Practice Makes Perfect!

29 Nov 2012 Leave a Comment

by lynnawiensmd in Just For Fun! And you might learn something too!, Newsworthy items, What's New in Medical Literature? Tags: , , ,

I had the privilege this week of watching my favorite sport….10 players dribbling an inflated ball up & down a court, trying to throw it through a steel hoop more times than the opposing team.  Yeah, it’s my passion.  The Thunder vs Bobcats and Oral Roberts University vs the Sooners of Oklahoma.  (little in state rivalry) What impressed me about the current state of basketball is how fast any human 6 ft 8 inches tall can get up and down the court!  As a devout Kansas Jayhawk fan growing up, we (of course I’m part of the team!) had some good exhibits, but never with the agility, speed, and shooting accuracy seen today.  Regardless of better nutrition, year round practice schedules, and the 3-point shot, we all practice to get better. I didn’t realize that despite many alternatives to oral steroids, our use of a “quick fix” is increasing.  Is that why we call this the “practice of medicine?”

I report here a study published barely one month ago on the use of steroids for treating many medical conditions.  Our approach to steroids (by mouth) is to use them when necessary, but substitute with inhaled steroids or other alternatives whenever possible.  Why?  Side effects.  In fact, did you know that based on systemic absorption, a 5 day “burst” of oral steroids is equal to 20 years of the inhaled route?  Based on this poster presentation, it would seem that we need more practice in reducing the use of steroids, especially in children!  My recommendations:

  1. As noted below, emergency rooms and urgent care clinics often don’t know how many times in one year a patient has been on steroids.  Patients often don’t go to the same clinic, and the doctor in that case has no way of monitoring overall steroid use and exposure.  The fix: communicate to ANY provider how many times you have used oral steroids.  You’ll be pleasantly surprised at the results!
  2. Inhaled steroids, allergy shots, avoidance of pets are all designed to reduce your need for bursts of oral steroids.  I agree, avoiding dust and animal dander can be a hassle, but you’ll have better control of asthma if you do and less of a need for oral steroids.  The fix:  take preventive medications as prescribed, avoid all known triggers of asthma (perfume included), and measure your peak flow reading at the first sign of coughing or wheezing. 
  3. Who gets tired of repeating the same list of medications every time you go to the doctor?  Oh, yes, I get tired of writing them down!  There is a reason for the madness….your arthritis doctor, allergist, and ER doctor all prescribe prednisone for different conditions, and unless each prescription is written down and recorded, it’s easy to get an overdose.   The fix: try to remember “in-between” medicine that you have received from one doctor visit to the next.  This is especially important to review with your “primary care doctor”. 

American College of Allergy, Asthma & Immunology (ACAAI) 2012 Annual Scientific Meeting: Abstract P313. Presented November 11, 2012.

English: Ball-and-stick model of the immunosup...

English: Ball-and-stick model of the immunosuppressant drug prednisone (Photo credit: Wikipedia)

The number of prescriptions for prednisone has been increasing steadily since 2000 in the United States, and not all prescriptions are appropriate, researchers reported in a poster session here at the American College of Allergy, Asthma & Immunology 2012 Annual Scientific Meeting.

“I have been in residency for the past 3 and a half years, and was surprised at the amount of steroids being prescribed and the diseases they were being prescribed for,” Tricia Lee, MD, 2012 chief resident in internal medicine and pediatrics at the University of Louisville in Kentucky, told Medscape Medical News.

“This impressed me because we are taught in medical school about all of the significant side effects of systemic steroids, which include weight gain, thinning of skin, psychiatric changes, and adrenal suppression. I wanted to see if we, as physicians, were truly prescribing more prednisone now than we were a few years ago,” Dr. Lee explained.

She and her group examined data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey databases, which were collected by the Centers for Disease Control and Prevention, from 2000 to 2009.

During that time, 11 billion visits were recorded in the 2 databases. Prednisone was prescribed in 178,655,280 visits for any diagnosis — an increase of 17% for all ages.

For adults, prednisone was prescribed 13% more frequently in 2009 than it was in 2000; for children, it was prescribed 38% more frequently, Dr. Lee said.

Diagnoses Associated With Prednisone Prescription

More than 1000 different primary diagnoses were associated with a prescription for prednisone. Asthma, allergy, bronchitis, rheumatoid arthritis, urticaria, contact dermatitis, acute upper respiratory infections, and pneumonia accounted for the majority of prescriptions.

For allergic rhinitis, prednisone prescriptions increased from 1.9% in 2000 to 2.2% in 2009, Dr. Lee noted.

“The worry is that a patient will go to one doctor to get a prescription for prednisone for his rheumatoid arthritis, go to another to get prednisone for a pain in his shoulder, go to another to get a prescription for his asthma, and so on, until he is taking a dangerous amount of prednisone, without all of his doctors being aware,” Dr. Lee said.

“The danger to the patient is that, in the span of a few months, they may be exposed to steroids for a chronic period,” she said.

Emergency Department Implicated

John Oppenheimer, MD, clinical professor of medicine at the New Jersey Medical School in Newark, was asked by Medscape Medical News to comment on the study. “This abstract highlights a significant rise in the use of prednisone, specifically in the emergency department setting,” he said.

He added that “in the case of allergic respiratory illness, this is overall the most effective therapy; however, as pointed out by Dr. Lee and her colleagues, it is not without side effects.”

Dr. Oppenheimer called this increase in the use of prednisone “alarming.”

“The authors postulate that this is the result of a lack of appreciation of potential side effects. However, one may also argue that this is the sequel to the undertreatment in a proactive approach of the underlying illness.”

 

How Can You Resist?

27 Nov 2012 Leave a Comment

by lynnawiensmd in Allergies, Environmental clean-up, What's New in Medical Literature? Tags: , ,

Our environment is so important for treating and controlling allergy.  The holiday season lets many triggers into our homes that normally wouldn’t be allowed.  Does your doctor ever make you mad by suggesting you remove a pet from your home because of allergy?  Granted, it doesn’t matter what clinical research says when your pet is at stake, but this editorial discusses the myth of hypoallergenic pets….by the way, do think the red bow would look good on Scamp for Christmas?

The Journal of Allergy and Clinical Immunology
Volume 130, Issue 4 , Pages 910-911, October 2012  Author: Dr. Richard Lockey.

William Osler, the father of American medicine, said “The practice of medicine is an art based on science.” The article by Vredegoor et al1 entitled “Can f 1 levels in hair and homes of different dog breeds: lack of evidence to describe any dog breed as hypoallergenic” gives credibility to Osler’s admonition. Sound science is fundamental to good medicine, and it is important for physicians and other health care professionals to use this science to provide quality care for their patients and to teach families to better care for themselves, in this case to understand that there is no such animal as a hypoallergenic dog.

What pertinent information can be gleaned from this article? First, the authors compare so-called “hypoallergenic dogs” (labradoodle, poodle, Spanish waterdog, and Airedale terrier) with “nonhypoallergenic” dogs (Labrador retriever and a control group composed of 47 different nonhypoallergenic dog breeds and several crossbreeds). The authors sampled dog hair and coat, settled floor dust, and airborne samples.

The article demonstrates that Can f 1 levels in hair and coat samples are significantly related to the breed, although high variability occurs within individual breeds. Can f 1 levels are significantly higher in hair and coat samples in dog breeds considered hypoallergenic, and they are no less allergenic than any other dogs. Although there is some variation in other characteristics, such as whether the dog was bathed, none of these parameters had significant outcomes on the conclusions of the study. These data are confirmed by another study, published in July 2011, which examined dog allergen levels in homes of hypoallergenic versus nonhypoallergenic dogs. It, too, indicates that there is no evidence for differential shedding of allergens by dogs grouped as hypoallergenic.2

Second, the allergic symptoms of all persons 6 years of age or older living in the homes of dog owners also were elicited. Most owners of hypoallergenic dogs selected them for this alleged characteristic. More than 80% of the allergic owners of hypoallergenic dogs stated that they had less symptoms with these versus other dogs, illustrating that their conclusion is not secondary to less Can f 1 in their home environment.

The United States has the highest number of household pets, with approximately 62% of households having 1 or more domestic animals.3 About 78.2 million dogs and 86.4 million cats occupy homes. The average cost for basic food, supplies, medical care, and training for a dog or a cat is $600 to $900 annually, indicating that if each animal costs $750 annually, up to $123 billion dollars or more are spent on these fur-bearing pets each year, equal to the gross national product of the 57th of the 182 countries of the world.4

Evidence also shows that high levels of Can f 1 are found in settled dust in carpets or soft furnishings, such as couches, pillows, and blankets, in homes. Also, Can f 1 allergen levels are present in classrooms, airplanes, automobiles, day care centers, hospitals, and households without dogs.5 Cat allergens, particularly Fel d 1, the main cat allergen, are also widely dispersed in indoor environments.6 As the prevalence of fur-bearing animals in homes has increased in the United States over the past 60 years, so has the incidence of allergic diseases.7 Is there a cause and effect? In the past, these fur-bearing animals were kept outdoors for a variety of reasons, including the fact that they cause allergic diseases, as well as because they were thought to be dirty, promoted flea infestation, and were associated with cat scratch disease, toxoplasmosis, and other infectious diseases.8 These same risks exist to this day.

Today, animals are considered part of the family and occupy the same territory in homes as the human residents, including beds. In fact, studies show that it is almost impossible to eliminate animals from the home, even when subjects with dog and cat allergy live in the same dwelling.9 A clinical vignette is helpful to illustrate this point. Two children, ages 6 and 8 years, accompanied by their mother were seen by me in the clinic. Both children had a history of multiple hospitalizations for asthma. Five cats lived in the home before the birth of the children and continued to occupy the entire home. Both children were historically allergic to cats and had very positive prick-puncture skin test results to cat extract. When I approached their mother about excluding the cats from the home, she refused and removed her children from my care. This story illustrates sometimes how difficult it is to remove animals from the homes of allergic subjects.

Would 5 smokers be permitted to smoke in the same home? Is chronic allergic inflammation caused by animal dander similar to the detrimental effects of passive smoke or direct smoke for allergic asthmatic patients? Are the persons with asthma who have airway remodeling and irreversible lung disease, possibly caused by continuous allergen exposure, comparable with those who smoke and have chronic obstructive lung disease?

It is a bit ironic that smoking, which has been associated with the onset and worsening of allergic and other respiratory diseases, is universally prohibited in many countries, yet cats and dogs are ubiquitous, even allowed in some restaurants and on planes, resulting in pet allergen contamination of both private and public dwellings and placing persons with dander allergy at risk.

Although there is some evidence that having a cat or dog in the home during the first year of life might prevent allergic disease, including asthma, the evidence remains controversial.10 One article even suggests that dog ownership significantly reduces the risk of eczema at age 4 years among dog-sensitive children, whereas cat ownership combined with cat sensitization significantly increases this risk.11 Many published studies are available about preventing allergic diseases and are summarized in a World Health Organization book devoted to prevention. It calls for the removal of relevant pets from the environment for primary, secondary, and tertiary prevention.12 Similarly, a 2012 review article about preventing allergy in children states that “Acquiring or avoiding a pet cannot be justified as a measure preventing allergy in an infant.”13

Although intelligent conversations about animal removal from a home might have taken place in the past with patients and family members allergic to such animals, today these conversations are often met with immediate resistance and the idea that the treating physician should prescribe a medication or cat and dog allergen immunotherapy, with their considerable cost, inconvenience, and even risk to the patient, to attempt to eliminate dander-associated symptoms.

Physicians and other health care professionals should be knowledgeable about the causes of pet dander allergy so they can educate their patients to help minimize and prevent exacerbations of allergic diseases and asthma. The concept of a hypoallergenic animal, in this case a dog, is not supported by scientific evidence, just as there is no evidence to support the concept of hypoallergenic cats.6 Therefore the implementation of more established practices, such as eliminating animals from the home, remains the treatment of choice.

Happy Thanksgiving message

22 Nov 2012 Leave a Comment

by lynnawiensmd in Just For Fun! And you might learn something too! Tags: , , , ,

If you’re anything like me, waking up on Thanksgiving morning brings to mind a flood of memories to truly appreciate.  Maybe its the intoxicating smell of turkey (and the tryptophan will make you want a nap)  mixed with pumpkin pie, or the anticipation of Christmas that entices us to slow down and reflect on what is truly important in our hectic lives.  For me, of course, my delightful family is always a “sweet spot” when I come home from work each day. 

All 5 to be thankful for!

Healthcare on the other hand, has come under criticism for many reasons, and my position is no exception.  Despite all of the challenges facing health providers, I still love the challenge of caring for patients with respiratory illness!  Despite all of the changes proposed by the “powers that be” to make health care better, the following principles remain:

  1.   If you understand the WHY about your condition, you’ll be better prepared to implement the HOW do I feel better!
  2.  Feeling better is a cooperative effort between patients, health care providers, support systems, the right diagnosis and the right treatment.  Solutions are never usually simple, easy, or a quick fix.
  3.  I’m reminded of a middle-aged woman who was frequently hospitalized for her asthma.  She was frequently on steroids (oral) for wheezing and almost died several times.  She made a decision to stop smoking, clean her environment, and took her medications on a regular basis.  She also attended classes on asthma and taught herself about what made her asthma so severe in the first place.  Was she successful?  I never hear from her anymore if that tells you something about her progress. 

Enjoy your holiday….and by the way if you get heartburn, I wrote last year about the inevitable!  Click on the link below. 

http://wp.me/p1O8HY-3a

Stay Up to Date with Food Allergy

20 Nov 2012 8 Comments

by lynnawiensmd in Just For Fun! And you might learn something too!, Newsworthy items Tags: , , , ,

I always enjoy National Medical Meetings….good food, meeting old friends, and yes, even learning something!  The College of Allergy annual meeting was held in California just one week ago……and what are the hot topics this year? 

Here’s an article and interview from Medscape about this year’s meeting.  Why am I interested? Dr. Portnoy was my mentor (professor) during my fellowship training in allergy.  Way to go Jay! 

Here’s what he had to say–This international food allergy conference features the latest on eosinophilic esophagitis, unusual and “off the beaten track” food allergies, spice allergies, and developments in food immunotherapy.

“Food allergy is always something that people are interested in,” Jay Portnoy, MD, professor of pediatrics at the University of Missouri, Kansas City, and Mercy Children’s Hospital, told Medscape Medical News. 

Children’s Mercy Hospital entrance

Dr. Portnoy, who chaired this year’s abstract committee, highlighted a few of the presentations on food allergy that he considers particularly noteworthy.

“Researchers at Northwestern University in Chicago have found that kids with egg and milk allergy are more likely to outgrow those allergies than if they have tree nut or shellfish allergy. So when the doctor says your child will probably outgrow their egg or milk allergy, they’re not too far off,” he said.

Another study examines how people who are allergic to hen eggs might be able to tolerate them when they are baked. “It turns out that baking the egg actually denatures or neutralizes the allergen, more so than if you just partially cook it. If you introduce cakes and cookies into your diet, you will be able to most likely broaden your diet and improve the quality of your life,” he said. 

One presentation of definite note is on a newly identified and possibly life-threatening allergic reaction to mammalian meat. Researchers have determined that the lone star tick is the primary reason for meat-induced alpha-gal allergic reactions.

“This new food allergy, alpha-gal, is more common than we thought. There is a high prevalence in some areas of the country, particularly in the central and southern regions of the United States,” Dr. Portnoy explained.

Alpha-gal is a sugar found in red meats such as beef, pork, and lamb. In the study to be presented, positive alpha-gal rates were 32% higher in areas with a lone star tick population than in other areas of the United States.

Symptoms of alpha-gal allergic reactions range from mild hives to potentially life-threatening anaphylaxis.

“The reaction is delayed. A lot of people have experienced this, and now we know what it is. This is why it is so important to come to the annual meeting and learn about these unusual allergic reactions,” he said.

The topic of spice allergies is also on the meeting agenda.

According to a statement issued by the ACAAI, spices are one of the most widely used products, and are found in foods, cosmetics, and dental products. The US Food and Drug Administration does not regulate spices, which means that they are often not noted on food labels.

As a result, they are one of the most difficult allergens to identify and avoid.

“While spice allergy seems to be rare, with the constantly increasing use of spices in the American diet and a variety of cosmetics, we anticipate that more and more Americans will develop this allergy,” said Sami Bahna, MD, DrPH, from the Louisiana State University Health Sciences Center in Shreveport.

“Food allergy is a very important topic for allergists because we need to understand the most current research; recently, the field has seen a lot of changes,” ACAAI President Stanley Fineman, MD, from the Atlanta Allergy and Asthma Clinic in Georgia, told Medscape Medical News.

“There is a lot of new understanding about food allergies, new diagnostic tools, and some potential treatments,” he said. “This is the place to find out the latest information; when you go back to your practice, you [will] be on the cutting edge.”

Back by popular demand is the annual literature review course, where experts present what they feel are the key articles of the year on topics such as immunology, allergic rhinitis, ocular allergies, and immunology. “We have almost 500 people already registered for this program. Some people look forward to this program all year long to catch up on the literature. It’s a very popular feature of the meeting,” Dr. Fineman said.

The slogan for this year’s meeting is “Over the Horizon: Expanding Expertise,” which captures the essence of what the conference is about, he noted.

“The program committee selected this theme to help us see what is going on in the future, to expand our expertise, to make sure that we are able to keep current, and to hone our skills so we can adapt to any changes in healthcare and any new research involved with treating our patients,” Dr. Fineman explained.

“Most allergists go to the meeting to find out what’s new in allergy, to keep their skills up, to interact with colleagues, and to validate what they do. Because, like most allergists and most physicians, if you are in practice and you don’t interact with other physicians, you can start to develop quirky styles of practice that may not be the best practices. It’s really a good idea to touch base with colleagues, interact, and hone your skills,” Dr. Portnoy added.

“At this meeting, allergists will hear about an unusual case and then remember a patient who had the same thing. That’s how advances in our field are made,” he said.

I could say it better.  With all the controversy swirling around health care reform, it’s refreshing to learn about what really matters for taking care of patients….that’s why I keep going to work every day!

Allergy Drops–Are We Closer to Getting Rid of Shots?

15 Nov 2012 Leave a Comment

by lynnawiensmd in Allergy shots, Newsworthy items, What's New in Medical Literature? Tags: ,

Wouldn’t it be nice to put some drops under your tongue and say goodbye to those painful shots for good?  Allergy treatment under the tongue (sublingual drops and now tablets) have actually been around for a long time.  Until recently, the science behind allergy drops has been lacking.  As you read this review, consider the following:

  1. At the present time, there are no products approved by the FDA for this type of therapy.  It is anticipated that products will be approved within the next 3-5 years, but don’t ever try to predict the FDA!
  2. Most allergy care in the US uses multiple allergens in preparation for allergy shots.  This means a combination of trees, grasses, weeds, molds, dust, cat, dog, and sometimes cockroach. How many of you would be satisfied using only grass pollen or dust mite in your allergy treatment?
  3. Oh, the pain of shots!  There are now high frequency vibrational devices that take the pain out of shots right on the spot.  Ask our nurses to help you try it out.  This might make shots easier to tolerate.
  4. I don’t usually include references in my posts, but there’s only 25; the list is very inclusive for a complete up-to-date review of studies in the United States.
  5. I’ve copied the authors introduction, and conclusions for your review.   I enjoy reading future predictions and we’ll have to see how accurate this is. 

Adult and Pediatric Clinical Trials of Sublingual Immunotherapy in the USA

Dai Park, Nora Daher, Michael S Blaiss. Expert Rev Clin Immunol. 2012;8(6):557-564.

Specific allergen immunotherapy has been practiced for allergic rhinoconjunctivitis for over 100 years and is the only treatment option that is disease modifying. In the USA, immunotherapy is usually administered via subcutaneous injection; this is the only route with a US FDA-approved formulation. There is growing interest in developing US-standardized formulations for the sublingual route, but up until recently there have been few US trials. Most of the experience with sublingual immunotherapy (SLIT) comes from Europe, where it is widely used and there is a large body of literature supporting its use. The purpose of this review is to summarize recent adult and pediatric clinical trials of SLIT in the USA. Most of the trials are for inhalant allergies, but there is some early work on SLIT as a novel therapy for food allergies.

Introduction

Presently, only subcutaneous immunotherapy is approved by the US FDA for inhalant and stinging insect allergies in the USA. Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is being viewed with increased interest by US allergists as an alternative to subcutaneous immunotherapy.

The first published double-blind, placebo-controlled, randomized clinical trial (DBPC-RCT) with inhalant SLIT came from London, UK in 1986.[1] This was followed by numerous studies from Europe in the last two decades, which confirmed the efficacy and safety of SLIT.[2] Some novel studies include the first DBPC-RCT on allergoid SLIT tablets in 1998[3] and the first DBPC-RCT of SLIT successfully treating atopic dermatitis in dust mite-sensitized children.[4]

Important work has also gone into elucidating the underlying mechanism of SLIT. The current thought is that tolerogenicity is induced by oral dendritic cells, which reside on the uppermost layers of oral tissue and in the context of SLIT, capture allergen and produce IL-10 and IL-12 cytokines. This thereby promotes a tolerogenic pathway and a T-cell shift from a Th2 to a Th1 and Treg phenotype. Treg cells further propagate the Th1 pathway by producing IL-10 and TGF-β that negatively feedback on Th2 cytokines and subsequently cause a decrease in IgE levels and an increase in IgG4 levels.[5]

In the USA, there was early work performed on SLIT for cat allergy in 1993;[6] however, this aside, there were no other published DBPC-RCTs until the past few years. Renewed interest may be, in part, due to the advent of two SLIT grass pollen tablets – Grazax®[7,8] and Oralair®,[9] approved for use in Europe in the late 2000s. These SLIT tablets are currently undergoing trials in the USA. Here we review those and other recent US clinical trials for inhalant and food SLIT.

Expert Review & Five-year View

SLIT has been demonstrated in US studies to be efficacious and safe in the limited number of allergens evaluated so far. Hopefully this will lead to FDA approval for this treatment in the near future. It appears from the studies discussed that SLIT by tablet will have a higher likelihood of FDA approval compared with SLIT drops. We should see the development of other common allergens in tablet form for SLIT, including dust mites, tree pollen and cat hair over the next several years. Studies will need to be performed to determine if mixed unrelated allergens given together by the SLIT method will demonstrate clinical efficacy and safety. We may likely see further studies looking at the disease-modifying aspects of SLIT and whether early treatment with SLIT in children at risk for allergy and asthma may prevent their development. Food studies will continue to assess the role of SLIT versus OIT that will hopefully lead to better and safer means of inducing desensitization and tolerance to improve the lives of the increasing growing population of people with food allergy in the USA.

 References

  1. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin. Allergy 16(5), 483–491(1986).
  2. Cox LS, Larenas Linnemann D, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J. Allergy Clin. Immunol. 117(5), 1021–1035(2006).
    • A detailed, comprehensive review on Sublingual immunotherapy (SLIT) worldwide and discusses unmet needs.
  3. Passalacqua G, Albano M, Fregonese L et al. Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. Lancet 351(9103), 629–632(1998).
  4. Pajno GB, Caminiti L, Vita D et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J. Allergy Clin. Immunol. 120(1), 164–170(2007).
  5. Moingeon P, Mascarell L. Induction of tolerance via the sublingual route: mechanisms and applications. Clin. Dev. Immunol. 2012, 623474(2012).
  6. Nelson HS, Oppenheimer J, Vatsia GA, Buchmeier A. A double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized cat extract. J. Allergy Clin. Immunol. 92(2), 229–236(1993).
  7. Durham SR, Emminger W, Kapp A et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J. Allergy Clin. Immunol. 129(3), 717–725.e5(2012).
    • Shows that the grass SLIT tablet, Grazax®, has a sustained disease modifying effect.
  8. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J. Allergy Clin. Immunol. 117(4), 802–809(2006).
  9. Didier A, Worm M, Horak F et al. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis. J. Allergy Clin. Immunol. 128(3), 559–566(2011).
    • Shows that the grass SLIT tablet, Oralair™, has a sustained disease modifying effect.
  10. Esch RE, Bush RK, Peden D, Lockey RF. Sublingual-oral administration of standardized allergenic extracts: Phase 1 safety and dosing results. Ann. Allergy Asthma Immunol. 100(5), 475–481(2008).
  11. Skoner D, Gentile D, Bush R, Fasano MB, McLaughlin A, Esch RE. Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by ragweed pollen. J. Allergy Clin. Immunol. 125(3), 660–6, 666.e1-e666.e4.(2010).
  12. Bush RK, Swenson C, Fahlberg B et al. House dust mite sublingual immunotherapy: results of a US trial. J. Allergy Clin. Immunol. 127(4), 974–81.e1(2011).
  13. Amar SM, Harbeck RJ, Sills M, Silveira LJ, O’Brien H, Nelson HS. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract. J. Allergy Clin. Immunol. 124(1), 150–156.e1–e5(2009).
  14. Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J. Allergy Clin. Immunol. 127(1), 72–80, 80.e1(2011).
    •• The first study to demonstrate efficacy of grass SLIT tablet in US adults.
  15. Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J. Allergy Clin. Immunol. 127(1), 64–71, 71.e1(2011).
    •• The first study to demonstrate efficacy of grass SLIT tablet in US children.
  16. Bufe A, Eberle P, Franke-Beckmann E et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J. Allergy Clin. Immunol. 123(1), 167–173.e7(2009).
  17. Cox L, Casale TB, Nayak A et al. A US study of 5-grass pollen allergen extract in adults with grass pollen-induced allergic rhinoconjunctivitis – results of secondary efficacy assessments. J. Allergy Clin. Immunol. 129(2), (Abstract AB46) (2012).
  18. Cox L, Casale T, Nayak A et al. Efficacy and safety of sublingual 300IR 5-grass pollen tablets in adult patients with grass-pollen rhinoconjunctivitis in United States. J. Allergy Clin. Immunol. 127(2), (Abstract AB74) (2011).
  19. Berman G, Nolte H, Maloney J et al. Ragweed allergy immunotherapy tablet reduces nasal and ocular symptoms of allergic rhinoconjunctivitis over the peak ragweed pollen season in North America. J. Allergy Clin. Immunol. 129(2), (Abstract AB249) (2012).
  20. Maloney J, Nolte H, Nekam K et al. Dose-related effects of ragweed allergy immunotherapy tablet on nasal and ocular symptoms of allergic rhinoconjunctivitis during the peak ragweed pollen seasons in Europe and North America. J. Allergy Clin. Immunol. 129(2), (Abstract AB47) (2012).
  21. Nolte H, Maloney J, Bernstein D et al. Efficacy and tolerability of a novel ragweed allergen immunotherapy tablet during peak season in North American and European patients. J. Allergy Clin. Immunol. 129(2), (Abstract AB143) (2012).
  22. Kim EH, Bird JA, Kulis M et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J. Allergy Clin. Immunol. 127(3), 640–6.e1(2011).
    • This is the first study to demonstrate efficacy of peanut SLIT in US children.
  23. Narisety SD, Keet C, Guerrerio P et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J. Allergy Clin Immunol. 129(2), (Abstract AB27) (2012).
  24. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J. Allergy Clin. Immunol. 129(2), 448–55, 455.e1(2012).
    • This is the first study to compare the efficacy of oral immunotherapy versus SLIT for cow’s milk allergy in children.
  25. Seopaul S, Keet CA, Frischmeyer-Guerrerio PA et al. Prolonged exposure to sublingual immunotherapy improves safety of oral immunotherapy. J. Allergy Clin. Immunol.129(2), (Abstract AB126) (2012).
  26. Website
    101. ClinicalTrials.gov. A service of the U.S. National Institutes of Health. http://clinicaltrials.gov

What’s New in Celiac Disease

13 Nov 2012 Leave a Comment

by lynnawiensmd in Food allergy, Newsworthy items, The problem with foods, What's New in Medical Literature? Tags: ,

 Has enough been said about the symptoms of Celiac Disease?  Better yet, does everyone have celiac disease?  If you can’t prove that you have gluten intolerance (another name for celiac disease), you might consider this collection of case studies.  And tell them I sent you!

Diagnosing Celiac Disease by Video Capsule Endoscopy (VCE) When Esophogastroduodenoscopy (EGD) and Biopsy is Unable to Provide a Diagnosis

Matthew S Chang, Moshe Rubin, Suzanne K Lewis, Peter H Green  BMC Gastroenterol. 2012;12(90) (Nov 01,2012)

Video capsule endoscopy (VCE) is mainly used to evaluate patients with celiac disease in whom their course after diagnosis has been unfavorable and the diagnosis of adenocarcinoma, lymphoma or refractory celiac disease is entertained, but it has been suggested that VCE could replace esophagogastroduodenoscopy (EGD) and biopsy under certain circumstances.
Methods: We report a single center case series of 8 patients with suspected celiac disease who were diagnosed by VCE.
Results: EGD and biopsy had been performed in 4 patients resulting in a negative biopsy, declined by 2, and contraindicated in 2 due to hemophilia and von Willebrand disease. In all patients, mucosal changes of scalloping, mucosal mosaicism and reduced folds were seen in either the duodenum or jejunum on VCE. Follow-up in 7 patients demonstrated improvement in either their serological abnormalities or their presenting clinical features on a gluten-free diet.
Conclusions:Our case series demonstrates that VCE and the visualization of the characteristic mucosal changes of villous atrophy may replace biopsy as the mode of diagnosis when EGD is either declined or contraindicated, or when duodenal biopsies are negative and there remains a high index of suspicion. Further study is needed to clarify the role and cost of diagnosing celiac disease with VCE.

Here’s my comments on this series:

1. New technology, although expensive, can really change the way we diagnose and treat disease.  This method (VCE) would bypass the need for endoscopy….what that means is no sedation and a less extensive bowel prep. 

2.  As with any new technology, results have to be confirmed in larger studies and by other research groups.  I’ll be waiting to hear about more published work.

3.  If it becomes easier to diagnose celiac disease, perhaps we can limit the number of patients who think they are intolerant to gluten but have never taken the time or money to find out conclusively. 

What do you think?  Would a video camera that you have to swallow make you more likely to find out if you really have celiac disease?

 

 

Can You Cure Allergies Only With Shots?

11 Jul 2012 Leave a Comment

by lynnawiensmd in Allergy shots, Newsworthy items, What's New in Medical Literature?

Novel Routes for Allergen Immunotherapy

Safety, Efficacy and Mode of Action

Philippe Moingeon; Laurent Mascarell

Immunotherapy. 2012;4(2):201-212. © 2012 Future Medicine Ltd.

I DON’T like shots!  And who does?  But alas, if you have to get shots for your allergies, they better be worth the fuss.  Allergen immunotherapy is the only curative treatment of IgE-mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) is used as a reference therapy and has transformed allergic treatments; it improves symptoms (asthma and rhinitis) as well as the quality of life of patients. SCIT requires repetitive administration and carries the risk of severe systemic adverse effects, including anaphylaxis. I have modified the schedule of SCIT by rapidly advancing to MONTHLY shots, which makes a big difference on compliance and convenience. 
 
In Europe, sublingual immunotherapy is now a valid noninvasive alternative to SCIT, as a safe and efficacious treatment for respiratory allergies. In the United States, however, sublingual drops have not been approved by the FDA and acceptance among practicing allergists has not reached a fervor.  In this article, we compare various routes of allergen immunotherapy, including SCIT and sublingual immunotherapy, as well as more exploratory routes currently under investigation (i.e., intralymphatic, epicutaneous, intranasal and oral). We discuss their respective advantages, as well as their foreseen modes of action.

Introduction

Last year, we celebrated the 100th anniversary of the first successful studies of allergen immunotherapy (AIT) performed on patients with hayfever.  Whereas the subcutaneous route is still a reference, tolerance induction via alternative routes has raised considerable interest over the last three decades. Importantly, sublingual immunotherapy (SLIT) is the only approach established as a valid noninvasive alternative to the subcutaneous route for immunotherapy (SCIT).

Tolerance Induction by Parenteral Routes of Administration

SCIT has been shown to be effective in decreasing both immediate and delayed symptoms, as well as the consumption of medication in patients with type I allergies to insect venom, HDM, grass and tree pollens, molds or animal dander In other words, allergy “shots” as we know them do work!  The application of SCIT is limited by several drawbacks, including the need for repeated injections over several years, and the risk of anaphylaxis, which is rare but potentially life-threatening.

Clinical Trials With Intralymphatic Allergen-specific Immunotherapy

Intralymphatic administration consists of the direct injection of the allergen into the lymph nodes. Yikes, this sounds painful and technically difficult.  But wait….It was initially tested to enhance protective immunity against viruses and tumors using vaccines based on proteins, peptides, naked DNA or tumor cells. As a potential alternative to SCIT, intralymphatic allergen-specific immunotherapy (ILIT) is now being investigated in humans in order to shorten the immunization scheme with low doses of allergen extracts (with a 100–1000-fold reduction when compared with SCIT), while maintaining efficacy. Studies in clinical trials have provided interesting results since ILIT with a reduced number of allergen shots and doses demonstrates some efficacy (i.e., better tolerance to allergen challenge)

For instance, a comparative clinical trial conducted in 165 grass pollen-allergic patients has shown that ILIT is comparable to SCIT in terms of its efficacy, even when very low doses of allergens are used. In this study, patients were randomized to receive either SCIT with pollen extracts for over 3 years (with cumulative allergen doses corresponding to 4 million standardized quality units) or ILIT consisting of three intralymphatic injections for over 2 months (with corresponding cumulative allergen doses of 3000 standardized quality units). In this setting, ILIT improved hayfever symptoms, reduced skin prick test reactivity while enhancing patient quality-of-life and compliance. In terms of safety, ILIT exhibited only mild side effects in the form of local pain or inflammation.  Could this be because the dose required is so much smaller than traditional SCIT?

Overall, ILIT has provided promising clinical results and, as such, represents an attractive new approach, potentially reducing treatment duration from years to weeks. However, additional developments are necessary, including the need to assess efficacy and to optimize treatment dose in large Phase III studies. In addition, the use of complex medical equipment associated with the training of skilled personnel may also hinder its broad use in humans.  Would you let a nurse stick your lymph node like this?

Clinical Trials With Epicutaneous Allergen-specific Immunotherapy

Epicutaneous (skin application) allergen-specific immunotherapy (EPIT) is growing in interest, as it represents a safe, noninvasive and patient friendly treatment for IgE-mediated allergic diseases linked with either respiratory or food allergens.  More than 50 years ago, pioneer studies demonstrated clinical efficacy following EPIT in grass pollen-allergic patients. However, the use of skin scarification (and you think a tatoo is bad!) was quite burdensome precluding its broad use in humans.  Currently, novel approaches have been developed to increase the safety and efficacy of EPIT. In particular, a recent study by Senti et al. reports the results from a Phase I/II study documenting the safety and efficacy of EPIT in patients allergic to grass pollen allergens (i.e., Phleum pratense extract).  Allergic symptoms were reduced in nasal provocation tests, even if the efficacy was not significantly higher in the active group when compared with the placebo. No serious adverse events were recorded except for local eczematous reactions, probably due to the tape-stripping of the skin before EPIT, which may induce the release of proinflammatory cytokines (i.e., IL-1, IL-6, IL-8 or TNF-α) by keratinocytes.

A new epicutaneous delivery systems (i.e., Viaskin®, DBV technology, Bagneux, France) is currently been tested in humans. It consists of a condensation chamber that allows the release of soluble allergens while hydrating layers of the epidermis. The evaluation of this delivery system in children allergic to cow’s milk in a pilot EPIT study confirmed that the treatment was well tolerated. However, neither clinical efficacy nor immunological changes (i.e., a decrease in cow’s milk-specific IgEs) were documented in this study.[27]

Taken together, those studies suggest that the EPIT approach is safe and well tolerated, and paves the way for further investigations into its efficacy for the treatment of respiratory or food allergies in large cohorts of patients. Further developments should take into account the allergen dose, as well as the number and duration of allergen administrations.

Clinical Trials With Intranasal Allergen-specific Immunotherapy

Local nasal immunotherapy (LNIT) consists of spraying allergen extracts into the nasal cavity. It was first investigated at the end of the 1970s, with encouraging clinical data ( Table 2 ). LNIT is performed by the administration of natural biological or chemically-modified (allergoid, preventing IgE reactivity) allergen extracts in a soluble form. It demonstrates a significant reduction in both symptoms and medication needed in patients allergic to ragweed and grass pollens.[28–31] Adverse effects are mainly limited to the site of administration.[30,32] Subsequent intranasal vaccines based on allergen extracts in macronized powder forms (e.g., Parietaria, birch and grass) or on allergen-coated strips (e.g., mites) enhance clinical efficacy, while decreasing local adverse effects in allergic patients.[32–38] Long-lasting effects of LNIT induced by a 4-year treatment are noticed on nasal symptoms.[39,40] Recently, LNIT with rBet v 1 reduced nasal flow in birch pollen-allergic patients.[41] Interestingly, the use of hypoallergenic rBet v 1 fragments had no effect on symptom scores, suggesting that the presence of IgE epitopes is mandatory in allergen-specific tolerance induction.[41]

Altogether, LNIT appears to be of interest in the treatment of allergic rhinitis patients, since it is safe and efficient. However, better compliance is needed due to frequent nasal reactions. Also, it remains difficult to control the exact dose of allergen administered when using this route. DBPC Phase III studies are required to further document its safety and efficacy prior to a wide use in humans.

Clinical Trials With Oral Allergen-specific Immunotherapy

The use of oral allergen-specific immunotherapy (OIT) started 30 years ago, in patients with pollen-induced allergic rhinitis ( Table 2 ).[42–50] Although well tolerated, OIT with grass pollen extracts (low and high doses) as an aqueous solution, a powder or enterosoluble forms, is clinically and immunologically ineffective in adults.[42–45] Alternatively, OIT with high doses of aqueous extracts (i.e., Dermatophagoides pteronyssinus or Artemisia)[49,51] or using encapsulated allergens (i.e., birch or ragweed)[46–48,50] is shown to be safe and efficient in both adults and children.

Today, OIT is mainly applied as a treatment for adults and children with food allergies, including cow’s milk, egg, peanuts, tree nuts, wheat, soy, fish and shellfish allergies. Most children with cow’s milk and egg allergies generally outgrow their disease in the first 6 years of life, whereas peanut, tree nut, fish or shellfish allergies are permanent and the reactions are often more severe. Owing to the risk of adverse effects, OIT requires the administration of small amounts of allergen (from micrograms to milligrams) by the oral route in order to re-establish a long-lasting tolerance to dietary proteins.[52] To monitor OIT efficacy, a food challenge is usually performed at the end of the study protocol. Many studies performed in children with allergies to egg[53] or cow’s milk[54–57] showed clinical efficacy results, as well as a good safety profile. Also, long-lasting effects were observed for up to 4–5 years after the end of treatment.[55] Nevertheless, some difficulties are faced in evaluating OIT efficacy in those studies since they often rely upon small cohorts of patients and have to take into account spontaneous recovery rates. Overcoming such limitations, a recent study that included children with a severe and lifelong allergy to cow’s milk (i.e., cow’s milk specific IgEs >85 kU/l) revealed a significant improvement in tolerated food allergen intake. Specifically, 36% of children became fully tolerant and 54% were able to drink limited amounts of cow’s milk. Interestingly, the control group maintained on a cow’s milk-free diet failed the food challenge after 1 year.[57] In addition, Skripak et al. performed the first DBPC study of OIT that confirmed the safety and efficacy of OIT in cow’s milk allergy.[58] Specifically, patients in the active group exhibited a significant increase in their tolerization threshold when compared with the placebo group, with a median cumulative dose of 5140 and 40 mg of allergen tolerated, respectively. Those observations were extended to peanut OIT, as demonstrated in a DBPC study providing evidence for a successful oral food challenge in the active group associated with reduced skin prick tests.[59]

Altogether, OIT has shown encouraging clinical data, especially in patients with food allergies. However, many questions remain unaddressed, such as the risks linked with OIT compared with eviction, dose incrementation and patient selection, as well as low allergen/protein bioavailability to the gut due to gastric enzymatic degradation. Further studies with large patients groups are necessary in order to address these concerns and firmly establish the clinical efficacy of OIT in humans.

Clinical Trials With Sublingual Allergen-specific Immunotherapy

Allergen-specific SLIT was introduced in 1970 for respiratory allergies[60] and shown to improve symptoms in allergic patients, although the optimal dose, the efficacy and associated mechanisms were not well documented until the early 2000s ( Table 2 ).[61–68] Today, many DBPC studies, as well as meta-analyses, have shown that SLIT is effective in decreasing both immediate- and late-phase symptoms, as well as the need for medication, in adult and pediatric patients with allergic rhinoconjunctivitis to either pollens (from common grasses, ragweed, Parietaria, birch, olive and Cupressus), HDM or cat dander.[63,69–76] SLIT consists into the administration of high doses of natural-allergen extracts (pollens, mites or animal dander) as drops or tablets under the tongue, prior to swallowing. Generally, SLIT is administered once-daily for a period of time (e.g., 1–3 years). An excellent safety profile is recorded in SLIT studies, with more than 2 billion doses administered to either adults or children.[63,69,77,78] Only moderate adverse events occur locally at the start of the treatment, including oral pruritus, throat irritation or tongue swelling, but severe systemic reactions are extremely rare.

To date, the pertinence of SLIT for tolerance induction in humans has been confirmed by multiple DBPC studies conducted in large cohorts of patients allergic to grass pollen.[3,5–10,79] Also, long-term clinical benefits of SLIT have been documented following a 3-year treatment with two different grass allergy immunotherapy tablets in adults with rhinitis, demonstrating clinical improvements sustained for at least 2 years after stopping the treatment (i.e., a ‘disease-modifying’ effect of SLIT).

Those observations are not restricted to grass pollen allergy. HDM sublingual tablets (with both D. pteronyssinus and Dermatophagoides farinae mite species) tested in 509 adult patients in a pivotal Phase IIb/III clinical trial, also induced a significant decrease in rhinitis symptoms, while demonstrating an excellent safety profile after only 1 year of treatment, with sustained clinical benefit during the second treatment-free year [Bergmann KC et al., Unpublished Data]. The efficacy and safety of SLIT using HDM extracts as a solution were also demonstrated in adult patients suffering from mild to moderate asthma in a Phase III, DBPC study (conducted in 484 adults), thus strengthening the pertinence of SLIT to promote allergen-specific tolerance in humans suffering from rhinitis to mild–moderate asthma [Bergmann KC et al., Unpublished Data]. Beyond respiratory diseases, encouraging preliminary data suggests that SLIT (and also SCIT) with HDM allergens may provide benefit to patients with atopic dermatitis, based upon severity symptom score (scoring atopic dermatitis) as well as the use of symptomatic medications.[80–82]

Collectively, these data compiled in a recent review show that SLIT efficacy is comparable to SCIT.[83] However, one of the advantages of SLIT is that it is safer than SCIT, with a significantly lower risk of inducing systemic reactions. Noticeably, the use of SLIT is recommended in position papers by the World Allergy Organization (WAO) and by the Allergic Rhinitis and its Impact on Asthma (ARIA) group.[2,84]

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