Straumann, Aceves, Blanchard, Collins, Furuta, Hirano, Schoepfer,Simon, and Simon

This was a very interesting review article on a very frustrating clinical condition, Eosinophilic Esophagitis (EE). There were nine authors from the United States and from Switzerland. The specialties represented by the authors were gastroenterology, pathology, allergy, dermatology, and pharmacology. This was a very interesting diverse mix of expertise for this topic. Italics will be used for my elaborations.

The article starts with a historical review. Case reports appeared in the early 1990s on what was to be EE. Over the last 10 years it has been shown that this is a T-helper cell, type 2 (Th2) inflammatory cell condition or response. The inflamed esophagus repairs or remodels in response to the inflammation. The remodeling causes abnormal functioning of the esophagus. Symptoms arise from food impacting in the inflamed, remodeled esophagus.

The authors report on concurrent allergic conditions such as allergic rhinitis, asthma, atopic dermatitis, and atopy (positive allergy tests without clinical correlation). The point is made that classic allergic problems are seen along with those who struggle with EE. A difference between the children and the adults who have EE is the propensity for this to be a food antigen-driven condition in the child, whereas in the adult the tendency is towards this being due to inhaled allergens. This is a very interesting separation.

The introduction of the paper refers to the 3 Ds of therapy for this condition; drugs, diet, and dilation.

Symptoms- in adults and teenagers there can be vague symptoms, compensatory behavior, or flagrant episodes of food impaction. In this group, the diagnosis can be delayed for 4-5 years. The complaints just do not point to any one clinical condition.

In children there is a wider array of presentations including; irritability, feeding problems, vomiting, and abdominal pain. The older child may have more of the adult presentations with dysphagia, heartburn, or food impaction.

Symptoms in Children

• Abdominal pain
• Chest pain
• Heartburn
• Coughing
• Food sticking in the esophagus
• Food refusal (eating is associated with discomfort)
• Choking/gagging
• Nausea
• Regurgitation
• Sleep difficulties
• Throat pain

Symptoms in Adults

• Food sticking (hard to pass a food bolus)
• Food impaction (the food bolus does not move)
• Retrosternal pain (mimicking heart issues)

Physical examination

                You really cannot evaluate the esophagus on a physical examination. However, there may be features of concomitant allergic problems such as asthma, atopic dermatitis, and nasal allergy that are amenable to examination. A child may have problems with failure to thrive.

Laboratory Evaluation

                A blood count may show high levels of the inflammatory cell involved with the condition- the eosinophil. Percent eosinophils can range from 5-50%. About 70% will have an elevation of IgE- the antibody that mediates allergic conditions.

Endoscopy

                This is the first diagnostic step in the work-up of eosinophilic esophagitis. You have to go into the esophagus to see what is going on and to perform a biopsy. In children active inflammation is usually found. In adults the inflammation appears to be more chronic- of longer duration.

                A biopsy is needed to confirm the diagnosis.

Immunopathogenesis

                The authors refer to a landmark study published in 2001 that demonstrated what immune cells are involved in EE. Biopsies show the eosinophil, T-cells, B-cells (lymphocytes), and mast cells which have IgE linked to the surface. These findings point to the possibility of allergy being involved. Links with atopy have been demonstrated, however there is an intrinsic (non-IgE mediated) form of the condition seen in both children and adults. In these cases, no relevant allergen was identified. The article has a very erudite discussion on the cells and mediators involved. At this point it is important to discern what a relevant allergen is. When an allergy test is positive and that food is removed from the diet two things may happen; improvement may be seen due to avoidance of a causative agent or no change due to the food being an irrelevant agent. If there is improvement with avoidance of a food and re-introduction of that food causes symptoms to return, then the food allergen is relevant. The food allergy test was positive however avoiding that food made no difference and symptoms did not return when the food was re-introduced. Food allergy tests are a starting point. Once positive food tests are discovered, the relevance of that food to the condition needs to be established.

Allergic Profile in Adults and Children with Eosinophilic Esophagitis

                In the introduction to this section, the authors suggest that EE may be a new manifestation of atopy. (A new allergic condition has evolved.)  For the children, this is a food antigen-driven condition with the majority responding to elimination of common dietary antigens (food protein that causes an immunologic reaction) and when the food is re-introduced, the condition returns (food challenge). Key points here are common dietary antigen. At one time I would skin test to those six foods that have been associated with well over 90% of food allergy in children; egg, milk, wheat, soy, peanut, and fish. Additional foods were added to our test array due to what others were reporting on. We got up to 25 foods that were tested. More recently, I hand the skin test sheet to the family and ask them to pick out foods that the child is actually exposed to. Relevance of exposure is important in selecting diagnostic studies. Food allergy panels include foods that are not usually or ever a part of the child’s diet. The best test for a food allergy is to perform a food challenge. There is no better way to establish relevance of a food trigger than to give the food and see what happens. One problem is that we do not have a surrogate for endoscopy/biopsy to see what is happening to the esophagus. Food challenges in the allergy clinic rely on symptoms.

                The adult with eosinophilic esophagitis may also be driven by food however aeroallergen (inhalant allergens) is the predominant causative stimulus. It is pointed out that this observation follows the known shifts in allergic sensitization; children with more food allergy and adults with more respiratory tract allergy.

More than 50% of those with eosinophilic esophagitis have a history of atopy (positive allergy test). In the literature, the criteria and severity of the concurrent allergic conditions is not standardized. The criteria for these other conditions vary. The best estimates for the incidence of known allergic conditions are as follows;

• Allergic Rhinitis- 40-75%
• Asthma – 14-70%
• Eczema – 4-60%

The point is made that the ranges are very wide.

Of note, despite this allergic tendency, immediate hypersensitivity to foods using guidelines for anaphylaxis is reported in up to 24%. This was an interesting point. I was unsure if 24% were indeed having signs and symptoms of anaphylaxis or did this refer to the point that for a food to cause an allergic reaction the criteria would be that with every exposure there would always be symptoms that would occur in a very short period of time after the exposure. Did the authors mean that 24% did have a real food allergy? This bothered me enough to pursue reference #36 . That reference is a letter to the editor. The article did not say anything about defining immediate hypersensitivity to food. In fact the words anaphylaxis and guidelines do not appear in the article. The letter has food sensitization in the population. This is an important issue- a critical reader who is concerned about the role of immediate hypersensitivity reactions to a food in EE should be able to review what the criteria were. Some other article must have the diagnostic criteria. The reference #54 is from Australia- it is this reference that shows that 24% of children with EE had anaphylaxis to a food. This paper also showed that food sensitization  prevalence decreased as the age of the patient increased.

The literature shows that 24% can have anaphylaxis to food. However, what percent of children have a relevant food allergy (not sensitization) accounting for the EE?

Adults Eosinophilic Esophagitis and Allergen Sensitization

                Reports indicate that elevated IgE is seen in 70% and other allergic diseases are seen in 77% of the adults with EE. In 63% of adults sensitized to food, cross-reactivity was seen. This was a different type of cross-reactivity. This concept can refer to problems between food groups- peanut sensitive patients cross-reacting to some of the tree nuts. Here the concept is aeroallergen and botanically related foods. For example grass as the aeroallergen and wheat and rye (both grasses) as the food allergen. However, in a small study of these adults, avoiding wheat and rye did not improve their symptoms. Recent work has shown that 86-93% of adults with this condition are sensitized to aeroallergens (point of sensitized vs. allergic) and 50-82% were sensitized to food. The common foods were;

• Peanut
• Soybean
• Egg White
• Cow’s Milk
• Tree Nuts
• Wheat
• Tomato
• Carrots
• Onions

Pediatric Eosinophilic Esophagitis and Food Sensitization

                Similar to what has been reported in adults more than 70% of the children has an elevation of IgE, the antibody that mediates type one allergic reactions. The track record on this measure, the total IgE, does not support the need to analyze or follow total IgE levels. A total IgE level is of no value in the evaluation of EE. 

                Children can be sensitized to allergens of the indoor and outdoor world. Grass pollen and mold (Alternaria) spore sensitization is seen in 26-37%. Fewer are sensitized to cockroach (16%) and house dust mites (19%). There may be seasonal changes with the symptoms of eosinophilic esophagitis, but the link between pollen and the presentation of the condition in children remains unclear.

                Foods tend to be more of a problem with the children. The paper points out a continually perplexing problem with allergy testing for foods. The serum or blood tests finds more positives than skin prick testing, with the clinical usefulness and the clinical significance of the increased detection is unclear. At this time, we do not know what this means.

                To date (up to the time the article was accepted-12-2011- not too long ago) there have been no studies published that document any correlation between the blood test values for food IgE with instigation(starting/causing) or propagating (continuing) EE. There are very few studies that use the blood tests results for any kind of elimination diet/intervention.

                The patch test has been used to detect a delayed food reaction. Patch testing for food has been done for children with EE. The combination of skin prick tests and food patch test results has had a high degree of success in predicting food allergens that may trigger EE. The point is made that the patch test may help in creating a directed (a diet that focuses on foods that were positive by testing) elimination diet, the test (patch testing) still needs standardization and validation for its use in children with EE. Of note, certain foods have been commonly found to be positive with all three diagnostic measures (skin prick, serum, and patch). These foods are;

• Milk
• Egg
• Wheat

These three were on my original skin test profile for food testin.

Using prick skin tests and patch tests the following foods were commonly positive with both techniques;

• Corn
• Beef
• Chicken
• Barley
• Oat
• Rice

This group of foods are more unusual and not commonly discovered when taking a history of cause/effect relationships with food exposures.

Importantly, the article points out that an empiric (this is a very appropriate word, it pertains to the use of practical experience to gain knowledge) elimination diet- the child is not given cow’s milk, egg, soy, wheat, peanuts, tree nuts, fish, and shellfish (with the exception of the shellfish and tree nuts, this empiric diet are those same foods that have been established a long time ago as the common culprits for food allergy in children.) followed by reintroduction has shown that four foods are the major culprits in most children- milk, wheat, egg, and soy. These are the ones to stay away from and see if there is improvement.

Treatment of EE

                It was pointed out that there is a debate regarding the endpoint of treatment. Should the program be directed against symptoms or resolution of the abnormal biopsy. The authors give three reasons to do both- make the symptoms go away and clear the inflammation;

                To improve the quality of life

                To reduce the risk of injury to the esophagus

                To prevent esophageal damage

                Treatment is the 3 Ds- Drugs, Diet, and Dilation.

Drugs-

                Proton pump inhibitors-never to be used alone

                Steroids- oral prednisone, topical fluticasone

                Leukotriene modifiers- not recommended

                Biologic agents/Immunosuppressants-mixed reports on preliminary use

Diet

                A 1995 study, noted as a landmark study by the authors, demonstrated the role of food in pediatric EE. The use of an elemental formula was found to be highly effective in >96% of children.

                One previously mentioned problem is the occurrence of multiple food sensitizations determined by skin prick testing or by blood testing.  These are not accurate and better diagnostics are a real need to help these children. Looking at the results of skin prick tests (not blood tests) combined with the patch test, the positive predictive value varied between 50-92% and the negative predictive value varied 41-100% for a variety of foods.  The positive predictive value is the probability that the food causes the illness when the test for that food is positive. The negative predictive value is the probability that the food does not cause a problem with the test for that food is negative. The wide variation in predictability underscores the need for standardizing and validating the tests that are used for food allergy in managing EE.

                The empiric diet- complete elimination of the common allergenic foods- milk, egg, soy, wheat, peanut, fish, shellfish, and tree nuts was successful in clearing the abnormal biopsy and relieving symptoms in 74%. When symptoms returned, milk, wheat, egg, and soy were the most common problematic foods. Milk was 18 times more likely to precipitate/cause a reaction than any other food.

This was a great article to review. There are many more questions out there than answers. There are real needs for better tests to find the relevant causative agents. This review focused on the allergy issues.

FEL 5-3-2012

This is an interesting article. This theme has appeared in the literature previously, here it is done on a much grander scale with over 1000 children in the study.

For those families/patients who start on this scary journey of peanut allergy an article like this gives an overall perspective regarding what could and what did happen to children with known peanut allergy. It is a nice survey of the troubles experienced. My feeling is that many families will have some reassurance regarding the diagnosis of peanut allergy after reviewing this publication. Other families may see similar risks and work to help avoid them.

The study is from Canada- yes they do eat peanut products there so the comparison is valid. The article recently appeared in the journal Pediatric Allergy and Immunology. The lead author was Nha Uyen Nguyen-Luu. The study was internally supported and funded. The lead author is in an allergy training program.

Overall the article is very interesting. It highlights a common problem of exposure and it gives a nice picture regarding some of the nuances of peanut exposure. For the readers who struggle with peanut allergy and their children with peanut allergy, this report may be also be an eye-opener.

As background it has been shown that accidental exposure to peanuts occurs between 3-75% of the peanut allergic population (US and UK studies).

Purpose This was an extension of an earlier study on children across Canada with peanut allergic children. This study looks at the incidence of accidental exposures to peanut, the severity of reactions due to those exposures, how the reactions were managed, and it looks at what may predict an accidental exposure.

Methods

Patient Selection: There were three sources used to identify children with peanut allergy; Montreal Children’s Hospital Allergy Clinics, advocacy organizations for food allergic patients, and organizations that provide products to allergic individuals.

Diagnostic Criteria:

• A convincing history of a reaction and a positive skin test or a peanut specific IgE >0.35 kU/L
• No/Uncertain history of a reaction and either a positive skin test, a peanut specific IgE >15 kU/L, or a positive peanut challenge

Results

                Patient Characteristics: There were 1,411 participants. From this number, 854 were recruited between the years 2000 to 2009. Overall (using the entire group) the average age when the peanut allergy was diagnosed was 2 years. Over 60% were boys. Over 88% had at least one other allergic condition and just over half had another food allergy. There were 231 children who had no or an uncertain history of a            peanut reaction.

                The peanut reaction histories varied;

•  No reaction 13.5% (but had a positive peanut test)
•  Mild reaction- 22.2%
•  Moderate reaction-49.8%
•  Severe reaction- 14.5%

                Rate, location, and management of accidental exposures: There were 266 accidental exposures in 221 children. Another way to look at this was that in 2227 patient-years, the annual incidence of an accidental exposure was 11.9%.

                Location of the accidental exposures-

•  The child’s home – 39.5%
•  Home of a relative/friend – 16.5%
•  Restaurant – 10.9%
•  School – 6.4%
•  School with peanut prohibition – 4.5%
•  Day care – 3.8%
•  Unknown/Other places – 22.9%

                Most of the children (87.2%) attended schools that prohibited peanuts.

                Nature of the accidental exposure:

• Oral ingestion – 174
• Skin contact – 65
• Inhalation – 13
• Unknown – 14

                Management of the exposures:

                                46.5% of the severe reactions were treated at home

                                21.3% of moderate and severe reactions got epinephrine

                                62.8% of the severe reactions did not get epinephrine

                Severity of initial reaction vs. accidental exposure:

                                Types of reactions with the accidental exposures

•  Mild – 26.7%
•  Moderate – 44%
•  Severe – 17.3%

There were 32 children (12%) who did not have a previous peanut exposure and experienced a reaction with an accidental exposure. 234 children with accidental exposures  had a previous peanut reaction.

                                Comparing the accidental exposure reaction to the initial reaction;

• Accidental exposure more severe than the initial reaction – 23.5%
• Accidental exposure was less severe than the initial reaction – 23.1%
• Accidental exposure and initial exposure reactions were the same -  53.4%

                Predictors of accidental exposure:  Children who were 13 years of age or older at the time of entry into the study and those                         children who had a servere previous reaction to peanut had an increased risk of an accidental exposure.                                           

                The longer the peanut allergy diagnosis was known the risk of an accidental exposure decreased.

Discussion

                This is the largest study published on the rate and predictors of accidental peanut exposures.  In these Canadian children, the annual rate of accidental exposure to peanuts was 11.9% of the children. There was also a decrease in the rate of exposures in those children who had the diagnosis of peanut allergy the longest. This was thought to be due to increased awareness and the development of avoidance strategies over time. More accidental exposures to peanut occur immediately after the diagnosis is made. Education about avoidance is critical during this interval.

                This rate of accidental exposure to peanut in the peanut allergic population is similar to what has been previously published in 2006 and is much lower than the rates of exposure published in earlier studies (50% and 60%).

                Just over 1/3 accidental exposures happened in the child’s home. Accidental exposures also occurred in ‘peanut-free’ schools.

                A previous study by these authors showed that 98.5% of the peanut allergic group was prescribed an epinephrine auto-injector, however moderate and severe reactions with the accidental exposure were not handled properly. In this study, 78.8% of the moderate and severe reactions to the accidental exposures were not treated with epinephrine. This included 45.5% of the reactions that were treated in a medical facility. A delay in the use of the epinephrine could result in a fatality. The point was made that it is crucial for parents and healthcare providers be better educated about the management of anaphylaxis.

Reviewer’s comments

                This is a very valuable contribution for families and for healthcare providers. When a family is told that the child has a peanut allergy, they embark on a very scary journey. The family may not have had any experience with a child with a food allergy. They may not know anyone with a peanut allergy.  They are told by healthcare professionals that the next exposure will be worse. They may have or not have an epinephrine auto-injector. They may not have been told how to use it, when to use it, why to use it, and what should be done once the injector is used. This website has a story shared by a mother who used an auto-injector for the first time.

                The family may have been told that this is a life-long food allergy. That the child has to sit at a peanut-free table and they need to closely watch what the child eats. This is a considerable burden. Families want to know what the wider experience with accidental exposures is. How do others do with this diagnosis? What might be in store for them? Can they be reassured by a report of a wider experience of children? Can they remedy the mistakes made by others if they are made aware of what those mistakes may have been? This study shares many findings on accidental peanut exposures in children in Canada.

                The key points to carry with you

1. Accidental exposures occur in 12% of the peanut sensitive children annually- exposures are not that common. We would hope that it would be 0%/year, but accidents can happen.
2. Most of these exposures were soon after the diagnosis was made- a critical time to educate and troubleshoot as the family starts off on this journey.
3. Education about avoidance is crucial at the time of the diagnosis and should be re-enforced- especially early on.
4. Almost all children (98%) with a positive test/story for peanut have an epinephrine auto-injector. Should not all children with this have an epinephrine auto-injector?  If the call is made the prescription should be written.
5. Not all accidental exposures caused more significant reactions, only about 25% were worse.
6. Not all reactions to peanut are severe, 15% were severe
7. About 15% of children in this study had a positive test to peanut and no history of a reaction
8. The most common route of an accidental exposure is oral.
9. Over 50% of the reactions occurred in the child’s home or the home of a relative/friend. This point I found unbelievable, especially when 40% of the exposures were in the child’s home! This can and must be changed for the sake of the peanut sensitive child.
10. Epinephrine was not used when it should have been used. When one troubleshoots a bad outcome from a peanut exposure one common theme arises; the use of epinephrine was too late to make a difference. Epinephrine is your best friend for a moderate/severe reaction. This point must be stressed to families and to healthcare providers.

There are a number of risks that can be eliminated.

FEL (4-18-2012)

Things Patients and Physicians Should Question is worth looking at. Various specialties made contributions. Listed below are those from the American Academy of Allergy, Asthma, and Immunology.

• IgG and IgE testing for allergies – the only proven diagnostic blood test is IgE for specific allergens based on the patient’s clinical history. Indiscriminate IgE batteries should be avoided.
• Sinus CT scans and antibiotics for uncomplicated acute rhinosinusitis – the condition is almost always caused by viruses and usually resolves without treatment.
• Routine diagnostic testing for chronic urticaria – definite causes are rarely identified and extensive testing is unproven to improve outcomes or to be cost-­‐effective.
• Replacement immunoglobulin therapy for recurrent infections – such treatment is warranted only when antibody responses to vaccines are clearly impaired.
• Diagnosing or managing asthma without spirometry – symptoms alone are not sufficient for a diagnosis and may overestimate as well as underestimate asthma control in treated patients.

Some of these are frequent themes in my postings. It is nice to see them critically reviewed and posted.

FEL 4-5-2012

Here goes (and I am reading this from his note)-

Medicine I take /and other stuff to now-

1. advare-2 puffs a day
2. ventalen-2 puffs a day
3. nasenex-1 spray in each nose a day
4. singular- 1 pill a day

I am alergic to = tree nuts

I have asmu

I go to doctors every four months

What caused me to hesitate was his medical condition. The medications sounded right, but I needed clarification on asmu-Wow did I get it!

Thanks Deac for sharing, Let me now if you want your list back.

FEL 4-4-2012

So what did I find exciting and thought provoking?

Delayed Anaphylaxis to Red Meat

This was a fascinating presentation and defies some of the established rules of allergy. We expect significant life-threatening reactions to occur within minutes and perhaps up to 2 hours after an exposure. The red meat story involves reactions that are 3-5 hours later. The unusal aspects of these cases are;

• Adult onset, delayed anaphylaxis
• Meat allergy which is rare in adults
• Reactions to foods are usually not delayed
• Skin testing gave poor or no results
• Skin tests reactions were seen with fresh meat extracts and done with intradermal testing
• Odd geographic distribution -Southeast United States

The theory is that this is seen in an endemic area for ticks, adults have a longer history of possible tick exposure (bites), the antibody (IgE) is to a common antigen in the meat and tick, and the delay may be due to absorption of chylomicrons which have a surface glycoprotein that is recognized by IgE causing an anaphylactic reaction.

Prediction of allergic sensitization

We all want to know what are the risk factors that predict the development of asthma in a child? Whenyou evaluate asthma through the allergist’s eyes we see;

• Aeroallergen sensitization
• Rhinovirus infection with wheezing- especially within the first few years of life

The thought here is that sensitization to an aeroallergen (an inhalant- not a food) makes it easier for the rhinovirus to set up shop in the airway and cause problems. The allergen sensitizes the child and the rhinovirus (one of the bugs that causes the common cold) comes along and in this sensitized child, causes a wheezing event.

This presentation talked about a Fc epsilonR1 receptor found on the basophils in the infant’s cord blood that predicted which children would become sensitized to an allergen and hence put them at risk for asthma.

Outdated Epinephrine Autoinjectors:Ejection volume integrity and epinephrine content and dose.

This was a poster by Dr. K.J.Simons. They looked at the outdated autoinjectors that were between 3-36 months past their expiration date. Those that were less than 20 months past the expiration were not discolored and had more than 90% of the epinephrine dose.

If you have an outdated injector, it may still work.

Egg Oral Immunotherapy- Stacie Jones, MD

This was an abstract presentation of work done on egg immunotherapy. Tolerance to egg was seen after two years of oral immunotherapy. The study involved older children who had less of a chance to outgrow their egg allergy (age 6-18 years). They all had a clinical reaction to egg and a specific IgE to egg of >12 kK/L.

Desensitization- when on treatment, small amounts of the food can be given without reactions- was seen in 22/40 children.

Tolerance- when the food, at usual serving sizes, does not cause reactions when the treatment has stopped- 18/40 became tolerant to egg.

Of note-15 children had to drop out due to untolerable side effects with the oral egg immunotherapy.

It seems from the total group recruited- 1/3 can’t do it, 1/3 become desensitized, and 1/3 become tolerant.

The authors stated that the procedure was safe, but must be done under supervison and that the results must be considered investigational.

Development of Clinical Tolerance after Peanut OIT (oral immunotherapy)- Wes Burks, MD

 Unfortunately, Dr. Burks did not present this information, one of his colleagues did the presentation. An important point was made at the onset- there is no FDA approved therapy for peanut allergy.

Tolerance within the context of food allergy is the idea that after a therapeutic program has been performed, here the OIT program, there is a persistence of effect (protection from reactions with specific food exposure) when the treatment program is stopped.

This was a report on a group of 19 children between the ages of 1-16 years. The average age was 11.2 years. They all had skin prick tests to peanut that were larger than a 3 mm wheal and a specific IgE to peanut that was over 15 kU/L or >7 kU/L if the peanut reaction was within the past 6 months. The average peanut IgE antibody level for peanut was 84.1 kU/L.

After 44 months of the peanut OIT program, 58% of the group were able to stop the treatments and consume peanuts as a regular part of their diet.

World Allergy Forum- Food Allergy- Pathogenesis and Prevention. Early Dietary Exposures and Feeding Practices by Scott Sicherer, MD.

This was a very nice presentation on potential ways to prevent allergic sensitization via diet. There have been a number of ways to address the problem;

• Diet during pregnancy
• Diet during breast feeding-
• Breast feeding with a change in mother’s diet
• Alternative formulas to breast milk
• Complementary foods- including when and which ones

When the child is breast fed and mother makes no change in her diet-

• Effect on the development of atopic dermatitis- Protective effect
• Effect on the development of asthma-Protective effect
• Effect on food sensitization in the child-1.5 times risk vs. a child who was never breast fed

When the child is breast fed and mother changes her diet during breast feeding (mother’s avoidance)

• Insufficient evidence existsto support the idea that mother’s avoidance prevents the development of atopic disease.
• There is a possible exception for atopic dermatitis
• Current food guidelines do not recommend that the mother’s diet be altered during breast feeding

How about the common recommendation that soy formula be substituted for cow’s milk formula to prevent a food allergy?

• Current food allergy guidelines do not recommend this for food allergy prevention
• There is no impact on the occurrence of asthma, atopic dermatitis, or rhinitis

Preventing Peanut Allergy- this was an eye opener!

Recommendations that were made in response to the peanut allergy epidemic observed in the 1990s- this is what we were told to advocate for a number of years.

• Avoid peanut during pregnancy, lactation, and wait until age 3 years to introduce peanuts
• Recommended by the American Academy of Pediatrics
• Recommended by the Committee on Toxicology – United Kingdom

What was observed with that guidance inplace;

• Prior to above advice- the incidence of peanut allergy in the U.S. was 0.4%
• In 2002- with the guidance inplace- the incidence of peanut allergy doubled to 0.8%
• Towards the end of the first decade of the 21st century (10 years of peanut avoidance) a continued increase in peanut allergy to 1.4%.

The speaker theorized that you may not be eating peanuts, but you touch them (environmental exposure) or have accidental periodic exposures/ingestions- can this lead to peanut sensitization?

Insect Hypersensitivity-Dr. David Golden

Large local reactions to hymenoptera (bees, wasps, yellow jackets, and hornets) do not require venom immunotherapy.

The injection schedule has changes- safety and continued protection has been demonstrated with a venom immunotherapy shot schedule of every 3 months at any point from 1-9 years of therapy and has also been shown to be safe and provide continued protection when given every 12 weeks after 4-5 years of treatment.

Anaphylaxis in the New Millenium- Dr. E. Simon

Anaphylaxis in infants is a concerning problem- they cannot describe their symptoms, the acute signs and symptoms are hard to interpret, and vital signs differ from those of adults. A serum tryptase level at the time of suspected reaction can help to sort out an allergic reaction.

Teenagers with anaphylaxis – a large and troublesome group to work with. They often have the co-morbid condition of asthma and tends towards significant risk taking behaviors.

Pro/Con Debate - Peanut Immunotherapy in the Office

This was a charged session. Dr. Wasserman took the pro position- he performs peanut immunotherapy in his office. Dr. Hugh Sampson was the arguer for the con positon. Dr. Sampson is one of the established researchers in the field of peanut allergy. I am a student of Dr. Sampson. He trained me – that will serve as my full disclosure regarding any interests in conflict (or vice versa).

This was one of those debates where an argument based on logic, science, and safety is pitted against an argument based on emotion. When anything debates emotion, emotion usually wins.

The pro argument was replete with testimony. It was hard felt, gripping, and effective to see and listen to videos on how peanut immunotherapy changed lives for the better.

However, as the arguement evolved on the con side, there were obvious far-reaching concerns and hopes that a bad outcome, and nothing would be worse than a death due to office-based peanut immunotherapy,  will  halt all the progress made to date. The end result would be that we would be left with nothing to offer.

Peanut orall immunotherapy is at this time still undergoing trials. It is research, not standard practice. It is an exciting work in progress and if things go as they are, it portends an exciting new life for the peanut allergic individual and their families. Note the the number of patients in these trials are very small. The research is not concluded, it has not been peer reviewed. We are all anxiously awaiting the conclusion to these studies. Remember, not too long ago we were taught that peanut allergy was a life-long sentence. Research has shown that 20% may outgrow their peanut allergy. Currently for the remaining 80% there may be a form of immunotherapy that will prevent reactions and may even lead to peanut tolerance. However, this is investigational. My understanding of investigational programs is that the patient or their insurance would/should not be charged for the investigation. Clearly, peanut immunotherapy is not the standard of clinical care in the community.

Also consider the risk that all this great progress may be put into moritorium, it may be stopped by the government if someone who is being given peanut immunotherapy in an office dies as a result. If death occurs because peanut immunotherapy is used prior to the conclusions of the studies, all may be lost. The hopes of those with peanut allergy will be dashed. The plea is for patience and care. This is still investigational.

FEL 4-4-2012

The clinic space does not exist at the Riley Outpatient Center (ROC) and I need space to run my clinic and to run food challenges. The clinic administration for the Riley Specialists at IU Health North have helped me find space and now I can expand my practice and take care of these food allergy needs.

Beginning in July, 2012, I will be moving my practice to the northside- IU Health North. I will no longer be runnning an allergy clinic at the ROC. Dr. Vitalpur will be taking on some of my clinics at the ROC and I will be up north seeing children everyday. The schedule will have dedicated rooms for performing food challenges.

I am looking forward to this change in venue,

FEL

I came across a very interesting and powerful editorial that summarized many issues dealing with the worldwide problem of allergy.

Allergy is a major health problem-clearly not in everyone and not in the majority of the population. Worldwide allergy affects 10-30% of people. As far as a single chronic clinical condition, that is a significant number. Also, the prevalence has increased.

The impact of an allergy can be life-threatening (acute severe episodes) or chronic (daily symptoms). The allergic condition does have a major socioeconomic burden and allergy also has the obvious effect on a patient or a family’s quality of life.

Despite advances in research on causes, associations, risk factors, and treatment of allergy there are many inadequacies and unanswered questions. This editorial shares those concerns.

This is a consensus statement from a group of 40 noted researchers and clinicians from four continents who met in Switzerland last year. The banner for the meeting was simply ‘Allergy and Allergic Diseases: Barriers to Cure’.

Allergic conditions deal with many broad areas of medicine. Allergy affects a wide range of organ systems; eyes, respiratory tract, gastrointestinal tract, and skin. The conditions vary in severity and their course.

Listed are the concerns and needs (these come from the experts and are my summations of their summation);

• The cause(s) for the increase in allergy prevalence is unknown. Environmental considerations    include; air quality, diet, climate, UV radiation, direct skin contact, and psycho-social interactions.
• A specific environment may protect or put someone at risk if they have the genetic predisposition towards allergy.
• Interactions between bacteria, pollutants, and the immune system are marginally understood.
• There is inadequate understanding of those natural mechanisms that lead to acute vs. chronic suffering with allergy or resolution of allergy.
• There needs to be a better classification system for severity/types of allergy.
• New therapies need to work on the pathways that lead to an allergic response.
• Better translational research is needed (taking what is learned in the laboratory to the bedside).
• Better tools are needed to analyze the information or data regarding allergy.
• There needs to be a plan for prevention of allergy.
• We need better tools for diagnosis and prediction of a response to treatment.

The article also noted the gap between what we know about allergy and the application of that knowledge to those who struggle with allergy.

• There is a shortage of well-trained allergists in most countries
• Education and training efforts regarding allergy need to start with the medical students, especially for a condition that affects so many people
• Awareness campaigns are needed for targeted groups such as nurses and school teachers
• There needs to be close cooperation with patient organizations
• Decision makers for developing and approving health policies and administration must be made more aware of the issues and problems of allergic diseases

Reviewer’s note-

It scary what we do not know and it is even scarier that we are not doing much about a few things when we can.

Allergy is a public health problem.

The editorial challenges us to make a change.

This year Dr. Vitalpur and I will be offering clinical teaching about the immune system and allergy in particular to first year medical students.

I have always wondered why allergy is not a required resident rotation – a requirement by the governing board of residencies. The condition affects so many children and is thought to affect so many more. I can easily see the impact of having at least a few weeks of exposure to the specialty in our allergy clinic.

We are most happy to speak at support groups or schools and we have done that many times. I am concerned that we are not asked more frequently to go out in the community.

We get involved with patient organizations and are willing to be involved with more.

It is unfortunate that we are not asked about policy or design. More often we have a reactive role in this regard.

The challenge is before us.

FEL (2-2-2012)

As with many offices, we also struggle with appointments made but not kept. What happened in my practice was that this created a waiting time for new patient appointments at three months. That was too long and unacceptable. I thought long and hard about how to increase the rate of show and hopefully cut down on that prolonged wait time for an appointment.

I recalled an article  for which I was the lead author. This publication looked at asthma adherence. Part of that study included appointment keeping behavior. When a family was given an appointment by a health care office about 2/3 kept that appointment. When a family was told to make an appointment, the rate of show was 95%.

I have always wondered about our tendency to try to schedule appointments ‘office to office’ and just how well that works. It is a nice service however it may not be very effective or efficient. It may have worked for a time in the past, but I have doubts about offering that policy today. When an appointment is failed, the time of the referring physician’s office staff and our staff was wasted. I have always thought that it may be better to have families make appointments themselves. This would be a form of empowerment for a family. When a family goes home and later calls to make an appointment they have had a chance to think about a consultation and whether or not they agree with the need. They may want to consider other providers for this service. There was a chance to discuss it with other family members. Their calendars were at hand. Travel could be considered. There are many positive outcomes for doing it this way.

All too often the family is not aware of their schedule when an office makes an appointment for them. Sometimes the families don’t agree with the need for a consultation. Consider also time, transportation, cost, and even results. When a family makes their own arrangements, they are more wedded to the idea. The family is talking directly to our representatives so issues of location, time, and preparation (stopping only antihistamines) are gone over directly and not later via a third person.

So why did we do so well in January 2012 with new patient appointments (in rank order of importance)?

• Families really wanted to see me
• Families made their own appointments
• It was a quirk and it will never happen again

Regardless, I like to stay busy. I cringe when I hear that my wait time is longer than 2 weeks. Hopefully this trend will continue.

FEL (2-1-2012)

There is a very nice review about histamine and antihistamines in the most recent Journal of Allergy and Clinical Immunology by Drs. Simons and Simons. The review was to commemorate 100 years since the discovery of histamine as a mediator and 70 years since antihistamines have been available for clinical use.

H1 antihistamines are the largest class of medication available with >45 available. These agents act against histamine’s effect on allergic inflammation. There are two general classes of these agents- first generation and second generation. Better put, the old ones that can get into the brain and cause sedation and the newer ones that tend to not to be sedating.

The older or first generation of antihistamines became available at a time when regulations were different and because of this, there is a lack of information about how these agents are handled in a variety of special populations; children and infants specifically. The new generation of these agents has undergone rigorous evaluations. These studies have shown that tolerance does not occur with the regular use of these agents. In other words, you do not become immune to these agents.

 Antihistamines work for and are indicated for the following conditions (where they are the medications of choice);

•  Allergic rhinitis (nasal allergy)
• Allergic conjunctivitis (eye allergy)
• Acute urticaria (hives)
• Other- mastocytosis, mosquito bite reactions, immunotherapy reactions

In these three conditions, there have been hundreds of well-designed studies that support their effects. The evidence is there.

A couple of points were made;

•  Antihistamines do not work in nasal symptoms not due to allergy
• Some will work within 15 minutes others may begin to show an effect in 2.5 hours
• Topical nasal antihistamines may work as good as or better than oral antihistamines for congestion
• Hives that last longer than 6 weeks, chronic hives, may require doses 4-fold higher
• Current guidance for chronic hives has the H2-class as the antihistamine of choice at high dose

 Conditions for which an antihistamine is not the medication of first choice;

•  Atopic dermatitis
• Asthma
• Anaphylaxis
• Nonallergic angioedema
• Other disorders

The points made regarding these conditions were;

•  There have been no high-quality studies to confirm their efficacy in atopic dermatitis
• The use of antihistamines in atopic dermatitis is still sometimes used for sedation effects (which would be the first generation antihistamines).
• A review of 2070 studies on the use of antihistamines with anaphylaxis could not identify a good study that provided solid evidence for the use of these agents in anaphylaxis. They decrease itch and hives. They do not prevent or relieve airway/throat swelling.
• The efficacy of antihistamines to treat colds, ear infections, sinus infections, nasal polyps, nonspecific cough, nonspecific itching has not been confirmed in well done studies.

 Conditions for which the first generation antihistamines have been used;

The first generation antihistamines have been used in a variety of conditions, however the evidence to support their use is considered weak. Most of these conditions involve the central nervous system;

•  Insomnia
•  Conscious sedation
•  Perioperative sedation
•  Analgesia
•  Anxiety
•  Serotonin syndrome
•  Akathisia
•  Migraine
•  Motion sickness
•  Vertigo

 Reviewer’s note-

Antihistamines are one of the most frequently used agents and have been used for a variety of conditions. They work for some things and not for others. I have seen multiple antihistamines used in the same child and choices made for perhaps the wrong reasons. Also of note is to keep in mind that when a study is done, there are responders and non-responders. Sometimes there are not enough responders to show a significant difference. The conclusion from such a study could be that the agent does not work and would not be recommended overall. A question to ask is whether it had an effect in anyone or was it a total non-response?

The take home messages for me- when they stop working think of some non-allergic issue, tolerance does not develop. If you use these for atopic dermatitis, you are looking for sedation. It would make more sense to go with the first generation agents in this condition. In conditions that do not respond, the dose may need to be increased as opposed to adding a second agent. Don’t ask more of the antihistamines than they can deliver.

FEL (December 24, 2011)

A few things to add. I prefer the use of the term ‘peanut-safe’ in deference to ‘peanut-free’. The terms safe and free may have the same intent, however they may be practiced differently. For example, peanut free would mean that no peanuts would pass through the threshold of the institution- that is the policy, that is the law. Now consider ‘peanut-safe’. When you are peanut-safe, it includes the previous concept and adds the idea of continued vigilance; always checking, always looking, being active about keeping peanuts away from those who may have life-theatening events with exposure.

The other item I would add is that at this time, since I write all the material for allergy at Riley, you would have to check out this website for more information. The www.RileyHospital.org gets you to the children’s hosptial website and how to access the children’s hospital. They are working on topic postings.

Thanks for looking,

Fred Leickly (12-11-2011)