Newer, less-sedating antihistamines are effective in the treatment of acquired cold urticaria

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Acquired cold urticaria (ACU) is a form of physical urticaria that has been traditionally treated with first-generation antihistamines.

Data were extracted via a MEDLINE search of the literature between 1950-2009 - comparing the treatment of patients with ACU with second- and third-generation antihistamine medications vs. placebo (98 patients from 4 studies)

Two trials demonstrated a reduction in wheal area after treatment with a second- or third-generation antihistamine.

Two trials demonstrated significant elimination of pruritus with second- or third-generation antihistamine.

All 4 studies assessed the tolerability of a second- or third-generation antihistamine vs placebo and found an increased rate of adverse events (OR, 3.04), most of them rates as mild.

The newer, less-sedating antihistamines seem to be effective in the treatment of ACU in terms of their ability to significantly reduce the presence of wheals and pruritus after cold exposure. These medications are usually well tolerated, with only mild adverse effects.


Diagnosis of Chronic Urticaria (click to enlarge the image).


Chronic Urticaria Treatment (click to enlarge the image).


Oral Antihistamines (click to enlarge the image).

References:
Efficacy and tolerability of second- and third-generation antihistamines in the treatment of acquired cold urticaria: a meta-analysis. Weinstein ME, Wolff AH, Bielory L. Ann Allergy Asthma Immunol. 2010 Jun;104(6):518-22.

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

Urticaria

Urticaria: Brief Review

Anti-FceR1 Autoantibodies in Chronic Urticaria

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Approximately 40% of patients with chronic idiopathic urticaria have antibodies to the alpha subunit of the high-affinity IgE receptor (FcεR1). In the patients, the cause of urticaria is not external; it is an autoimmune reaction. Patients with autoantibodies could be identified by histamine release assay, autologous serum skin tests and Western blot.


An antibody has Fab (fragment, antigen-binding) and Fc (fragment, crystalizable) regions. Fc receptors bind to the Fc region. Image source: Wikipedia, public domain.


Fc receptor interaction with an antibody-coated microbial pathogen. Image source: Wikipedia, public domain.



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

CD203c is a basophil activation marker known to be upregulated by cross-linking of the Fc (epsilon) RI alpha receptor and may serve as a useful marker to identify these patients. CD203 is expressed specifically on basophils, mast cells and their CD34+ progenitor cells and is upregulated by cross-linking of the FcεR1.

Sera from patients with chronic urticaria significantly upregulate basophil CD203c expression as measured by flow cytometry. Activated basophils from whole blood are identified by flow cytometry on the basis of the presence of CD203c on high-expressing IgE positive cells. CD203c expression correlates with basophil histamine release and the size of the autologous serum skin test.

Test code: IGERAB (it can be ordered through the Mayo Clinic lab service). Reference Lab: Sent to National Jewish via Mayo Clinic.

Test description: Anti-FCe Receptor Assay. More info: Anti-IgE Receptor I antibody, anti-CD203c, Chronic urticaria assay.

Method: Flow Cytometry

Reference range: greater than 2%, or by report.

Specimen Required: Draw blood in a plain, red-top tube (serum gel tube is not acceptable). Allow blood to clot and separate within one hour. Send 1 mL of serum frozen.

Specimen requirements: 1 ml of serum

Transport requirements: Sera should be shipped frozen and received in the laboratory within 24 hours after drawing. Days test is performed: Mondays. Turn around time: 1 week.

CPT code: 88184, 88185

References:
Chronic urticaria sera increase basophile CD203c expression. Yasnowsky KM, Dreskin SC, Efaw B, Schoen D, Vedanthan PK, Alam R, Harbeck RJ. J Allergy Clin Immunol 2006;117:1430-4.

Clinical Reference Laboratories at National Jewish - 2007 newsletter (PDF).

Anti-IgE Receptor Antibody - Mayo Clinic test catalog.

Anti-FceR1 Autoantibodies in Chronic Urticaria

Patients hospitalized for acute asthma have poor perception of airflow obstruction

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In a prospective study of inner-city adults hospitalized for acute asthma, symptom control and airflow obstruction (forced expiratory volume in 1 second [FEV1] percentage predicted) were evaluated at discharge and 2 weeks after discharge.

Flow-volume loop showing successful FVC maneuver. Image source: Spirometry, from Wikipedia, the free encyclopedia, GNU Free Documentation License.

In 80.4% of patients, change in symptom control was not significantly associated with change in airflow obstruction, indicating poor perception of change in airflow obstruction.

Patients hospitalized for acute asthma have poor perception of airflow obstruction and change in airflow obstruction. Objective measurements of lung function should guide treatment decisions.

References:
Perception of airflow obstruction in patients hospitalized for acute asthma. Davis SQ, Permutt Z, Permutt S, Naureckas ET, Bilderback AL, Rand CS, Stein BD, Krishnan JA. Ann Allergy Asthma Immunol. 2009 Jun;102(6):455-61.

Twitter updates from the 2010 Annual Meeting of the American College of Allergy Asthma and Immunology (ACAAI)

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Anaphylaxis

From @MatthewBowdish:

Dr. Lieberman: Treatment of anaphylaxis: epi, epi, epi, then other modalities.

At 30 min po intake Benadryl, only 16% drug is 'active'. Just because someone w/ anaphylaxis gets better w/ Benadryl, doesn't mean the Benadryl successfully treated the condition.

Hypotension tended to be more common in anaphylaxis pts over 65.

Two complications of epi in these 54 'elderly' pts (age >50y) - one chest pain and one NSTEMI. Lieberman: shouldn't worry abt tx anaphylaxis in ASCVD pts with epinephrine. Epi doesn't restrict coronary blood flow.

About 60% pts given epipen on discharge from ER/inpatient. About a third had allergist follow-up.

@ACAAI: ACAAI President says peanut-free zones in schools & airlines unnecessary; allergists help acute sufferers deal: http://bit.ly/9rSqnp

Immunotherapy

Advances in immunotherapy

From @MatthewBowdish:

Dr. Finegold: Immunotherapy first became available clinically in 1911. What will the next century of immunotherapy involve?

Dr. Casale: intranasal toll-like receptor-8 agonist increased IL10, IL-12 and IFNg (VRXP-B103 study) with symptom score improvement in AR.

A newer form of CpG is still under development after the Cretticos product never panned out. Cytos CpG data of recent asthma study showing dec in steroids, maintained FEV1 and improvement in symptoms scores.

SLIT

Contrary to popular belief, anaphylaxis does occur in SLIT. More common: oral pruritus, angioedema, mucosal ulceration, etc.

Some ENTs in CO are doing SLIT, but they've called our clinic on three occasions with pts having systemic rxns. Are these rxns for the ENTs problem with standardization? multi-sensitized pts? inappropriate pt selection?

Other issues with SLIT in US: effective dose not known, risk factors in US pts not known and relative values are hard to know.

Dr. Canonica is suggesting that some of the less than impressive evidence for SLIT may be related to patient non-compliance. SLIT is not without risk, although thought to be more safe than traditional subcutaneous IT (SCIT)

Most allergistis not using SLIT because of lack of FDA approval. Estimated that only 5-6% allergists in US providing SLIT, with most using multiple allergens and taking cash w/o billing insurance. Billing insurance for SLIT might even be considered fraud.

Immunodeficiency

Dr. Steihm: transient hypogammaglobulinemia of infancy can persist past infancy...up to ages 5-6.

Dr. Orange: for every 121 mg/dL increase in IgG trough (not dose), there is a subsequent 27% decrease in pneumonia incidence (new meta analysis).

Poster sessions

From @MatthewBowdish:

Another reason why I'm in the best specialty: poster session has everything from tangerine seed anaphylaxis to hairy cell leukemia. Perhaps the most peculiar poster at the ACAAI meeting today - Urticaria to bologna.

Related:

Twitter Updates from the 2009 Annual Meeting of the American Academy of Allergy Asthma and Immunology (AAAAI)

Internet-based Approaches to Enhance Education of Allergy and Immunology Fellows: Practical Examples

Consequences of PhRMA Code on the Annual AAAAI Meeting

Maternal ingestion of peanut during pregnancy was associated with peanut sensitization in children

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The Peanut Question: Can Food Allergies Develop in the Womb? - Video - TIME.com.

Peanut allergy is typically severe, lifelong, and prevalent.

The study authors evaluated 503 infants 3 to 15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A peanut IgE level equal/or greater than 5 kU(A)/L was considered likely indicative of peanut allergy. 27.8% infants had peanut IgE levels equal/or greater than 5 kU(A)/L.

Primary factors associated with peanut IgE equal/or greater than 5 kU(A)/L included:

- frequent peanut consumption during pregnancy (odds ratio, 2.9)
- IgE levels to milk and egg
- male sex
- nonwhite race

Among 71 infants never breast-fed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥5 kU(A)/L (odds ratio, 4.99).

In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization.

References:
Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants. Sicherer SH, Wood RA, Stablein D, Lindblad R, Burks AW, Liu AH, Jones SM, Fleischer DM, Leung DY, Sampson HA. J Allergy Clin Immunol. 2010 Oct 27

Asthma Inhalers (diagram)

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Asthma Inhalers, including the cost of each inhaler (click to enlarge the image).

Inhaled corticosteroid (ICS)

Relative binding affinity for glucocorticoid receptor (GR): mometasone > fluticasone > budesonide > triamcinolone.

Relative anti-inflammatory potency: mometasone = fluticasone > budesonide = beclomethasone > triamcinolone.

The only pregnancy category B inhaled steroid is budesonide. This is easy to remember:

B

B category in pregnancy

Budesonide - both inhaled and intranasal steroid

Related:

Proper techniques for the administration of inhaled medications to treat asthma - AAAAI - Ask the Expert, 2011.

Xopenex (levalbuterol) - marketing brochure

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Xopenex (levalbuterol) causes less tachycardia in some studies of patients with asthma as compared to its "less refined brother" albuterol (called salbutamol in the UK). The clinical significance of this finding is unclear.

"Forest bathing" (exposure to parks and forests) may increase immunity

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"Shinrin-yoku", which can be defined as "taking in the forest atmosphere or forest bathing", has been receiving increasing attention in Japan in recent years for its capacity to provide relaxation and reduce stress.

The researchers have conducted physiological experiments, both in actual forests and in the laboratory, to elucidate the physiological effects on individuals of exposure to the total environment of forests or to only certain elements of this environment, such as:

- odor of wood
- sound of running stream water
- scenery of the forest

On one day, some people were instructed to walk through a forest or wooded area for a few hours, while others walked through a city area. On the second day, they traded places. The scientists found that being among plants produced “lower concentrations of cortisol, lower pulse rate, and lower blood pressure,” among other things.

Men who took two-hour walks in a forest over two days had a 50% increase in levels of natural killer cells.

References:
Trends in research related to "Shinrin-yoku" (taking in the forest atmosphere or forest bathing) in Japan. Tsunetsugu Y, Park BJ, Miyazaki Y. Environ Health Prev Med. 2010 Jan;15(1):27-37.
Exposure to Plants and Parks Can Boost Immunity - NYTimes.com, 2010.
Image source: A conifer forest in the Swiss Alps (National Park), Hansueli Krapf, Wikipedia, GNU Free Documentation License.

Low vitamin D level associated with impaired lung function in asthma

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Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma.

54 nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function and airway hyperresponsiveness (AHR).

FEV(1) was 82.9 % predicted at baseline, the mean serum vitamin D levels was 28 ng/ml.

Higher vitamin D levels were associated with greater lung function, with a 22.7 ml increase in FEV(1) for each nanogram per milliliter increase in vitamin D.

Participants with vitamin D insufficiency (lower than 30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine.

The authors concluded that in asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response. Supplementation of vitamin D levels may improve multiple parameters of asthma severity and treatment response.

References:

Vitamin D levels, lung function, and steroid response in adult asthma. Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DY. Am J Respir Crit Care Med. 2010 Apr 1;181(7):699-704. Epub 2010 Jan 14.

Cord-blood level of vit D had inverse association with risk of resp infection and childhood wheezing, but not asthma. Pediatrics, 2010. http://goo.gl/Rjnl5

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

Low vitamin D at age 6 was a predictor of atopy and asthma at 14 http://goo.gl/LJCmX
Both low and high levels of cord blood 25(OH) vitamin D were associated with increased aeroallergen sensitization. JACI, 2011.

Image source: Wikipedia, public domain.

Child's food allergy has an adverse impact on parents' personal relationships

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In this U.S.-based study, 2945 parents were recruited nationally to complete a web-based survey:

- 52% of parents incorrectly believed young children are at higher risk for fatal anaphylaxis than adolescents

- 85% agreed children should carry an EpiPen

- 91% felt schools should have staff trained in food allergy

- 25% reported food allergy caused a strain on their marriage/relationship

- 40% reported experiencing hostility from other parents when trying to accommodate their child's food allergy

A large proportion of parents reported that their child's food allergy had an adverse impact on personal relationships.


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:
Food allergy knowledge, attitudes, and beliefs of parents with food-allergic children in the United States. Gupta RS, Springston EE, Smith B, Kim JS, Pongracic JA, Wang X, Holl J. Pediatr Allergy Immunol. 2010 May 14.

Increased prevalence of behavioral problems in children with asthma. http://goo.gl/qz3Bm

Image source: Wikipedia, public domain.