75% and 90%, respectively.
Intradermal tests seem to be useful in workup in children with suspected clarithromycin hypersensitivity and may help reduce the need for OPTs.
Classification of adverse reactions to drugs.
SOAP III mnemonic for classification of adverse reactions to drugs.
References:
Sensitivity and specificity of skin tests in the diagnosis of clarithromycin allergy. Ann Allergy Asthma Immunol. 2010 May;104(5):417-9. Mori F, Barni S, Pucci N, Rossi E, Azzari C, de Martino M, Novembre E.
Drug provocation tests remain the key to diagnosing macrolide allergy http://goo.gl/WM5rj
Pearls and Pitfalls of Allergen Testing - JCAAI http://goo.gl/6ThcC and http://goo.gl/Bfnhn
Image source: Clarithromycin structure, Wikipedia, public domain.
Twitter comments:
@AllergyNet: Macrolide antibiotic allergy: Which tests are really useful? http://j.mp/jAr3zV Bottom line: NONE (except challenge) Full PDF
Walgreens' Sinus Wash
Walgreens' Sinus Wash
Related reading:
SinuSurf (nasal saline rinse with surfactant) associated with loss of smell "for months to years". Discontinue use (PDF) http://goo.gl/awQUP
Allergy and Immunology News from the Journal Nature
Mast cell-orchestrated immunity to pathogens
Although mast cells were discovered more than a century ago, their functions beyond their role in allergic responses remained elusive until recently. However, there is a growing appreciation that an important physiological function of these cells is the recognition of pathogens and modulation of appropriate immune responses. Because of their ability to instantly release several pro-inflammatory mediators from intracellular stores and their location at the host–environment interface, mast cells have been shown to be crucial for optimal immune responses during infection. http://www.nature.com/nri/journal/v10/n6/abs/nri2782.html
Although mast cells were discovered more than a century ago, their functions beyond their role in allergic responses remained elusive until recently. However, there is a growing appreciation that an important physiological function of these cells is the recognition of pathogens and modulation of appropriate immune responses. Because of their ability to instantly release several pro-inflammatory mediators from intracellular stores and their location at the host–environment interface, mast cells have been shown to be crucial for optimal immune responses during infection. http://www.nature.com/nri/journal/v10/n6/abs/nri2782.html
The SYK tyrosine kinase: an evolutionarily ancient crucial player in diverse biological functions
Spleen tyrosine kinase (SYK) is known to have a crucial role in adaptive immune receptor signalling. However, recent reports indicate that SYK also mediates other, unexpectedly diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. SYK is activated by C-type lectins and integrins, and activates new targets, including the CARD9–BCL-10–MALT1 pathway and the NLRP3 inflammasome. There is an evolutionarily ancient origin of SYK-mediated signalling. Moreover, SYK has a crucial role in autoimmune diseases and haematological malignancies. http://www.nature.com/nri/journal/v10/n6/abs/nri2765.html
Spleen tyrosine kinase (SYK) is known to have a crucial role in adaptive immune receptor signalling. However, recent reports indicate that SYK also mediates other, unexpectedly diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. SYK is activated by C-type lectins and integrins, and activates new targets, including the CARD9–BCL-10–MALT1 pathway and the NLRP3 inflammasome. There is an evolutionarily ancient origin of SYK-mediated signalling. Moreover, SYK has a crucial role in autoimmune diseases and haematological malignancies. http://www.nature.com/nri/journal/v10/n6/abs/nri2765.html
More News
PU.1 is a unique transcription factor for the pro-allergic 'TH9 cell' lineage. http://www.nature.com/doifinder/10.1038/nri2793
TLR2 directly regulates TH17 cell responses and TH17 cell-mediated autoimmune disease. http://www.nature.com/doifinder/10.1038/nri2797
K63-linked polyubiquitin chains are potent intracellular signalling molecules of innate immunity. http://www.nature.com/doifinder/10.1038/nri2783
Eosinophilic esophagitis linked to chromosome 5 and TSLP gene
A genome-wide association study has led to the discovery of the first major gene site responsible for the severe food allergy eosinophilic esophagitis (EoE), a disorder that features the accumulation of eosinophils in the esophagus.
The investigators found that EoE, which has been increasing over the past 20 years, is linked to a region of chromosome 5 that includes the TSLP gene, which encodes a hematopoietic cytokine called thymic stromal lymphopoietin (TSLP). They also discovered that the TSLP gene exhibits increased activity in esophageal biopsies from children with EoE. The gene has been previously linked to allergic inflammatory diseases, such as asthma and atopic dermatitis.
Image source: Eosinophilic esophagitis, Wikipedia, GNU Free Documentation License.
Allergies Are Serious but Can Be Treated Effectively with Injections (SCIT)
From the NYTimes:
"Allergy shots have come in for criticism over the years because, well, they are shots and require repeat visits to the doctor’s office — two things children really don’t like.
And many parents may wonder — in some cases, rightfully, alas — whether the allergy doctor is overdiagnosing allergies and overtreating their children. Dr. Cox argues that allergists get to the root of the cause instead of just treating symptoms.
A new study published last month in the peer-reviewed Annals of Allergy, Asthma and Immunology found that allergy shots, also known as immunotherapy, could actually help eliminate allergy symptoms after only 18 months. What’s more, shots may help save you money in the long run. Among the children with allergic rhinitis studied, shots helped to reduce total health care costs by a third, and prescription drug costs by 16 percent, said Dr. Cox, who was a co-author of the study
The first year of allergy shots, which includes a three-month build-up period during which a child receives injections as often as twice a week until the proper dosage is found, would cost a bit less than $1,000 for the year, according to Dr. Cox. The next year, with twice-a-month injections, would total an estimated $350."
References:
A Child’s Allergies Are Serious but Can Be Treated Effectively. NYTimes, 2010.
Image source: OpenClipArt.org, public domain.
Lactose Intolerance Management Guidelines
Many lactose-intolerant individuals can tolerate up to 24 g lactose daily (the amount in 2 cups of milk) if it is ingested throughout the day. Lactose intolerance is not milk allergy.
Lactose reduced milk may be an effective strategy to reduce some lactose intolerance (LI) symptoms.
The new guidelines are available from these websites:
Lactase - Costco.
Summer mailing of timothy grass extract did not reduce potency
Allergen extracts can degrade when exposed to temperatures beyond the optimum storage recommendation of 4 degrees C. Many allergen extracts are mailed to their final destinations throughout the year with exposure to varied environmental conditions.
Standardized timothy grass extracts, 10,000 and 100,000 BAU/mL, were mailed round-trip between San Antonio, Texas, and Phoenix, Arizona, during August 2007. In-transit temperatures were recorded using a temperature logger. Measured extract exposure temperatures were greater than 20 degrees C for 11 days and 30 degrees C for 6 hours during standard mailing in weather temperatures exceeding 38 degrees C.
After mailing of the extracts, the researchers performed in vitro enzyme-linked immunosorbent assay inhibition and in vivo ID50 EAL (Intradermal Dilution for 50-mm Sum of Erythema Determines Bioequivalent Allergy Units) analysis.
These were not statistically significant differences on either test.
Mailing of timothy grass extract produced no significant reductions in in vitro relative potencies or in vivo skin test reactivity in 3 sensitive patients.
Pollen-producing plants (weeds and trees). V. Dimov, M.D.
References:
Effects of summer mailing on in vivo and in vitro relative potencies of standardized timothy grass extract. Moore M, Tucker M, Grier T, Quinn J. Ann Allergy Asthma Immunol. 2010 Feb;104(2):147-51.
"Maintenance and reliever" (M+R) approach to asthma control
The authors examined the efficacy of the maintenance and reliever (M+R) approach in the treatment of asthma exacerbations by database searches using the key words formoterol and budesonide, dynamic dosing, adjustable dosing, and M+R therapy.
Several studies have examined dynamic dosing of the long-acting beta-agonist (LABA) formoterol combined with budesonide in the treatment of asthma. Most of these studies have shown reductions in asthma exacerbations. Although obvious concern arises regarding increase in dose of the long-acting beta-agonist component, no significant signal of morbidity or mortality has been seen.
Potential concerns regarding the studies performed thus far include the fact that all have been sponsored by the pharmaceutical industry and have required beta-agonist response as an inclusion criterion.
Although many of the data regarding this approach are positive, not all the studies have demonstrated efficacy.
References:
Is the maintenance and reliever approach the answer? Oppenheimer JJ, Peters SP. Ann Allergy Asthma Immunol. 2010 Feb;104(2):112-7.
Image source: Combination formulation containing budesonide and formoterol - unopened Symbicort Turbuhaler (left) and opened (middle and right), Wikipedia, public domain.
Profilin is a major allergen in watermelon
Plant profilins have been reported as minor allergens. They are a well-known pan-allergen family responsible for cross-reactivity between plant-derived foods and pollens.
Watermelon profilin is a major allergen in watermelon (Citrullus lanatus).
The aim of this Spanish study was to characterize recombinant watermelon profilin, confirming its reactivity for diagnosis and the development of immunotherapy.
Native profilin was purified from watermelon extract. Recombinant His-tagged profilin was produced. ELISA and immunoblot were carried out with sera from 17 watermelon-allergic patients. Biological activity was tested by basophil activation test.
Similarities were found in the IgE-binding patterns and biological activity of recombinant profilin and native profilin. Recombinant profilin may be useful for diagnosis.
References:
Watermelon Profilin: Characterization of a Major Allergen as a Model for Plant-Derived Food Profilins. Cases B, Pastor-Vargas C, Gil Dones F, Perez-Gordo M, Maroto AS, de Las Heras M, Vivanco F, Cuesta-Herranz J. Int Arch Allergy Immunol. 2010 May 18;153(3):215-222.
Cross Reactions Among Foods (PDF).
Image source: Watermelons on display by a roadside vendor in Delhi, India, Wikipedia, Steve Evans, Creative Commons Attribution 2.0 Generic license.
Increased risk of adverse drug reactions to cephalosporins in patients with penicillin allergy
Cephalosporin administration in patients with a history of penicillin allergy is controversial.
This Mayo Clinic study included a cohort of patients with a history of penicillin allergy and a positive or negative penicillin skin test. 85 patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin.
6% (of the 85 patients) had an adverse drug reaction to cephalosporin as compared to 0.7% of the referent population. The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2% compared to 0.1% of 726 amongst the referent population.
A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. The study authors recommended penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.
Read more here: Which Cephalosporins to Use in Penicillin Allergy?
References:
Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test. Park MA, Koch CA, Klemawesch P, Joshi A, Li JT. Int Arch Allergy Immunol. 2010 May 19;153(3):268-273.
References:
Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test. Park MA, Koch CA, Klemawesch P, Joshi A, Li JT. Int Arch Allergy Immunol. 2010 May 19;153(3):268-273.
Which Cephalosporins to Use in Penicillin Allergy?
There's a 25% chance that patients with hypersensitivity to cephalosporins will also react to penicillins http://goo.gl/SFyE
There's a 25% chance that patients with hypersensitivity to cephalosporins will also react to penicillins http://goo.gl/SFyE
IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. JACI, 2010 http://goo.gl/MHVz5
Image source: Penicillin nucleus, Wikipedia, GNU Free Documentation License.
Solar Angioedema - Local Angioedema Following Sun Exposure
Angioedema is a hereditary or acquired disease characterized by localized non-pitting swelling of the subcutaneous tissue which can affect either skin or mucous membranes.
Acquired angioedema can often be related to a heterogeneous group of factors including physical stimuli, although up to 38% of cases remain idiopathic.
This Italian study describes 5 patients who developed an angioedema following sun exposures. All patients reported an intensely stinging angioedema strictly limited to face and extremities, when exposed to solar light. Urticarial wheals were never observed or reported by patients, and oral antihistamines proved to be of no help in preventing or improving the condition of lesions.
Laboratory and phototesting data ruled out other acquired or inherited diseases characterized by photosensitivity. According to the authors, solar angioedema should be considered a novel clinical entity.
References:
Local Angioedema following Sun Exposures: A Report of Five Cases. Calzavara-Pinton P, Sala R, Venturini M, Rossi MT, Tosoni C, Lodi Rizzini F, Zane C. Int Arch Allergy Immunol. 2010 May 20;153(3):315-320.
Image source: OpenClipArt.org, public domain.
Doxycycline for 3 weeks is effective for treatment of nasal polyps
There is little scientific evidence to support the current practice of using oral glucocorticosteroids and antibiotics to treat patients with chronic rhinosinusitis and nasal polyps.
In a double-blind, placebo-controlled, multicenter trial, 47 patients with bilateral nasal polyps randomly assigned to receive for 20 days either:
- methylprednisolone in decreasing doses (32-8 mg once daily)
- doxycycline (200 mg on the first day, followed by 100 mg once daily)
- placebo
Nose and nasal cavities. Image source: Wikipedia, public domain.
Methylprednisolone and doxycycline each significantly decreased nasal polyp size compared with placebo. The effect of methylprednisolone was maximal at week 3 and lasted until week 8, whereas the effect of doxycycline was moderate but present for 12 weeks.
The study showed a significant effect of oral methylprednisolone and doxycycline on size of nasal polyps, nasal symptoms, and mucosal and systemic markers of inflammation.
References:
Oral steroids and doxycycline: two different approaches to treat nasal polyps. Van Zele T, Gevaert P, Holtappels G, Beule A, Wormald PJ, Mayr S, Hens G, Hellings P, Ebbens FA, Fokkens W, Van Cauwenberge P, Bachert C. J Allergy Clin Immunol. 2010 May;125(5):1069-1076.e4.
Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) have a potential role in chronic rhinosinusitis/polyps http://goo.gl/QAS4r
Intranasal corticosteroids are effective in reducing nasal polyp size and relieving nasal symptoms http://goo.gl/5gcO6
Lack of efficacy of long-term, low-dose azithromycin in chronic sinusitis (3 months) http://bit.ly/o6EEuN
Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. JACI, 2011.
Intranasal antinuclear autoantibodies (ANA) in patients with chronic rhinosinusitis with nasal polyps. JACI, 2011.
Lack of efficacy of long-term, low-dose azithromycin in chronic sinusitis (3 months) http://bit.ly/o6EEuN
Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. JACI, 2011.
Intranasal antinuclear autoantibodies (ANA) in patients with chronic rhinosinusitis with nasal polyps. JACI, 2011.
How common is peanut, tree nut, fish, shellfish, and sesame allergy?
Recent studies suggest an increased prevalence of food-induced allergy and an increased incidence of food-related anaphylaxis.
The researchers performed a cross-Canada, random telephone survey. Food allergy was defined as:
- perceived (based on self-report)
- probable (based on convincing history or self-report of physician diagnosis)
- confirmed (based on history and evidence of confirmatory tests)
Of 10,596 households surveyed in 2008 and 2009, 34.6% responded.
The prevalence of perceived peanut allergy was 1.00%; tree nut, 1.22%; fish, 0.51%; shellfish, 1.60%; and sesame, 0.10%.
The prevalence of probable allergy was 0.93%; 1.14%; 0.48%; 1.42%, 1.18%-1.66%; and 0.09%, respectively.
Because of the infrequency of confirmatory tests and the difficulty in obtaining results if performed, the prevalence of confirmed allergy was much lower - so low that is was not reported in the abstract.
Some of the "culprits" in food allergy. Image source: Mcclatchy-Tribune.
Eight top allergens account for 90 percent of all food allergies. The 8 top allergens can be remembered by the mnemonic TEMPS WFS:
Tree nuts (almonds, cashews, walnuts)
Eggs
Milk
Peanuts
Shellfish (crab, lobster, shrimp)
Wheat
Fish (bass, cod, flounder)
Soy
Eight top allergens account for 90 percent of all food allergies. See more Allergy and Immunology mind maps here.
References:
A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada. Ben-Shoshan M, Harrington DW, Soller L, Fragapane J, Joseph L, St Pierre Y, Godefroy SB, Elliot SJ, Clarke AE. J Allergy Clin Immunol. 2010 May 6.
Food Allergy: A Short Review. Allergy Cases.
Cross Reactions Among Foods (PDF).
Levels of specific IgE that predict food allergy reaction
The level of IgE increases during childhood until about 10 years of age. At age 10, the total IgE reaches a value that is typically maintained throughout adult life.
- egg, 6 kilounits of allergen-specific IgE per liter kU
- milk, 32 kU (or 15 in newer studies)
- peanut, 15 kU
- fish, 20 kU
For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 50% certainty, were identified:
- egg, 2 kilounits of allergen-specific IgE per liter kU
- milk, 2 kU
- peanut, 2 kU
References:
http://www.ncbi.nlm.nih.gov/pubmed/9338535
http://www.ncbi.nlm.nih.gov/pubmed/11344358
http://www.questdiagnostics.com/hcp/topics/immunocap/immunocap.html
Pearls and Pitfalls of Allergen Testing - JCAAI http://goo.gl/6ThcC and http://goo.gl/Bfnhn
Levels of specific IgE that predict food allergy reaction (click to enlarge the image).
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).
Levels of specific IgE that predict food allergy reaction (click to enlarge the image).
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).
Overdiagnosis of Food Allergy: IgE and skin-prick testing should be confined to the realm of experts (allergists). Medscape, 2011.
What are the most common fungal allergens?
Respiratory exposure to a wide range of fungal spores and fragments is almost constant and 189 fungal species are thought to produce allergens.
Many fungi are capable of causing IgE-mediated hypersensitivity in humans. However, the most predominant fungi implicated in allergy belong to the genera Aspergillus, Alternaria, Cladosporium, and Penicillium.
Various fungi including Penicillium and Aspergillus spp. growing in axenic culture. Image source:Wikipedia, Dr. David Midgley Cultures: Dr. David Midgley University of Sydney, Australia, Creative Commons Attribution ShareAlike 2.5 License.
Reviews of allergen sensitization conducted in geographically diverse areas suggest the most common causes of fungal sensitization in populations are Aspergillus, Alternaria and Cladosporium spp. These genera together with Penicillium are frequently among the most common fungi encountered in surveys of airborne fungi in indoor and outdoor environments worldwide.
A recent survey of spore levels in the UK suggests that the combined level of Aspergillus, Penicillium, Alternaria and Cladosporium spores forms approximately 15% of the total airborne fungal matter, much of the rest of which is accounted for by ascospores and basidiomycetes.
References:
Comparative genomics of fungal allergens and epitopes shows widespread distribution of closely related allergen and epitope orthologues. BMC Genomics 2006, 7:251doi:10.1186/1471-2164-7-251.
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