Everyday I teach patients the difference between “allergy” and “irritant” reaction. TV ads are overloaded with allergy advertisements in an attempt to sell antihistamines, so why wouldn’t you think that everyone has allergy of some kind. The link below is a question about allergy (anaphylaxis in this case) to chemicals. Consider the following:
- Adverse reactions to pollen, food, chemicals can be divided into “allergy” or “intolerance/irritants“.
- Allergy is defined as the production of IgE to the substance in question. This is why you have positive skin tests and blood testing. Why does this matter?
- You can only be “desensitized” to allergens, not chemicals. IgE can be decreased and if you don’t have IgE to begin with you can’t delete its effect.
- The only treatment for irritants is to avoid them, regardless of whether the substance is a food or chemical.
- For chemical reactions or food intolerance, there’s not much to say except to stay away. Click on the link below just to make sure!
Thanks for following along with the diagnosis and treatment of eosinophilic esophagitis (EoE)–a condition that during my fellowship training in allergy wasn’t even recognized as a cause of abdominal pain.
Treatment options for EoE are currently:
- Corticosteroids–both oral and inhaled
- Dietary avoidance of known allergic triggers, including but not limited to foods
- Use of PPIs such as Nexium & Protonix
- Treatment principles focus on reducing symptoms and eosinophil counts while, importantly, protecting and preserving quality of life.
- Maintaining diet and nutrition which is harder than it looks! Don’t forget that restoring growth parameters are also essential for adults as well as in children.
As with all diseases, treatment is updated constantly, and new recommendations emerge. As with many inflammatory conditions, steroids work great, but are NOT less filling. Side effects from steroids are many and any time an alternative is successful, you’re better off. Remember, topical steroids are fine, it’s the oral systemic absorption of steroids that contributes to the side effect profile.
Due to the long-term side effects associated with high dose corticosteroids and a tendency for relapse after discontinuation, this therapy is not first-line outside of using short bursts and tapers for severe symptoms needing urgent relief (eg, critical dysphagia, stricture, dehydration and acute weight loss.
Topical corticosteroid are used in EoE through 1 of 2 routes:
- “Gulping” the expressed actuations of an inhaled device; or
- Expressing the contents of a nebulizer respule into a cup, forming a thickened slurry by mixing it with sucralose/maltodextrose (Splenda®), and water.
Use in this manner provides “local” or tailored coating of esophageal tissue, at lower doses (220 μg-1 mg per dose). Faubion and colleagues demonstrated that 880 μg/day of swallowed fluticasone propionate or beclomethasone diproprionate resulted in symptomatic improvement in 4/4 pediatric patients Noel and group at the Cincinnati Children’s Medical Center, noted that non-atopic patients had a better response rate to the topical steroid than the atopic patients. A randomized, controlled trial by Konikoff and colleagues confirmed similar findings independent of pre-treatment eosinophil numbers.
Oral viscous budesonide (OVB) is quickly becoming the preferred therapy to fluticasone.
Dosing for fluticasone ranges from 220 to 880 μg per day, and for budesonide, from 0.5 to 2 mg per day; both doses are similar to those used in asthma. With either agent, patients are instructed to not eat or drink for 30 minutes after administration. Complications from topical treatment include oral/esophageal candidiasis. In a 3-year case series studying recurrence, approximately 90% of adults relapsed at a mean of 8 months post discontinuation of 6 weeks of therapy. Just like asthma, when you stop using the controller medication, symptoms will come back. No study of optimal dose or duration of therapy has been performed, but most adult providers recommend a 6-week course while pediatric providers suggest a 12-week course. No long-term safety data exist pertaining to bone or adrenal effects from such small but more readily bioavailable dosing methods used in EoE.
Technically, EoE should not be diagnosed until response to PPI therapy has been determined, according to the 2007 and 2011 consensus guidelines. A certain subset of patients will have PPI-responsive esophageal eosinophilia. Typically, dosing is either 10-40 mg omeprazole or 15-30 mg lansoprazole per dose for 2-3 months. High-dose PPI therapy may distinguish GERD from EoE.
Immunomodulating therapies may offer some promise. The best studied therapy is anti-IL-5. In mice, anti-IL-5 decreases blood and tissue eosinophils, and decreases eotaxin-3 levels. Garret and fellow researchers studied anti-IL-5 in 4 patients with hypereosinophilic syndrome. Symptoms and eosinophilia resolved, and in 1 patient who also had EoE, dysphagia and esophageal eosinophils decreased. Stein and colleagues, in an open-label phase I study of anti-IL-5, noted that blood eosinophilia was reduced but not correlated to decreased levels of IL-5, eotaxin-3, or esophageal eosinophilia. Similarly, there was no significant difference between groups in symptom improvement. Studies of other agents, such as anti-IgE or anti-TNF (infliximab), failed to demonstrate any symptomatic or esophageal histologic improvement. Presently, anti-IL-3 is under investigation in a phase 1 trial, but no data are available pertaining to its safety or efficacy.
Dilation relieves critical esophageal narrowing and related symptoms, but will not alter the underlying pathophysiology. Its benefit is maximized for dysphagia and impaction from ring/stricture or other critical narrowing. Several studies have demonstrated the efficacy of dilation, though it is balanced by risks including perforation, deep mucosal tears, pain, linear renting, and bacteremia. Relief is also likely to be transient, because 75%-50% of patients who receive this therapy have recurrence at 2-20 months and need additional dilation.
A 6-week trial of 10 patients conducted by Kellyand colleagues in 1995 demonstrated the role of an exclusively elemental diet. At the conclusion of the study, 8/10 had complete histologic and symptomatic resolution and the other 2 subjects showed drastic improvement, demonstrating an elemental diet as a potential treatment. As with steroid therapy, however, upon discontinuation, all patients relapsed. A larger study of elemental diet therapy in 51 patients was conducted by Markowitz and colleagues. The researchers noted symptomatic response by 8 days and normalization in biopsy by 1 month in 49 of the patients studied. Liacouras and colleagues followed 389 patients with EoE over 10 years, 160 whom were treated with elemental diet and noted a 97% response rate to the diet and biopsy counts that were comparatively lower than 75 patients on swallowed fluticasone. Though exceptionally effective, elemental therapy is limited in that a patient’s only source of nutrition is a very specific hypoallergenic formula. This may not be appropriate for adolescents or adults. Some cases require placement of gastrostomy tube to assist with feeding.
An alternative approach is a tailored/guided diet that avoids only an individual’s known food sensitizations based on skin prick and/or patch testing. Spergel and colleagues described 120 patients placed on a guided elimination diet based on allergen testing. After 6-8 weeks, 112 had near complete tissue resolution, though 39 relapsed upon reintroducing eliminated foods. In this cohort, 77% had at least 1 positive prick skin test, and 85% had 1 positive atopy patch test. Prick skin tests were most commonly positive to milk, egg, soy, and peanut. The foods that were most commonly positive to atopy patch test were corn, soy, wheat, and milk. Most patients were sensitized to multiple foods, and dietary nonresponders had more sensitizations than responders. Positive predictive value and negative predictive value for 13 commonly positive foods in EoE were published in a previous post.
Follow-up of patients with EoE should be frequent, at least 4 times per year, with consideration for repeat endoscopy at those intervals as well. Repeat endoscopy is the only way to monitor disease progress, because symptoms do not always correlate with disease progression. One pediatric study found that an initial cell count of 6 or greater was predictive of a repeat positive biopsy.
At each follow-up visit, diet should be reviewed, diet/medication compliance assessed, and consideration given for additional food testing if symptoms or histology are not improving. As noted previously, there are no studies that have evaluated adequate or optimal duration of treatment for either dietary avoidance or topical steroid duration. Very little formal guidance is available to determine key long term predictors of disease resolution, the optimal interval for repeat biopsy, and the effect of these factors on the development of long term sequelae.
Complications from EoE include:
- Schatzki ring
- Esophageal trachealization and stretching,
- Esophageal furrowing and narrowing, microabscesses, webbing,
- Food impaction, persistent/progressive dysphagia, and lamina propria fibrosis.
Esophageal remodeling in EoE occurs as a result of subepithelial fibrosis and is reported in 15%-40% of affected adults. Predictors that influence the likelihood of developing fibrosis are presently unknown. To date, there is no identified association with progression to malignancy directly from the presence of EoE. Some have observed a potential link between celiac disease and EoE, which may share some common gene upregulations with EoE, but this association is not well understood.
The natural history of food allergy/sensitization within EoE has not been well-described. Lastly, while preliminary work and observation indicates that quality of life can be affected significantly, little formal study of EoE quality of life exists. This particular area of research is very important to continue to define, as the quality of life issues that affected families face are distinct from those of the general food allergy community.
Europe and the United States differ on many things including how we look at war and how often we pick our noses…yes it’s true about rhinotillexomania (nose picking). Perhaps this is why Europeans will reach for a nose spray FIRST to treat allergies and then go for antihistamines. Yes, there’s even a Dr Oz video on the subject: http://www.oprah.com/oprahshow/Dr-Oz-on-Health-and-Hygiene
So what is the point of all this nonsense? Treatment of asthma also differs between the United States and Europe.
The Misuse of Asthma Drugs
Gene L Colice Expert Rev Resp Med. 2013;7(3):307-320.
There are three major problems with asthma care in the USA today and misuse of asthma drugs contributes to each.
First, multiple sources document that symptom control of most Americans with asthma in the general population does not meet standards established in the National Asthma Education and Prevention Program Expert Panel Report III (EPR3). In the CHOICE survey, 1000 patients with asthma randomly chosen across the USA were asked about their care and burden of disease. Almost half of these patients (49%) reported that they did not use asthma controller medications, although 79% had evidence of persistent disease. Of the 51% of the patients reporting the use of asthma controller medications in this survey, 85.7% had not well controlled or very poorly controlled disease. Numerous previous surveys of asthma patients in the USA and Europe, using either telephone interviews or questionnaires, have reported similarly high levels of uncontrolled disease. In the Exercise-Induced Bronchospasm Landmark Survey, 78.8% of the children with asthma and 83% of adults with asthma described respiratory symptoms with exercise. Children and adults with asthma commonly described being limited in their ability to perform sports and outdoor activities by their disease in this survey.
I know most patients would like to stop their asthma medications ASAP, but it comes at the cost of losing asthma control. I’ve previously discussed when to stop asthma medications…I’d like to know what you think? Are doctors prescribing unneccesary medications?
Second, in addition to difficulties with symptom control on a daily basis, patients with asthma in the USA frequently suffer exacerbations.
In the CHOICE survey, 5% of the patients reported being hospitalized and 14.4% described either an emergency department (ED) or urgent outpatient visit for an asthma exacerbation in the past year. Patients interviewed in this survey with more severe, persistent or uncontrolled asthma were more likely to have suffered asthma exacerbations. Previous surveys have reported similarly high rates of asthma exacerbations resulting in ED visits and hospitalizations. Data from the US CDC confirm that nationwide rates of ED visits and hospitalizations for asthma exacerbations remain unacceptably high.
So what are parents to do? The choice between giving your child steroids and having to rush to the emergency room for an asthma flare can be a “no win” proposition.
Third, asthma is an expensive disease.
The CDC has recently estimated that asthma costs the US economy approximately US$56 billion annually. On average, an asthma patient has been calculated to generate approximately US$2000–$4000 more in healthcare costs per year than a nonasthma control patient. Indirect costs due to work loss, school absenteeism, reduced productivity and so on, further contribute to the economic impact of asthma. Healthcare costs of asthma increase in patients with more severe disease. In patients with moderate and severe persistent asthma, exacerbations will further substantially increase healthcare costs.
I know the most common reason that patients stop their medication is simple: medications are too expensive. Here are some tips to reduce the cost of your prescribed medications for asthma:
- Make sure the medications you are picking up at your pharmacy are needed year round. Some patients need asthma inhalers only during the cold winter months.
- Educate yourself…know your triggers for asthma attacks to keep you out of the ER and better yet to use inhalers as prevention! (I have links to the American College of Allergy and the American Academy of Allergy, Asthma, and Immunology)
- Monitor your symptoms with a peak flow meter and pay attention to how much exercise you can do, and how well you sleep. Both of these indicators will tell you several days in advance if your asthma is flaring.
- Use coupons for your inhalers. In years past, pharmacy reps would leave samples for us to hand out to get patients started on asthma prevention. This is no longer the case because of health care reform. But….coupons are available for a similar value. Just don’t forget to take the coupon in to your pharmacist when you pick up your inhaler.
In summary, having reviewed the data, the EPR3 predisposes to under treatment of asthma. The tendency is for healthcare providers to underestimate asthma severity and to correspondingly undertreat the disease. In most asthma patients, the result will be persistent asthma symptoms. In important subsets of asthma patients, particularly smokers, the efficacy of ICS seems impaired. For a given categorization of asthma severity (even if accurately calculated by the healthcare provider), the corresponding recommended treatment with ICS in the EPR3 might be insufficient in smoking and obese asthma patients. Again, the consequence will be persistent asthma symptoms. Asthma tragedies occur all the time…let’s make sure it doesn’t happen to someone you know!
Burn out! The very mention of the word conjures up a mid-life crisis with broken relationships, declining work performance, and substance abuse. Not to mention the pot belly that accompanies those of us in that blessed 5th decade of life. Doctors and other health care providers are not immune from this most dreaded disease; in fact, we may be more susceptible because we either deny its existence or simply don’t have the time to address the cause. Continue reading Not All Docs are “Burned Out”
Not really, but now that I have your attention, patients can learn lots of information from a good YouTube channel.
My YouTube channel has several videos that should interest you:
- How to use an inhaler from National Jewish Hospital. It’s better to use a spacer (yes, always), but often the spacer gets separated from the inhaler. Think I’m kidding…just check your purse. If you’ve lost your spacer, use the three finger bridge technique that’s illustrated on this video.
- What can I expect from skin testing? Does it hurt? My colleagues from Allergy Partners will explain the who, what, when, where and why about skin testing. And no, it doesn’t hurt like you think.
- And what would a blog be without celebrities? Does anyone remember Shaq playing basketball? You will remember his story about apnea!
Enjoy your weekend.
Oh, if I only knew of a more interesting subject for MY next cocktail party. When kids’ drama, and the latest neighborhood gossip just won’t do, try your luck at the newest asthma mediation!
A special thanks to Reuters for their excellent reporting…my comments will be in RED.
Medscape Medical News from the American Thoracic Society (ATS) 2013 International Conference
Regeneron, Sanofi Asthma Drug Seen as Potential Game Changer
By Ransdell Pierson
(Reuters) – A new type of asthma drug meant to attack the underlying causes of the respiratory disease slashed episodes by 87% in a mid-stage trial, making it a potential game changer for patients with moderate to severe disease, researchers said on Tuesday.
Slashing episodes by 50% is pretty dramatic, much less results of 87%. Too good to be true always lurks in the background with medical studies. Am I cynical? Unfortunately, I’ve been burned by too many drugs, gadgets, and the next best nutritional supplement to accept this news without a grain of salt.
“Overall, these are the most exciting data we’ve seen in asthma in 20 years,” said Dr. Sally Wenzel, lead investigator for the 104-patient study of dupilumab, an injectable treatment being developed by Regeneron Pharmaceuticals Inc and French drugmaker Sanofi.
The drug also met all its secondary goals, such as improving symptoms and lung function and reducing the need for standard drugs called beta agonists.
Although far larger trials will be needed to confirm findings from the “proof of concept” study, researchers expressed optimism. They noted that dupilumab has also shown the ability to tame atopic dermatitis or severe eczema.
The medicine, if approved, could hold promise for patients with moderate to severe persistent asthma that is not well controlled by standard drugs.
“We have been treating asthma with sort of Band-Aid therapies that didn’t get at the underlying causes,” Dr. Wenzel said in an interview, adding that dupilumab could be an important step in going to the root of the problem.
The drug works by simultaneously blocking proteins that have been linked to inflammation, interleukin-4 (IL-4) and interleukin-13 (IL-13).
Dr. Wenzel, director of the Asthma Institute at the University of Pittsburgh, said other drugmakers have tested medicines that block one or both of the proteins, but without success.
The trial recruited patients with high levels of eosinophils. Such patients were deemed likely to benefit from treatment.
This new form of medication, called monoclonal antibodies, targets single molecules to avoid the side effects of steroids. Our prototype for asthma is Omalizumab or Xolair which just celebrated its 10th year out in the market. Other than Xolair, I’m limited to using steroids for severe asthma. 😦
All patients initially stayed on their standard asthma treatments, meaning medium-to-high doses of inhaled glucocorticoids, as well as long-acting beta agonists. But patients gradually tapered off on those drugs and were no longer taking either of them after nine weeks.
Throughout the Phase IIa trial, half the patients also received weekly injections of dupilumab, while half received placebo injections.
After the ninth week, about 25% of those on placebos had experienced exacerbations, i.e., the need to take a beta agonist, a decrease in lung function, the need for an oral or inhaled corticosteroid, or admission to the hospital or emergency room for worsening asthma.
“By end of the trial, after 12 weeks, 44% of those in the placebo group had exacerbations, compared with 5% of those on dupilumab,” Dr. Wenzel said.
That represented an overall 87% reduction in exacerbations, which Dr. Wenzel said was highly statistically significant.
She said dupilumab was well tolerated, with side effects similar to placebo. But she cautioned that longer trials are needed to fully assess the drug.
Regeneron and Sanofi said standard drugs are unable to control asthma well in 10% to 20% of patients. They estimate that inflammation caused by Th2 cells – the type of inflammation among patients they tested – plays a role in half of those moderate to severe cases and affects as many as 2.5 million people in the United States and up to 30 million worldwide.
Dupilumab has also shown strong hints of safety and effectiveness in two early-stage trials that involved 67 patients with atopic dermatitis. Larger studies are slated to begin later this year.
Atopic dermatitis is inherited and involves patches of highly itchy skin on any part of the body. Patients, many of whom also have asthma and hay fever, have compared the sensation to having unending poison ivy.
“This asthma data and the data we already have in atopic dermatitis really raises the possibility the scientific community has finally hit upon the key pathway across all these allergic diseases,” George Yancopoulos, Regeneron’s research chief, said in an interview.
And there you have it….next time don’t be stuck with boring conversation about the weather, talk about Dupilumab!
Sleep and allergy….I never would have known the connection. Sleep is important for all persons in promoting physical and mental health. High-quality sleep is crucial for learning and effective development in children. Believe me, when I don’t sleep well, I become a scrooge or a troll and usually somewhere in-between. Just ask my wife if you don’t believe me. Looks like that happened to Shaq as well.
So what’s the big deal about not enough sleep?
- Deprivation in sleep can alter immune function in healthy subjects
- Sleep deprivation alters wound healing in animal models
- Sleep works because adequate amounts of sleep enhance the secretion of melatonin which in turn improves the immune response.
- Sleep also enhances the secretion of growth hormone, which promotes wound healing.
So now that you know WHY sleep is important, is sleep deprivation really that important? According to the National Center on Sleep Disorders Research, sleep disturbance is very important as an indicator of poor control of allergy and has relevance for a patient’s daytime functioning and overall quality of life.
Treating your allergies and sinus congestion will most likely improve sleep-disordered breathing events, including apnea, hypopnea, and snoring. The most recent summary of Sleep and Allergic disease can be found here—Sleep and allergic disease: A summary of the literature and future directions for research. Here’s the abstract for your review:
Atopic diseases, such as asthma and allergic rhinitis, are
common conditions that can influence sleep and subsequent
daytime functioning. Children and patients with allergic
conditions from ethnic minority groups might be particularly
vulnerable to poor sleep and compromised daytime functioning
because of the prevalence of these illnesses in these groups and
the high level of morbidity. Research over the past 10 years has
shed light on the pathophysiologic mechanisms (eg,
inflammatory mediators) involved in many atopic diseases that
can underlie sleep disruptions as a consequence of the presence
of nocturnal symptoms. Associations between nocturnal
symptoms and sleep and poorer quality of life as a result of
missed sleep have been demonstrated across studies. Patients
with severe illness and poor control appear to bear the most
burden in terms of sleep impairment. Sleep-disordered
breathing is also more common in patients with allergic
diseases. Upper and lower airway resistance can increase the
risk for sleep-disordered breathing events. In patients with
allergic rhinitis, nasal congestion is a risk factor for apnea and
snoring. Finally, consistent and appropriate use of medications
can minimize nocturnal asthma or allergic symptoms that might
disrupt sleep. Despite these advances, there is much room for
improvement in this area. A summary of the sleep and allergic
disease literature is reviewed, with methodological, conceptual,
and clinical suggestions presented for future research. (J Allergy
Clin Immunol 2012;130:1275-81.)
Great article in Saturday’s paper on mold identification and how to treat. Many misconceptions about mold! I will be using this information as a resource for patients with suspected mold allergy or exposure.
“The following story uses fictional names to comply with HIPPA regulations and is not intended to offer medical advice. If you have specific questions regarding your asthma, please contact my office or call your regular doctor. ”
“And what medications are you taking now?” This wasn’t my usual style to get right to the point, but I was running behind schedule.
“Oh, the ones that are in my chart”, replied Mr. Williams with a broad grin that always let me know he was glad to see me. Continue reading When Can I Stop My Medicine?