What is Chronic Urticaria Index?

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Patented test, not FDA-approved

"Chronic Urticaria Index" (TM) is a trademarked term and test which consists of basophil histamine release assay. If the test is positive (index greater than 10), the patient may have chronic autoimmune urticaria.

Literature review

The test is nonspecific - it measures only histamine release from the patient's cells and compares it to a normal control. It does not measure antibodies or autoantibodies. Anti-FcεRI may be more specific in patients with chronic autoimmune urticaria. As of December 2, 2009, there are no published studies of the "Chronic Urticaria Index" in medical literature or book references although the general method itself has been described in several journal article.

CU Index (Chronic Urticaria Index) is available from a few reference laboratories (ARUP is one of them). Patients with a chronic form of urticaria with a positive functional anti-FcεR test result likely have an autoimmune basis for their disease. A positive result does not indicate which autoantibody (anti-IgE, anti-FcεRI, or anti-FcεRII) is present. This test is usually combined with thyroid function, antithyroid microsomal titers, and peroxidase antibody titers.

How is the test done?

The result is reported as an index value. The reference range for a healthy non-CU population is less than 10. Values greater than or equal to 10 indicate that donor basophils were stimulated by patient serum to release histamine. The larger the value the more histamine released.

Method:

1. Ex-Vivo challenge and cell culture. Donor blood cells are incubated with patient serum, a negative control and a positive control. Following the ex-vivo challenge, the cells are centrifuged and the supernatant is recovered for assay of histamine released.

2. Histamine analysis. Using a quantitative enzyme immunoassay, the histamine released into the supernatant is measured and compared to the total histamine in the basophils.

The has not been approved or cleared by the FDA.

According to one of the laboratories, "patients with a chronic form of urticaria who are positive with the CU Index (Functional Anti-FcεR test) have an autoimmune basis for their disease. A positive result does not indicate which autoantibody (anti-IgE, anti-FcεRI or anti-FcεRII) is present."

The name "Functional Anti-FcεR test" is a misnomer because the test is really a basophil histamine release assay rather than an assessment of the function of any specific antibody.

Recommendations

Until new evidence becomes available, it is probably better to use anti-FcεRI for assessment of patients with suspected chronic autoimmune urticaria rather than the Chronic Urticaria Index (TM).



Anti-FceR1 autoantibodies in chronic autoimmune urticaria: IgG against FceRI (receptor for IgE) (click to enlarge the image).

References

Urticaria, Chronic: Differential Diagnoses & Workup. eMedicine Specialties > Dermatology > Allergy & Immunology, 2009.
Chronic Urticaria Index™ test. IBT Laboratories (PDF).
Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity. Sabroe RA, Fiebiger E, Francis DM, Maurer D, Seed PT, Grattan CE, Black AK, Stingl G, Greaves MW, Barr RM. J Allergy Clin Immunol. 2002 Sep;110(3):492-9.
Urticaria: A Short Review

Anti-FceR1 Autoantibodies in Chronic Urticaria
Tests for "autoimmune" urticaria - AAAAI Ask the Expert, 2011.
Mind Maps: Urticaria
Mnemonics: Urticaria
Image source: Urticaria, Wikipedia, public domain.

Related books:

13% of patients with anaphylaxis required repeated epinephrine doses

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A medical record review included 208 patients with anaphylaxis. Treatment included epinephrine in 50% of patients. Repeated doses were used in 13%.

The inciting agents were:

- food (29.6%)
- insects (11.1%)
- medications (22.2%)
- others (7.4%)
- unknown (29.6%)

Patients who received repeated doses were more likely to have wheezing, cyanosis, hypotension and shock, stridor and laryngeal edema, nausea and emesis, arrhythmias, and cough. They were also more likely to be admitted to the hospital.


Mind map diagram of anaphylaxis.

References:

Factors associated with repeated use of epinephrine for the treatment of anaphylaxis. Manivannan V, Campbell RL, Bellolio MF, Stead LG, Li JT, Decker WW. Ann Allergy Asthma Immunol. 2009 Nov;103(5):395-400.

Anaphylaxis guidelines by World Allergy Organization. JACI, 2011.

@AllergyNet: Coroner's Report of anaphylactic death due to food allergy in Australiahttp://bit.ly/k2QK0c - A lot to be learned from this tragic episode.

Possible role of vitamin D in the pathogenesis of anaphylaxis

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Epinephrine autoinjector (EpiPen) prescriptions (2006-2007) and anaphylaxis hospital admission rates (2002-2007) were used as surrogate markers of anaphylaxis. Australia is a particularly good place for vitamin D studies as it spans nearly 3000 miles from north to south (http://goo.gl/ZR7hM).

EpiPen prescription rates (per 100,000 population per year) were higher in children from birth to the age of 4 years than in the overall population. Decreasing latitude was associated with a decrease in EpiPen prescription rates - the rates were higher in southern compared with northern regions of Australia. There is more sun exposure in the northern regions (opposite of the U.S.).

Anaphylaxis admission rates showed a similar south-north gradient, such that admission rates were higher in southern compared with northern regions of Australia.

EpiPen prescription rates and anaphylaxis admissions are more common in southern regions of Australia. These data may support a possible role of vitamin D in the pathogenesis of anaphylaxis.

References:

Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis. Mullins, Raymond J.; Clark, Sunday; Camargo, Carlos A. Annals of Allergy, Asthma and Immunology, Volume 103, Number 6, December 2009 , pp. 488-495(8).

EpiPen prescriptions in the U.S. - click to see the results on a map.

Bacterial components plus vitamin D: The ultimate solution to the asthma (autoimmune disease) epidemic? JACI, 2011 (PDF).
Image source: Wikipedia, public domain.

Differences in allergen immunotherapy practices between the United States and Europe

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In regards to allergen specific immunotherapy (SIT), there are significant differences between Europe and the United States in:

- allergen extract regulation
- standardization
- formulation
- types of allergen extracts
- routes of administration
- reimbursement

Most SIT is formulated in US allergists' offices, whereas virtually all SIT is formulated by extract manufacturers in Europe.

Sublingual immunotherapy (SLIT) represents 45% of SIT treatment in Europe but only a small percentage of US allergists (approximately 5.9%) prescribe SLIT.

What are the 4 standardized allergen extracts?

(A) Dog

(B) Trees

(C) Cat

(D) Molds

(E) Dust Mite

(F) Grass

(G) Ragweed

The 4 standardized extracts are Cat, Dust Mite, Grass and Ragweed.

References:
Comparison of allergen immunotherapy practice patterns in the United States and Europe. Cox, Linda; Jacobsen, Lars. Annals of Allergy, Asthma and Immunology, Volume 103, Number 6, December 2009 , pp. 451-460(10).
Image source: OpenClipArt.org, public domain.

Pea Allergy

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Vicilin and convicilin are potential major allergens from pea seeds.

The frequency of pea allergy varies among different populations. Legume allergy, mainly to lentils and chickpeas, is the fifth most common cause of food allergy in Spanish children.

Cross-reactivity between peanut allergy and pea allergy is relatively common. Please review the text below for a detailed description.

Legumes and lentils

Peanuts and soybeans are the major legumes involved in human food allergy. Fewer data exist on adverse reactions to other temperate legumes, such as lentils.

Lentils, chickpeas, beans, and peas are the most common consumed legumes in the Mediterranean area.

Allergic reactions to lentils started early in life, usually below 4 years of age; oropharyngeal symptoms and acute urticaria were the most common symptoms through ingestion, and symptomatic reactivity to chick peas is frequently associated.

Sensitization to lupine is common peanut-sensitized adults

The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients.

39 peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy (Peeters KA et al, Allergy. 2009). Clinical reactivity was measured by double-blind placebo-controlled food challenges (DBPCFC) for lupine, and by history for pea and soy. None of the patients was aware of the use of lupine in food.

82% of patients were sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively.

The lowest eliciting dose (ED) for lupine, inducing mild subjective symptoms, was 0.5 mg.

In this study (Peeters KA et al, Allergy. 2009), peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut.

Cross-reactivity between legumes is common

Serological cross-reactivity among legumes is frequent, but its clinical relevance is controversial. In Spanish study (Martínez San Ireneo M et al, Int Arch Allergy Immunol. 2008), the cross-reactivity among lentils, chickpeas, peas, white beans and peanuts and its clinical relevance was investigated in 54 pediatric patients. All children had a clinical allergy to legumes. Cross-reactivity was evaluated by ELISA inhibition experiments and oral food challenges to legumes.

ELISA inhibition demonstrated more than 80% inhibition with lentil, chickpea and pea extracts. The oral legume challenges demonstrated that 69% of children were allergic to 2 or more legumes (median 3 legumes).

The most frequent associations were allergy to lentils and chickpeas (57%), allergy to lentils and peas (54%) and allergy to lentils, chickpeas and peas (43%).

In vitro inhibition demonstrated a high degree of cross-reactivity among lentils, chickpeas and peas. Food challenges confirmed that clinical allergy to all three legumes is frequent.

References

Clinical features of legume allergy in children from a Mediterranean area. Martínez San Ireneo M, Ibáñez MD, Sánchez JJ, Carnés J, Fernández-Caldas E. Ann Allergy Asthma Immunol. 2008 Aug;101(2):179-84.

In vitro and in vivo cross-reactivity studies of legume allergy in a Mediterranean population. Martínez San Ireneo M, Ibáñez MD, Fernández-Caldas E, Carnés J. Int Arch Allergy Immunol. 2008;147(3):222-30. Epub 2008 Jul 2.
http://www.ncbi.nlm.nih.gov/pubmed/18594152

Vicilin and convicilin are potential major allergens from pea. R. Sanchez-Monge et al. Clinical & Experimental Allergy, Volume 34 Issue 11, Pages 1747 - 1753, 2004.
http://www3.interscience.wiley.com/journal/118792246/abstract

Allergy to lentils in Mediterranean pediatric patients. Pascual CY et al. J Allergy Clin Immunol. 1999 Jan;103(1 Pt 1):154-8.
http://www.ncbi.nlm.nih.gov/pubmed/9893199

Clinical relevance of sensitization to lupine in peanut-sensitized adults. Peeters KA, Koppelman SJ, Penninks AH, Lebens A, Bruijnzeel-Koomen CA, Hefle SL, Taylor SL, van Hoffen E, Knulst AC. Allergy. 2009 Apr;64(4):549-55. Epub 2008 Dec 4.
http://www.ncbi.nlm.nih.gov/pubmed/19076544

Cross Reactions Among Foods (PDF).

Image source: Frozen green peas. Wikipedia, Jina Lee, GNU Free Documentation License.

Video Shows an Unusual Cause of Epistaxis: A Leech

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From the NEJM:



A 44-year-old man presented with a 7-day history of epistaxis on the left side. He reported that he had washed his face in a freshwater stream 7 days before the onset of symptoms.

A suspected blood clot was seen in the left middle turbinate on anterior rhinoscopy, although endoscopic examination showed that the possible clot was a living leech. The leech was retrieved with an aspirator. The epistaxis subsequently resolved.

Acupuncture may reduce itching in atopic dermatitis (eczema)

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Pruritus (itch) is a major symptom of allergic skin diseases. Acupuncture has been shown to reduce histamine-induced itch in healthy volunteers.

The study authors investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double-blind, randomized, placebo-controlled, crossover trial.

An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before and after:

- acupuncture at points Quchi and Xuehai, verum acupuncture (VA)

- 'placebo-point' acupuncture (PA)

- no acupuncture (NA)

Itch intensity was recorded on a visual analogue scale and with a questionnaire. After 10 min, wheal and flare size and skin perfusion (via LASER-Doppler) were measured.

Itch intensity was lower in VA compared to NA and PA. In the preventive approach, wheal and flare size were smaller in VA.

The authors concluded that acupuncture reduced type I hypersensitivity itch in patients with atopic eczema.

Atopic Dermatitis Treatment - Illustrated (click here for full size image).

References:
Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema. F. Pfab et al. Allergy, 11 Dec 2009.

http://www3.interscience.wiley.com/journal/123210618/abstract

Image source: Needles being inserted into a patient's skin, Wikipedia, public domain.

Cause of Eosinophilia: Colonoscopy Video Demonstrating a Moving Worm

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From the NEJM:



A 60-year-old woman presented with abdominal discomfort that had developed over the previous several weeks. Laboratory evaluation was notable for the white-cell count, which included 1.8% eosinophils. Colonoscopy demonstrated a worm, which moved. The worm was 20 cm in length and was removed with an endoscopic snare and identified as Ascaris lumbricoides. The patient was given mebendazole. The abdominal discomfort resolved after the worm was removed.

Related:
Colonoscopy Developer Dies at 94 - NYTimes http://goo.gl/iBnOp - Dr. Wolff was unconventional and surely made headlines in his day.

Bacterial lipopolysaccharide (LPS, endotoxin) and CD14 play a role in development of atopy

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Atopy is highly prevalent and remains the biggest risk factor for asthma. Atopy has a heritable component but is not due to genetic factors alone.

Lipopolysaccharide (LPS) and its bioactive moiety endotoxin are common to all gram-negative bacteria, and have been used as a surrogate of microbial load. Endotoxin is found in dust collected from homes. The structure of a lipopolysaccharide(LPS) is shown on the right (image source: Wikipedia, public domain).

Our innate immune system recognizes LPS via the LPS signal transduction pathway, which has the trimolecular complex of CD14/TLR4/MD2 at the core. CD14 was the first described pattern recognition receptor (PAMP receptor).

TLR4 (for LPS)

CD14

Generally, there is an inverse dose-response relationship between exposure to endotoxin and the risk of atopy.

High exposure to endotoxin in the domestic environment is protective against the development of atopy, but only among carriers of certain alleles.


Pathogen Recognition Receptors, TLRs. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

SNPs associated with atopic diseases

Filaggrin gene

Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene

ORMDL3 protein defects associated with asthma.

5q22-32 gene

CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene

CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene

TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene

IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene

ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene

Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

References:

The role of lipopolysaccharide in the development of atopy in humans. Simpson A, Martinez FD. Clin Exp Allergy. 2009 Nov 25. [Epub ahead of print]
Toll-like receptors (TLRs)

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Role of sphingosine kinase 1(S1P) in allergen-induced pulmonary vascular remodeling and hyperresponsiveness http://bit.ly/1GjMsr

Asthma phenotypes dictate therapy: Only half of asthmatics have increased levels of IL-13–inducible genes http://bit.ly/2cZphR

Swimming pool chlorine increases atopy risk: swimming more than 1000 hr increases risk of allergic rhinitis & asthma http://bit.ly/2VAUwi

Dangerous Anaphylaxis Waiting Game: 40% of people suffering an episode of anaphylaxis wait before seeking med attention http://bit.ly/1HxXan

Hematopoietic stem cell transplantation in SCID results in long-term survival even w/o pretransplantation conditioning http://bit.ly/109xXf

Peripheral blood eosinophil counts could serve as a marker of inflammation to guide asthma therapy http://bit.ly/3T40Yk

Possible association between antibiotic use in first year of life and asthma, AR , and eczema in children 6-7 years old http://bit.ly/4mSZCj

Broad Spectrum Chemokine Inhibitor FX125L Is "Safe and Well Tolerated" in First Human Trial http://bit.ly/1a9qLx

Gelatin is the Culprit in Some Vaccine Reactions http://bit.ly/42A8rx

"The sinus doctor said I have inflamed tornadoes in my nose." - Dr. Grumpy: "You mean inflamed turbinates?" http://bit.ly/4EKtng

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Video: Acetaminophen may be linked to asthma

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From Cleveland Clinic:



"It is one of the most widely-used pain relievers around. But a new study finds acetaminophen may be associated with an increased risk of asthma or wheezing in both adults and children."

This research is preliminary and no evidence-based conclusions can be drawn from it regarding therapeutic changes or recommendations.

Related reading:

Paracetamol (acetaminophen) and Antibiotics in Childhood and Later Wheezing/Asthma: Association or Causation? Medscape, 2011.
"Acetaminophen phobia" is not warranted until we see confirmatory studies in children with asthma. Journal Watch, 2012.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Successful treatment of vocal cord dysfunction (VCD) with low-dose amitriptyline http://bit.ly/6JKaPF

Egg white specific IgE levels - good diagnostic test that could eliminate the need to perform oral challenges in many patients? http://bit.ly/5iOUDJ -- Many allergists will disagree with this statement by the study authors.

IL-10 and IFN-γ production could be defective in allergic children prone to develop polysensitization http://bit.ly/4RyKLV

Phadia Immunocap Blog reviews SLIT http://bit.ly/6wU939 - 6% of U.S. allergists used SLIT in 2006. Dr. Mitchell is a respected proponent of SLIT (http://bit.ly/800b0G) but his blogging skills may need some improvement http://bit.ly/7PsRsk

Food Allergy & Anaphylaxis Network (FAAN) Launches a Redesigned Website http://bit.ly/Q3t2a

Yellow Fever Vaccine Induces a Broad and Polyfunctional Memory CD8+ T Cell Response http://bit.ly/8KzBGX

Alternative medicine: "Asthmatics under anthroposophic treatment had long-term improvements of symptoms and quality of life" http://bit.ly/6pxTiQ

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How to predict who will "outgrow" food allergy to cow's milk: low specific IgE, high IgA and high IgG4

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The development of tolerance in IgE-mediated allergies has been associated with:

- lower cow's milk (CM)-specific IgE levels
- increasing levels of specific IgG4
- increasing IgA

This study investigated if specific antibody responses to CM proteins differ between:

- patients who recovered from cow's milk allergy (CMA) by the age of 3 years (early in life)- patients who developed tolerance only after the age of 8 years (later in life)

83 patients with IgE-mediated CMA were included.

Serum levels were measured for:

- IgE antibodies to cow's milk (CM)
- IgA, IgG1 and IgG4 antibodies to β-lactoglobulin and α-casein

Patients with persistent CMA at the age of 8 years had higher CM-specific IgE levels compared with patients who became tolerant by 3 years. They had lower serum IgA levels to β-lactoglobulin at diagnosis, and lower IgG4 levels to β-lactoglobulin and α-casein at follow-up.

The authors concluded that high cow's milk-specific IgE levels predict the persistence of food allergy.

On the other hand, development of tolerance is associated with elevated levels of β-lactoglobulin-specific IgA at the time of diagnosis, and later increasing specific IgG4 levels to β-lactoglobulin and α-casein.

What is the most common food allergen in children?

(A) Gal d (egg)
(B) Tri a 19 (wheat)
(C) Mal d 1 (apple)
(D) Gly m (soy)
(E) Ara h (peanut)
(F) Bos d (milk)
(G) Api g 4 (celery)

Answer: F.

ImmunoCAP Immunoassay

The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:

1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").

2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.

3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").

Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.


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).

Who will "outgrow" food allergy? It depends on the epitope

Each food is composed of many proteins and these proteins have multiple areas, termed epitopes, to which the immune system can respond. Epitopes that are dependent upon the folding of the proteins are called conformational epitopes. Epitopes that are not dependent upon folding are called linear epitopes.

A linear epitope oftens means a more prolonged allergy which is “stable” and persistent. A conformational epitope (egg, milk) often means a mild, transient allergy.

In children, 85% of cow’s milk, egg, wheat, and soy allergy resolves by five years. In contrast, only 20% of children “outgrow” their peanut allergy, and only 9% of tree nut-allergic patients do so.

References:

Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to β-lactoglobulin. E. M. Savilahti et al. Clinical & Experimental Allergy, 2009.
http://www3.interscience.wiley.com/journal/123197439/abstract
In children, casein-specific IgE linked to cow's milk allergy while IgG4 antibodies possibly linked to tolerance. Clinical and Molecular Allergy 2012, 10:1.
Image source: Wikipedia, GNU Free Documentation License.

Related books:

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

PCDH1 is a Novel Susceptibility Gene for Bronchial Hyperresponsiveness http://bit.ly/71sDHa

Maternal Depression Worsens Child's Asthma http://bit.ly/71TxZj

Xolair Is Effective in Allergics with a Low Serum IgE Level http://bit.ly/8VjHAG

Dirty pigs are healthy pigs - Study finds link between outdoor living and immune health http://bit.ly/8FtuQI

People who work in detergent factories are at increased risk of developing respiratory problems, including asthma http://bit.ly/5ISfnG)

Spreadsheets: Impact of Medicare 2010 Fee Changes by Specialty http://bit.ly/4yc3e4 & Consult Billing http://bit.ly/5nDz4T by Tex Med Assoc. Impact of 2010 Medicare Fee Schedule, by Texas Medical Association (links to Excel Spreadsheets) http://bit.ly/8FcE7M

Immunomodulators in the treatment of asthma (free full text) from Allergy and Asthma Proceedings http://bit.ly/6PxdtF

Sub-Lingual Immunotherapy (SLIT): World Allergy Organization (WAO) Position Paper 2009 http://bit.ly/4WMBMw

David Beckham has had asthma since he was a child http://bit.ly/61Vfwd and http://bit.ly/7kDm96 -- Alice Cooper- Rock Star With Asthma  http://goo.gl/xjBoU

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There is a difference between food sensitization (positive specific IgE) and food allergy. How to predict who will develop allergy?

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Food allergy is common, especially in childhood, where 6–8% of children are affected. Identification of markers for later development of food allergy is important.

This study examined the ability of repeated measurements of food sensitization (by specific IgE) in early childhood to predict doctor-diagnosed food allergy (DDFA) at the age of 6 years.

Blood samples were obtained at 2 and 6 years of age from 1082 children.

Early food allergen sensitization was a strong risk for food allergy (DDFA) at 6 years [odds ratio (OR)=4.7].

Persistent food allergen sensitization increased the risk of food allergy (DDFA) at 6 years even more (OR=6.1).

Early sensitized children with a history of parental atopy showed the highest risk for food allergy (DDFA) at 6 years.

The study authors concluded that food-sensitized children during the first 2 years of life, especially with a family history of atopy, are susceptible to development of food allergy later in life.


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).

References:
Prospective association between food sensitization and food allergy: results of the LISA birth cohort study. E. Schnabel et al. Clinical & Experimental Allergy, 2009.
Images source: Wikipedia, public domain.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, LABA/ICS improved airway function when compared with ICS. Patients should continue to be treated with LABA/ICS irrespective of B16 genotype - The Lancet http://bit.ly/82QEFb

FDA panel recommends against approving omalizumab (Xolair) for severe asthma in children aged 6-11 years - see the AAAAI/ACAAI statement http://bit.ly/5npJgt

Recognize 'discords' of 'immune-system symphonic orchestra', brighten up dark and winding road of immunodeficiencies http://bit.ly/OqOTy

Never Underestimate the Power of a Neutrophil http://bit.ly/7JxmOt

Explore Google images through Swirl interface http://bit.ly/4yGMvi) - See urticaria example http://bit.ly/22hH4i

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Antioxidants for treatment of allergic rhinitis

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Oxidative stress plays a causative role in upper airway inflammation.

Antioxidant therapies for airway inflammation may be grouped into 3 categories:

- endogenous metabolic agents

- vitamins/nutrients

- botanical extracts

Studies examining effects in upper airway inflammation are limited and primarily consist of in-vitro human and in-vivo animal models.

Human studies suggest that subpopulations affected by specific genetic, environmental, dietary factors are most likely to benefit from antioxidant therapy.

My opinion: It is too early to tell. More studies are needed but this is an area that one can keep an eye on.

References:
Novel antioxidant approaches to the treatment of upper airway inflammation. Braskett M, Riedl MA. Curr Opin Allergy Clin Immunol. 2009 Nov 20. [Epub ahead of print].
Image source: Space-filling model of the antioxidant metabolite glutathione. Wikipedia, public domain.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Number of children with food allergies has gone up 18% and number seeking treatment at ER has tripled since 1993. 8.9% of U.S. children had experienced atopic dermatitis in 2007, compared with 7.9% in 1997. Food allergies in children, including peanut allergy, have increased by nearly 20% in the last 10 years http://bit.ly/3AjDHQ

Hypersensitivity reactions to mAbs: experience with rapid desensitization to rituximab, infliximab, and trastuzumab http://bit.ly/30b1xd

Psychological distress from food allergy: Maternal reports of child symptoms were higher than child self-reports http://bit.ly/1HD5ff

Familial atypical cold urticaria: Description of a new hereditary disease. http://bit.ly/77gtV

Add-on omalizumab is effective and well tolerated in children (6-12 years) with allergic asthma not controlled with ICS http://bit.ly/1NnyJR -- Yet, the FDA rejected its approval in this age group in November 2009.

High parental education protects children from non-atopic wheeze due to lower smoking and higher breastfeeding rates http://bit.ly/3GprQJ

A boy with severe food allergy and the dog who saved his life http://bit.ly/2dIHtR

RT @wheezemd "We knew it would happen. Onder Law Firm Offers Free XOLAIR Case Review http://is.gd/4VuXa"

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Oral Tolerance Induction in Children with Egg Allergy

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Currently, the only "treatment" for food allergy is to avoid the allergy-causing food. Some trials of specific oral tolerance induction (SOTI) have been carried out, but the rate of tolerance induction was generally low despite long treatment periods of 3 months to several years.

The objectives of this study were to:

- perform our rush SOTI for school-age patients with severe egg allergy
- evaluate the safety and efficacy of SOTI for one year

Six (6) school-age children (7-12 years of age) with IgE-mediated egg allergy confirmed by double-blind, placebo-controlled food challenge (DBPCFC) underwent rush SOTI. Patients ingested increasing doses of egg several times every day. After rush SOTI, patients ingested the maintenance dose of egg at least twice a week.

All subjects acquired tolerance to more than one whole egg (60g). It took 12 days on average. None experienced a serious reaction.

Laboratory findings after rush SOTI included:

- decrease in IL-10 and an increase in TGF-beta1 at 6 months
- decrease in egg-specific IgE and an increase in egg white-specific IgG(4) at 12 months

The authors concluded that rush SOTI is a safe and effective treatment for severe food allergy and only a few weeks are needed to acquire tolerance. SOTI could replace allergen avoidance as treatment for food allergy.

My opinion: Those are strong conclusions but they stem from a very small study. More evidence is needed before we can make final recommendations.

References:

Rush Specific Oral Tolerance Induction in School-Age Children with Severe Egg Allergy: One Year Follow Up. Itoh N, Itagaki Y, Kurihara K. Allergol Int. 2010 Nov 25;59(1). [Epub ahead of print]
Is specific oral tolerance induction with foods an option in allergic children? JACI News Beyond Our Pages.
Specific oral tolerance (SOTI) cannot be recommended for routine clinical practice for food allergy treatment yet - JACI http://goo.gl/AKBy
Peanut oral immunotherapy is not ready for clinical use - From the experts in the field. JACI, 2010 http://goo.gl/YipT
Office-based oral immunotherapy for food allergy is safe and effective - according to Texas allergist group that use it http://goo.gl/S4N8W
Tolerance to egg-containing baked foods (cake, bread) does not exclude the possibility of egg allergy (AAAAI Ask The Expert).
Ovomucoid- and ovalbumin-specific IgE/IgG(4) ratios  predict reactivity to baked egg. JACI, 2012.
Image source: Wikipedia, public domain.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Combination budesonide/formoterol produced a greater improvement in lung function than budesonide MDI alone http://bit.ly/3BdMVs

Only 29% of parents removed their animals from home after allergist told them to do so for their child's health http://bit.ly/46HvCJ

Literature review: No signs of a declining trend in asthma prevalence http://bit.ly/3HjEDy - Google Trends tells a different story however.

Fatal reactions to SCIT may be on the decline, 6 fatalities between 2001 and 2007 http://bit.ly/2yzWF7

Ovomucoid is the major allergen of egg, strict avoidance is the key in management http://bit.ly/2Q6mbQ

Relationship between hormones and asthma: oral contraceptives may reduce asthma symptoms http://bit.ly/3AtGrM

HRCT is an important diagnostic tool for pulmonary complications in CVID at the time of diagnosis and during follow-up http://bit.ly/30Z4C4

Tricyclic antidepressants should be withheld for 2 to 3 days before allergy skin testing to avoid interference http://bit.ly/1I442X

Lung function at 10 yrs is not improved by early corticosteroid treatment in asthmatic children http://bit.ly/3dfhj4

Treating asthmatic children with montelukast (Singulair) appears effective - the study was sponsored by Merck http://bit.ly/3Fu5tF

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Saline Nasal Irrigation: 2009 Review

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From AFP and Medscape:

Saline nasal irrigation bathes the nasal cavity with liquid or spray by instilling saline into 1 nostril and allowing it to drain out of the other nostril (typically, it drains from both nostrils and the mouth - author's note).

Techniques and devices

Techniques and devices include:

- low positive pressure from a spray or squirt bottle

- gravity-based pressure using a neti pot or other vessel with a nasal spout


SinusRinse video.

Solution concentration

0.9% (normal saline) to 3% (hypertonic) saline solutions are used. Optimal salinity (solution concentration), pH, and temperature are unknown.

Nasal irrigation may be helpful to manage symptoms of chronic rhinosinusitis (symptoms for more than 12 weeks) and this is the most common indication.

In one study, daily use of 2% liquid (not spray) was associated with a 64% reduction in symptom severity vs routine care alone.

Indications

A range of conditions may respond to saline nasal irrigation but the evidence supporting its use is less conclusive:

- allergic rhinitis

- acute upper respiratory tract infections (URTI)

- rhinitis of pregnancy

- acute rhinosinusitis

The exact mechanism of action of saline nasal irrigation is unknown. Saline nasal irrigation may improve nasal mucosa function through direct cleansing; removal of inflammatory mediators, and improved mucociliary function, as suggested by increased ciliary beat frequency.

Adverse effects

Fewer than 10% of patients reported adverse effects:

- self-limited sensation of ear fullness

- "stinging" of the nasal mucosa

- rarely epistaxis

Contraindications

Contraindications for saline nasal irrigation include:

- incompletely healed facial trauma

- increased risk for aspiration, such as intention tremor or other neurologic or musculoskeletal problems.

Recommendations

- For chronic rhinosinusitis, nasal irrigation is an effective adjunctive therapy (level of evidence, A).

- Limited evidence for effective adjunctive treatment of irritant or allergic rhinitis, viral upper respiratory tract infection, and postoperative care after endoscopic sinus surgery (level of evidence, B).

- rhinitis of pregnancy, acute rhinosinusitis, sinonasal sarcoidosis, and Wegener's granulomatosis (level of evidence, C).

References:

Use of Saline Nasal Irrigation Reviewed. Laurie Barclay, MD. Medscape, 2009.

Saline Nasal Irrigation for Upper Respiratory Conditions. Am Fam Physician. 2009 November 15; 80(10): 1117–1119 (PDF).

Nasal Irrigation as part of daily hygiene routine? "They brush their teeth, they wash their face, they rinse their nose" http://goo.gl/F0N11
Neti Pot, Nasal Irrigation - Pros and Cons and Slideshow. WebMD, 2011.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

The Buteyko method: A Breathing Technique Offers Help for People With Asthma http://bit.ly/3ueFU

Early trials of anti-IL-13 therapies in asthma have shown promise, results of further efficacy studies are awaited http://bit.ly/1mZZsC

Vinegar addition during the cooking process may decrease lentil and chicken allergenicity http://bit.ly/1cqOQC

Subcutaneous allergen immunotherapy restores dendritic cell innate immune function http://bit.ly/YAcWI

Paracetamol might be a risk factor for the development of asthma http://bit.ly/4BPdL

Asthma associated with more sweating during exercise in boys, and ICS decrease the amount of sweating http://bit.ly/2E2SJT

Potential treatment for priapism (painful erections longer than 4 hours): adenosine deaminase used for SCID therapy http://bit.ly/1QgPUf

Treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling http://bit.ly/1E3ssJ

Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy, different approach from SCIT http://bit.ly/2CogxY

Asociation between antibiotic use in the first year of life and asthma, rhinoconjunctivitis, eczema at 6-7 years old http://bit.ly/2CZ0ZE

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

T Helper 17 Cells Promote Cytotoxic T Cell Activation in Tumor Immunity http://bit.ly/1I4XYC

Pertussis (Whooping Cough) Immunity May Last 30 Years or More http://bit.ly/18M8m1

The viral march: a connection between early life wheezing and subsequent asthma http://bit.ly/2oFgMw

Budesonide may decrease episodes of wheezing in infants/preschoolers with recurrent wheezing, independently of atopy http://bit.ly/1wNIqS

24 million in US have COPD, but only half know it. Follow NHLBI campaign at http://bit.ly/29IOOp

Beneficial effect of grass allergy immunotherapy tablet on rhinoconjunctivitis quality of life http://bit.ly/2aP0c4

RSS feeds of all Allergy and Immunology journals by the University of Wisconsin http://bit.ly/1QQpQg and http://bit.ly/4zxxdg -- (better view) http://bit.ly/4C9KeM

My list of allergists on Twitter - please reply to this tweet if you want to be included http://bit.ly/2QJLK7

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Omalizumab-associated anaphylactic reactions

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The FDA reports for 2007-2008 were queried for new adverse reactions suspected to be due to omalizumab.

There were 85 cases with an anaphylaxis descriptor and additional 33 cases consistent with anaphylaxis (118 total).

32 reactions occurred after the first dose and 14 were after the second dose of omalizumab.

19 reactions occurred within 1 hour of omalizumab injection.

You can read our case description here: Anaphylactic Reaction to Omalizumab (Xolair) in a Patient with Severe Asthma.

References:

Omalizumab-associated anaphylactic reactions reported between January 2007 and June 2008. Lin RY, Rodriguez-Baez G, Bhargave GA. Ann Allergy Asthma Immunol. 2009 Nov;103(5):442-5.

Image source: Wikipedia, public domain.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Negative predictive value of PCN provocation isn't 100% but none of false negatives had a life-threatening reaction http://bit.ly/3xVAvD

Should common variable immunedeficiency (CVID) patients receive chemoprophylaxis for influenza? http://bit.ly/4coHdD - No good evidence.

High sensitization rate to food allergens in breastfed infants with atopic dermatitis. http://bit.ly/VYCNf

Differences in physicians' knowledge and attitudes toward the black box warning on long-acting beta-agonists http://bit.ly/hbpLU

Improved sleep after treatment of allergic rhinitis. http://bit.ly/2eDBVW

Atopic march is a useful paradigm to describe the clinically observed progression of atopy in certain children. http://bit.ly/8Vkub

Smoking cessation toolbox for allergists - tobacco use treatment 5 A's (ask, advise, assess, assist, and arrange) http://bit.ly/XX2KP

Homozygous mutations in the CARD9 gene are associated with chronic mucocutaneous candidiasis. Dysfunction of CARD9 impairs the innate signaling of dectin-1, an antifungal pattern-recognition receptor http://bit.ly/2JilD5

Cold-Induced Urticaria: Positive ice-cube test & early hive marking edge up cup filled with ice http://twitpic.com/nikxz via @MatthewBowdish

Allergy 2.0: Medical Web 2.0 Guidance Package http://bit.ly/4DouhA

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Intranasal antihistamines as first-line treatment of allergic rhinitis

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Azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%, have rapid onsets of action, are well tolerated, and have clinical efficacy for treating allergic rhinitis that is equal or superior to oral second-generation antihistamines.

Both have a significant effect on nasal congestion. Azelastine is also approved for nonallergic rhinitis.


Medications for Allergic Rhinitis (click to enlarge the image).

Older data suggest that intranasal steroids have greater efficacy than nasal antihistamines but more recent comparisons in mild to moderate allergic rhinitis have shown equal or noninferior efficacy.

In addition, the combination of a nasal antihistamine and intranasal steroid may provide additive benefits in more severe rhinitis. Premixed antihistamine-steroid combinations may offer additional benefits in the treatment of mixed (AR/non-AR) rhinitis.

Azelastine. Image source: Wikipedia, public domain.


Olopatadine. Image source: Wikipedia, public domain.

This literature review supports current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis.

References:

Azelastine and olopatadine in the treatment of allergic rhinitis. Kaliner MA. Ann Allergy Asthma Immunol. 2009 Nov;103(5):373-80.
Allergic Rhinitis: A Short Review
Mind Maps: Allergic Rhinitis
Mnemonics: Allergic Rhinitis
Image source: Wikipedia, a Creative Commons license.

Subcutaneous kallikrein inhibitor ecallantide (Kalbitor) approved for treatment of hereditary angioedema (HAE)

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What is HAE?

Between 8,000 and 10,000 people in the U.S. are affected by the most common form of HAE which is caused by an autosomal dominant mutation that decreases C1 inhibitor levels.

Plasma kallikrein plays a major role in the kallikrein-kinin cascade producing bradykinin. Bradykinin is a vasodilator, which increases vascular permeability, activates inflammation and produces pain.

Ecallantide (DX-88, Kalbitor)

Ecallantide (DX-88, Kalbitor) is a subcutaneous kallikrein inhibitor which was approved for treatment of hereditary angioedema (HAE) in patients 16 years of age and older on December 2, 2009.


New therapies for hereditary angioedema (HAE) (click to enlarge the image).

The drug is to be launched in the first quarter of 2010 and see an ex-U.S. partnership in the first half of next year. Kalbitor is the only approved treatment for life-threatening laryngeal attacks.

The drug's short half-life is the main reason for its suitability as a treatment for acute attacks only and not as a preventive therapy.

Kalbitor has a half-life of about two hours, while Cinryze has a half-life of about 56 hours and Berinert has about 22 hours.

Black-box warning

The labelling of the drug includes a black-box warning for possible allergic reactions which usually occur within 10 minutes of the injection. This means that the injections will typically be administered in a supervised setting (doctor's office) rather than by the patient at home.

As a condition of the FDA approval, Dyax is required to set up a risk management program to warn patients that Kalbitor can cause severe allergic reactions.

Other treatments of HAE

Cinryze is only approved as a preventive therapy.

Berinert was approved by the FDA in October 2009 for only acute abdominal and facial attacks of the disease. HAE patients can self-administer Berinert C1-INH by IV infusion - FDA, 2012. 

References:

Dyax shares soar after FDA approves genetic-disorder drug. Reuters.

Subcutaneous kallikrein inhibitor ecallantide as a treatment for hereditary angioedema (HAE)

FDA Approves Two New Drugs: BioBuzz. TheStreet.com.

Virtually No Relapses After Ecallantide for Acute HAE attacks, despite short half-life. Medscape, 2011.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

People with difficult-to-control asthma are often not taking their anti-asthma medication as prescribed by their doctor. Even when prescribed high doses of inhaled steroids, 5% of adults with asthma remain difficult to control. Women were most apt to be lax in taking their asthma controller medication as prescribed. Among 51 asthma patients who were supposed to be using oral steroids, blood tests showed that 45% were nonadherent http://bit.ly/2Ak9ce -- Difficult asthma may be due to difficult patients http://is.gd/4zFka

Recombinant Major Cat Allergen, Fel d 1, becomes available for immunological investigations, diagnosis and treatment http://bit.ly/v0eac

New antihistamine bilastine 20 mg as effective as levocetirizine 5 mg for treatment of chronic idiopathic urticaria http://bit.ly/4bt89z

The Longest Wheal Diameter Is the Optimal Measurement for the Evaluation of Skin Prick Tests http://bit.ly/3SETBH

Allergy Treatment Pyramid http://bit.ly/AbFMQ

Anaphylaxis action plans http://bit.ly/3SBXWm and Food Allergy Action Plan http://bit.ly/5KryG

If you have asthma, be sure to get the injectable influenza vaccines, not the vaccine nasal spray - AAAAI http://bit.ly/4rQEEQ -- Live attenuated influenza vaccine (nasal spray) not recommended for patients with asthma - it can trigger exacerbation http://bit.ly/4rQEEQ

Sample online appointment form: http://bit.ly/3WcuiK

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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Dysphagia and anorexia/early satiety may distinguish eosinophilic esophagitis from GERD

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Eosinophilic esophagitis (EE) is difficult to distinguish clinically from other causes of esophagitis, especially gastroesophageal reflux disease (GERD).

A prospective study evaluated a symptom scoring tool in patients with EE and patients with GERD, allergic and nonallergic controls.

The total symptom score was higher among patients with EE and GERD.

Only dysphagia and anorexia/early satiety in EE patients helped discriminate EE from GERD. These symptoms also correlated with the severity of histologic and endoscopic findings.

The study authors concluded that dysphagia and anorexia/early satiety identify pediatric patients with EE and correlate symptoms with tissue inflammation.

References:

A symptom scoring tool for identifying pediatric patients with eosinophilic esophagitis and correlating symptoms with inflammation. Aceves SS, Newbury RO, Dohil MA, Bastian JF, Dohil R. Ann Allergy Asthma Immunol. 2009 Nov;103(5):401-6.

Eosinophilic Esophagitis: A Short Review
Mind Maps: Eosinophilic Esophagitis
Mnemonics: Eosinophilic Esophagitis

Image source: Eosinophilic esophagitis, Wikipedia, GNU Free Documentation License.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

Prophylactic antipyretics at the time of vaccination may reduce antibody responses to several vaccine antigens http://bit.ly/BR3XR

FDA requests more information from Novartis prior to QAB149 (indacaterol) approval http://bit.ly/3w6bpH -- QAB149, indacaterol, the first once-daily LABA is already approved in Europe. Noavrtis to address FDA's dosing concerns http://bit.ly/3w6bpH

Omalizumab Highly Effective for Refractory Urticaria in Randomized Trial http://bit.ly/2KCtEX

ICS fluticasone decreases inflammation and FEV1 decline in COPD. Adding LABAs does not enhance these effects. http://bit.ly/1uK7Q4

How does a tick bite trigger a sudden allergy to meat? WaPost http://bit.ly/15CqtN

Belimumab (Benlysta) is a human monoclonal antibody that could become the first new drug for SLE in five decades http://bit.ly/4CSdAq -- Belimumab inhibits B-Lymphocyte stimulator (BLyS), also known as B cell activation factor of the TNF family (BAFF) http://bit.ly/C9aEz

It can happen: Methylprednisolone-induced anaphylaxis http://bit.ly/1Trki9

Eosinophilic panniculitis: a new form of local reaction with specific immunotherapy http://bit.ly/4ev0tC

Th17 immunity may be also involved in the pathogenesis of allergic asthma http://bit.ly/3fIX2s

Medical news tweets are not research articles - they are 140-character messages - please always go to the original source, links, etc. Tweets and links do not represent endorsement, approval or support. Image source: OpenClipArt.org, public domain.

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