Fungal Allergen Decreases CD44 Expression in Bronchial Epithelium and Impairs Healing

Pen ch 13 is an alkaline serine protease and a major allergen from Penicillium chrysogenum. CD44 adhesion molecules play important roles in resolving lung inflammation and repairing epithelial damages during bronchial asthma.

Pen ch 13 allergen down-regulated CD44 protein expression in airway epithelial cells. It may contribute to atopic asthma by influencing the resolution of lung inflammation and prolonging the repair response of damaged bronchial epithelial cells.


Various fungi including Penicillium and Aspergillus spp. growing in axenic culture. Image source: Wikipedia, Dr. David Midgley Cultures: Dr. David Midgley University of Sydney, Australia, Creative Commons Attribution ShareAlike 2.5 License.

References:
Pen ch 13 Major Fungal Allergen Decreases CD44 Expression in Human Bronchial Epithelial Cells. Tai HY, Tam MF, Chou H, Perng DW, Shen HD. Int Arch Allergy Immunol. 2010 Jun 17;153(4):367-371.


Educational Toys: 3 Dust Mites in a Petri Dish by GIANTmicrobes/Amazon

GIANTmicrobes is a toy company based in Stamford, CT. GIANTmicrobes manufactures plush toys resembling microbes, including a number of clinically important human pathogens. The toys were developed primarily for educational, if not in some cases ironic, value.

Dust mites from GIANTmicrobesDust mites from GIANTmicrobes
3 Dust Mites in a Petri Dish by GIANTmicrobes/Amazon. These are cuter in person and one patient named them "Dusty, Rusty and Trusty." The toys are not exactly anatomically correct, of course. For example, dust mites do not have eyes or antennae. They have 8 legs and a mouth-like appendage. I use the plush toys below in most of my lectures and clinic visits related to indoor allergens, asthma, and allergic rhinitis. They make an unforgettable impressions and drive home the message that the dust mite is "real" and it is the most important indoor allergen.


Dust mites from GIANTmicrobesDust mites from GIANTmicrobes

The appearance of each 5-7 inch long toy is based on electron micrographs of the real microbe, thus the toys represent an approximate million-fold magnification of the actual organisms. In order to appeal to the general public and present an air of lovability, many of the toys are brightly colored and furry. To further anthropomorphize them, they typically feature two eyes and in some cases other facial features.

The toys typically maintain the salient features of their biological counterparts, such as the presence of "surface glycoproteins, cilia, flagella", and overall morphology. Each toy has a tag showing the micrograph upon which their appearance is based, the scientific nomenclature of the microbe, and some general clinical facts related to the disease it causes.

Recently, the toys have become available in miniature size ("minimicrobes"), 3 microbe toys packaged in a petri dish-style box, while 15-20" sizes, called "GIGANTICmicrobes!", have been released.

There are currently more than 40 microbes and other pathogens which have been represented in plush form.



Dust mite allergen avoidance. The main allergen is in the dust mite feces. Use 3 control measures for 3-6 months to see an effect on the allergy symptoms (click to enlarge the image).

References:
GIANTmicrobes. Wikipedia, 2010.
House dust mite sensitization in toddlers predicts wheeze at age 12 years (JACI, 2011).

Related:


Lung function and HRCT deteriorate in CVID patients despite treatment with immunoglobulins

Patients with common variable immunodeficiency (CVID) have low serum IgG, IgA, and/or IgM levels and recurrent airway infections. Radiologic pulmonary abnormalities and impaired function are common complications.

In a retrospective, longitudinal study of 54 patients with CVID already treated with immunoglobulins, the researches examined changes of lung function and findings on high-resolution computed tomography (HRCT), obtained at 2 time points 2 to 7 years apart (T0 to T1).


Immunoglobuln (Ig) structures. Image source: Wikipedia.

Despite a mean (SD) serum IgG level of 7.6 (2.3) g/L for all the patients during the entire study period, lung function decreased from T0 to T1. The combination of a low serum IgA level and serum MBL was associated with the presence of bronchiectasis and lower lung function and with worsening of several HRCT abnormalities. Increased serum levels of TNF-alpha were related to deterioration of gas diffusion.

A mean serum IgG level less than 5 g/L between T0 and T1 was associated with worsening of linear and/or irregular opacities seen on HRCT.

For a period of 4 years, lung function and HRCT deteriorated in CVID patients treated with immunoglobulins.

References:
Development of pulmonary abnormalities in patients with common variable immunodeficiency: associations with clinical and immunologic factors. Gregersen S, Aaløkken TM, Mynarek G, Fevang B, Holm AM, Ueland T, Aukrust P, Kongerud J, Johansen B, Frøland SS. Ann Allergy Asthma Immunol. 2010 Jun;104(6):503-10.

CVID patients (higher radiation sensitivity) might be evaluated by chest MRI - a radiation-free alternative to CT http://goo.gl/0ohqb


Montelukast works better than salmeterol for exercise-induced asthma in children (study sponsored by Merck)

The prevalence of exercise-induced bronchoconstriction (EIB) is 10% in the general population, up to 90% of those with asthma, and 50% of those with allergic rhinitis.

This Merck-sponsored study evaluated the effect of montelukast 5 mg, or inhaled salmeterol, 50 mcg, added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) after an exercise challenge and response to rescue bronchodilation with albuterol in 154 children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction (EIB).

Exercise challenges were performed at baseline (pre-randomization) and at the end of each active treatment period.

Montelukast, compared with salmeterol, significantly reduced the percentage decrease in FEV1 (10.6% vs 13.8%) and time to recovery (6.0 vs 11.1 minutes).

Response to albuterol rescue after exercise challenge was significantly greater with montelukast.

Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment.

References:

Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children. Ann Allergy Asthma Immunol. 2010 Jun;104(6):511-7. Fogel RB, Rosario N, Aristizabal G, Loeys T, Noonan G, Gaile S, Smugar SS, Polos PG.
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
Image source: Montelukast, from Wikipedia, the free encyclopedia, public domain.


"Ask the Expert" from AAAAI goes RSS - get your updates automatically

From AAAAI:

Do you enjoy reading Ask the Expert questions but do not have time to check back on a regular basis for new questions? To remedy the situation we added a Really Simple Syndication (RSS) feed to the Ask the Expert page. The RSS feed will automatically insert updates into your web-based news reader. To subscribe, simply click on the orange RSS icon on the Ask the Expert page and subscribe through your reader:


http://feeds.feedburner.com/AaaaiAskTheExpertFeed

Great news! This is one of the changes I suggested during the recent Website Reviewers Retreat at the American Academy of Allergy, Asthma & Immunology (AAAAI) headquarters.

Now we just need to have Ask the Expert on Twitter and YouTube...

Image source: Wikipedia.


Ecallantide as an effective and safe treatment for acute attacks of HAE

Hereditary angioedema (HAE) is a genetic disorder resulting from low levels of C1-inhibitor activity that manifests as acute attacks of variable and sometimes life-threatening edema. Ecallantide is a novel potent inhibitor of human plasma kallikrein, a key mediator of the excessive formation of bradykinin associated with the signs and symptoms of an HAE attack.



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

In this double-blind, placebo-controlled study, 96 patients with a moderate to severe HAE attack were randomized to receive 30 mg of subcutaneous ecallantide or placebo.

Mean change from baseline in symptom complex severity score 4 hours after dosing was significantly greater with ecallantide use (-0.8 compared with placebo use (-0.4).

The benefit of ecallantide was apparent within 2 hours after dosing and was maintained through 24 hours after dosing. The safety profile was similar between the treatment groups.

The study authors concluded that ecallantide is an effective and safe treatment for acute attacks of HAE.

References:

EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Levy RJ, Lumry WR, McNeil DL, Li HH, Campion M, Horn PT, Pullman WE. Ann Allergy Asthma Immunol. 2010 Jun;104(6):523-9.

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


Survey: 3 severe reactions for every 100,000 visits for subcutaneous immunotherapy (SCIT) ("allergy shots")

Although systemic reactions (SRs) to subcutaneous immunotherapy (SCIT) injections are not uncommon, life-threatening and fatal reactions are rare.

Physicians were asked to complete a Web-based survey reporting numbers of injections administered, injection- and skin test-related fatal reactions, and all nonfatal SRs in their clinical practices during the previous 12 months. The SR events were classified as mild (grade 1: cutaneous or upper respiratory symptoms), moderate (grade 2: asthma with reduced lung function), or severe (grade 3: life-threatening airway compromise or hypotension).

In 2008, 806 physicians responded, representing 1,922 SCIT prescribers. No fatal reactions to SCIT injections were identified during the first 12 months, although 6 SCIT fatal reactions were reported retrospectively between 2001 and 2007.

82% of practices reported SRs to SCIT (10.2 SRs per 10,000 = 0.1% of injection visits). Most were grade 1 (74%) or grade 2 (23%) SRs.

However, 3% were grade 3 anaphylactic events (3 severe reactions for every 100,000 injection visits).

References:
Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes of the ACAAI and AAAAI collaborative study. Bernstein DI, Epstein T, Murphy-Berendts K, Liss GM. Ann Allergy Asthma Immunol. 2010 Jun;104(6):530-5.

The most recent SCIT-related fatal reaction occurred in 2007 - AAAAI http://goo.gl/k2QaN
Image source: OpenClipArt.org, public domain.


Probiotics cannot be recommended for treating eczema (atopic dermatitis)

Probiotics have been proposed as a treatment for eczema, but the results of intervention trials have been mixed.

This meta-analysis included 12 trials (781 participants). Data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective.

The adverse events search identified case reports of sepsis and bowel ischaemia caused by probiotics.

Currently, probiotics cannot be recommended for treating eczema.



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

References:
Probiotics for the treatment of eczema: a systematic review. R. J. Boyle et al. Clinical & Experimental Allergy. Published Online: 1 Jul 2009.
Formula supplementation with a prebiotics was effective as primary prevention of atopic dermatitis http://goo.gl/clTx
New evidence relates prebiotics to reduced occurrence of AD. JACI Journal Club http://goo.gl/qUyE
Probiotics given to pregnant women reduced incidence of atopic dermatitis, but had no effect on atopic sensitization. http://goo.gl/xcQi
Probiotics and Prebiotics in Pediatrics http://goo.gl/daCiz
Probiotics and Prebiotics in Pediatrics. PEDIATRICS Vol. 126 No. 6 December 2010, pp. 1217-1231 (doi:10.1542/peds.2010-2548).
Image source: Cacık, a Turkish cold appetiser yoghurt variety, Wikipedia, Creative Commons Attribution ShareAlike 3.0 License.


Majority of college students with food allergy do not avoid food allergens and do not carry EpiPen

Food allergy trends and behavioral attitudes were assessed on a large university campus. An online survey was distributed by email to a local university undergraduate students.

A total of 513 individuals responded, with 57% reporting an allergic reaction to food. Of this group, 36.2% reported symptoms of anaphylaxis.

Allergy to milk, tree nut, shellfish, and peanut was significantly associated with having symptoms of anaphylaxis.

Some form of emergency medication was maintained in 47.7%, including self-injectable epinephrine (SIE; 21%), but only 6.6% reported always carrying this device.

Only 39.7% reported always avoiding foods to which they were allergic.

Potentially life-threatening anaphylactic reactions to foods are occurring on college campuses. Only 39.7% of students with food allergy avoided a self-identified food allergen, and more than three fourths did not carry EpiPen. Such behaviors places these students at increased risk for adverse events.

Remember the simple rule: "No Epi, no eat-y"

References:


Food allergy and food allergy attitudes among college students. J Greenhawt M, M Singer A, P Baptist A. J Allergy Clin Immunol. 2009 Jun 26.
@AllergyNet: Coroner's Report of anaphylactic death due to food allergy in Australia http://bit.ly/k2QK0c - A lot to be learned from this tragic episode.
Image source: Roasted peanuts as snack food, Wikipedia, public domain.

Twitter comments:

@lissaRFAK: I think I found my new personal slogan. Let's make t-shirts. RT @Allergy One allergist used to say: "No Epi, no eat-y" (always be prepared).


Exhaled nitric oxide level decreases after methacholine inhalation challenge

Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation in asthma.

Spirometry, impulse oscillometry, and eNO measurements were performed before and after methacholine inhalation challenge (bronchoconstriction phase) and after beta2-agonist inhalation (bronchodilation phase) in 62 children with asthma, 13 "wheezy" children, and 17 healthy children.

A significant decrease occurred in the eNO level after methacholine inhalation challenge. This decrease did not correlate with the percentage decrease in forced expiratory volume in 1 second (FEV1) but it did correlate with the percentage decline in maximal expiratory flow at 50% vital capacity and with the change in small airway resistance.

eNO recovered to the previous level immediately after beta2-agonist inhalation.

The study authors concluded that the eNO level decreases after methacholine inhalation challenge. This decrease primarily depends on bronchoconstriction of the small airways.



Inflammation in asthma (mind map). FeNO is a marker of oxidative stress. See more Allergy and Immunology mind maps here.

If methacholine challenge is negative but FeNO is higher than 30 ppb, perform adenosine challenge to rule out asthma (Ann of Allergy and Imm, 2012).

References:

Effect of bronchoconstriction on exhaled nitric oxide levels in healthy and asthmatic children. Tadaki H, Mochizuki H, Muramastu R, Hagiwara S, Takami S, Mizuno T, Arakawa H. Ann Allergy Asthma Immunol. 2009 Jun;102(6):469-74.
Exhaled nitric oxide correlated with control in recurrent infantile wheeze treated with inhaled corticosteroids. http://goo.gl/AS7I
Methacholine not as sensitive to diagnose asthma as previously thought, Medscape, 2011. http://goo.gl/ajn0S


32% of caregivers describe inappropriate home use of albuterol for asthma exacerbations

To reduce symptoms and emergency department (ED) visits, the National Asthma Education and Prevention Program (NAEPP) guidelines recommend early treatment of acute asthma symptoms with albuterol and oral corticosteroids.

A total of 114 caregivers of low-income, urban children completed a 20-minute telephone interview with an asthma nurse to evaluate home management of their child's acute asthma symptoms.

Albuterol use for worsening asthma symptoms was appropriate for only 68% of caregivers and was more likely if the children had an ED visit or hospitalization for asthma in the prior year.

The remaining 32% of caregivers used albuterol inappropriately (overtreatment or undertreatment).

Appropriate albuterol use was not associated with caregiver report of having an asthma action plan (AAP) or a recent primary care physician visit to discuss asthma maintenance care.


Dr. House tries his best: "Are you using your inhaler right?" - "Do I look like an idiot?!"


The correct way to use your metered dose inhaler (MDI).

References:
Videos: How to use your asthma inhalers
Video: How to Use Asthma Devices -- Inhalers, Spacers, Peak Flow Meters

References:
Home use of albuterol for asthma exacerbations. Garbutt JM, Freiner D, Highstein GR, Nelson KA, Smith SR, Strunk RC. Ann Allergy Asthma Immunol. 2009 Jun;102(6):504-9.


Hydroxyzine more effective than nonsedating antihistamines in suppressing histamine-induced or allergen-induced skin reactions

Nonsedating antihistamines (nsAHs) are recommended as first-line treatment of mast cell-driven disorders, including allergic rhinitis and urticaria. However, their superiority over first-generation AHs (fgAHs) has been called into question due to lack of supporting head-to-head studies.



Histamine structure. Image source: Wikipedia.

The study authors compared the effects of 3 modem nsAHs with those of the fgAH hydroxyzine on histamine- and allergen-induced skin reactions in a double-blind trial.

The nsAHs prevented the development of positive reactions to histamine in only 10-20% of all individuals tested. In contrast, more than 50% of all hydroxyzine-treated individuals showed negative test reactions to histamine. Similar differences, although less pronounced, were detected with D pteronyssinus prick (dust mite) testing in sensitized individuals.

The authors concluded that hydroxyzine is more effective than nsAHs in suppressing histamine-induced or allergic skin reactions.

Higher doses of nsAHs than those currently recommended may be required to obtain antihistaminic and antiallergic effects that are equivalent to those of fgAHs.



Oral Antihistamines (mind map)

References:
Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines. dos Santos RV, Magerl M, Mlynek A, Lima HC. Ann Allergy Asthma Immunol. 2009 Jun;102(6):495-9.
Patient response to different antihistamines will vary http://goo.gl/Q2PiV


Ocular antihistamines (eye drops) (mind map)



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


Indolent systemic mastocytosis has a low disease progression rate, normal life expectancy in most adults

Indolent systemic mastocytosis is a group of rare diseases for which reliable predictors of progression and outcome are still lacking.

Analysis showed that serum beta2-microglobulin and mast/stem cell growth factor receptor gene (KIT) mutation in mast cells plus myeloid and lymphoid hematopoietic lineages was the best combination for predicting disease progression.


Mast cells. Image source: Wikipedia.

The authors concluded that indolent systemic mastocytosis in adults has a low disease progression rate, and the great majority of patients have a normal life expectancy.

The presence of KIT mutation in all hematopoietic lineages and increased serum beta2-microglobulin are the most powerful independent parameters for predicting transformation into a more aggressive form of the disease.

References:
Prognosis in adult indolent systemic mastocytosis: A long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. Escribano L, Alvarez-Twose I, Sánchez-Muñoz L, Garcia-Montero A, Núñez R, Almeida J, Jara-Acevedo M, Teodósio C, García-Cosío M, Bellas C, Orfao A. J Allergy Clin Immunol. 2009 Jun 19.

Neuropeptide blood levels correlate with mast cell load in patients with mastocytosis http://goo.gl/vlQhm


Contact Information


Contact Information


Video: Using a spacer device for inhalation



westwoodmansfield | July 09, 2010 | Using a Breathing Chamber.


Early wheezing associated with cognitive deficit in 3-year-old children

In a birth cohort study, wheezing symptoms were recorded postpartum over two first years of age and subsequently cognitive status of children at the age of 3 yr was assessed with the Bayley Mental Development Index (MDI).

The MDI score correlated inversely with the number of wheezing days recorded over 24 months, lead cord blood concentration, number of siblings and the number of cigarettes smoked daily by other household members at home over the pregnancy period.

According to the study authors, this is the first report in the iterature showing that early wheezing is associated the cognitive deficit in very young children. Observed cognitive deficit may be caused by RSV infections or can be related to lower lung function attributed to persistent wheezing, which reducing oxygen supply would affect rapidly developing brain.

However, considering that the number of siblings was also associated with cognitive decline, we should await more studies before making final conclusions.

References:
Early wheezing phenotypes and cognitive development of 3-yr-olds. Community-recruited birth cohort study. Wieslaw Jedrychowski et al. Pediatric Allergy and Immunology, 06/2009.

Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. http://goo.gl/PghX
A simple clinical prediction rule identifies healthy newborns at risk of RSV Bronchiolitis in Healthy Newborns http://goo.gl/EVlSi
Image source: Wikipedia, public domain.


Oral Antihistamines (mind map)



Oral Antihistamines (mind map)


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


"ImmunoCAP rapid wheeze/rhinitis" test for allergy diagnosis in children with respiratory symptoms

Recurrent respiratory symptoms are very frequent in childhood.

In this study, the value of an in vitro diagnostic device testing 10 common allergens, the ImmunoCAP® rapid wheeze/rhinitis Child, was investigated for the primary evaluation of allergy.

The investigators carried out their usual diagnostic work-up including IgE tests. The ImmunoCAP® Rapid test was performed with capillary whole blood.

The physicians' diagnostic conclusions on major triggering allergens were compared to the ImmunoCAP® Rapid test results. The sensitivity of the ImmunoCAP® Rapid test for unveiling allergic disease was 92% and the specificity 97%.

For children with asthma falling, sensitivity was 100% and specificity 100%, for children with rhinitis sensitivity was 93% and the specificity 100%.

The investigators concluded that ImmunoCAP® Rapid test was an accurate test, with high specificity, for diagnosing allergy in children with recurrent respiratory diseases in primary care settings.

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.

References:
The ImmunoCAP® rapid wheeze/rhinitis child test is useful in the initial allergy diagnosis of children with respiratory symptoms. Philippe A. Eigenmann et al. Pediatric Allergy and Immunology, 06/2009.
Image source: ImmunoCAP Rapid.


Cross-reactivity in Oral Allergy Syndrome (mind map)


Cross-reactivity in Pollen-Food Allergy Syndrome (PFAS) or Oral Allergy Syndrome (OAS) (click to enlarge the image).

Cross-reactivity in Pollen-Food Allergy Syndrome (PFAS) or Oral Allergy Syndrome (OAS)

Related:
Profilin may be a pan-allergen among plants that crossreacts between pollen, fruits, vegetables and latex http://goo.gl/ZUPRQ

Flavored Coffee May Trigger Seasonal Allergies - due to oral allergy syndrome. Fox News, 2011.
In birch-apple syndrome (oral allergy syndrome), eating apple does not affect the respiratory tract. Annals of Allergy, Asthma and Immunology, 2011.


Personal air filtration system to deliver "allergen-free" air to patient's breathing zone during sleep

The PureZone personal air filtration system employs a HEPA filter air purifier, delivering air to a patient's breathing zone while he or she sleeps.

In a randomized placebo controlled cross-over clinical trial, the PureZone personal air filtration system was shown to reduce (by 99.99%) airborne allergens in the breathing zone for all bedroom environments. These exposure reductions led to significant improvements in nocturnal nasal and ocular allergy symptoms (P lower than 0.001) and quality of life (P lower than 0.001) (see the AAAAI abstract below). A decrease in nocturnal symptom was demonstrated after the first night of use and were maintained for the duration of treatment; these reductions resulted in meaningful improvements in sleep quality (P=0.005).



The efficacy data is available from the manufacturer website.

References:


Stillerman A, Tierney N. Efficacy of PUREZONE(TM), a Novel Local High Efficiency Particulate Air (HEPA) Filtration Pillow Device, in Patients With Perennial Allergic Rhinoconjunctivitis (PARC): A Double-Blind, Placebo-Controlled Randomized Clinical Trial (RCT). Journal of Allergy and Clinical Immunology. 2009 Feb;123(2, Supplement 1):S271.

HEPA Air Cleaners Not Very Effective For Decreasing Visits and Asthma Symptoms in Children Exposed to Tobacco Smoke http://goo.gl/fhAmh

Disclaimer: The manufacturer of the PureZone personal air filtration system has advertised on this website. They do not have influence on the editorial content and/or this blog post.


Can Helicobacter pylori infection cause urticaria and angioedema?

Can Helicobacter pylori infection cause urticaria and angioedema?

Yes.

Helicobacter pylori (Hp) infection has been implicated in chronic urticaria. Despite the fact that a causal association between the infection and the development of urticaria has not been definitely established, treatment of Hp often leads to symptom remmission.

Helicobacter pylori, the most important cause of gastritis and peptic ulcer, has also been associated with several extradigestive diseases.

A study assessed the prevalence of Helicobacter pylori infection and the effects of bacterium eradication in 42 consecutive patients affected by idiopathic chronic urticaria. Helicobacter pylori was assessed by [13C]urea breath test. Amoxicillin, clarithromycin, and lansoprazole were given to infected patients for seven days. 55% of patients proved to be infected by Helicobacter pylori. 88% of infected patients in whom the bacterium was eradicated after therapy showed a total or partial remission of urticaria symptoms. Symptoms remained unchanged in all uninfected patients.


The study authors concluded that Helicobacter pylori affects a high percentage of patients with idiopathic chronic urticaria; however, typical gastrointestinal symptoms do not identify infection status. Bacterium eradication is associated with a remission of urticaria symptoms.

In another study of 100 patients with chronic urticaria (mean duration 33 months), 26 had Helicobacter pylori-associated gastritis. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori-specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3-12 weeks. In contrast, only 50% of untreated H. pylori-seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks.

Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%).

The authors concluded that measurement of H. pylori-specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment.

H. pylori eradication therapy

If patient is taking a NSAID (including aspirin), it should be discontinued if possible.

The typical H. pylori eradication therapy includes triple therapy (a PPI plus 2 antibiotics). Triple therapy has been historically preferred over quadruple therapy (a PPI plus bismuth plus 2 antibiotics) because it is simpler.

However, bismuth-based regimens and sequential therapy (i.e., 5 days of a PPI plus amoxicillin, followed by 5 days of a PPI plus clarithromycin and tinidazole) are now preferred due to problems with increasing antibiotic resistance with H. pylori.

All regimens contain antibiotics and therefore may cause diarrhea, increase the risk of opportunistic infections, and interfere with absorption of many other drugs, including oral contraceptives.

If the patient is allergic to penicillins, a regimen that includes metronidazole instead of amoxicillin should be given.

Treatment course: 7 days (quadruple therapy), 10 days (sequential therapy), or 14 days (triple therapy). Check for eradication of H pylori 1 month after the end of therapy.

Quadruple therapy for 7 days

omeprazole 20 mg orally twice daily (or lansoprazole 30 mg orally twice daily, or esomeprazole 40 mg orally twice daily)

AND

bismuth subsalicylate 525 mg orally four times daily

AND

metronidazole 500 mg orally four times daily

AND

tetracycline 500 mg orally four times daily

Sequential therapy for 10 days

omeprazole 20 mg orally twice daily (or lansoprazole 30 mg orally twice daily, esomeprazole 40 mg orally twice daily)

AND

amoxicillin 1000 mg orally twice daily on days 1-5

AND

clarithromycin 500 mg orally twice daily on days 6-10

AND

tinidazole 500 mg orally twice daily on days 6-10

Triple therapy for 14 days

omeprazole 20 mg orally twice daily (or lansoprazole 30 mg orally twice daily, esomeprazole 40 mg orally twice daily)

AND

clarithromycin 500 mg orally twice daily

AND

amoxicillin 1000 mg orally twice daily or metronidazole 500 mg orally twice daily

Source: Peptic ulcer disease, Epocrates, BMJ.

References:

The effect of antibiotic therapy for patients infected with Helicobacter pylori who have chronic urticaria. Journal of the American Academy of Dermatology, Volume 49, Issue 5 , Pages 861-864, November 2003.

Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Di Campli C; Gasbarrini A; Nucera E; Franceschi F; Ojetti V; Sanz Torre E; Schiavino D; Pola P; Patriarca G; Gasbarrini G. Dig Dis Sci 1998 Jun;43(6):1226-9.
Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria. Wedi B; Wagner S; Werfel T; Manns MP; Kapp A. Int Arch Allergy Immunol 1998 Aug;116(4):288-94.
Asthma: The secret face of H. pylori. Early infection with H. pylori prevents asthma in a T reg cell-dependent manner http://bit.ly/pHl6dm
H. pylori eradication provides benefits to patients with functional dyspepsia http://goo.gl/UwxsT
The effect of antibiotic therapy for patients infected with Helicobacter pylori who have chronic urticaria. Journal of the American Academy of Dermatology, Volume 49, Issue 5 , Pages 861-864, November 2003.
H. pylori image courtesy of www.hpylori.com.au.

Comments from Twitter:

@ChazzaiA: I didn't know that until Twitter told me - MT @AllergyNet Important cause. @DrVes: Can H. pylori cause chronic urticaria? goo.gl/3gTI

@AllergyNet (Dr John Weiner): Can H. pylori infection cause urticaria? http://t.co/fZmqNfr-- Yes. I agree. Always worth 'H.pyl breath test' in chronic hives.

@DrVes: H. pylori diagnostic test of choice in CIU here is H. pylori IgG, followed by triple therapy, if positive.

@AllergyNet: Interesting. In Australia, serology for H. pylori only used for survey studies, dropped in favor of breath test to detect active infection. Important cause. Breathtest used in Australia to diagnose it.

@Allergy: I was reviewing CIU in UpToDate recently and they also recommend H. pylori IgG - there are regional differences in practice between U.S. and AUS. Stool test for H. pylori antigen is another useful test.

@MatthewBowdish (Matthew Bowdish MD): I've had only one patient test positive to H pylori AND respond to abx. She's still hive-free & off meds after 2 years.

@AllergyNet (Dr John Weiner): I get a few a year. Do you test all chronic urticaria patients, do you use serology or breath test, do you treat all positive even if asymptomatic?


Cyclosporine beneficial in 82% of patients with severe chronic urticaria

The treatment of severe chronic urticaria (CU) remains a difficult goal to achieve. Many patients do not respond to anti-histamine therapy, even when off-label doses are given. Thus, cyclosporine-A (CsA) has been considered as therapeutic option for severe patients.


Among 2000 patients with CU who were referred to an outpatient clinic, 120 patients who suffered from a very severe CU began treatment with CsA 3 mg/kg.

In 20 patients, CsA was discontinued within 2-15 days after initiation because of side-effects.

Among 62 of the remaining 100 patients (62%), CsA was administered for a period of 3 months with a highly beneficial outcome.

In another 20 patients (20%), CsA was considered beneficial; however, it was required for a longer period of time, 5-10 years for some of the cases.

For 18 patients (18%), CsA therapy was reported as failed.

A low dose of CsA may be a good option for patients who suffer from especially severe CU.

Cyclosporine blocks T cell cytokine production by inhibiting activation of the NFAT transcription factor (note: different from NFkB).


Ciclosporin (INN), cyclosporine (USAN) or cyclosporin (former BAN). Image source: Wikipedia, public domain.

Together with tacrolimus, cyclosporine is a calcineurin inhibitor (CNI). Initially isolated from a Norwegian soil sample, Ciclosporin A, the main form of the drug, is a cyclic peptide of 11 amino acids produced by the fungus Beauveria nivea.


Cyclophilin. Image source: Wikipedia, public domain.

Cyclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances induces the transcription of interleukin-2.

References:
Kessel A, Toubi E. Cyclosporine-A in severe chronic urticaria: the option for long-term therapy. Allergy 2010; DOI:10.1111/j.1398-9995.2010.02419.x.
Ciclosporin. Wikipedia.


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