Skin testing useful for diagnosis of contrast medium allergy

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Skin testing in hypersensitivity reactions to iodinated contrast media

Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions.

The study included skin prick, intradermal and patch tests with a series of contrast media in 220 patients with either immediate or nonimmediate reaction.

Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls.

Skin test specificity was 96-100%.

50% of immediate reactors and 47% of nonimmediate reactors were skin test positive.

For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors.

The authors concluded that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism.

Skin testing appears to be a useful tool for diagnosis of contrast medium allergy.

References:

Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study. Brockow K, Romano A, Aberer W, Bircher AJ, Barbaud A, Bonadonna P, Faria E, Kanny G, Lerch M, Pichler WJ, Ring J, Rodrigues Cernadas J, Tomaz E, Demoly P, Christiansen C; European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. Allergy. 2009 Feb;64(2):234-41.

Pearls and Pitfalls of Allergen Testing - JCAAI http://goo.gl/6ThcC and http://goo.gl/Bfnhn
3% of patients who are exposed to iodinated contrast media develop delayed hypersensitivity reactions. Skin prick test is negative but the patch test is positive. Medscape and JACI, 2011.
Image source: Wikipedia, GNU Free Documentation License and public domain.

Twitter comments:

@AllergyNet: Do you feel a reasonable clinical approach is to give all reactors the same advice and forgo skin testing?

@Alergy: Yes. Pre-procedure protocols generally work well. We do not do routine testing at this time: http://goo.gl/uPVvY

Photos: Skin Prick Testing from a Patient's Perspective

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From Willsfca's photostream (a Creative Commons license):


"Halfway through: After about 20 little shots of allergens. There were 42 total. I didn't think they would shoot them one at a time, but they did. This was only for the indoor allergens. There's another round later for the outdoor ones."


"Dust mites and cats: apparently i'm allergic to both types of dust mites and cats."

References:
Diagnosing Allergy: A Short Review
Procedure Guide: Allergy Skin Prick Testing

JACI: Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008

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- a rise in anaphylaxis in a population-based study

- lower rates of peanut allergy in Israel, where infants consume peanut products early

- IgE epitope mapping that discloses the likelihood and severity of allergy

- correlating likelihood of clinical reactivity with food-specific IgE to sesame, peanut, milk, and tree nuts

- majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods

- promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity

- skin barrier dysfunction is important in the pathophysiology of atopic dermatitis (AD)

- immunologic defects contribute to the propensity of patients with AD to develop viral and bacterial infection

References:
Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008. Sicherer SH, Leung DY. J Allergy Clin Immunol. 2009 Feb;123(2):319-327.

Topical treatments in atopic dermatitis may lead to contact dermatitis

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640 children with atopic dermatitis (AD) were patch tested with 7 agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child.

41 positive patch tests were found in 6% of patients.

Allergens were:

- emollients (47%)
- chlorhexidine (42%)
- hexamidine (7.5%)
- tixocortol pivalate and bufexamac (2.5% each)

Risk factors associated with sensitization to AD treatment were:

- AD severity
- AD onset before the age of 6 months
- IgE-mediated sensitization

The authors concluded that topical treatments for AD are associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers.



Atopic Dermatitis Treatment - Illustrated (click to enlarge the image).

References:

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children. Mailhol C, Lauwers-Cances V, Rancé F, Paul C, Giordano-Labadie F. Allergy. 2009 Jan 29.

Image source: Moisturizer, White Petrolatum (vaseline), Wikipedia, GNU Free Documentation License.

Olopatadine eye drops superior to fluticasone nasal spray for allergic conjunctivitis

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Olopatadine hydrochloride is an antihistamine and mast cell stabilizer, sold as a prescription eye drops (trademark Pataday, 0.2.%, QD or Patanol, 0.1%, BID), manufactured by Alcon). A nasal spray formulation is sold as trademark Patanase.


Olopatadine. Image source: Wikipedia, public domain.


Fluticasone furoate, Veramyst (US) and Avamys (EU and Canada), is different in structure from fluticasone propionate (see below). Image source: Wikipedia, public domain.


Fluticasone propionate, Flonase (US and Canada) Flixonase (EU and Brazil). Image source: Wikipedia, public domain.

In a study of 60 patients, olopatadine 0.2% ophthalmic solution showed superiority over fluticasone furoate nasal spray for ocular itching, redness, tearing, chemosis, and eyelid swelling.

The authors concluded that olopatadine was statistically and clinically superior to fluticasone nasal spray for the relief of signs and symptoms of allergic conjunctivitis.

Fluticasone furoate nasal spray is the only intranasal corticosteroid to reduce the ocular symptoms of seasonal allergic rhinitis consistently, JACI, 2010. http://goo.gl/oQ2n2


Classification of ocular allergy


Medications for Allergic Conjunctivitis



Ocular antihistamines (eye drops) (click to enlarge the image)


Ocular allergy. V. Dimov, M.D., 09/2008.

References:
A comparison of olopatadine 0.2% ophthalmic solution versus fluticasone furoate nasal spray for the treatment of allergic conjunctivitis. Rosenwasser, Lanny et al. Allergy and Asthma Proceedings, Volume 29, Number 6, November/December 2008 , pp. 644-653(10)
Ocular Allergy: Allergic Conjunctivitis and Related Conditions, a Short Review
Mind Maps: Allergic Conjunctivitis
Mnemonics: Allergic Conjunctivitis

Rapid diagnosis of bacterial sinusitis using a simple test of nasal secretions

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Diagnosis of sinusitis is often made based on history and physical exam. Sinus films or CT scans are helpful but expensive.


Nose and nasal cavities. Image source: Wikipedia, public domain.


Left-sided maxillar sinusitis (absence of the air transparency of left maxillar sinus). Image source: Wikipedia, public domain.

The authors studied whether analysis of 4 four easily measured substances in nasal secretions could predict bacterial sinusitis:

1. protein
2. pH
3. leukocyte esterase
4. nitrite

Those 4 substances are the same ones tested by the urine dipstick used to diagnose UTI.

A scoring system was developed to compute the results of the 4 assays in a single clinical score.

All patients with scores of 0 or 1 were CT or x-ray negative for bacterial sinusitis. All patients with scores higher than 4 were imaging study positive.

The authors concluded that combining 4 simple assays on nasal secretion can rule in or rule out bacterial sinusitis in 90% of patients.

Twitter comments: the tweets below are part of the series Medical Geek Humor on Twitter:

AllergyNotes Diagnosis of bacterial sinusitis (>90%) using a test of nasal secretions (4 = protein, pH, leuk esterase, nitrite) http://tinyurl.com/aqe6vy 21 minutes ago from TweetDeck

grahamwalker @AllergyNotes Re: bact sinusitis: Hmm. Can you just use a urine dipstick then? 9 minutes ago from web in reply to AllergyNotes

AllergyNotes @grahamwalker: "Re: bact sinusitis: Hmm. Can you just use a urine dipstick then?" - I don't think investigators looked at it from that point. You should email them. Full text is subscription only. 5 minutes ago from TweetDeck in reply to grahamwalker

A typical medical urinalysis (UA) usually includes:

- pH - normally 4.8 to 7.5.
- protein - normally negative (absent)
- nitrites
- leukocyte esterase


UA shows gross hematuria and bacteria. Image source: ClinicalCases.org.

References:
Rapid diagnosis of bacterial sinusitis in patients using a simple test of nasal secretions. Huang, Shih-Wen; Small, Parker A. Allergy and Asthma Proceedings, Volume 29, Number 6, November/December 2008 , pp. 640-643(4)
Hematuria and Weight Loss due to Bladder Cancer

Medical Geek Humor on Twitter

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From @Allergy:

- Question: "Do you have any wheezing?" -- Answer: "My hearing is bad, so even if I have, I can't hear it."

- Transcriptionist made up a new word for an asthma dictation: "Since she was not able to tolerate beta agonase" - Correct: "beta-AR2 agonist"

- Dictation transcribed: "He has a remote history of history, not symptomatic now." - It was supposed to be "remote history of asthma".

- Creative transcription: "He is allergic to marijuana" - It was supposed to be: "He is allergic to weed".

- "7-10% of patients with oral allergy syndrome may have systemic reactions, 1% of them may have anaphylaxis" was transcribed as "70% of patients with oral allergy syndrome may have systemic reactions, one of them may have anaphylaxis".

Natural history of food allergy in Israel

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Non-IgE-mediated food allergy (particularly milk and soy allergy) were likely to resolve completely with time.

Sesame allergy (IgE mediated) was one of the most frequent allergies but resolved in only very few patients.

References:
Natural history of food allergy in infants and children in Israel. Aaronov D, Tasher D, Levine A, Somekh E, Serour F, Dalal I. Ann Allergy Asthma Immunol. 2008 Dec;101(6):637-40.
Sesame Food Allergy: Questions and Answers
Image source: Wikipedia, public domain.

Apoptosis Animation

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Apoptosis Animation:

"This stunning Maya animation covers the death receptor signaling pathway that originates with binding of the Fas/TNF family of ligands, triggering of the caspase cascade, cytochrome C release from the mitochondria, apoptosome activation, and ensuing signal amplification."

View the animation movie (35 MB)


This video describes the process by which apoptosis is activated by T cells. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

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.

• Children with eczema are 54 percent more likely to have ADHD http://is.gd/k3eN
  
  
• 20 percent of children in Western nations have atopic eczema by age 6 http://is.gd/k3eN
  
  
• Anaphylactic reaction after the first dose of sublingual immunotherapy with grass pollen tablet http://is.gd/k82a
  
  
• Sorbitan Sesquioleate (SSO), a Common Emulsifier in Topical Corticosteroids, May be an Important Contact Allergen http://is.gd/k3gE
  
  
• MMR-vaccinated children are less often hospitalized with asthma and use less asthma medication than unvaccinated children http://is.gd/k3gX
  
  
• Psoriasis Drug Raptiva (Efalizumab) Linked to progressive multifocal leukoencephalopathy (PML) in 3 Cases http://is.gd/k9dX
  
  
• Raptiva (Efalizumab) already has a black box warning about the risk of life-threatening infections, including PML http://is.gd/k9dX
  
  
• Efalizumab (Raptiva) is a recombinant humanized monoclonal antibody that binds to CD11a, a component of LFA-1 (integrin) http://is.gd/k9fK
  
  
• "Hundreds of people on this 747 were about to release almond particles into the air at once & I'm allergic to tree nuts" http://is.gd/k9gv
  
  
• Headline of the day: "It can get nutty at 30,000 feet" - a comment on food allergies and airlines http://is.gd/k9qt

Image source: OpenClipArt.org, public domain.

Body fat, lower HDL and higher LDL associated with greater risk of allergic sensitization

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Obesity and allergic diseases have increased dramatically in recent decades.

This study included 1187 rural Chinese twins with skin prick tests, anthropometric and dual-energy x-ray absorptiometry-assessed adiposity measures, and lipid assessments.

Allergic sensitization was defined as positive SPT to one or more allergens (9 foods and 5 aeroallergens tested).

Men had higher rates of allergic sensitization (56.2% vs 36.7%) than women.

Higher percent of body fat (adiposity), lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in men.

References:
Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women. Ouyang F, Kumar R, Pongracic J, Story RE, Liu X, Wang B, Xing H, Liu X, Li Z, Zhang W, Fang Y, Zhang S, Xu X, Wang X. J Allergy Clin Immunol. 2009 Jan 7.

Monounsaturated fats found in vegetable oils, nuts and avocados increase "good" HDL cholesterol levels by 12% http://goo.gl/GBQa5
Image source: Cholesterol. 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.

• Homeopathic hot pepper nose spray with capsaicin relieves allergic rhinitis? http://is.gd/jRR7
  
  
• Patients in the study with Sinol-M hot pepper nose spray instructed to use it as needed up to 12 times a day for hay fever http://is.gd/jRR7
  
  
• Quadrivalent meningococcal glycoconjugate vaccine is more immunogenic than the currently licensed unconjugated vaccine http://is.gd/jTk8
  
  
• Updated recommendations for the use of quadrivalent (serogroups A, C, Y, and W-135) meningococcal conjugate vaccines http://goo.gl/BPwON
• 
  
• DNA vaccines may be used to treat allergy in the future, Medscape: http://tinyurl.com/d68zzd
  
  
• Mechanism of DNA vaccines for allergy: vaccines could polarize dendritic cells to induce antiallergic T regulatory cells http://is.gd/jTm2
  
  

Image source: OpenClipArt.org, public domain.

Prostatic kallikrein (PSA): A new major dog allergen

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Dog dander is an important cause of respiratory allergy, but the spectrum of known dog allergens appears incomplete.

The 2 lipocalins, Can f 1 and Can f 2, and serum albumin, Can f 3, do not fully account for the IgE antibody-binding activity of dog dander extract.

The study authors focused on allergen activity of dog urine.

Dog urine was fractionated by size exclusion chromatography and examined for IgE antibody binding. One particular protein displaying IgE antibody-binding activity was identified by N-terminal sequencing and mass spectrometry.

This IgE antibody-binding protein isolated from dog urine was identified as prostatic kallikrein.

Prostatic kallikrein bound IgE antibodies from 70% of subjects with dog allergy, some of which reacted to none of Can f 1, Can f 2, or Can f 3.

The authors concluded that prostatic kallikrein was a new major dog allergen.

In addition, dog prostatic kallikrein cross-reacts with human prostate-specific antigen (PSA), a key culprit in IgE-mediated vaginal reactions to semen.

Kallikreins are peptidases (enzymes that cleave peptide bonds in proteins), a subgroup of the serine protease family. There are at least 15 known kallikreins. Prostate specific antigen (PSA) is a kallikrein which liquefies the semen and allows sperm to swim freely.


Mind map: Indoor allergens


Mind map: Animal Dander Avoidance

See more Allergy and Immunology mind maps at AllergyCases.org.

References:
Prostatic kallikrein: A new major dog allergen. Mattsson L, Lundgren T, Everberg H, Larsson H, Lidholm J. J Allergy Clin Immunol. 2009 Jan 7.
Prostate specific antigen, from Wikipedia, the free encyclopedia.
CNN: Allergic and wheezing, but still keeping pets
From the Blogosphere: Barrack Obama's Daughter Has Asthma, Gets a Hypoallergenic Dog
Indoor Allergen Avoidance. Allergy Cases.
Children with a family history of allergies are less likely to develop eczema if they live with a dog starting in infancy http://goo.gl/gost

Video: A neutrophil chasing bacteria

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Video: A neutrophil chasing bacteria, set to music.

Airlines and Peanut Snacks

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From Twitter:

• Re-introduction of peanuts on Northwest Airlines prompt protests from allergy sufferers http://is.gd/jIzO
  
  
• "If someone is sitting next to her and eating peanuts, the odor is enough to trigger an allergic reaction" http://is.gd/jIzO
  
  
• NWA and peanut allergy: "We'll create a buffer zone of three rows in front of and three rows behind your seat" http://is.gd/jIzO
  
  
• According to most studies, skin contact or inhalation are unlikely to cause systemic reactions in food-allergic patients http://is.gd/jIL1
  
  
• Airlines that don't provide packaged peanuts are Air Canada, AirTran, American, Continental, JetBlue, Midwest, Sun Country, United and US Airways.
  
  
• If alerted that someone with a peanut allergy is on board, Southwest will not serve peanuts on that flight.
  
  

Eight top allergens account for 90 percent of all food allergies. The 8 top allergens can be remembered by the mnemonic TEMPS WFS.

Two of the few studies showing a correlation between "inhalation" of food particles and allergic reactions consisted only of self-reported events. Please see the discussion below.

Skin contact and inhalation

Allergic reactions occur after ingestion. Skin contact or inhalation are unlikely to cause systemic reactions in food-allergic patients.

Contact urticaria to peanut is not uncommon but systemic reactions secondary to skin exposure are unlikely.

There is a difference between smelling a food and inhaling an aerosolized food.

In inhalation of aerosolized food, there is a contact between actual food matter and the respiratory mucosa in the nose and lungs.

Aerosolization of food can occur in boiling, frying, grating, shredding, grinding.

Inhalation of aerosolized food can induce wheezing in sensitive individuals.

References:
Northwest serving peanuts again: Families of children with allergies angry over snack change. Suzanne Ziegler | McClatchy/Tribune newspapers, 02/2009.
Food Allergen Avoidance
Food Allergen Avoidance. UpToDate, 16.2.
Self-reported allergic reactions to peanut on commercial airliners. Sicherer SH, Furlong TJ, DeSimone J, Sampson HA. J Allergy Clin Immunol. 1999 Jul;104(1):186-9.
Allergic reactions to peanuts, tree nuts, and seeds aboard commercial airliners. Comstock SS, DeMera R, Vega LC, Boren EJ, Deane S, Haapanen LA, Teuber SS. Ann Allergy Asthma Immunol. 2008 Jul;101(1):51-6.

Related:
Hiding from nuts on planes. CNN.

Parents upset children use extensive cleaning measures to ensure they don’t sicken a classmate with peanut allergy http://goo.gl/mK2Qb

Peanuts on planes protected by a law passed in 1999 - CNN.

"Allergic to cashews, but thought it would be OK to eat almonds on AirFrance flight" - allergist on board saved his life http://goo.gl/P8Yh4

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.

• Re-introduction of peanuts on Northwest Airlines prompt protests from allergy sufferers http://is.gd/jIzO
  
  
• "If someone is sitting next to her and eating peanuts, the odor is enough to trigger an allergic reaction" http://is.gd/jIzO
  
  
• NWA and peanut allergy: "We'll create a buffer zone of three rows in front of and three rows behind your seat" http://is.gd/jIzO
  
  
• According to most studies, skin contact or inhalation are unlikely to cause systemic reactions in food-allergic patients http://is.gd/jIL1
  
  
• Comparison of SLIT vs budesonide in mild persistent asthma due to grass pollen: equally effective http://is.gd/jidB
  
  
• SLIT vs budesonide in asthma- It may not be "fair" to compare the seasonal use of budesonide to the continuous use of SLIT http://is.gd/jidB
  
  
• Onset of action of ciclesonide in the treatment of seasonal allergic rhinitis: 6 hours http://www.ncbi.nlm.nih.gov...
  
  
• CCR5-delta32 mutation reduces risk of nonatopic asthma http://www.ncbi.nlm.nih.gov...
  
  
• Fetal Exposure to Traffic Pollution May Affect Asthma Risk http://is.gd/jIAC

Image source: OpenClipArt.org, public domain.

Traffic exposure associated with decreased lung function in asthma

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A growing body of scientific literature supports the concept that exposure to roadways with high traffic density is associated with adverse general health and asthma effects. Heavy-duty diesel-powered vehicles like trucks and buses are often driven more frequently on roadways with high traffic density and, as such, diesel exhaust has been suspected to be a major cause of traffic-associated asthma morbidity.

Diesel exhaust is similar to tobacco smoke in that it is a mixture of particles and gases with many chemical constituents. Diesel exhaust particulate (DEP) is mostly carbon with 20–40% adsorbed organic compounds, but sulfates, nitrates and metals are also present.

In a cohort of adults with asthma or rhinitis (176 adults; 145 with asthma), the study authors assessed exposures to traffic by geocoding subjects' residential addresses and assigning distance to roadways.

FEV1% predicted was positively associated with distance from both nearest roadway and nearest major roadway.

Quality of life (QoL) was not significantly associated with either traffic variable.

Traffic exposure was associated with decreased lung function in adults with asthma.

References:
Exposure to traffic: Lung function and health status in adults with asthma. Balmes JR, Earnest G, Katz PP, Yelin EH, Eisner MD, Chen H, Trupin L, Lurmann F, Blanc PD. J Allergy Clin Immunol. 2009 Jan 17.
Fetal Exposure to Traffic Pollution May Affect Asthma Risk. Todd Neale, Staff Writer, MedPage Today.

How does diesel exhaust impact asthma? Thorax, 2010.
Image source: Interstate 80, seen here in Berkeley, California, is a freeway with many lanes and heavy traffic, Wikipedia, GNU Free Documentation License.

Montelukast (Singulair) Not Effective in Controlling Allergic Symptoms Outside the Airways

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Patients with atopic syndromes often perceive symptoms from various organs. A single drug that acts on all the syndrome's manifestations would be the ideal treatment.

Montelukast (Singulair), a cysteinyl-leukotriene receptor antagonist, is well-established in treatment of allergic rhinitis and asthma.

The effect of montelukast was assessed in a randomised, double-blind, placebo-controlled crossover study of 45 pollen-sensitised subjects who had allergic symptoms from both the upper and lower airways and allergic symptoms outside the airways (conjunctivitis, oral symptoms, eczema and/or urticaria).

Montelukast was not effective in treating allergic symptoms outside the airways. It should be considered only as a drug for asthma and rhinitis.

Montelukast should not be prescribed in urticaria, conjunctivitis and atopic dermatitis.

Leukotriene Receptor Antagonists (LTRA)

Antagonists of the CysLT1 receptor (LTRA) are efficacious as controller therapy in asthma and montelukast is FDA-approved for treatment of seasonal allergic rhinitis.

Mast cells quickly generate different mediators from the metabolism of arachidonic acid: leukotrienes and prostglandins (LTC4, LTB4, PGD2). These substances are produced within minutes of IgE-receptor crosslinking on the surface of mast cells.


Eicosanoids are signaling molecules made by oxygenation of 20-carbon essential fatty acids. There are 4 families of eicosanoids (PP-LT): prostaglandins (PG), prostacyclins (PGI), leukotrienes (LT) and thromboxanes (TX).


Mast cell mediators including (PP-LT): prostaglandins (PG), prostacyclins (PGI), leukotrienes (LT) and thromboxanes (TX). See more Allergy and Immunology mind maps here.

What is the most potent bronchoconstrictor?

(A) LTB4

(B) LTC4

(C) acetylcholine

(D) histamine

(E) thromboxane A2 (TXA2)

(F) methacholine

Answer: B

CysLTs are the most potent bronchoconstrictor agents yet discovered, about 100-1000 times more potent than histamine. The second most potent bronchoconstrictor is thromboxane A2 (TXA2).

Cysteinyl‐LTs and LTB4 are, respectively, the most potent bronchoconstrictor agents and one of the most effective leukocyte chemotaxins yet.

References:

Montelukast Is Not Effective in Controlling Allergic Symptoms Outside the Airways. A Randomised Double-Blind Placebo-Controlled Crossover Study. Lehtimäki L, Petäys T, Haahtela T. Int Arch Allergy Immunol. 2009 Jan 6;149(2):150-153.

Urinary leukotriene E(4)/exhaled nitric oxide ratio predicts montelukast response in childhood asthma http://goo.gl/i5cG
Montelukast failure index that may be helpful in predicting response in patients with asthma http://goo.gl/AzRPF
Mast Cells and Basophils. Allergy Cases.
Pathogenesis of Asthma. Allergy Cases.
Image source: Montelukast, from Wikipedia, the free encyclopedia, public domain.

Rhinitis/sinusitis and asthma relationship is a "two-way street"

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The upper and lower airways do not exist as separate units both neither anatomically nor functionally.


Nose and nasal cavities. Image source: Wikipedia, public domain.

There is a 2-way relationship between the nose/sinuses and lower airway:

1. Allergic rhinitis and rhinosinusitis may impact asthma and those patients should be monitored for development of asthma.

2. Patients with asthma should be considered to have either rhinitis or rhinosinusitis.


Left-sided maxillar sinusitis (absence of the air transparency of left maxillar sinus). Image source: Wikipedia, public domain.

The 1999 WHO workshop ‘Allergic Rhinitis and its Impact on Asthma’ recommended:

- patients with persistent allergic rhinitis should be evaluated for asthma by history, chest examination, and possibly assessment of airflow obstruction before and after bronchodilator

- history and examination of the upper respiratory tract for allergic rhinitis should be performed in patients with asthma

References:
The upper and lower airways: The epidemiological and pathophysiological connection. Slavin, Raymond G. Allergy and Asthma Proceedings, Volume 29, Number 6, 11/12 2008 , pp. 553-556(4).
More than a "runny nose" - allergic rhinitis and asthma

Adult Sinusitis: A Short Review
United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis. Guilemany JM, Angrill J, Alobid I, Centellas S, Pujols L, Bartra J, Bernal-Sprekelsen M, Valero A, Picado C, Mullol J. Allergy. 2009 Feb 6.

Multi-symptom Asthma is Closely Related to Nasal Blockage, Rhinorrhea and Symptoms of Chronic Rhinosinusitis http://goo.gl/sU4AU
Staphylococcus aureus biofilm and and superantigens are associated with chronic sinusitis, cause T-helper 2 skewing http://bit.ly/ngnxBe
Rhinitis is common in asthma and impairs asthma control. Allergy. 2011.

Photo: "Early exposure to allergens may prevent development of hypersensitivity later in life"

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"Early exposure to allergens may prevent development of hypersensitivity later in life" -- click here to see the photo.

Biomarkers to help diagnose abdominal attacks in angioedema due to C1-inhibitor deficiency, prevent unnecessary surgery

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C1-inhibitor (C1-INH) deficiency leads to recurrent attacks of mucocutaneous edema. The deficiency may be:

- inherited (hereditary angioedema [HAE]
- acquired (acquired angioedema [AAE]

Both condition have the same clinical picture presenting with angioedema involving:

- skin
- gastrointestinal tract
- larynx

Skin swelling is evident but abdominal angioedema may be a diagnostic challenge. In fact, attacks of abdominal angioedema may mimic surgical emergencies and lead to unnecessary surgeries.


C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia. Patients with acquired angioedema have low C1q levels AND low C4/C2 levels. In contrast, in hereditary angioedema (HAE) the C1q level is normal.


Classical and alternative complement pathways. Image source: Wikipedia.

Currently, there no laboratory marker to diagnose angioedema attacks.

Coagulation and fibrinolysis are activated during angioedema attacks. This Italian study measured:

- plasma prothrombin fragment F1 + 2 (marker of thrombin generation)
- D-dimer (marker of fibrin degradation)

Prothrombin is produced in the liver. Thrombin is produced by the enzymatic cleavage of two sites on prothrombin.


The coagulation cascade. Image source: Wikipedia, GNU Free Documentation License.

Plasma F1 + 2 level was higher in patients with C1-INH deficiency during remission and further increased during attacks.

Patients without C1-INH deficiency had a normal F1 + 2 level during abdominal colics.

Plasma D-dimer level was also higher in patients with C1-INH deficiency during remission and increased during angioedema attacks.

The authors concluded that patients with C1-INH deficiency have high prothrombin fragment F1 + 2 and D-dimer levels both at baseline and during attacks. Plasma F1 + 2 was more specific than D-dimer since F1 + 2 level was normal in controls without C1-inhibitor (C1-INH) deficiency.

Measurement of F1 + 2 and D-dimer levels may help diagnose acute abdominal attacks in angioedema due to C1-inhibitor deficiency and avoid unnecessary surgery.

References:

Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Allergy. 2009 Feb;64(2):254-7. Epub 2008 Dec 4.
Angioedema: A Short Review

Biomarkers of asthma: Increased serum fibroblast growth factor, hepatocyte growth factor, stem cell growth factor-beta http://goo.gl/vsOlT
Asthma is associated with a procoagulant state in the bronchoalveolar space. Blood, 01/2012.

PPAR-gamma Agonists Rosiglitazone (Avandia) and Pioglitazone (Actos), and Their Effect in Asthma

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

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes.

The medication class of thiazolidinedione (also called glitazones) was introduced in the late 1990s as an adjunctive therapy for diabetes mellitus (type 2). Avandia (rosiglitazone) and Actos (pioglitazone) bind to PPAR-gamma activate them.


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

PPARα and PPARγ are the molecular targets of a number of marketed drugs, e.g. fibrates and thiazolidinediones.

One of my current research projects includes The long Avandia endgame - The Lancet, 2011 http://goo.gl/qcMzNThe Effects of the PPAR-gamma Agonist Rosiglitazone on Airway Hyperreactivity, registered at http://clinicaltrials.gov/ct2/show/NCT00614874. A presentation is embedded below:


PPAR-gamma Agonists and Asthma: Human Studies

References:

The Use of Rosiglitazone to Treat Asthma. ClinicalTrials.gov.

The long Avandia endgame - The Lancet, 2011 http://goo.gl/qcMzN

Peroxisome proliferator-activated receptor γ-mediated suppression of dendritic cell function prevents the onset of atopic dermatitis in mice. JACI. http://goo.gl/Ju6Qz

Peroxisome proliferator-activated receptor, from Wikipedia, the free encyclopedia.

Flickr: "It's not cat allergy, it's a cat with allergy"

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"It's not cat allergy, it's a cat with allergy" -- click to see the photo.

Related reading:

Peptide immunotherapy vaccine for cat allergy - effective as a single dose in a German studyhttp://goo.gl/4l4Vq
Getting a cat increases allergy risk in adults - getting one in adulthood nearly doubles the risk. Reuters and JACI, 2012. 

New Ideas in Allergy and Immunology on Twitter

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1. wheezemd Does global warming increase the risk of allergy? I'm working on a new lecture on the subject. Anyone know any new data? about 3 hours ago from web
2. wheezemd Discussed the role of histamine 4 receptor in the inflammatory response-will we develop new agents that modulate this receptor? about 3 hours ago from web
3. wheezemd Back from Miami. Learned about Th17 cells--are they important in allergic inflammation? It was easier with just Th1 and Th2. about 3 hours ago from web
   
   

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.

• Children born by cesarean delivery are at increased risk for developing asthma http://is.gd/iuEM
  
  
• Children delivered by c-section were 79 percent more likely to develop asthma than children born vaginally http://is.gd/iuEM
  
  
• RSV far more widespread among children than once thought and puts more of them in the hospital than influenza http://is.gd/iuFn
  
  
• RSV responsible for 20% of hospitalizations, 18% of ER visits, 15% office visits for resp. infections in children under 5 http://is.gd/iuFn
  
  
• Researchers should place more emphasis on finding a vaccine for RSV http://is.gd/iuFn
  
  
• Only 3 percent of the RSV cases were correctly diagnosed http://is.gd/iuFn

Image source: OpenClipArt.org, public domain.

How to predict risk of developing asthma in allergic rhinitis? Use serum eosinophil granule proteins ECP and EPO

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Allergic rhinitis is a very common condition and some patients go on to develop asthma. Predicting who those patients will be, may offer the possibility for prevention.

How to predict risk of developing asthma in allergic rhinitis?

A Dannish study of 45 patients evaluated eosinophil proteins as indicators of deteriorating allergic airway disease:

- serum eosinophil cationic protein (ECP)
- serum eosinophil peroxidase (EPO)


Eosinophil. Image source: Wikipedia.

Patients developing asthma had significantly higher serum ECP and EPO. Blood eosinophils and nasal lavage parameters were not related to development of asthma.

The authors concluded that serum ECP and EPO in patients with allergic rhinitis can predict later development of asthma.


Mediators from Eosinophils

References:
Serum eosinophil granule proteins predict asthma risk in allergic rhinitis. Nielsen LP, Peterson CG, Dahl R. Allergy. 2008 Dec 24.
Eosinophils. Allergy Cases, 2009.

How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN?

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Answer: daily.

Chronic idiopathic urticaria (CIU) impairs quality of life and the aim is to control symptoms but no consensus exists regarding how second-generation H(1)-antihistamines should be taken long-term: daily or only PRN.


Mast cells. Image source: Wikipedia.


Histamine structure. Image source: Wikipedia.

In a French study, the patients taking desloratadine daily showed significant improvements in scores for daily living activity, mood state, and social functioning vs PRN use.

The authors concluded that desloratadine 5 mg po is a better regimen than PRN for treatment of CIU.


Mind map diagram of chronic urticaria.

References:
How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of life. Grob JJ, Auquier P, Dreyfus I, Ortonne JP. Allergy. 2008 Dec 30.
Chronic Idiopathic Urticaria (Hives)
Autologous serum skin test in chronic idiopathic urticaria
Urticaria: A Short Review
Mind Maps: Urticaria
Mnemonics: Urticaria

Anti-FceR1 Autoantibodies in Chronic Urticaria

Patient response to different antihistamines will vary http://goo.gl/Q2PiV

Update: Intranasal Corticosteroids for Allergic Rhinoconjunctivitis

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Allergic rhinitis affects 30% of adults and 40% of children in the USA, and up to 75% of these individuals complain of allergic eye symptoms as well.

Only 10% of individuals with allergic eye symptoms seek out medical attention.

Intranasal corticosteroids (INS) may be effective at alleviating ocular symptoms as well and this represents a class effect.

There are currently 7 INSs available in the USA: beclomethasone, budesonide, ciclesonide, fluticasone propionate, fluticasone furoate, mometasone, and triamcinolone.

References:
Intranasal Corticosteroids and Allergic Rhinoconjunctivitis. Catherine Origlieri, BA; Leonard Bielory, MD, Current Opinion in Allergy and Clinical Immunology, Medscape, Jan 2009.
Image source: Wikipedia, a Creative Commons license.

This Week's Grand Rounds

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Check out Grand Rounds, the weekly summary of the best posts in the medical blogosphere.

Grand Rounds has become the contemporary weekly portrait of medicine through the eyes of the medical bloggers. Pre-Rounds is an article series about the hosts of Grand Rounds on Medscape.com. Nick Genes of Blogborygmi, who writes the Medscape column, is the founder of Grand Rounds and the archive host.

What's Different About The New HFA Inhalers for Asthma? Twitter Updates

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AllergyNotes What's Different About The New HFA Inhalers for asthma? The Tampa Tribune: http://tinyurl.com/8w7u2y 21 minutes ago from web

AllergyNotes HFA inhalers are more expensive because any drug combined with a new propellant is considered a new drug by FDA http://tinyurl.com/8w7u2y 20 minutes ago from web

AllergyNotes The new albuterol HFA inhalers cost $30 to $60, whereas the CFC inhalers ran about $5 to $25 apiece http://tinyurl.com/8w7u2y 19 minutes ago from web

AllergyNotes New HFA inhalers contain 200 puffs, more than enough to last months for everyone whose asthma is well-controlled http://tinyurl.com/8w7u2y 18 minutes ago from web

AllergyNotes 3 of new the HFA inhalers (Proventil, ProAir & Ventolin) dispense albuterol, 4th (Xopenex) contains levalbuterol http://tinyurl.com/8w7u2y 16 minutes ago from web

AllergyNotes You have to clean your new HFA inhaler at least once a week http://tinyurl.com/8w7u2y 15 minutes ago from web

A $9-albuterol (Ventolin) HFA inhaler is available from Wal-Mart. It is less expensive than most HFA inhalers but it contains only 90 "puffs" as opposed to 200 "puffs" for all other albuterol inhalers.

References:
What's Different About The New HFA Inhalers? The Tampa Tribune.
Doctors Hear Gripes About HFA Inhalers. Kristina Fiore, Staff Writer, MedPage Today, 03/2009.

Updated: 03/22/2009