What are the predictors of persistence of atopic dermatitis in adolescence?

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German participants of the International Study of Asthma and Allergies in Childhood Phase II were followed prospectively. The dataset comprised 2857 adolescents.

The incidence of atopic dermatitis (AD) between ages 9-11 and 16-20 years was 1.7%, and recurrence was 2.4%.

AD persisted in 47.6% of adolescents with AD symptoms at baseline (n = 424).

What were the predictors of persistence of atopic dermatitis in adolescence?

- high socioeconomic status
- female sex
- asthma symptoms
- positive skin prick test response at baseline

- parental history of rhinitis/AD

- having worked in a high-risk job

With all the factors present, the probability of the incidence of AD was 21.4% and increased up to 81.7% for recurrence of AD and 87.6% for persistence of AD among those affected by AD.


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

References:
Prediction of the incidence, recurrence, and persistence of atopic dermatitis in adolescence: A prospective cohort study. Peters AS, Kellberger J, Vogelberg C, Dressel H, Windstetter D, Weinmayr G, Genuneit J, Nowak D, von Mutius E, Radon K. J Allergy Clin Immunol. 2010 Sep;126(3):590-595.e3.

Former Olympian and coach died of antihistamine overdose

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Antonio Pettigrew, who was stripped of an Olympic gold medal for using performance-enhancing drugs, died of an overdose of an antihistamine used in sleeping aids, according to an autopsy report. The medical examiner ruled the death a suicide.

The autopsy report states that he died of a "lethal concentration of diphenhydramine" (the same medication found in Benadryl). The investigators found an empty bottle of Unisom, a sleeping aid in which diphenhydramine is an ingredient, in victim's car.

Pettigrew was part of the 4x400-meter relay team that won gold at the 2000 Summer Olympics in Sydney, Australia. Two years ago, the International Olympic Committee stripped him and other team members of their medals after he testified in federal court that he took human growth hormone and EPO, which boosts oxygen, between 1997 and 2001.


4x400m World Record (YouTube video). The men's World Record in the 4x400m relay, set at the 1998 Goodwill Games. Relay members were Jerome Young, Antionio Pettigrew, Tyree Washington and Michael Johson.

Since 2006, Pettigrew had coached sprinters, hurdlers and relay teams at the University of North Carolina at Chapel Hill.

A lethal intoxication with diphenhydramine was described in a 1983 case report: The patient was a 28 year old male who went into hyperpyrexia and tachycardia and died from sudden cardiac arrest. Hemorrhagic pulmonary edema and renal shock were the most prominent pathomorphological findings. At the time of death, the concentration of diphenhydramine was 5 mg/l plasma and was particularly high in the lungs (55 mg/kg) and kidneys (50 mg/kg).


Opsoclonus Due to Diphenhydramine (Benadryl) Poisoning - NEJM video.

References:
Autopsy: Olympian died of antihistamine overdose. WralSportsfan.
Lethal intoxication with diphenhydramine. Report of a case with analytical follow-up. Hausmann E, Wewer H, Wellhöner HH, Weller JP. Arch Toxicol. 1983 May;53(1):33-9.

Related:

What is AllergoOncology?

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According to this review, AllergoOncology is a new field which potentially could give new insights into the role of IgE in malignancies, thus opening new avenues for tumor therapy.

Some studies suggest inverse associations between allergic diseases and malignancies.

IgE antibodies specific to tumor antigens have shown antibody-dependent cellular cytotoxicity and phagocytosis. IgE nonspecifically attached to tumor cells proved to be an adjuvant establishing tumor-specific immune memory.

IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control. Eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become anti-tumor effectors, able to trace viable tumor cells in the tissues.

According a literature review, individuals with any type of allergy have a decreased risk for cancer (compared with the general population), including:

• glioma
• colorectal cancer
• cancer of the larynx
• non-Hodgkin lymphoma
• cancer of the esophagus
• oral cancer
• pancreatic cancer
• stomach cancer
• uterine body cancer

However, an increased risk for the following cancers was observed among those with allergies:

• bladder cancer
• lymphoma
• myeloma
• prostate cancer

Further research is needed to verify these results and to determine why such associations may exist.

References:
AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy. 2008 Jul 29.

The association between allergies and cancer: what is currently known? Merrill RM, Isakson RT, Beck RE. Ann Allergy Asthma Immunol. 2007 Aug;99(2):102-16; quiz 117-9, 150.

Can allergies prevent tumors? Can antihistamines increase risk? CNN - Probably not. Most pts with allergies take anthistamines.

Assessment of Type of Allergy and Antihistamine Use in the Development of Glioma http://goo.gl/105HQ

Image source: Cancers are caused by a series of mutations. Wikipedia, public domain.

Vitamin D inhibits IgE production

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An increased incidence of allergic diseases has been associated with vitamin D deficiency. Calcitriol, the active form of vitamin D, inhibits ε germline transcription, a prerequisite for IgE production.

Calcitriol-activated vitamin D receptor (VDR) binds together with retinoid X receptor α to the Iε region (ε germline gene promoter (Iε)). The heterodimer interacts with silencing mediator for retinoid and thyroid hormone receptors, which recruits histone deacetylases (HDAC).

The inhibition of IgE production by calcitriol is mediated through the VDR-corepressor complex affecting chromatin compacting around the Iε region.

The level of IgE increases during childhood until about 10 years of age. At age 10, the total IgE reaches a value that is typically maintained throughout adult life.

References:

Vitamin D receptor binds to the ε germline gene promoter and exhibits transrepressive activity.
Milovanovic M, Heine G, Hallatschek W, Opitz B, Radbruch A, Worm M. J Allergy Clin Immunol. 2010 Oct 4. [Epub ahead of print]

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.

3 groups of severe asthma

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Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment.

A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide.



Severe asthma - differential diagnosis and management (click to enlarge the image).

Uncontrolled asthma can result in:

- risk of frequent severe exacerbations (or death)
- adverse reactions to medications
- chronic morbidity (including impaired lung function or reduced lung growth in children)

Severe asthma includes 3 groups:

(1) untreated severe asthma
(2) difficult-to-treat severe asthma
(3) treatment-resistant severe asthma

The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.

References:
Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol. 2010 Oct 4. [Epub ahead of print]

An approach to recalcitrant, severe asthma - AAAAI Ask the Expert, 2011.

Entopy: Up to 40% of patients with idiopathic rhinitis have locally produced IgE

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Local IgE has been found in a variety of tissues, including nasal and bronchial mucosa. IgE is produced in these local tissues and not simply the product of migration to the tissue from regional lymphoid tissue or blood.

Local IgE has been identified in most of both atopic and nonatopic asthmatic patients and allergic rhinitis patients.

Up to 40% of patients with idiopathic rhinitis (IR) and a positive nasal provocation test result have evidence of locally produced IgE, which has been coined entopy.

There are a large number of IR patients for whom current treatment regimens are suboptimal. The concept of local allergy in IR patients is both intriguing and controversial.

Studies have reported conflicting results, and currently there is no single best test to evaluate for entopy.

References:
Local production of IgE in the respiratory mucosa and the concept of entopy: does allergy exist in nonallergic rhinitis? Forester JP, Calabria CW. Ann Allergy Asthma Immunol. 2010 Oct;105(4):249-255. Epub 2010 Apr 14.

Image source: Illustration for "Aquiline or Roman Nose", Wikipedia, GNU Free Documentation License.

How to use a nose spray - video

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The National Asthma Council Australia launched new instructional 'how to' videos - Using Your Nasal Inhaler.

Nosebleeds are among the most commonly reported adverse effect of intranasal corticosteroid sprays. However, they tend to result from incorrect positioning of the device ("hitting" the septum in the middle), rather than an adverse reaction to the medication.

Common errors to avoid when using a nose spray include the following:

- forgetting to prime the spray device;
- skipping doses
- wrong head position (should be tilted forward, not back)
- pushing nozzle too hard or too far into the nose;
- blowing nose hard after spraying (the medicine is lost)
- sniffing hard after spraying (the medicine is deposited in the throat instead of the nose)
- using saline sprays or irrigations after using corticosteroid spray, instead of before


Using your Nasonex


Using your Veramyst (Avamys in Australia)


Using your Rhinocort

References:
Intranasal corticosteroid spray technique
Using your asthma inhaler

Food allergy bullies - ABC video

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The reported prevalence of food allergy has increased dramatically in recent years. In 1997, one in 250 children had a peanut allergy. Today, it's one in 70 children.

Dr. Sicherer at Mount Sinai School of Medicine is the first to study links between bullying and food allergies. Acoording to his survey, 35% of kids with allergies over 5 years old are bullied, teased or harassed.

The warning signs are similar to other forms of bullying. A child may be withdrawn or will not want to go to school. These children may also change their eating habits or come home hungry.

References:

Food allergy bullies. ABC.

Amid Protest, Florida School Stands Behind Tough New Peanut Allergy Regulations http://goo.gl/joUsS - Little evidence to back this approach: http://goo.gl/59VKU

Helping Families Manage Food Allergy in Schools - Medscape http://goo.gl/kCsTs

Management of food allergy in schools - AAAAI Ask the Expert, 2011.

Overhyped Panics - WSJ, 2011.

Recombinant human C1-inhibitor for treatment hereditary angioedema (HAE)

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Hereditary angioedema (HAE) results from a genetic deficiency of C1-inhibitor. C1-inhibitor has been produced in glycosylated form in the milk of transgenic rabbits.


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

Patients with an eligible attack were randomized to a single intravenous dose of recombinant human C1-inhibitor (rhC1INH) or saline.

Therapeutic failure occurred in 59% of the saline group compared with 0% of the 50 U/kg group and 10% of the 100 U/kg group. No postexposure antibody responses against rhC1INH were observed.

Administration of rhC1INH at 100 or 50 U/kg was highly effective as a treatment of acute attacks in patients with HAE. It was also safe and well tolerated.

References:

Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010 Oct;126(4):821-827.e14.

HAE: annual drug cost alone for prophylactic C1 esterase inhibitor is $450k - nearly $5 mln for every decade of life http://goo.gl/BCVtu

Optimal efficacy of C1INH therapy in HAE is achieved at doses ≥50 U/kg, target level ≥0.7 U/ml (70% of normal) http://goo.gl/HJM4X

Doubtful asthma cure: Indian healers make people swallow live fish with herbs

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From Animal Planet TV: "Two brothers in Hyderabad, India share their unusual cure for asthma with thousands of people every year" (the video is available on YouTube, embedding is disabled).

According to The Times of India, "while rationalists rubbish this 'miracle cure' as humbug, Goud brothers maintain that their prasadam, a yellow paste the ingredients of which are a family secret, offers a "100 per cent cure" for asthma.

Bogged down by controversy, the Gouds have changed the name of the yellow paste from 'medicine' to 'prasadam' to "herbal food supplement'' now. They continue to hardsell it though, stating that the paste in the fish's mouth cures asthmatics of their bouts of breathlessness. How? Well, the Gouds state that the "live fish travels, wagging its tail and fins, through the throat and negotiates the phlegm congestion'' and thus curing the patient."

A more detailed 6-minute video is available here.

Related:

No Chinese manufacturer has successfully registered herbal medicinal products in the EU - all will be banned in May. The Lancet, 2011.

Comments from Twitter:

@ksayona (Sohil Makwana MD,MPH): That has being going on for years in rural parts of India. I don't believe in that and Govt. should do something to stop it.

The First Food Allergy Management Guidelines by the NIH

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The first Food Allergy Clinical Practice Guidelines were published on December 6 by the National Institute of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health (NIH).

The free full text is available at JACI: Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel

The PDF summary is embedded below. A summary for patients is also available.






Related reading:

New Rules for Food Allergies - WSJ - Check the illustration showing what not to do vs. what to do: http://goo.gl/QNXZT
UK National Guidelines for Food Allergy, 2011 (PDF).

New Guidelines For Handling Food Allergies - 30-minute NPR program http://goo.gl/WTl3N

Free pamphlets (brochures) from National Institutes of Health - Publications Order Form.

Food Allergy: An Overview for Patients (PDF)

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Executive Summary of the NIAID-Sponsored Expert Panel Report (PDF)

Japanese guideline for food allergy. Allergol Int. 2011 Mar;60(2):221-36.
NIAID-Sponsored 2010 Guidelines for Managing Food Allergy: Applications in the Pediatric Population. Pediatrics, 2011.
Food allergy in children and young people - UK NICE guideline (PDF), 2012.

Food allergy could be an under-recognized risk factor for problematic asthma

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8203 participants in the U.S. National Health and Nutrition Examination Survey 2005-2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp.

The estimated prevalence of clinical food allergy (FA) was 2.5% (peanut, 1.3%; milk, 0.4%; egg, 0.2%; shrimp, 1.0%; not mutually exclusive).

Risk of possible FA/likely FA was increased in non-Hispanic blacks, males, and children.

Study participants with doctor-diagnosed asthma (vs no asthma) exhibited increased risk of all measures of food sensitization. In those with likely FA, the adjusted odds ratio for current asthma (3.8) and an emergency department visit for asthma in the past year (6.9) were both notably increased.

Food allergy (FA) could be an under-recognized risk factor for problematic asthma.


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:
National prevalence and risk factors for food allergy and relationship to asthma: Results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2010 Oct;126(4):798-806.e13.

Loss-of-function mutations in filaggrin gene are associated with atopic dermatitis, and now with peanut allergy too. JACI, 2011.
Early food sensitization and FLG mutation in infants with early eczema increase the risk for later asthma (JACI, 2011).

What's new in allergy and immunology from UpToDate

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35% of UpToDate topics are updated every four months. The editors select a small number of the most important updates and share them via "What's new" page. I selected the brief excerpts below from What's new in allergy and immunology:

Epinephrine autoinjectors

New epinephrine autoinjectors are available and some of these differ significantly. Doctors should write the specific name of the drug intended to be dispensed on the prescription rather than generic "epinephrine autoinjector." They should provide patient education that is specific to that product to avoid confusion.

Montelukast versus inhaled glucocorticoids in asthma

Children with mild-to-moderate persistent asthma who were treated with inhaled glucocorticoids had better pulmonary function and asthma control (eg, fewer asthma exacerbations requiring systemic glucocorticoids, less albuterol use, and lower symptom scores) than those treated with montelukast.

Step-up therapy in asthma

Options for step-up therapy include:

- increasing the dose of inhaled glucocorticoid
- adding a long-acting beta agonist (LABA)
- adding a leukotriene receptor antagonist (LTRA)

Step-up strategies can be used serially if the initial approach does not improve asthma control. Potential issues with long-term use of LABAs should be considered when choosing step-up therapy, especially in children younger than 12 years.

Food allergen avoidance

A survey of products with milk advisory labeling (eg, "may contain...", "processed in a facility with...", "manufactured on shared equipment with...") found that these items had a much higher frequency of contamination (42 percent) than products with peanut advisory labeling (7 percent).

Natural history of soy allergy

Earlier studies suggested that soy allergy is typically outgrown in the preschool-age years. However, a new study found that only 50 percent of children had outgrown soy allergy by seven years of age.

Formula selection in high risk infants

Infants who were fed partially hydrolyzed formula (pHF) had a lower risk of atopic dermatitis (AD) than those fed cow's milk (CM) formula. This was particularly true in those infants at high risk because of family history of atopic disease.

Venom immunotherapy

The majority of patients are protected from a repeat systemic reaction to a challenge sting within one week of reaching a maintenance dose of 100 micrograms of venom. Challenge sting: to bee or not to bee? Sting challenges don't add much to current diagnostic testing & increase risk http://goo.gl/F50dX

Montelukast and immunotherapy

The administration of montelukast during subcutaneous immunotherapy (SCIT) may reduce the clinical and immunologic efficacy of SCIT. Induction of regulatory T cells, one of proposed therapeutic mechanisms of SCIT, was diminished in the group receiving montelukast.

References:
What's new in allergy and immunology. UpToDate.