Tag Archives: Immunotherapy

Can I Prevent an Allergy Shot Reaction?

Risk Factors for Systemic Reactions to Allergen Immunotherapy

Alfredo Iglesias-Cadarso; Pilar Hernández-Weigand

Purpose of review To update safety information regarding allergen-specific immunotherapy (ASIT) in clinical practice and highlight the risk factors associated with the adverse reactions, product and each dose.
Recent findings Efforts in recent years have focused on increasing our understanding of the efficacy and safety of ASIT, especially the sublingual variety (SLIT), in multicenter studies. Moreover, new Clinical Practice Guidelines (CPGs) and an international consensus concerning ASIT have been published recently. Although no deaths as a result of subcutaneous immunotherapy or SLIT have been reported in the last 2 years, systemic reactions mainly arising from administration errors still appear. Recent studies support the safety of new forms of specific immunotherapy.
Summary An understanding of the risk factors for each patient, product and dose, and the implementation of CPGs are the main factors that could improve the safety of ASIT. The standardization of all procedures for prescribing and administering ASIT, and the systematic collection of standardized safety data in a multicenter database (postmarketing surveillance), may be required to generate new information on the safety of ASIT.

Why Do We Even Care About Safety of Allergy Shots?

Allergen-specific immunotherapy (ASIT), both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been shown to be effective for the treatment of allergic respiratory disease in randomized controlled trials and meta-analyses.  Indeed, SCIT is the treatment of choice for preventing anaphylaxis in patients with systemic reactions to hymenoptera (bee stings).

The greatest drawback to the more widespread use of ASIT is the associated risk of severe side-effects, as the dose which has been shown to be well tolerated and effective in a group of patients may not be so for a specific patient. Here again, everyone is different and what may be the best dose for one patient, may cause an adverse reaction for someone else.

Systemic reactions are those which produce symptoms and signs far from the administration site. They may be immediate systemic reaction (ISR), appearing in the first 30 min postadministration, or delayed systemic reaction (DSR), occurring after the first 30 min, with the former tending to be more severe.

The incidence of systemic reactions has been estimated at between 1 and 34% of patients and around 0.2–0.3% of doses, depending on the type of study, patient, diagnosis, extract or treatment scheme.  

Historical reviews of ASIT-related mortalityhighlighted severe or poorly controlled asthma and administration errors as the main causes of fatal systemic reactions. These findings led to the drafting of Clinical Practice Guidelines (CPGs) for ASIT treatment,and their subsequent updates, in the 1990s. Adherence to such guidelines is the main reason behind the reduced frequency and severity of systemic reactions in the past 20 years. The statistics regarding mortality and systemic reactions prior to these CPGs are no longer applicable.

Let’s look at some individual factors that increase your chances of a systemic reaction to an allergy shot!

  • What do you put in my serum? No specific allergen is currently thought to produce higher mortality or a greater chance of a large local reaction.
  • Very few fatal reactions to pure hymenoptera venom immunotherapy (VIT) have been reported. Indeed, several studieshave found a lower incidence of systemic reactions with hymenoptera vaccines, with bee vaccines being tolerated worse than wasp vaccines.
  • Systemic reactions appear to be more frequent when aqueous extracts are used.  This is presumably due to the fact that the allergen is absorbed very quickly after it’s injected.

Dose-related Risk Factors

  • Administration errors are the main identifiable and avoidable cause of ASIT-related systemic reactions, including SLIT. (SLIT is the oral allergy drops)
  • Any delay in the treatment of a systemic reaction increases its severity. This is why I instruct my nurses to give epinephrine first, then call.
  • Although CPGs provide recommendations to avoid such errors, they continue to occur with a greater than expected frequency. 
  • I could write a book on the types of errors that occur with the dose of allergy shots.  Would this be a best-seller or what?
  • Research has shown that a large local reaction does not predict the occurance of a more severe systemic reaction; a concept that can be difficult to grasp for patients.  (see below)

Dosing Scheme

In the case of SCIT with airborne allergens, the use of fast regimens (rush and cluster) has been associated with a higher number of systemic reactions, although more recent studies have shown their safety to be similar to that of conventional schemes. Patients tend to like the rapid schedule because they can avoid the prolonged build-up of conventional treatment. 

Omalizumab (Xolair) has been used to reduce the systemic reaction incidence in patients receiving SCIT with inhaled allergens and VIT (venom shots),  with good results.

It is possible, but not confirmed, that systemic reactions increase during the pollen season, but patients generally do not decrease their dose at this time.

Prior Reactions

Together with poorly controlled asthma, the presence of a prior systemic reaction during AIT is the main risk factor associated with a new systemic reaction. 

There is currently no evidence that the dose adjustments recommended in clinical guidelines reduce recurrent systemic reaction in a patient.

Premedication with antihistamines or omalizumab has been shown to be useful in some studies, although such treatment is not recommended as standard.

Local reactions do not predict the appearance of a systemic reaction, although some studies have suggested them to be a risk factor.  The dose adjustments subsequent to major local reactions recommended in the clinical guidelines do not reduce the frequency of future systemic reactions. For additional information regarding the safety of allergy shots, refer to the reference below:

  • Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1-S55.
    •• Latest and extended update of the Joint Task Force (AAAAI-ACAAI) on Practice Parameters concerning all aspects of allergen-specific immunotherapy.

What is Available for Milk Allergy?

Sublingual and Oral Immunotherapy Shows Promise for Milk Allergy

 I’ll summarize the most recent advances in treating milk allergy from the article below.  Why is our current therapy not enough?  Guess what happens when a patient allergic to milk suffers from accidental ingestion?  Anaphylaxis! Why not cure the disease–Johns Hopkins is a long way from Oklahoma, but patients have access to this same research here in the Midwest. 

 By Will Boggs, MD

NEW YORK (Reuters Health) Jan 02 – Sublingual and oral immunotherapy may help some children with milk allergy, but clinical desensitization is quickly lost and systemic reactions occur with oral therapy, a new study shows.

“We found that both sublingual and oral immunotherapy benefited children with cow’s milk allergy in that they were able to consume much more milk without symptoms at the end of the study than they could at the beginning of the study,” said Dr. Corinne A. Keet from Johns Hopkins University School of Medicine in Baltimore.

“However, oral immunotherapy, which used higher doses, was more effective,” she told Reuters Health by email.

The new findings appeared online November 30 in the Journal of Allergy and Clinical Immunology.

All children started out on sublingual therapy, with dose escalation over six weeks. Then they were randomized to either sublingual maintenance therapy (goal dose, 7 mg) or one of two doses of oral maintenance therapy (goal dose, 1 g and 2 g). The maintenance periods lasted 60 weeks each.

“One result that surprised us was how quickly children could lose desensitization,” Dr. Keet said. “This is another reason for caution with these methods.”

“These methods are far from perfect, and I think are not ready for general use in allergy practices,” Dr. Keet concluded. “They show a lot of promise, but many aspects, including both safety and efficacy, need to be improved before widespread adoption of this method.”

“One alternative which is getting more attention recently is to use milk in baked goods to desensitize,” Dr. Keet added. “For some children, this is a good option, but some children are unable to tolerate even the small amounts of milk in baked goods needed to start desensitization. So, for many children with milk allergy there aren’t any good alternatives.”

SOURCE: http://bit.ly/tYwuuh

J Allergy Clin Immunol 2011.

Here’s what you need to know:

1.  DON’T try this at home

2. Milk allergy may be a “curable” disease, but we don’t know how long patients will have to ingest milk to become “desensitized”.

3.  If you’re interested in participating in a clinical research trial here in the Midwest on milk allergy, please let me know. 

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.