Tag Archives: Immunoglobulin E

Drug Reps Will Give You Asthma

I know you’ve been there before….waiting in the doctor’s office for your appointment and some smartly dressed man or woman barely has to say hello to the receptionist and walks right by your seat, straight to the doctor’s office. “Hey, that’s not fair,” you say to yourself as you dig your nose into that outdated magazine trying to mask the irritation.  “My time is just as valuable as theirs is, put me to the front of the line!”  As a patient, my frustration with the #health care system only percolates at the injustice.  Isn’t the cost of #medication so high in America because of all the drug companies?  If there were no drug reps, wouldn’t my doctor have a better and certainly more unbiased selection of medications?  Granted, the goal of any #pharmaceutical company (employer of drug reps) is to make profit, but they can’t do that unless a product (medication) works well and is taken as directed.  In the end, drug companies want you to be adherent to medications prescribed so they’ll work, you get better, all of which is good for the bottom line.  Almost sounds too good to be true when everybody wins, but hang on and I’ll show you how this is possible. Continue reading Drug Reps Will Give You Asthma

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Contradictory skin test and ImmunoCAP results–which is better?

This question comes up in my office almost everyday….should I do skin testing or blood work?  As you can see from the response of national experts, it depends.  There is NO test that can boast 100% accuracy to predict whether or not you will react to a food.  In fact, the gold standard if you will, is still the oral food challenge.  Here is some food for thought (really, do you have to pun)

  1. Clinical history is very important in determining food allergy.  If you can eat a food without difficulty breathing, rash, or hives, you are most likely not allergic.  You may have a positive test, but that only means you’ve had previous exposure to the food.
  2. I will often obtain both skin testing and ImmunoCap (blood work) to clarify the presence of IgE-mediated allergy. If both tests are negative, you may have an adverse reaction to a food, not the severe life-threatening anaphylaxis.  Very important distinction!
  3. If in doubt, a food challenge is always a procedure to consider.  Here’s why.
  4. Sometimes the food in question just isn’t worth the trouble to challenge.  No one says you have to eat strawberries!
  5. If you challenge peanuts for example, in the doctor’s office and experience anaphylaxis, better there than at home.  Epinephrine is more readily available and in many cases, IV access and full resuscitation is available within minutes of your reaction. 
  6. This is another reason why a single test or treating allergy without experience is not a good idea.  Read the link below and tell me just how complicated things can become!

Contradictory skin test and ImmunoCAP results.

Put This Myth to Rest-(Dirt Jet Pro/SCRUBS hand sanitizer wipes)

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:

  1. Adverse reactions to pollen, food, chemicals can be divided into “allergy” or “intolerance/irritants“.
  2. 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?
  3. 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.
  4. The only treatment for irritants is to avoid them, regardless of whether the substance is a food or chemical.
  5. 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!

Possible anaphylaxis to chemicals contained in cleaning agents (Dirt Jet Pro/SCRUBS hand sanitizer wipes).

How to Cure Milk Allergy!

Milk allergy may cause life-threatening anaphylaxis in children & adults.  Wouldn’t it be nice if milk allergy could be “cured?” 

The adverse immune reactions to cow’s milk proteins can range from immediate, potentially life-threatening reactions to chronic disorders. Cow’s milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2–3% of general population.  That’s a lot of kids! Most studies have shown the prognosis for developing tolerance to cow’s milk to be good, with the majority outgrowing their allergy by age 3 years. 

Because no treatments are available to cure or provide long-term remission from food allergy, allergen-specific treatments and strategies that attempt to alter the allergic response to specific food allergens are expected. The approach that attracts a significant interest in the scientific community, as well as the public and media, is oral immunotherapy (OIT).

To begin treatment for food allergy, your doctor should do the following:

  • IgE must be demonstrated to the food in question.  That means skin testing or blood tests.
  • Who wants to be cured?  That’s what desensitization accomplishes.  If you gradually increase the amount of offending food (milk powder for instance), sensitive patients will no longer react to an accidental ingestion.  Pretty cool…but wait, that’s not all!
  • Permanent tolerance, as illustrated, means are you protected from ingestion of milk when you haven’t had exposure for say 2 months?  Because it’s not known how to predict whether patients develop tolerance, this procedure of OIT is not recommended for clinical use at this time. 

Almost all children receiving oral desensitization (OIT) experienced allergic symptoms during the protocol that primarily involved urticaria and angioedema. That’s mild and treatable.

Table 1. Oral food desensitization for IgE-mediated cow’s milk allergy

Study Patients (N) Success rate Comments
Staden et al. [15], CM and egg CM 14; egg 11; control group 20; age 0.6–12.9 years 9/35 (36%) permanent tolerance; 3/25 (12%) tolerance with regular intake (desensitization); 4/25 (16%) achieved partial tolerance The first randomized clinical trial of OIT. The rate of spontaneous food allergy resolution in the control group (7/29, 35%) was similar to the treatment group.
Longo et al. [16], CM CM 60; 30 active group; 30 control group; age 5–17 years 11/30 (37%) tolerated 150 ml f CM; 13/30 (53%) tolerated 5–150 ml The first study including children with previous anaphylaxis to cow’s milk; 3 children 10% discontinued the study because of severe systemic reaction. 17/30 children of active group reported side-effects at home.
Skripak et al. [17], CM CM 20; active to placebo; ratio 2 : 1; age 6–21 years 12 (92%) of active group reached the dose 5140mg of CM (range 2540–8140 mg); no change in the placebo group The first double-blinded, placebo-controlled clinical trial for OIT; the median frequency of side-effect was 35% in the active group compared with 1% of the placebo group.
Pajno et al. [19•], CM CM 30; active to placebo; ratio 1 : 1; age 4–13 years 10 (76%) of active group tolerated 200 ml CM; no change in the placebo group The first blinded trial with the weekly up-dosing regimen carried out in 18 weeks. Two children (15%) of active group discontinued the trial because of systemic reaction.

Legend for the above table:  CM, cow’s milk; OIT, oral immunotherapy.

Desensitization state can be achieved by approximately 36–92% of the children treated with specific immunotherapy; the rate of permanent tolerance is unknown.

An alternative route of allergen delivery is through an epicutaneous patch (EPIT). CMA was confirmed by an oral food challenge at baseline. Children received three 48-h applications (1mg of skimmed milk powder or 1mg of glucose as placebo) through a skin patch each week for 3 months. EPIT-treated children had a trend toward an increased threshold dose in the follow-up oral milk challenge. There was no change in the placebo group. The most common side-effects were local pruritus and eczema at the site of EPIT application.

The possibility of the appearance of adverse events or reactions during OIT is quite frequent. Side-effects have been reported by patients in all trials.

Severe systemic side-effects have been reported with either rush schedule or weekly up-dosing regimen.  The frequency of serious events and the severity of reactions are greatest on the initial days and least on the days following desensitization when high doses of cow’s milk intake are reached by patients.

Mild reactions such as abdominal pain, throat pruritus, gritty eyes, watery eyes, transient erythema and sneezing usually do not require stopping desensitization. On the contrary, when rhinitis, dyspnea, asthma, generalized urticaria and hypotension occur as a single symptom or in combination, OIT should be postponed or stopped.

A life-threatening asthma reaction caused by desensitization to milk was described by Nieto et al.  Adverse events are largely unpredictable, and they can occur during home dosing. Several systemic reactions have occurred at previously tolerated doses in the setting of exercise,viral illness and suboptimally controlled asthma.

Of note, these reactions had been well controlled by antihistamines, steroids or epinephrine. Because desensitization( s) place patients at risk for systemic reactions, it is not appropriate to implement OIT in clinical practice settings at this time. Therefore, OIT can be performed for research purposes or as ‘avant-garde’ and modern therapy for IgE-mediated food allergy in specialized pediatric centers.

  • Patriarca G, Nucera E, Roncallo C,et al. Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 2003; 17:459–465.
  • Nieto A, Fernandez-Silveira L, Mazon A, Caballero L. Life-threatening asthma reaction caused by desensitization to milk. Allergy 2010; 65:1342–1343.

Best Immunotherapy for Allergic Rhinitis and Asthma?: Conclusion & Future Perspective

I didn’t think that all of you wanted to read the full article so here’s the link for the “brainiacs” in the group! Comparing drops to shots!

Conclusion & Future Perspective

The  clinical efficacy of SCIT (typical shots)  is well established for both rhinitis and asthma.  SLIT (sublingual drops) has also been validated in regards to rhinitis and asthma.   Two recent meta-analyses in children showed that sublingual delivery of allergen vaccination constitutes a safe and effective alternative to the injectable route to reduce allergic respiratory symptoms and drug intake.  Assessment of possible long-term benefits, including long-term disease remissions, suppression of new allergic sensitizations, and reduction of progression from rhinitis to asthma in children, as has been shown for the subcutaneous route, are future requirements for “proof” of benefits for sublingual drops. 

The immunological effects of SLIT and how these relate to clinical efficacy are yet incompletely understood. Large-scale trials have confirmed the induction of allergen-specific IgG antibodies to be dose dependent. There is no early suppression of allergen-specific IgE antibodies and a transient early increase in specific IgE antibodies as in SCIT.

Current models of SCIT propose the induction of antigen-specific Tregs (cell type in the body), which then orchestrate the observed antibody and mucosal changes observed during treatment. As of yet there is only scarce evidence that such mechanisms operate during SLIT. Comparative clinical studies of sublingual and subcutaneous treatment yielded heterogeneous results demonstrating efficacy of both modes, but SLIT to be a safer approach.

In conclusion, understanding of the interaction of allergen and antigen-presenting cells within the oral mucosa may allow improved targeting of SLIT vaccines. In the near future the combination of allergen products with adjuvants may improve efficacy of immunotherapy via the sublingual route.

So here’s the bottom line:

  • Sublingual drops are not yet approved by the FDA and I can’t bill insurance for the product like allergists now do for subQ shots. 
  • Why not use Rapid immunotherapy to achieve maintenance in ONE month, followed by MONTHLY shots instead of weekly?  With this method, you get the best of both worlds–good, proven benefits at a convenient dosing schedule. 
  • Sublingual drops have to be given multiple days per week and compliance isn’t all that impressive. 

This issue isn’t going away, so stay tuned!

Are we harming ourselves?

“I’m allergic to everything!”  Ah, you’re smiling.  Is this really possible to be allergic to multiple drugs?  Evidently this is true according to a recent study published in Ann Allergy Asthma Immunol 108 (2012) 88–93.

Multiple drug intolerance syndrome: prevalence, clinical characteristics, and management byEric Macy, MD and Ngoc J. Ho, PhD.

So what is this condition? Multiple drug intolerance syndrome (MDIS) is generally defined as intolerance to 3 or more unrelated medications.  This can be antibiotics, ibuprofen, or high blood pressure medication.  The problem with adverse drug reactions is that intolerances are typically recorded in the “allergy” field of the medical record. This makes doctors and patients alike worry about anaphylaxis with any accidental use.  Relax….most adverse drug reactions are not going to result in a severe reaction without warning.  The authors of this paper use the word “allergy” in quotes throughout this paper to remind us that most of the drug “allergy” reports in the medical record are not immunoglobulin (IgE)-mediated.  

Now don’t misunderstand, a true IgE-mediated allergy requires sensitization, and every systemic exposure in a sensitized individual can potentially result in anaphylaxis and death. But this is not the type of reaction we’re dealing with in this study.

If you have Multiple Drug Intolerance Syndrome, what can you do?

  1. Most individuals with a record of any drug “allergy” have only 1 implicated medication, and they simply avoid that drug or class of medication. Individuals with multiple drug “allergies” are a special case.
  2. Antibiotic overuse probably accounts for a significant proportion of the antibiotic “allergy” reported.  Not only should antibiotics be avoided to prevent resistance, but overuse of antibiotics contributes to MDIS.
  3. Challenge testing has typically shown tolerance to most medications in patients with MDIS. Schiavino et al performed 1,808 challenges on 480 patients, 84.4% female, most ages 40 to 60, with histories of ADRs to at least 3 unrelated medications.
  4. All of these patients were evaluated at a specialized drug allergy clinic in Rome between January 1, 2000 and December 31, 2005. Two hundred twenty-four (12.4%) positive challenges were seen. In virtually all patients, either the index medication was tolerated on rechallenge or an acceptable alternative was identified.  

Multiple drug “allergy” is relatively uncommon in children, and most adverse drug reactions (ADRs) in children are associated with antibiotic use. Park et al provided demographic information on 97 children with 2 or more antibiotic “allergies” seen in a specialized drug allergy center in Canada. The accompanying editorial concluded that rare individuals may truly have allergic reactions to unrelated antibiotics, but it also might just be opportunity and bad luck.

 One often may stop multiple medications safely in the elderly. This may be the most important way to reduce the incidence of MDIS. In the presence of a life-threatening condition that would benefit from a particular medication associated with a historical reaction, based on a careful history, one may possibly safely test or rechallenge most individuals with MDIS.

 So is there anyone who should NOT be challenged with a drug they suspect is causing MDIS?

  • Individuals who have experienced drug-associated toxic epidermal necrolysis, Stevens-Johnson syndrome, blistering, desquamation.  These reactions are usually MORE severe after the second exposure! 

    example of Stevens Johnson syndrome

    Here’s what this type of reaction looks like:

  • Severe hepatitis, nephritis, or hemolytic anemia should not be rechallenged.  The risk of inducing severe reactions is just too great.  Fortunately, these severe reactions are rare.

  • Angiotensin-converting enzyme inhibitor–associated angioedema can be lethal, and rechallenge is not recommended.

If I have MDIS, when would a challenge be appropriate?

  • Urticaria or angioedema associated with NSAID use outside of aspirin-exacerbated respiratory disease is often transient, and rechallenge often can be safely performed.
  • Individuals with aspirin-exacerbated respiratory disease can be challenged with aspirin and desensitized.
  • Appropriate skin testing or in vitro IgE measurements can be used to evaluate individuals with MDIS who experienced classic IgE-mediated reactions such as anaphylaxis, shortness of breath, or hives. If negative, they can be rechallenged under observation.
  • If positive, they can be desensitized for 1 therapeutic course.
  • Multiple drug intolerance syndrome subjects with most other mild ADRs such as macular papular rashes, fixed drug eruptions, nausea, vomiting, gastrointestinal upset, diarrhea, drug fevers, other mild symptoms, or unknown symptoms can generally be safely rechallenged.

In closing, what’s the bottom line for patients with multiple drug “allergies?”

  1. Multiple drug intolerance syndrome may be considered partially an iatrogenic condition.
  2. Multiple drug intolerance syndrome is most prevalent in elderly women with high overall health care and pharmaceutical utilization.
  3. Multiple drug intolerance syndrome is associated with anxiety but not with life-threatening illnesses or IgE-mediated allergy.
  4. Coordinated efforts to reduce poly-pharmacy may be helpful in reducing iatrogenic MDIS.
  5. Drug hypersensitivity testing or drug challenges can be used safely to help manage many individuals with MDIS.

Call me with questions; I’d be happy to help you out!

 

Allergic to Antihistamines—really!

 

This is from Gary Stadtmauer, MD’s blog. 

How many times have we heard patients say they are “allergic” to drugs like antihistamines and corticosteroids?  Hypersenstivities to medications used to treat allergic diseases are fortunately uncommon. 

This is Dr. Stadtmauer’s experience with “allergy” to Benadryl….check the references below–it’s legit! 

“I have seen a couple of cases of drug exanthem from antihistamines but never immediate hypersensitivity…until now.  I recently saw a young woman who has had recurrent urticaria/angioedema of immediate onset due to Benadryl.  She had no associated symptoms.  Scratch testing to Benadryl 5mg/ml was negative but ID was positive at 0.5 mg/ml (W/F of 4/10) and 5 mg/ml (W/F o 5/10).  See image below.

One could question whether this is an IgE-mediated event.  Perhaps it is or perhaps in the occasional patient the antihistamine acts as an agonist, binding to the receptor instead of blocking it thereby triggering histamine release.  Anaphylactic shock caused by a challenge with 12.5 mg oral diphenhydramine has been reported and the authors of this case suggest the mechanism was IgE-mediated.

Benadryl Skin TestSo what?  Never say never when a patient comes in with a bizarre drug allergy or states that are allergic to Benadryl….you might be surprised!

Citations re:  Antihistamine Allergy
1. Barranco P, López-Serrano MC, Moreno-Ancillo A. Anaphylactic
reaction due to diphenhydramine. Allergy. 1998; 53: 814.
2. Weidinger S, Mempel M, Ollert M, Elser I, Rakoski J, Köhn FM,
Ring J. Anaphylaxis to mizolastine. J Allergy Clin Immunol.
2004; 114:979-81.
3. Rodríguez del Río P, González-Gutierrez ML, Sánchez-López J,
Núñez-Acevedo B, Bartolomé Álvarez JM, Martínez-Cócera C.
Urticaria caused by antihistamines: report of 5 cases. J Investig
Allergol Clin Immunol. 2009; 19 (4): 317-20.
4. Gonzalo-Garijo MA, Jiménez-Ferrera G, Bobadilla-González P,
Cordobés-Durán C. Hypersensitivity reaction to mizolastine:
study of cross reactions. J Investig Allergol Clin Immunol. 2006;
16 (6): 391-3.
5. Demoly P, Messaad D, Benahmed S, Sahla H, Bousquet J.
Hypersensitivity to H1-antihistamines. Allergy. 2000; 55: 679-80.
6. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez
J, Brockow K, Pichler WJ, Demoly P for EDNA and the EAACI
interest group on drug hypersentitivity. Drug provocation
testing in the diagnosis of drug hypersensitivity reactions:
general considerations. Allergy. 2003; 58: 854-63.

It’s time for my shot!

It’s time for my allergy shot, but I don’t wanna!  If getting shots makes you nervous, watch this girl….a real trooper and funny at that:

Please review the following information on allergy shots…you’ll save some time and learn a lot. 

The only "bad" question is the one you didn't ask!

Questions patients ask:

1.  How often can I get shots? Once you are at the maintenance dose, you may receive shots every 2-4 weeks.  Please adjust your shots based on your allergy symptoms. (ie, shots every 2 weeks during the spring/fall and every 4 weeks during the winter)

2.  How long does it take to “build up?”  I’m glad you asked that.  You can build-up with weekly shots like we’ve always done it and take 4-6 months to reach the maintenance dose–conventional.  If you want to reach the maximum benefit earlier, I prefer the “rapid desensitization” which will achieve maintenance in one month.  Big difference in convenience!

3.  What to do about local reactions?  Don’t ignore them.  Local swelling doesn’t mean you will develop more severe reactions, but talk to your allergy shot nurse about air lock, application of ice, diluting your serum, just to name a few.  I want to know if your arm swells after your shots….the only bad question is–you get the hint. 

4.  Do shots really work?–I tell patients that after 3-5 years on allergy shots at high dilutions, 70 to 80% of patients don’t have to go back on injections.  What this means is that symptoms of allergy go down and need for medication also goes down, leaving you free to enjoy the outdoors! 

5.  Here’s what allergy serum should look like at the maintenance concentration–if your serum is clear, you may not be receiving the full benefit of shots in the first place. Notice the dark, cola-colored allergy serum…should be your maintenance if tolerated.

Here's what maintenance concentration of serum should look like!

Last but not least…..are shots safe long-term?  This study published in 2011 is very encouraging.  Association of subcutaneous allergen-specific immunotherapy with incidence of autoimmune disease, ischemic heart disease, and mortality. J Allergy Clin Immunol 2011.  Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. In this registry-based observational study, receiving SCIT (allergy shots) compared with medications only was associated with lower risk of autoimmune disease and heart disease, as well as decreased all-cause mortality (early death).

 Sooo….pull up your sleeve and let’s get you feeling better!

I'm getting my allergy shot....and still smiling!

For the last 100 years, the pioneering technique of subcutaneous allergen desensitization first developed by Noon and Freeman has proven quite resilient and, in fact, central to the practice of clinical allergy. It remains the only therapeutic modality by which long-term immune modification can be achieved and has afforded not only symptomatic relief to untold numbers of allergic patients, but also life-saving benefit in the case of venom hypersensitivity. So while we are indebted to generations of scientists and physicians for their outstanding contributions to the understanding of the mechanisms and clinical application of immunotherapy, we embrace the many new technological approaches that hold promise for the treatment of allergic patients and that perhaps one day may give rise to a cure for atopic diseases.

My nose won’t stop running

Patients often come into the office with the complaint of “my allergies are bothering me!” 

Grab the Kleenex!

So what’s really going on with allergies?  What if skin testing is negative–I know I have allergies.

1.  The basic problem for patients with runny nose, sneezing, and congestion (you know the allergy nose) is nasal INFLAMMATION.  Nasal inflammation can be a result of allergic and non-allergic causes–and sometimes both!

2.  The term “allergy” means that your body produces IgE–antibodies that cause the symptoms of allergy….sneezing, congestion, and hay fever.  If you don’t produce IgE you have Vasomotor Rhinitis or irritation.  Skin testing and blood testing for allergy measures the same thing: IgE antibodies lurking in your body just waiting to find pollen or dust. Here’s a cartoon of what IgE can do:

I'm a science geek...what can I say?

3.  Don’t get me wrong, patients with irritation can be just as miserable as those with allergy. 

4.  Is treatment any different?  YES

5.  Allergy treatment uses strict avoidance of the offending agent (dust, mold, animals).  Vasomotor rhinitis is more difficult to control with avoidance because there are so many irritants in the air & in your home.  Did anyone notice the ozone alerts in Tulsa?  That’s an irritant!

6.  Medications are similar between allergy and irritant nasal inflammation.  Be careful, however, if you are using antihistamines (Zyrtec, Benadryl, Loratadine, OTC) for vasomotor rhinitis (irritation).  If you don’t have allergy, antihistamines will only dry you out and won’t stop your runny nose!  It’s always helpful to find out if you have allergy or not, so you won’t spend money on OTC medications you don’t even need. 

7.  Allergy Immunotherapy (shots)–will cure your allergies, but do nothing for irritant rhinitis. 

8.  So….whether your sneezing is due to “allergy” or “irritant”, there is hope for you.

Allergy or Irritant--that is the question!

Want more info?–click the links for Allergic Rhinitis or Non-allergic (vasomotor) Rhinitis and enjoy the outdoors!