What is an allergy challenge test

What is a Food Challenge?

A food challenge is a definitive procedure for testing whether your kid can tolerate a specific food. The test can confirm if your kid has a specific food allergy or determine if they own outgrown the food allergy. Only one food can be tested at a time.

During the challenge, your kid will be given little — but increasing — amounts of the food in question and monitored extremely closely for a reaction. Your kid will be in a hospital setting during testing, so if they own an adverse reaction, clinicians can reply quickly.

At the Food Challenge

Registration

Please report to the fourth floor of CHOP’s Wood Middle by 7:30 a.m.

on the day of your child’s food challenge test. You will register at the desk and then be seated in the waiting room. An allergy nurse will meet you in the waiting room to bring you and your kid to the Food Challenge Unit, where the food challenge will be performed.

The morning of the Food Challenge

Your kid may not own any breakfast the morning of the food challenge test. They may continue to drink clear liquids only.

If your kid is still breastfeeding, they may continue to do so.

Why would clinicians recommend a Food Challenge for my child?

There are several reasons clinicians may recommend food challenge testing for your kid, including:

  1. To expand your child’s diet.

    This is especially significant when your kid may be allergic to several foods and avoiding those foods.

  2. When food is suspected to own caused a significant allergic reaction but specific allergy testing is negative.
  3. To assess foods that were removed from the diet or not introduced into the diet based primarily on positive allergy tests.
  4. For FPIES, allergy test results are not always helpful, and a food challenge may be necessary to assess if your kid has outgrown the food allergy.

Frequently Asked Questions

Where can I park for the Food Challenge?

For families participating in the Food Challenge, parking is available at the Wood Middle behind the hospital at 3401 Civic Middle Blvd., Philadelphia, PA, 19104.

Get directions.

Please permit 15-20 minutes to park and discover the registration desk.

Are there bathrooms on the Food Challenge unit?

Yes, there are two bathroom on the unit.

Where can parents get coffee near the unit?

Coffee is available to purchase on the first floor of the Wood Building, and at several nearby shops love Starbucks and Au Bon Pain.

What can kids do on the unit during testing?

Children can watch TV, frolic games, use electronic devices, talk, sleep or hang out in the playroom.

Can my kid leave the unit during testing?

No.

We need to closely monitor your kid until they are cleared to go home. Children are capable to stroll around the unit, use the playroom and bathrooms, but must stay on the unit for the duration of the challenge.

How can I prepare my kid for the Food Challenge?

Food challenges can be stressful for children and families. We are asking children to eat the extremely food they’ve been warned to avoid, and there is a risk of experiencing an adverse reaction.

What we desire you to know — and to share with your kid — is that our Food Challenge Middle at Children’s Hospital of Philadelphia is the safest put to attempt these foods. We are prepared for any reaction your kid may experience and own a dedicated team of experts available to help.

Preparation for a food challenge includes:

  1. Medication changes
  2. Illness
  3. Mental preparation

Monitoring after the challenge

Along with monitoring your kid for the duration of their food challenge, clinicians will also monitor your kid after the final dose of challenge food has been istered.

Children undergoing IgE-mediated testing will remain on the Food Challenge Unit for at least 2½ hours after the final dose of the food or the final adverse reaction.

If there are no unexpected or adverse events, your kid will likely be discharged around 1-2 p.m. If there are tardy adverse reactions, discharge may be later. Children who experience a significant reaction may be observed up to 4 hours or more.

Children undergoing FPIES testing are monitored for 4 hours after dosing. Because these children only get one dose, they are often discharged between noon and 1 p.m. If the kid has a severe reaction, they may remain on the unit longer or be transferred to another unit for longer term care.

The Night Before

Your kid cannot own anything to eat after midnight the night before their food challenge test. During this time, you may give your kid clear liquids only.

What is an allergy challenge test

If your kid is younger than 12 months, formula or breastfeeding is allowed.

Clear liquids include:

  1. Water
  2. Gatorade
  3. Fruit juices with no pulp
  4. Iced Tea
  5. Apple Juice
  6. Jell-O
  7. Popsicles or water ice without fruit chunks

The following are not clear liquids:

  1. Milk
  2. Orange Juice
  3. Formula (for children older than 1 year old)
  4. Soda
  5. Hot cocoa

Please enquire about any food or drink not named on this list.

Nutritional importance of the food

Food challenges may permit for expansion of the diet. This is especially significant in a kid whose nutritional status is negatively impacted because of the avoidance of multiple foods.

If your kid is allergic to a food that they will not continue to eat or be exposed to in the future, food challenges offer minimal benefit.

Monitoring for adverse reactions

If your kid develops any mild allergic symptoms, they will be treated in the Day Medicine Unit area with oral medication and/or epinephrine and monitored closely for any further symptoms.

In rare cases, a kid may experience a extremely serious adverse allergic reaction during the Food Challenge. In such instances, the kid will be treated with epinephrine to stop the reaction, and may be taken to the Emergency Department and/or admitted to the hospital.

Children with FPIES may experience vomiting during the Food Challenge.

To ensure they remain hydrated, our team will deliver IV fluids, as needed, on the unit.

Tolerates

Children who successfully tolerate a food challenge will be instructed to hold the food in their diet regularly. This may include eating the trigger food in little amounts each week.

Recurrence of a food allergy after challenge testing has been reported, but it is infrequent and is generally associated with a child’s continued avoidance of the food allergen or not ingesting the food as prescribed.

IgE-mediated

Most children with IgE-mediated food allergies who tolerate the food challenge will be instructed by clinicians to start eating the «dose» about three times a week.

FPIES

Children who tolerate an FPIES food challenge will be instructed to eat the targeted food at slightly increasing dosages — sure by clinicians — over the next 9 days.

If your kid experiences an adverse reaction at any point, contact your child’s allergist or the Cut allergist on-call at 215-590-1000.

Patient/family preference

Some families may prefer to wait until there is a greater chance of passing the challenge depending on the necessity in the diet of the food in question. Additionally, if your kid is too anxious to ingest the food which they own been warned to avoid until this point, it may be better to postpone the challenge until they are mentally ready.

Your kid should know that the challenge site is a safe put to eat the food. It is helpful if you can explain this to your kid and offer assurance.

Dosing details (IgE and FPIES)

At the start of the food challenge, your kid will be given a little quantity of the food being tested. Most foods will be in powder form and mixed with a food your kid enjoys such as applesauce, low-fat pudding or low-fat yogurt.

Dosing for IgE-mediated food challenges and FPIES food challenges differ in the number of exposures to the food being tested and the length of time your kid will be monitored at the hospital.

  1. Children undergoing IgE-mediated testing will get five to eight doses of increasing amounts, about every 20 minutes.
  2. Children undergoing FPIES testing will only get one dose of the food.

If your kid has a severe reaction, the challenge is stopped and your kid is considered allergic to that food.

If your kid can tolerate a full serving of the food, the challenge is stopped and your kid is considered not allergic to that food.

Risk of reaction

Your kid should own at least a 50 percent chance of passing the challenge. Results of skin and blood testing and the history of the reaction to the specific foods are considered when estimating the risk of a current allergy.

Illness

Food challenge testing should not be performed if your kid is ill or still symptomatic from a recent asthma flare.

Additionally, if your kid has been wheezing or having increased coughing within the past 1-2 weeks, rescheduling the challenge is recommended.

Eczema flares or other skin rashes may also interfere with the challenge.

If your kid has these symptoms or you own questions, please call to discuss rescheduling the challenge at 267-426-8617. If your kid gets ill within 24 hours of their food challenge, please call the main Allergy line at 215-590-2549.

Medication changes

In the days leading up to your child’s food challenge, certain medications may need to be stopped so they don’t interfere with the test.

Your child’s healthcare team will give you specific instructions for your kid, but under is a list of general guidelines.

Antihistamines

Stop every antihistamines at least three days (72 hours) prior to the food challenge. This includes:

  1. Claritin (Loratadine), which should be stopped seven (7) days before the challenge
  2. Benadryl (Diphenhydramine)
  3. Zyrtec (Cetirizine)
  4. Xyzal (Levocetirizine)
  5. Allegra (Fexofenadine)
  6. Atarax (Hydroxyzine)
  7. Zantac (Ranitidine)

Combination medicines, love Extendryl and numerous over-the-counter cough and freezing preparations also contain antihistamines.

If you are not certain, please call our office at 267-426-8617 at least three (3) days prior to the challenge to double check.

Asthma medications

On the morning of the challenge, do not give your child:

  1. Albuterol (Proventil, Ventolin®)
  2. Levalbuterol (Xopenex)
  3. Other save inhalers

Do continue giving your kid daily maintenance asthma medications, such as:

  1. Singulair (montelukast)
  2. Nasal sprays (Flonase®, Nasonex®, Rhinocort®, Astelin, etc.)
  3. Inhaled asthma steroid medication (Flovent, Qvar®, Asmanex®)

Reacts

If your kid experienced a severe reaction during the food challenge or was unable to finish the predetermined «dose» of the targeted food, they will be instructed to relax and take it simple for the relax of the day.

Children with FPIES who own experienced significant vomiting may additionally need to be rehydrated with IV fluids. When your kid feels better, they can be discharged home.

If your kid reacts to a food challenge, clinicians will urge you to follow up with your child’s allergist in 6 months. At that time, clinicians can decide whether a follow-up food challenge is recommended for your child.

If your kid experiences an allergic reaction at home after the food challenge, contact your child’s allergist or the Cut allergist on-call at 215-590-1000.

Role of parent/guardian during testing

The most significant role of a parent or guardian during food challenge testing is helping your kid stay calm and relaxed.

The best way to do this is for you to remain calm.

Remember:

  1. The hospital is the safest put for your kid to eat the food that may cause an allergic reaction.
  2. A team of expert clinicians are monitoring your kid and will determine if additional medications and treatments — which are available at the bedside —are needed to stabilize your child.

What factors should be considered prior to a Food Challenge?

You and your child’s primary allergist should consent that a food challenge is needed for any of the reasons discussed previously.

You should also both consent that your kid will realistically be capable to participate in the challenge.

Several factors to consider:

  1. Risk of reaction
  2. Nutritional importance of food
  3. Patient and family preference
  4. Other issues

Food protein-induced enterocolitis syndrome (FPIES)

Food challenges may also be appropriate for children with food protein-induced enterocolitis syndrome (FPIES), a rare food allergy that affects the gastrointestinal tract. Unlike most food allergies, symptoms of FPIES do not start immediately after eating, it can take hours before severe symptoms start.

Typical symptoms of FPIES include severe vomiting, diarrhea and dehydration. These symptoms can lead to other complications, including changes in blood pressure and body temperature, as well as lethargy.

Results of the Food Challenge

There are two primary results from an IgE-mediated or FPIES food challenge:

  1. Tolerate: Your kid has successfully eaten the test food without severe reactions.
  2. React: Your kid had a severe reaction and the test was halted.

For children with food allergies that produce immediate reactions, results of the food challenge — tolerate or react — will be sure before your kid is discharged from the Food Challenge Unit, and next steps will be discussed.

In some cases, a kid may be unable to finish the full dose of a tested food.

If so, they will be monitored for 2.5 hours from the final ingestion/reaction. Your child’s allergy result for this food is considered Indeterminate.

Once your kid has completed the food challenge and returned home, there is a rare chance of a delayed allergic reaction. If this happens, immediately contact your child’s allergist or the Cut allergist on-call at 215-590-1000.

After the Food Challenge: What to Expect

What happens after a food challenge depends on if your kid passed or failed the test.

On the Food Challenge Unit

The Food Challenge Unit includes eight designated areas where children can relax in comfortable, reclining chairs, watch individual TVs, talk with parents nearby, and draw a curtain for privacy.

A nurse is within arms’ reach of each bed and each kid is monitored constantly.

Pre-challenge Evaluation

Before the food challenge begins, a doctor will examine your kid, particularly his or her breathing and skin condition. If we do not feel your kid is well enough to safely participate in the challenge, we will reschedule the test. If your kid has FPIES and is undergoing a food challenge, we will put an IV to deliver fluids in case your kid becomes dehydrated due to vomiting.

Other issues to consider

Food challenges are beneficial only when the food is expected to become part of the diet.

Food allergies rarely recur after a tolerated food challenge, but can happen. In these instances, the recurrence of allergy was associated with infrequent ingestion or continued avoidance of the food.

What to Bring to the Food Challenge

Due to limited space, we request that only 1-2 adults accompany your kid to the food challenge testing. Please do not bring other children, and hold the items that you bring to a minimum, if possible.

What you should bring to the food challenge:

  1. Toy or distraction — You and your kid will be here for several hours. Favorite toys, DVDs, books, and comfort items can assist your kid stay occupied.
  2. Challenge food — Bring the challenge food prepared exactly as described by the allergy nurse.

    Please also bring the packaging of the challenge food. Please bring a food that your kid enjoys in which we can stir the powdered food to be tested. Some examples include: applesauce, low-fat pudding or low-fat yogurt without fruit. If there is another food that will permit incorporation of the powdered food that you feel would work better for your kid, feel free to bring that food in as well.

  3. Snacks — Please bring about 32 oz. of clear liquids for your kid to drink during the challenge. Juice boxes, Jell-O and other clear liquids as listed above are excellent choices.
  4. Change of clothing — Bring a new outfit for yourself and your kid in case of vomiting.
  5. Lunch — Please bring lunch for you and your kid.

    Your kid may be permitted to eat lunch or snacks approximately one hour after the final dose of food is given.

  6. Insurance — Please bring every insurance cards and/or referrals.

Preparing for the Food Challenge

For most foods, we will be dosing your kid — at least initially — with a powdered version of the food. Please bring a food that your kid enjoys (and tolerates) so we can stir the powder into that food.

Some example include:

  1. Applesauce
  2. Low-fat pudding
  3. Low-fat yogurt without fruit

*A nurse will contact you before your child’s first Food Challenge or if your kid has not had a Food Challenge within the past 12 months.

The nurse will make certain your kid is not ill, ensure they’re off antihistamines and own not started any new medications, and that they come with an empty stomach.

IgE-mediated food allergies

Most children who undergo food challenges own IgE-mediated food allergies and own had severe allergic reactions to specific foods love nuts, milk, eggs, seeds or other foods. Reactions to these foods are immediate and can affect multiple body systems, causing anaphylaxis, a potentially life-threatening allergic reaction. Anaphylaxis can cause hives, swelling, trouble breathing, vomiting, abdominal pain and loss of consciousness.

Mental Preparation

It’s understandable your kid may own some anxiety leading into a food challenge.

Reassure them that our office at Children’s Hospital of Philadelphia (CHOP) is the one safe put to attempt the food. Start to prepare your kid to eat the food you’ve told them to avoid in the past.

Be certain to remind your kid that:

  1. This is the safest put to attempt the food.
  2. Medication will be immediately available to treat any severe allergic reactions.
  3. There will be trained doctors and nurses at the bedside to monitor them.
  4. The food challenge could produce long-term benefits — potentially decreasing their sensitivity to the targeted food or determining they are no longer allergic to the item.

Which type of food allergies can be tested in a Food Challenge?

Does Not Finish (Indeterminate)

In rare cases, a kid may be unable to finish the full dose of a tested food.

If so, they will be monitored for 2.5 hours from the final ingestion/reaction. Your child’s allergy result for this food is considered Indeterminate.

Children who get an indeterminate result may return in the future to repeat the full dose of food.

If your kid experiences an allergic reaction at home after the food challenge, contact your child’s allergist or the Cut allergist on-call at 215-590-1000.

Questions and Concerns

If you require referrals with your insurance, please remember to contact the primary care physician to obtain the necessary referral for your upcoming appointment(s).

To avoid any billing issues, please contact your insurance company for specific coverage benefits.

Please call if:

  1. You are not certain about the medicine your kid is taking.
  2. Your kid is ill. If your kid has a fever, asthma flare (coughing and/or wheezing), and/or eczema flare, food challenge testing cannot be done. If your kid has these symptoms, please call to reschedule the test at 267-426-8617.

Penicillin allergy testing can assist extend the scope of your practice and provide a valuable service to your patients.

But ICD-10 and CPT coding for penicillin allergy testing can be confusing. Here’s what you need to know to get reimbursed for this significant service.


Allergen Database Search Routines

Full-length FASTA

This website includes a sequence comparison routine, FASTA (Pearson and Lipman, 1988) which may be used to compare a protein sequence (the query sequence) to entries in the allergen database. This version of the FASTA search interface utilizes the FASTA3 (Pearson, 2000) algorithm. The purpose of the comparison routine is to assess whether the query protein sequence is identical to, or homologous with known or putative allergens in the database.

Alignments with high identity scores may indicate a potential for allergenic cross-reactions. However, there is not sufficient scientific data to establish a simple scoring boundary (E-score or percent identity), beyond which cross-reactivity is certain, or under which cross-reactivity is not possible. Based on historical data, cross-reactivity is not likely for proteins with less than 50% identity over the entire protein sequence, and is fairly common above 70% identity (Aalberse, 2000).

Through experience we discover that sequences of two proteins having published evidence of cross-reactivity will align in AllergenOnline.org with a relatively high percent identity (>50% over almost full-length) and own an E score (statistical expectation score) smaller than 1e-7 (0.0000001). Thus if a query protein matches a sequence in AllergenOnline.org with higher identity and smaller E scores, the protein should be considered as likely to be cross-reactive in the absence of extensive testing (IgE binding and possibly clinical challenges). Proteins sharing lower identity matches by FASTA alignment and having higher E scores are not likely to share IgE binding.

Experimental studies would be needed to confirm that proteins sharing identities lower than 50% and having E scores larger than 1e-4 share IgE binding and clinical reactivity. Evaluation of literature regarding the matched allergen would assist to identify appropriately allergic study subjects.

Sliding 80mer FASTA

In addition to the full-length FASTA search, we own added an option to automatically scan each possible 80 amino acid segment (1-80, 2-81, 3-82, etc.) of the entered search protein against the AllergenOnline database, looking for matches of at least 35% identity.

The 35% identity for 80 amino acid segments was suggested in a scientific advisory to regulators for evaluating proteins in genetically modified crops (see FAO/WHO 2001, and Codex 2003). This short segment matching routine evaluating segments of 80 amino acids appears to be fairly conservative, and precautionary as discussed in Goodman et al. (2005) and Goodman and Hefle (2005). However, the 80 amino acid segment search appears to be far more likely to be informative than a search for shorter identical segments of 6 or 8 contiguous amino acids as originally recommended by Metcalfe et al. (1996) or the FAO/WHO 2001 approach, based on evaluations by Hileman et al., (2002) and Silvanovich et al.

(2006). See also the summary report from the bioinformatics workshop on evaluating potential allergenicity (Goodman, 2006).In the past AllergenOnline.org has employed an E()-value (E-score) threshold of 100 as a statistical cutoff limit in the 80-mer search in identifying alignments with >35% identity matches that should be evaluated further. However, we own sure that the extremely large E score allows alignments with multiple gaps and leads to alignments in some cases that do not make sense when compared to full-length alignments.

Reexamination of publications by Pearson in 2004 and earlier publications clearly support the use of the default E = 10 as a limit for FASTA or in exceptional cases with specialized, little databases or sequences, the limit could be set lower (e.g. E = 0.01). We own therefore modified the search parameters to assess only alignments with E scores = 10 or less in the release of AllergenOnline.org version 15 (12 January, 2015). It is significant to hold in mind that the default E()-value is simply a starting threshold used to permit alignments to be observed and then investigated using 35% identity and 80 amino acid overlap as the criteria. In cases when the alignment identified matches of >35% identity in the sliding 80mer search, additional bioinformatics comparisons maybe useful to assess likely biological significance, or specific serum testing may prove useful if appropriate specifically allergic serum donors can be identified to assess the potential cross-reactivity suggested by the match.

8mer Identity Match

Although the CODEX mentions using short segment (6 or 8 amino acid) sequence matches, it also indicates that searches must be based on scientific proof.

As we own searched for, and been unable to discover examples where an isolated identity match of 6 or 8 amino acids was found between cross-reactive proteins unless there was at least a 35% identity match over 80 amino acids, we previously did not include that search routine on our database (Goodman et al. 2008). However, since some countries still require an eight amino acid identity search, even in the lack of evidence demonstrating a positive predictive worth, we now provide that as an option.


CPT coding for drug allergy testing and oral challenge

CPT 95018 is the correct code to use when skin testing for an allergy to any drug.

It should be used for both prick testing and intradermal testing. On the claim form, on one line, enter 95018 and the entire number of prick and intradermal tests performed. Note that Medicare does not permit billing for positive or negative controls, so you cannot count those tests when billing Medicare. Most commercial carriers will pay for controls, but we recommend checking with individual carriers to confirm their policies.

CPT 95076and 95079 are the codes to use for any additional oral drug challenge.

  • 95076 is billed for the first 61-120 minutes of the challenge.
    1. “Time” begins as soon as work begins on the challenge (including explaining the test to the patient) and ends with a negative result or with reactions that need to be treated.
    2. If you spend less than 61 minutes on this challenge (for example if a patient has a positive reaction so testing is stopped), bill an E&M code instead.
    3. A minimum of 61 minutes (more than 50% of the entire time for the code) must be spent on this challenge before you are eligible to bill this code.
    4. Note that this code requires “sequential and incremental ingestion of test items,” which suggests at least two doses be used for the oral challenge.
  • 95079 is billed in addition to 95076 after testing has reached at least 151 minutes.
    1. It is billable for each additional hour beyond the first 120 minutes of the challenge.
    2. An additional 31 minutes (>50% of the entire time) must pass before it can be added to 95076.

    For everything you need to know about penicillin allergy testing, check out our Penicillin Toolkit.

    It includes instructions for penicillin skin testing, consent forms, an insurance appeal letter template, patient education and more. You can also join the College in supporting National Penicillin Allergy Day on Sept. 28. Use the tools there within your health system, practice and community to show your support for testing unverified penicillin allergy.

    Frequently Asked Questions about Food Protein-Induced Enterocolitis Syndrome (FPIES)

    What Does FPIES Stand For?

    FPIES is Food Protein-Induced Enterocolitis Syndrome.

    It is commonly pronounced «F-Pies», as in «apple pies», though some physicians may refer to it as FIES (pronounced «fees», considering food-protein as one word). Enterocolitis is inflammation involving both the little intestine and the colon (large intestine).

    What are Some Common FPIES Triggers?

    The most common FPIES triggers are traditional first foods, such as dairy and soy. Other common triggers are rice, oat, barley, green beans, peas, sweet potatoes, squash, chicken and turkey.

    What is an allergy challenge test

    A reaction to one common food does not mean that every of the common foods will be an issue, but patients are often advised to proceed with caution with those foods. Note that while the above foods are the most prevalent, they are not exclusive triggers. Any food has the potential to trigger an FPIES reaction. Even trace amounts can cause a reaction.

    When Do FPIES Reactions Occur?

    FPIES reactions often show up in the first weeks or months of life, or at an older age for the exclusively breastfed kid.

    Reactions generally happen upon introducing first solid foods, such as baby cereals or formulas, which are typically made with dairy or soy. (Infant formulas are considered solids for FPIES purposes.) While a kid may own allergies and intolerances to food proteins they are exposed to through breastmilk, FPIES reactions generally don’t happen from breastmilk, regardless of the mother’s diet. An FPIES reaction typically takes put when the kid has directly ingested the trigger food(s).

    Does FPIES Require Epinephrine?

    Not generally, because epinephrine reverses IgE-mediated symptoms, and FPIES is not IgE-mediated.

    Based on the patient’s history, some doctors might prescribe epinephrine to reverse specific symptoms of shock (e.g., low blood pressure). However, this is only prescribed in specific cases.

    How Do You Treat an FPIES Reaction?

    Always follow your doctor’s emergency plan pertaining to your specific situation. Rapid dehydration and shock are medical emergencies. If your kid is experiencing symptoms of FPIES or shock, immediately contact your local emergency services (9-1-1). If you are uncertain if your kid is in need of emergency services, contact 9-1-1 or your physician for guidance. The most critical treatment during an FPIES reaction is intravenous (IV) fluids, because of the risk and prevalence of dehydration.

    Children experiencing more severe symptoms may also need steroids and in-hospital monitoring. Mild reactions may be capable to be treated at home with oral electrolyte re-hydration (e.g., Pedialyte®).

    What Does IgE vs Cell Mediated Mean?

    IgE stands for Immunoglobulin E. It is a type of antibody, formed to protect the body from infection, that functions in allergic reactions. IgE-mediated reactions are considered immediate hypersensitivity immune system reactions, while cell mediated reactions are considered delayed hypersensitivity. Antibodies are not involved in cell mediated reactions. For the purpose of understanding FPIES, you can disregard every you know about IgE-mediated reactions.

    How Do I know If My Kid Has Outgrown FPIES?

    Together with your child’s doctor, you should determine if/when it is likely that your kid may own outgrown any triggers.

    Obviously, determining if a kid has outgrown a trigger is something that needs to be evaluated on a food-by-food basis. As stated earlier, APT testing may be an option to assess oral challenge readiness. Another factor for you and your doctor to consider is if your kid would physically be capable to handle a possible failed challenge.

    When the time comes to orally challenge an FPIES trigger, most doctors familiar with FPIES will desire to schedule an in-office food challenge.

    Some doctors (especially those not practicing in a hospital clinic setting) may select to challenge in the hospital, with an IV already in put, in case of emergency. Each doctor may own his or her own protocol, but an FPIES trigger is something you should definitely NOT challenge without discussing thoroughly with your doctor.

    Be aware that if a kid passes the in-office portion of the challenge, it does not mean this food is automatically guaranteed «safe.» If a child’s delay in reaction is fairly short, a kid may fail an FPIES food challenge while still at the office/hospital. For those with longer reaction times, it may not be until later that day that symptoms manifest.

    Some may react up to three days later. Delay times may vary by food as well. If a kid has FPIES to multiple foods, one food may trigger symptoms within four hours; a diverse food may not trigger symptoms until six or eight hours after ingestion.

    What is Shock and What are the Symptoms?

    Shock is a life-threatening condition. Shock may develop as the result of sudden illness, injury, or bleeding. When the body cannot get enough blood to the vital organs, it goes into shock.

    Signs of shock include:
    Weakness, dizziness, and fainting.
    Cool, pale, clammy skin.
    Weak, quick pulse.
    Shallow, quick breathing.
    Low blood pressure.
    Extreme thirst, nausea, or vomiting.
    Confusion or anxiety.

    What is a Typical FPIES Reaction?

    As with every things, each kid is diverse, and the range, severity and duration of symptoms may vary from reaction to reaction.

    Unlike traditional IgE-mediated allergies, FPIES reactions do not manifest with itching, hives, swelling, coughing or wheezing, etc. Symptoms typically only involve the gastrointestinal system, and other body organs are not involved. FPIES reactions almost always start with delayed onset vomiting (usually two hours after ingestion, sometimes as tardy as eight hours after). Symptoms can range from mild (an increase in reflux and several days of runny stools) to life threatening (shock). In severe cases, after repeatedly vomiting, children often start vomiting bile.

    Commonly, diarrhea follows and can final up to several days. In the worst reactions (about 20% of the time), the kid has such severe vomiting and diarrhea that s/he rapidly becomes seriously dehydrated and may go into shock.

    How is FPIES Diagnosed?

    FPIES is hard to diagnose, unless the reaction has happened more than once, as it is diagnosed by symptom presentation. Typically, foods that trigger FPIES reactions are negative with standard skin and blood allergy tests (SPT, RAST) because they glance for IgE-mediated responses.

    However, as stated before, FPIES is not IgE-mediated.

    Atopy patch testing (APT) is being studied for its effectiveness in diagnosing FPIES, as well as predicting if the problem food is no longer a trigger. Thus, the outcome of APT may determine if the kid is a potential candidate for an oral food challenge (OFC). APT involves placing the trigger food in a metal cap, which is left on the skin for 48 hours. The skin is then watched for symptoms in the following days after removal. Please consult your child’s doctor to discuss if APT is indicated in your situation.

    How Do You Care for a Kid With FPIES?

    Treatment varies, depending on the patient and his/her specific reactions.

    Often, infants who own reacted to both dairy and soy formulas will be placed on hypoallergenic or elemental formula. Some children do well breastfeeding. Other children who own fewer triggers may just strictly avoid the offending food(s).

    New foods are generally introduced extremely slowly, one food at a time, for an extended period of time per food. Some doctors recommend trialing a single food for up to three weeks before introducing another.

    Because it’s a rare, but serious condition, in the event of an emergency, it is vital to get the correct treatment.

    Some doctors provide their patients with a letter containing a brief description of FPIES and its proper treatment. In the event of a reaction, this letter can be taken to the ER with the child.

    Is FPIES A Lifelong Condition?

    Typically, no. Numerous children outgrow FPIES by about age three. Note, however, that the time varies per individual and the offending food, so statistics are a guide, but not an absolute. In one study, 100% of children with FPIES reactions to barley had outgrown and were tolerating barley by age three. However, only 40% of those with FPIES to rice, and 60% to dairy tolerated it by the same age.

    What is FPIES?

    FPIES is a non-IgE mediated immune reaction in the gastrointestinal system to one or more specific foods, commonly characterized by profuse vomiting and diarrhea.

    FPIES is presumed to be cell mediated. Poor growth may happen with continual ingestion. Upon removing the problem food(s), every FPIES symptoms subside. (Note: Having FPIES does not preclude one from having other allergies/intolerances with the food.) The most common FPIES triggers are cow’s milk (dairy) and soy. However, any food can cause an FPIES reaction, even those not commonly considered allergens, such as rice, oat and barley.

    A kid with FPIES may experience what appears to be a severe stomach bug, but the «bug» only starts a couple hours after the offending food is given. Numerous FPIES parents own rushed their children to the ER, limp from extreme, repeated projectile vomiting, only to be told, «It’s the stomach flu.» However, the next time they feed their children the same solids, the dramatic symptoms return.

    How is FPIES Diverse From MSPI, MSPIES, MPIES, Etc.?

    MPIES (milk-protein induced enterocolitis syndrome) is FPIES to cow’s milk only.

    MSPIES (milk- and soy-protein induced enterocolitis syndrome) is FPIES to milk and soy. Some doctors do create these subdivisions, while others declare that milk and soy are simply the two most common FPIES triggers and give the diagnosis of «FPIES to milk and/or soy.»

    MSPI is milk and soy protein intolerance. Symptoms are those of allergic colitis and can include colic, vomiting, diarrhea and blood in stools. These reactions are not as severe or immediate as an FPIES reaction.

    References

    Fogg MI, Brown-Whitehorn TA, Pawlowski NA, Spergel JM. (2006). Atopy Patch Test for the Diagnosis of Food Protein-Induced Enterocolitis Syndrome. Pediatric Allergy and Immunology 17: 351–355.

    Retrieved on December 31, 2007 from http://pediatrics.aappublications.org/cgi/content/abstract/120/Supplement_3/S116.

    Burks, AW. (2006). Don’t Feed Her That! Diagnosing and Managing Pediatric Food Allergy. Pediatric Basics. Gerber Products Company: 115. Retrieved on December 31, 2007 from http://www.gerber.com/content/usa/html/pages/pediatricbasics/articles/115_01-dontfeed.html.

    Moore, D. Food Protein-Induced Enterocolitis Syndrome. (2007, April 11). Retrieved on December 31, 2007 from http://allergies.about.com/od/foodallergies/a/fpies.htm.

    Sicherer, SH. (2005). Food Protein-Induced Enterocolitis Syndrome: Case Presentations and Management Lessons.

    Journal of Allergy and Clinical Immunology Vol. 115, 1:149-156. Retrieved on December 31, 2007 from http://www.jacionline.org/article/PIIS0091674904024881/fulltext.

    Nowak-Wegrzyn, A., Sampson, HA, Wood, RA, Sicherer, SH. MD, Robert A. Wood, MD and Scott H. Sicherer, MD. (2003). Food Protein-Induced Enterocolitis Syndrome Caused by Solid Food Proteins. Pediatrics. Vol. 111. 4: 829-835. Retrieved on December 31, 2007 from http://pediatrics.aappublications.org/cgi/content/full/111/4/829#T1.

    Nocerino, A., Guandalini, S. (2006, April 11).

    Protein Intolerance. Retrieved on December 31, 2007 from http://www.emedicine.com/ped/topic1908.htm. WebMD Medical Reference from Healthwise. (2006, May 31). Shock, Topic Overview. Retrieved on December 31, 2007 from http://www.webmd.com/a-to-z-guides/shock-topic-overview.

    American Academy of Allergy, Asthma and Immunology. (2007). Tips to Remember: What is an Allergic Reaction? Retrieved on December 31, 2007 from http://www.aaaai.org/patients/publicedmat/tips/whatisallergicreaction.stm.

    Sicherer, SH. (2006). Understanding and Managing Your Child’s Food Allergies. A Johns Hopkins Press Health Book. 336.

    Medical Review February 2008.

    Allergy Diagnostic Testing

    Updated: July 2014
    Originally posted: November 2007

    Dr.

    John Oppenheimer
    Director of Clinical Research,
    Pulmonary and Allergy Associates
    Denville, NJ, USA

    Prof. Stephen Durham
    Department Allergy and Respiratory Medicine,
    Imperial College, London, UK

    Dr. Harold Nelson
    National Jewish Medical and Research Center
    Denver, CO, USA

    Dr. Ole D. Wolthers
    Clinical Institute, Health, Aarhus University
    Asthma and Allergy Clinic, Children’s Clinic Randers
    Randers, Denmark

    Credit for the first skin testing goes to Charles H.

    Blackley, who in 1865 abraded a quarter-inch area of his skin with a lancet, applied grass pollen on a piece of wet lint, and covered the scarified area with an occlusive bandage. This resulted in intense itching and a extremely large cutaneous response.

    Percutaneous skin test ranks first in confirming the presence of IgE-mediated sensitization in the allergist's office. This should come as no surprise, as it has numerous advantages. Skin testing is minimally invasive, and when it is performed correctly it has excellent reproducibility, is easily quantified, and allows the evaluation of multiple allergens at one session.

    The results correlates within vivochallenges.in vitrotesting is an alternative, generally a back up tool for diagnosing allergic illness. Skin testing alone or in combination within vitrotesting is relied upon for the evaluation of allergic rhinitis, asthma, eczema, food allergy, insect sting allergy, drug allergy (especially beta-lactam and local anesthetic allergy), occupational disease and anaphylaxis. However, the reliability of these tests depends on a number of factors. In the case of skin testing, it is significant that the technician performing the skin tests and the clinician ordering or interpreting these tests are aware of the advantages and pitfalls of the type of skin testing, the device used, the location of the tests on the body, the extracts used and the potential for suppression of the skin response by medications used to treat allergies or depression.

    These issues own been reviewed elsewhere in greater detail.1Forin vitrotesting, it is imperative that quality standards be met. These include calibration of the assay, training and experience of the technician and the use of quality allergens in the solid phase.2As in any diagnostic test, it is of paramount importance that the clinician consider the positive and negative predictive worth of the tests performed. These tests should always be considered as adjuncts to the medical history and physical exam in formulating the diagnosis in each individual case, bearing in mind that both test types can yield untrue positive or, less commonly, untrue negative results.

    Methods of Skin Testing

    Skin testing may be performed using either the prick/puncture (percutaneous) or intradermal (intracutaneous) technique.

    Intradermal testing is far more sensitive than prick/puncture testing, which means that it requires about 1000-fold less concentrated extracts than those used for prick/puncture testing to achieve a similar response. Although direct comparisons indicate that intradermal testing is more reproducible than percutaneous testing, there are numerous factors that favor the routine use of percutaneous allergy tests. These include economy of time, patient comfort and patient safety. Percutaneous testing allows the use of extract in 50% glycerin, which provides greater extract stability. Intradermal testing cannot use this diluent, as it may incite a false-positive irritant response.

    However, the most significant consideration is that results of percutaneous testing correlate better with clinical allergy. The higher sensitivity of intradermal skin tests does not generally offer added benefit, since the results of skin prick tests performed with potent extracts are of sufficient sensitivity for use in clinical practice.

    Two studies reinforce this concept.3,4Each study compared intradermal with skin prick tests by correlating their results with patients' responses to natural exposure to allergen as well as by allergen challenge testing. In the first study, three groups of patients with seasonal rhinitis were compared.

    These subjects were classified into 3 groups based on their degree of sensitization to Timothy grass pollen. They were either skin prick test positive, only intradermal test positive, or were negative by both skin prick and intradermal testing. Both nasal allergen provocation testing and symptom scores during the pollen season correlated best with a positive skin prick test (>60% of subjects with positive skin prick tests had symptoms on allergen exposure). The frequency of positive nasal provocation (11%) and symptom scores (21%) in subjects with positive intradermal testing alone were not diverse from subjects who were skin prick test and intradermal test negative.

    The authors conclude that under the conditions of this study, the presence of a positive intradermal skin test response to Timothy grass in the presence of a negative skin prick test did not indicate the presence of clinically significant sensitivity to this grass.

    In the second study, patients were challenged with cat exposure for one hour.4Both positive skin prick tests andin vitrotests to cat were highly predictive of the development of symptoms upon allergen exposure in the cat challenge room.4Subjects with a negative skin prick test were just as likely to own a positive challenge result if they had a negative intradermal skin test (31%) as subjects with a positive intradermal skin test (24%).

    The authors conclude that, at least with regard to cat allergy, major therapeutic decisions, such as environmental control or immunotherapy, should never be based on a positive intradermal skin test alone.

    Both of these studies were performed in adults and both relied upon skin testing with relatively potent allergens (Timothy grass and cat). The clinical applicability of these results to less potent allergens, such as dog, or to younger patients (especially infants) is a matter of clinical judgment, because no specific evidence is available for these groups.

    Proficiency Testing

    Like every other laboratory tests, it is imperative that quality assurance standards be met to ensure that the testing technique produces precise results.

    To confirm such standards, it is recommended that every technicians performing skin testing undergo evaluation of their technique.11 Certainly, it would be comforting to know that skin test technicians achieve some degree of consistency in skin test performance. Although there are no formal standards available for skin test proficiency testing, several publications propose some possible criteria. European publications propose a coefficient of variation of less than 20% following repeated skin test control applications, and the Childhood Asthma Management Program study requires that a coefficient of variation of less than 30% be attained with repeated testing with histamine and consistently negative reactions to saline to confirm proficiency in skin testing.

    The National Committee for Clinical Laboratory Standards recommends quality control procedures for daily performance ofin vitroallergy testing, with a recommended coefficient of variation of less than or equal to 15%.2Even with such calibration and the increased use of automation,in vitroassays still own flaws.

    Williams and colleagues examined the performance of 6 large commercial laboratories on tests of blinded samples of the same sera, both diluted and non-diluted.12They found that only two of the laboratories demonstrated acceptable precision and accuracy.

    Skin Testing Devices

    Whereas intradermal skin tests are always performed using a hypodermic syringe and needle, percutaneous tests may be performed with a variety of devices. Comparisons of percutaneous devices own been reviewed elsewhere in greater detail.5 Some devices own a single stylus with one or several points, whereas others own multiple heads and permit up to 10 tests to be accomplished with one application.

    The degree of skin trauma created by these devices for percutaneous testing varies and so may result in differences in the size of positive reactions, and the likelihood of producing a reaction at the site of the negative control. Thus, they require diverse criteria for what constitutes a positive reaction (see Table 1).

    Table 1. Wheal size indicating a positive response to skin tests using various devices.a

    a Positive response is defined as a wheal greater than 99% of wheals generated by the istration of saline to the subject's back by the same operator.

    Adapted from ref. 14.
    b HS = Hollister Steir, Greer = Greer laboratories, Lincoln = Lincoln Diagnostics, ALK = ALK America, ALO = Labs of Ohio

    Comparing in vivo to in vitro Testing:

    The preponderance of comparative studies protest skin tests to be more sensitive thanin vitrotests. However, the majority of these studies were performed with earlier generationin vitrotests. The newerin vitrotests produce higher test sensitivity and specificity13by using a matrix capsule containing antigen bound to a hydrophilic carrier to produce enhanced specific IgE binding with lower nonspecific IgE binding.2Levels of specific IgE measured by diverse commercial assays are not equivalent, as each assay differs in the composition of allergen reagents, methods of measurement and standardization procedures.

    The advantages ofin vitrotesting are largely related to use in patients with extensive dermatoses (e.g., atopic dermatitis), resulting in an inability to act out tests on unaffected skin, or in patients who are unable to discontinue medicines that block the histamine response, i.e., antihistamines or tricyclic antidepressants.

    The disadvantages ofin vitrotesting include a potential decrease in sensitivity, added cost, and lack of immediate and visible response. Performing bothin vitroandin vivotests may yield improved sensitivity.15

    Recording and Scoring of Skin Test Results

    Skin test results are often reported by clinicians in semi-quantitative terms. They may record results only as positive or negative, or express them on a 0 to 4+ scale without any indication of the size of the reactions that these numbers represent.

    However, allergy patients may own to change their allergist for numerous reasons, and it is significant that records of prior allergy testing be interpretable by the receiving physician. At the extremely least, a record of skin testing should contain sufficient information to permit another physician to interpret the results and avoid the need to repeat skin testing. Standardized forms own been developed and are available through the American Academy of Allergy Asthma and Immunology website (for an exampleAAAAI's Skin Test and Immunotherapy Forms).

    Although the area of the wheal and erythema are the most precise measurements, the longest diameter or two diameters at correct angles to each other correlate with area (r > 0.9).8The importance of performing such measurements is exemplified by the study of McCann and Ownby in which allergists were asked to interpret photographs of skin test reactions.

    The scoring and interpretation of the skin test results varied greatly.9The authors of this study reinforce the thought that the most dependable method of reporting a skin test reaction is to measure and record the reaction size. At the extremely minimum, skin test results should be graded 0 to 4+, and the criteria for each grade of reaction clearly stated along with the skin test results.

    Various investigators propose diverse criteria for interpreting a skin test response as positive.

    To assess the reliability of diverse means of interpreting the results of skin prick testing, Vanto and colleagues studied a group of 202 children sensitive to dogs.10A determination of sensitivity to dog was based on a composite score derived from the history, RAST, and bronchial or conjunctival allergen challenges. Although in this study the overall efficacy was greatest with the histamine reference method (in which the allergy skin test response is compared to a histamine control, with a positive response considered to be a response at least as grand as that of the histamine control), maximal sensitivity was achieved when using a cutoff of a wheal 3 mm.

    If a clinician wishes to maximize sensitivity, the latter criterion would be most useful; however, adjustment must be made for the device used. Therefore, the criteria for a positive test should be: 1) the larger of a 3 mm mean wheal diameter or 2) equal to or greater than the 99th percentile reaction with that device at negative control sites (see Table 1).

    "Gold Standard" Confirmation of Allergy

    Although there are challenge protocols available in the research setting to confirm allergic rhinitis and asthma, the standard tool available to the clinician is a careful history and physical exam.

    Skin testing correlates with results of nasal challenge and with bronchial challenges when allowance is made for nonspecific airway responsiveness.

    When evaluating potential food allergy, the clinical history is the initial screening, with skin testing orin vitrotests used to corroborate the history. Oral food challenges represent the "gold standard" for the confirmation of food allergy. These can be performed as open challenges or in a single- or double-blind fashion.

    Food challenges are not without risk and thus require that appropriate supportive care be available. Several studies protest that the magnitude of thein vitrotest or the skin test reaction size may be useful in determining the utility of performing a food challenge.16,17One additional advantage of skin testing for food allergies is the ability to act out skin testing with the unused food, "prick-prick" test. Several reports protest that unused foods provide greater sensitivity for certain foods.18, 19This is particularly significant in assessing allergy to fruit; however, useful results own also been demonstrated for other foods, including seafood, peanut, tree nuts, vegetables, milk and eggs.

    Molecular-based allergy diagnostic

    It is hoped that the predictive worth of allergy diagnostic testing can be improved with the use of molecular-based allergy diagnostics.

    This methodology is used to map the allergen sensitization of a patient at the epitope level, using purified natural or recombinant allergenic molecules (components) 20,21Molecular-based allergy diagnostics is available either using singleplex platforms which utilize panels of single allergens together with the corresponding allergen extract or can also be performed using multiplex technology to measure serum IgE antibodies against multiple allergens in a single assay 20-22 The technique allows for the testing of a large number of allergens using a little quantity of serum (as little as 20 µL; conventional specific IgE tests use 50 µL per allergen).

    Currently one multiplex platform is available on the market (the Immuno-Solid phase Allergen Chip (ISAC) platform) 23,24 Though a higher degree of variability in low IgE levels own been found, ISAC results own been similar to those obtained from singleplex platforms 25,26 At low serum IgE levels singleplex platforms may be more sensitive than ISAC and thus this should be considered when interpreting testing using the ISAC. Although more than 130 epitopes own been identified, the clinical relevance of numerous of these is not known.

    Evidence, however, has been provided for use of several epitopes in clinical practice, such as peanut.

    In numerous cases of peanut sensitization detected solely by prick skin testing or by whole allergen specific IgE it is hard to decide whether true allergy exists versus sensitization with no clinical symptoms as a manifestation of cross reactivity to pollen. In such cases there is excellent evidence for analyzing IgE to the epitopes Ara h 2 (genuine IgE mediated allergy) and Ara h 8 (Bet v 1 (birch pollen) homologue; a marker of cross-reactivity) 27,28 IgE sensitization to Ara h 2 often correlates with positive IgE against Ara h 1 and Ara h 3. If there were IgE antibodies in serum to Ara h 2 and/or Ara h 1/Ara h 3, more than 95% of patients own reported symptoms when ingesting peanuts 29 If there was IgE only to Ara h 2 and not to Ara h 1, 3 or 8, 87% reported symptoms.

    Whether there may be a threshold level of serum IgE to Ara h 2 above which peanut allergy may be diagnosed with a sufficient sensitivity and specificity which may forsake the need for oral provocation remains to be prospectively evaluated 30If there was only IgE to Ara h 8 and not to Ara h 1, 2 or 3 only around 18% of patients own reported symptoms, and these were generally extremely mild 29 More serious symptoms cannot be ruled out, however, in Ara h 8 sensitized patients.

    In the event of itching and swelling in the mouth and throat both Ara h 2 and Ara h 8 should be sure, and, at the same time, assessment of sensitization to birch pollen should be made by analyzing IgE to Bet v 1.

    Bet v 1, PR-10 protein is the major allergen in birch pollen and approximately 95% of birch pollen sensitized patients own specific IgE antibodies to Bet v 1 31 Specific IgE to Bet v 1 may also be found in patients with primary sensitization to other tree pollens (e.g.

    elm: Aln g 1; hazel pollen: Cor a 1) as well as to foods (hazelnut, apple, soy, peanut (Ara h 8), kiwi, celery). IgE antibodies to Bet v 2 (profilin) and/or Bet v 4 (calcium-binding protein) are markers of cross-reactivity 31 and as opposed to Bet v 1 if increased are indicators that the patient is primarily sensitized to another pollen. IgE to Bet v 2 is a marker of cross-reactivity with numerous pollens and vegetable foods 32 while IgE to Bet v 4 is a marker of cross-reactivity only with other pollen allergens 33

    IgE antibodies to Phl p 1 and Phl p 5 are specific markers for sensitization to Phleum pratense (Timothy grass).

    Phl p 7 (calcium-binding protein) and Phl p 12 (profilin) are markers of cross-reactivity with fruits and vegetables. Increased IgE to these components and not to Phl p 1 and/or Phl p 5 indicates primary sensitization to a diverse species of grass pollen than Phleum pratense 34 It has been suggested that if relevant symptoms are present in addition to elevated IgE Phl p 1 and p 5 levels immunotherapy with phleum pratense extract would likely be clinically effective because phleum pratense extracts contain mainly Phl p5 and p6 24,35

    Molecular-based allergy diagnostics are also likely to be of utility when considering immunotherapy for dust mite allergy.

    Der p 1 and Der p 2 are the most significant component markers for sensitization to home dust mites 36as more than 80-90% of patients allergic to home dust mites own IgE antibodies to these epitopes. Approximately 10% of patients allergic to home dust mites, however, own increased IgE levels to Der p 10 37 These patients will not benefit from specific immunotherapy since home mite extracts contain mainly Der p 1 and Der p 2 and variable or low amounts of Der p 10.

    Whether molecular-based allergy diagnostics may increase the effect ratio of immunotherapy of Phleum pratense and houst dust mite allergic patients has not, however, been tested in prospectively planned trials.

    Positive IgE to both bee and wasp venom is often due to cross-reactivity between cross-reactive carbohydrate-determining reagents (CCD) 38 shared in these two species. In the frequently occurring clinical situation of an uncertain history and positive IgE to both allergens, determination of specific molecular epitopes may be of aid. An increase in both Api m 1 and Ves v 5 would indicate a true double sensitization and immunotherapy with both bee and wasp extracts would be indicated 38,39

    Understanding the paucity of data, a recent consensus document concluded that molecular-based allergy diagnosis may be considered for investigation of 20

    1. patients with insect allergy (Api m1; Ves v5).
    2. Ferrer M, Sanz ML, Sastre et al.

      Molecular diagnosis in allergologgy: application of the microarray technique. J Investig Allergol Clin Immunol 2009;19(suppl 1):19-24.

    3. Ownby DR. Computerized measurement of allergen-induced skin reactions. J Allergy Clin Immunol 69:536-8, 1982;
    4. Wolthers OD. Component-resolved diagnosis in pediatrics. ISRN Pediatrics 2012; 2012:806920. doi: 10.5402/2012/806920. Epub 2012 Aug 5.
    5. Sampson H Update on food allergy Jl Every Clin Immunol 2004;113: 805-819
    6. Yoon I-K, Martin BL, Carr WW.

      A comparison of two single-headed and two multi-headed allergen skin test devices. Allergy Asthma Proc 2006;27:473-8.

    7. Constantin C, Quirce S, Poorafshar M et al. Micro-arrayed wheat seed and grass pollen allergens for component-resolved diagnosis.

      What is an allergy challenge test

      Allergy 2009;64:1030-7.

    8. Oppenheimer J, Nelson HS. Skin Testing. Ann Every Asthma Immunol. 2006;96:S6-12.
    9. MS Dykewicz, JK Lemmon, DL Keaney. Comparison of the Multi-Test II and Skintestor Omni allergy skin test devices. Ann Allergy Asthma Immunol 2007; 98:559-62
    10. Williams, PB ; Barnes, J; Szeinbach, S; Sullivan, T Analytic precision and accuracy of commercial immunoassays for specific IgE: Establishing a standard J Every Clin Immunol 2000;105:1221-30
    11. Sastre J.

      Molecular diagnosis in allergy. Clin Exper Allergy 2010;40(10):1442-60.

    12. Canonica GW, Ansetegui IJ, Pawankar R, et al. A WAO-ARIA-GA2LEN consensus document on molecular-based allergy diagnostics. WAOJ 2013;&:1-17.
    13. Pittner G, Vrtala S, Thomas WR et al. Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens. Clin Exp allergy 2004;34:597-603.
    14. Turkeltaub P. Performance standards for allergen skin testing: An approach to proficiency testing in Skin Testing Dolen W (ed): Immunology and Allergy Clinics of North America Philadelphia, WB Saunders 2001, p321-8.
    15. Fernandes J, Reshef A, Patton L, Ayuso R, Reese G, Lehrer SB.

      Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomysin, in unexposed Orthodox Jews. Clin Exp Allergy 2003;33:956-61.

    16. Dreborg S. ed. Skin tests used in type I allergy testing Position paper. Allergy 1989;44:s1-59.
    17. Oppenheimer J. Devices for epicutaneous skin testing. in Skin Testing Dolen W (ed): Immunology and Allergy Clinics of North America Philadelphia, WB Saunders 2001, p 263-72.
    18. Yunginger, J.

      MD a; Ahlstedt, S; Eggleston, P. et al. Quantitative IgE antibody assays in allergic diseases JACI 2000;105:1077-84

    19. Flinterman AE, van Hoffen E, den Hartog Jager CF et al. Children with peanut allergy recognize predominantly Ara h 2 and Ara h 6, which remains stable over time. Clin Exp Allergy 2007;37:1221-8.
    20. Valenta R, Hayek B, Seiberler S et al. Calcium-binding allergens: from plants to man. Int Arch Allergy Immunol 1998;117:160-6.
    21. Bilo BM, Rueff F, Mobech H, Bonifazi F, Oude-Elberink JN. Diagnosis of hymenoptera venom allergy. Allergy 2005;60:1339-49.
    22. Wood RA, Phipatanakul W, Hamilton RG, Eggleston PA.

      A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy. J Allergy Clin Immunol 103:773-9, 1999.

    23. Nelson HS, Oppenheimer JJ, Buchmeier A, et al. An assessment of the role of intradermal skin testing in the diagnosis of clinically relevant allergy to timothy grass. J Allergy Clin Immunol 97:1193-1201, 1996.
    24. Swoboda I, Twaroch T, Valenta R, Grote M. Tree pollen allergens. Clin Allergy Immunol 2008;21:87-105.
    25. Nicolaou N, Murray C, Belgrave D et al. Quantification of specific IgE to whole peanut extract and peanut components in prediction of peanut alergy. J Allergy Clin Immunol 2011:127:684-5.
    26. Sporik, R0, Hill DJ, Hosking, CS0 Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children.

      Clin and Exp Every 2000;30:1540-6

    27. Meliol G, Bonifazi F, Bonni S, et al.

      What is an allergy challenge test

      The ImmunoCAP ISAC molecular allergologyappraoch in adult multi-sensitized Italian parents with respiratory symptoms. Clin Biochem 2011; 44:1005-1011.

    28. Martinez A, Asturias JA, Monteseirin J et al. The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen. Allergy 2002;57(suppl 71):17-23.
    29. Vanto T. Efficacy of diverse skin test methods in diagnosis of allergy to dogs. Ann Every 1982:49:340
    30. Adkinson NF Jr. The radioallergosorbent test in 1981-limitations and refinements Jl Every Clin Immunol 1981;67:87-9
    31. McCann WA, Ownby, DR.

      The reproducibility of the allergy skin test scoring and interpretation by board-certified/board-eligible allergists. Ann Every Asthma Immunol 2002;89:368-71

    32. Liebermann JA, Glaumann S, Batelson S, Borres MP, Sampson HA, Nilsson C. The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations. J Allergy Clin Immunol Pract 2013; Jan;1(1):75-82. doi: 10.1016/j.jaip.2012.11.002. Epub 2012 Dec 27.
    33. patients and triggering allergens for specific immunotherapy, specifically
      — grass, (Phl p1, p5, p12)
      — home dust mites, (Der p1, p2, p10)
      — hymenoptera venom (Api m1; Ves v5).
    34. Droste JH, Kerkhof M, de Monchy JGR et al.

      Association of skin test reactivity, specific IgE, entire IgE, and eosinophils with nasal symptoms in a community-based population study J Every Clin Immunol 1996;97:922-32

    35. Hejl C, Wurtzen PA, Kleine-Tebbe J, Johansen N, Broge L, Ipsen H. Phleum pratense alone is sufficient for allergen-specific immunotherapy against allergy to pooideae grass pollens. Clin Exp Allergy 2009;39:752-9.
    36. Gadisseur R, Chapelle JP, Cavalier E: A new tool in the field of in-vitro diagnosis of allergy: preliminary results in the comparison of ImmunoCAP© with the ImmucoCAP© ISAC. Clin Chem Lab Med 2011;49:277-280.
    37. Rosen JP, Selcow JE, Mendelson LM et al.

      Skin testing with natural foods in patients suspected of having food allergies: Is it a necessity? Jl Every Clin Immunol 1994;93:1068.

    38. Ortolani C, Ispano M., Pastorello EA.,. Ansaloni R, Magri GC Comparison of results of skin prick tests (with unused foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome Jl Every Clin Immunol 1989;83:683-90
    39. selected cases of suspected peanut allergy, birch pollen allergy and associated cross-reactivity (Ara h2, h8 (h1, h3) (Bet v1, v2, v4).
    40. Eller E, Bindslev-Jensen C.

      Clinical worth of component-resolved diagnostics in peanut-allergic patients. Allergy. 2013 Feb;68(2):190-4. doi: 10.1111/all.12075. Epub 2012 Dec 14.

    41. Hiller R, Laffer S, Harwanegg C, Huber M, et al. Microarrayed molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002;16:414-416
    42. De Graaf DC, Aerts M, Danneels E, Devreese B. Bee, wasp and ant venomics pave the way for a component-resolved diagnosis of sting allergy. J Proteomics 2009;72:145-54.

    Rather than classic testing, alternative molecular-based allergy diagnostics should be seen as an adjunct to the traditional whole allergen specific IgE tests.

    It is significant to remember that numerous patients can still be sufficiently assessed using conventional prick skin testing or specific IgE to whole allergens in the blood in addition to a thorough history and clinical examination 20 The clinical significance of sensitization detected via molecular-based allergy diagnostics should only be used in relation to the clinical history and physical signs.

    ISAC testing is likely to be most useful in poly-sensitized patients for evaluation of sensitization to cross-reacting food and airborne allergens. Prospectively planned studies should be undertaken to determine to what extent such extensive panel screening may be helpful in clinical practice. Robust evidence has not yet been provided to prove that molecular-based allergy diagnostics can be utilized in lieu of oral challenge testing in food allergy.

    ConclusionDiagnostic testing remains an essential tool for the evaluation of the allergic patient.

    Several variables should be controlled to produce more dependable skin test results and improve the predictive values of allergy skin testing. It is also imperative that allergists ensure that the results of skin testing are dependable by conducting proficiency testing. In addition, the results must be properly documented to make them easily understandable by others. Similar standards must be applied toin vitrotesting; as in the case of skin testing, it is imperative that the ordering physician be familiar with the operating characteristics that thein vitrolab employs.

    Lastly, it is likely that in the future, molecular based allergy diagnostics will frolic a bigger role in the evaluation of allergic patients.

    References

    • Yunginger, J. MD a; Ahlstedt, S; Eggleston, P. et al. Quantitative IgE antibody assays in allergic diseases JACI 2000;105:1077-84
    • Sastre J. Molecular diagnosis in allergy. Clin Exper Allergy 2010;40(10):1442-60.
    • Turkeltaub P. Performance standards for allergen skin testing: An approach to proficiency testing in Skin Testing Dolen W (ed): Immunology and Allergy Clinics of North America Philadelphia, WB Saunders 2001, p321-8.
    • Ferrer M, Sanz ML, Sastre et al.

      Molecular diagnosis in allergologgy: application of the microarray technique. J Investig Allergol Clin Immunol 2009;19(suppl 1):19-24.

    • Ortolani C, Ispano M., Pastorello EA.,. Ansaloni R, Magri GC Comparison of results of skin prick tests (with unused foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome Jl Every Clin Immunol 1989;83:683-90
    • Ownby DR. Computerized measurement of allergen-induced skin reactions. J Allergy Clin Immunol 69:536-8, 1982;
    • Hejl C, Wurtzen PA, Kleine-Tebbe J, Johansen N, Broge L, Ipsen H. Phleum pratense alone is sufficient for allergen-specific immunotherapy against allergy to pooideae grass pollens.

      Clin Exp Allergy 2009;39:752-9.

    • Sampson H Update on food allergy Jl Every Clin Immunol 2004;113: 805-819
    • Vanto T. Efficacy of diverse skin test methods in diagnosis of allergy to dogs. Ann Every 1982:49:340
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    The Food Allergy Research and Resource Program (FARRP) AllergenOnline.org database has been updated to version 19 on February 10, 2019. Version 19 contains a comprehensive list (2129 protein (amino acid) sequence entries that are categorized into 853 taxonomic-protein groups of unique proven or putative allergens (food, airway, venom/salivary and contact)from 384 species.

    Some of the allergenic wheat gliadins or glutenins may also cause celiac disease (see Celiac Database ), however they are listed on the allergen site if there is evidence of IgE binding.

    The annual update process includes collecting new sequences designated as «allerg*» in reference files from NCBI protein database (compiled from GenBank, RefSeq and TPA databases as well as protein sequences from SwissProt, PIR, PRF and PDB databases). In a few instances, sequences are taken directly from a peer reviewed publication as they own not been entered into the NCBI or other available databases. Duplicate and inappropriate sequences are removed by a process described under.

    The sequences are categorized by taxonomic group (genus/species) and protein sequence identity (close homology). The new draft dataset is compared with sequences contained in the previous version of AllergenOnline.org and integrated into existing groups if appropriate, or classified into new groups. Peer-reviewed publications are identified from PubMed and other resources, then collected and reviewed for evidence of allergenicity of the source organism and the specific protein. Additional information is gathered from the Allergen Nomenclature Committee website of WHO/IUIS (World Health Organization/International Union of Immunological Societies) and occasionally Wikipedia. This information was reviewed for each group of sequences as described under to classify the entries as likely «allergenic» (absolute proof including challenge testing, or putative, specific IgE binding using sera from individuals with allergies to the source organism), or «insufficient proof» of allergy due to a lack of convincing evidence of allergenicity.

    During the review process, an attempt is made to identify new publications demonstrating proof of allergy for groups of potential allergens that were designated as having insufficient proof of allergenicity in previous versions. A consensus decision by the whole peer review panel is normally reached for each group regarding the designation as an «allergen» or having «insufficient proof». However in a few instances a majority decision is taken.

    Criteria used to reach a decision to include or exclude each sequence or allergen group is described below.

    The Food Allergy Research and Resource Program (FARRP) AllergenOnline.org database has been updated to version 19 on February 10, 2019. Version 19 contains a comprehensive list (2129 protein (amino acid) sequence entries that are categorized into 853 taxonomic-protein groups of unique proven or putative allergens (food, airway, venom/salivary and contact)from 384 species. Some of the allergenic wheat gliadins or glutenins may also cause celiac disease (see Celiac Database ), however they are listed on the allergen site if there is evidence of IgE binding.

    The annual update process includes collecting new sequences designated as «allerg*» in reference files from NCBI protein database (compiled from GenBank, RefSeq and TPA databases as well as protein sequences from SwissProt, PIR, PRF and PDB databases).

    In a few instances, sequences are taken directly from a peer reviewed publication as they own not been entered into the NCBI or other available databases. Duplicate and inappropriate sequences are removed by a process described under. The sequences are categorized by taxonomic group (genus/species) and protein sequence identity (close homology). The new draft dataset is compared with sequences contained in the previous version of AllergenOnline.org and integrated into existing groups if appropriate, or classified into new groups. Peer-reviewed publications are identified from PubMed and other resources, then collected and reviewed for evidence of allergenicity of the source organism and the specific protein.

    Additional information is gathered from the Allergen Nomenclature Committee website of WHO/IUIS (World Health Organization/International Union of Immunological Societies) and occasionally Wikipedia. This information was reviewed for each group of sequences as described under to classify the entries as likely «allergenic» (absolute proof including challenge testing, or putative, specific IgE binding using sera from individuals with allergies to the source organism), or «insufficient proof» of allergy due to a lack of convincing evidence of allergenicity. During the review process, an attempt is made to identify new publications demonstrating proof of allergy for groups of potential allergens that were designated as having insufficient proof of allergenicity in previous versions.

    A consensus decision by the whole peer review panel is normally reached for each group regarding the designation as an «allergen» or having «insufficient proof». However in a few instances a majority decision is taken. Criteria used to reach a decision to include or exclude each sequence or allergen group is described below.


    Peer Review Process for Categorizing Sequence Groups: Proof of Allergenicity

    Goal: To update and curate the list of sequences included in the AllergenOnline.org (FARRP) database on an annual basis to include only protein sequences that are supported by evidence demonstrating that the protein is a proven allergen or that there is substantial proof of allergy to the source of the protein as well as immunoglobulin E (IgE) binding to the specific protein using sera from individuals with allergies to the source.

    Almost identical sequences in the same taxonomic / protein group are included if it is clear there are variants of the protein that might contribute to allergy.

    Rationale: The AllergenOnline database is intended for use as a tool for evaluating the safety of proteins included in foods through processing or genetic modification. The Codex Alimentarius Guidelines (2003 and 2009) established a process for evaluating potential allergenicity based on evidence that the protein is likely to cause allergic reactions in consumers. A key component in the evaluation process is comparison of candidate products (proteins) with those of known allergens using a bioinformatics approach such as FASTA or BLASTP local alignment tools to identify proteins that would require further testing by serum IgE binding and/or clinical testing to assess safety.

    It is therefore significant to own scientific evidence that the database entries are allergens or probable (putative) allergens in order to maximize the reliability of bioinformatics searches.

    Peer Review Process: In 2005, FARRP brought together a panel of seven food allergy experts to define criteria for inclusion in future versions of the database. A protocol was developed for including sequences for consideration, for classifying sequences into groups (allergen, putative allergen, insufficient evidence to classify as an allergen or putative allergen), collecting publications for review, providing information to reviewers and finally for voting to accept sequences as allergens or putative allergens.

    In general we own included sequences in the taxonomic allergen group that are at least 67% identical to the protein that is the subject of peer-reviewed published study supporting IgE binding to the protein, using sera from clinically defined subjects allergic to the source. The identity limit was initially suggested by the IUIS Allergen Nomenclature Subcommittee as a limit for defining isoallergen groups. Information regarding the individual proteins should protest the protein is actually expressed in the source material that causes allergic reactions.

    Criteria for three classes of assignment were agreed to: Allergen is a protein that has been demonstrated to specifically bind IgE using sera from individuals with clear allergies to the source of the gene/protein and further that the protein causes basophil activation or histamine release, skin test reactivity or challenge test reactivity using subjects allergic to the source.

    Putative allergen is a protein that has met most of the criteria of an allergen, but has a missing component, generally biological activity (basophil activation or in vivo reactivity), less well defined clinical population or lack of data demonstrating the specific protein was used in reported testing. Both Allergens and Putative Allergens are retained in the list of sequence searchable protein entries in AllergenOnline.org. The third category, those with Insufficient Evidence of Allergenicity (Unproven), are not included in the sequence searchable protein list because they were judged to be lacking critical evidence of specific IgE binding, the serum donors were not demonstrated to be allergic to the source and there was no allergic biological activity demonstrated for the protein.

    The proteins categorized as «Insufficient evidence» are maintained in a list for future annual reviews as new candidate «allergens» are identified from NCBI and the published literature. If new evidence supports reclassification in the opinion of the reviewers, they would be included in future versions of the database. In rare instances after 2007 individual sequence entries in the database that were previously included in the searchable allergen list own been removed after more detailed reviews own failed to identify published evidence the protein is expressed in allergenic material or that the original review miss-interpreted the data in the available publications.

    The quantity and quality of published objective data supporting the classification of various proteins as allergens varies remarkably.

    For numerous food, airway or contact allergens there is unquestionable objective data of the identity, characterization and purity of the protein and clear evidence that human subjects with relevant allergic histories and symptoms were tested to protest reactions upon challenge, or at least clear evidence of specific IgE binding. However, there are also a number of proteins labeled as allergens in the literature or in the NCBI sequence database (or in UniProt) for which there is not sufficient objective data characterizing the protein used in testing, or data to protest human reactivity or specific IgE binding.

    Our peer review process is designed to review the collective literature for individual proteins and classify the individual allergen groups based on our stated criteria.

    The review process includes triage and initial evaluation summary Dr. Goodman at FARRP. Often additional references are identified and added for further review. Then each sequence group is assigned to two other reviewers from the expert panel. The detailed review comments from every three reviewers are compiled and presented to the entire group of seven experts for a final circular of reviews. Comments and votes are recorded in the database files as an archive file.

    Later changes in status and reasons for changes are also included in the archive. A list of relevant references that were included in the review process are included in the public view of each version of the database. At the finish of the review period a search is made of the WHO/IUIS Allergen Nomenclature website (www.allergen.org) and new entries that are not in AllergenOnline are reviewed for published evidence and these are added to the review list. The WHO/IUIS entries are often identified prior to publication. Therefore the entries are reviewed again each year.

    Before release of the database the sequences, GI numbers (now accession numbers since NCBI has stopped issuing GI numbers), taxonomy of the source and reference lists are compiled and checked before release of the new version to the public.

    The public website shows relevant information for each sequence.

    Peer Review Panel

    Baumert, Joe, PhD, FARRP, University of Nebraska, USA
    Bohle, Barbara, PhD, Division of Immunopathology, Medical University of Vienna, Austria
    Ebisawa, Motohiro, MD, Pediatric Allergy, National Sagamihara Hospital, Japan
    Fatima Ferreira, PhD, University of Salzburg, Austria
    Goodman, Rick, PhD, FARRP, University of Nebraska, USA
    Joerg Kleine-Tebbe, MD, Allergy & Asthma Middle, Westend. Berlin, Germany
    Taylor, Steve, PhD, FARRP, University of Nebraska, USA
    van Ree, Ronald, PhD, University of Amsterdam, The Netherlands

    Former Members:

    Sampson, Hugh, MD, Pediatric Allergy, Mount Sinai Medical Middle, New York, USA
    Vieths, Stefan, PhD, Paul-Ehrlich-Institut, Germany (2005-2012)
    Hefle, Sue, PhD, FARRP, University of Nebraska, USA (2005-2006)

    Financial Support

    Financial support for this database has been provided by grants from corporate subscribers and by FARRP (the Food Allergy Research and Resource Program, Department of Food Science & Technology at the University of Nebraska-Lincoln) and faculty.

    The majority of the scientific information for the Allergen database and now for the Celiac database is collected and evaluated by Rick Goodman, then verified by the review team.

    The database is updated annually. The database construction was performed by John Wise, who now consults to assist maintain it.

    Subscribers (2016 — 2017):

    1. Nuseed
    2. BASF Plant Science, LP
    3. J.R. Simplot Company
    4. Pioneer Hi-Bred International, Inc., DuPont
    5. Unilever

    Sponsors (2004 — 2015):

    1. Syngenta Crop Protection, LLC
    2. BASF Plant Science, LP
    3. Monsanto Company
    4. Pioneer Hi-Bred International, Inc., DuPont
    5. Bayer CropScience, AG
    6. Dow AgroSciences, LLC
    7. KWS SAAT AG
    8. Vilmorin & Cie

    Subscribers 2018:


    Removal of «False» Entries

    A protein sequence search strategy used for the current update is described in the publication describing construction and curation of the AllergenOnline database (Goodman et al., 2016).

    Each year the NCBI Protein database is searched using a keyword limit of «allerg*», with date limits from the final download (for version 19) to the current download (May, 2019). This year a few thousand new sequences were considered, but that was paired below to 134 that appeared to represent potential allergens. PubMed and Web of Science were searched to remove irrelevant entries. The sequences are grouped into taxonomic protein groups using FASTA comparisons. The 134 sequemces and any associated publications were reviewed by Dr.

    What is an allergy challenge test

    Goodman and if there were publications showing data on serum IgE binding or allergy, the committee of six reviewers were involved in either entering the protein as a putative allergen or a proven allergen based on scientific data. Otherwise the entry was set aside as not having sufficient proof of IgE binding or biological activity of basophil activity or skin prick tests. Innformation is recorded from the initial entry through reviewers comments. Compilation of a list of sequences for review by the entire expert panel includes screening to remove sequences that are included only based on being «similar to» an allergen, or homologous.

    Numerous peptides are from a taxonomic organism that is associated with allergy (e.g. Aspergillus sp., Alternaria sp.). In order to reduce the list to manageable size without excluding likely true allergens we exclude sequences from genome model organisms (e.g. Drosophila melanogaster, Arabidopsis thaliana, Caenorhabditis elegans, etc.). However, proteins from allergenic species that are also genetic models (rice, mice and corn) that own information suggesting allergenicity are included in the initial list, but without inclusion of published references related to allergenicity are excluded.

    Proteins that are obviously merely associated with an allergic response (e.g. cytokines, chemokines, immunoglobulins and transcription factors) are also excluded. Sequences are then screened and grouped based on sequence identity and taxonomic identity to those already in the AllergenOnline.org database (e.g. allergens, putative allergens or sequences with insufficient evidence to protest allergy, see below) from previous versions. Relevant publications are collected for the review panel, using references from the NCBI sequence entry as well as separate searches of the PubMed database, based on keyword searches of the taxa, common name and sequence authors.

    The information for each allergen group is triaged to collect more specific information and reviewed by the expert panel in a three stage process as described below.


    ICD-10 coding for drug allergy testing

    T codesare used when evaluatingpatients for drug allergies.To code for an adverse effect of a drug that has been correctly prescribed and properly istered:

    First, select one adverse effect from under (1,2,3,4 or other):

    • L27.1: Dermatitis (localized), due to drugs taken internally
    • T88.6XXA: Anaphylactic reaction due to an adverse effect of correct drug properly istered, initial encounter (or D- subsequent visit following completed evaluation.)
    • L27.0: Dermatitis (generalized), due to drugs taken internally
    • L50.0: Urticaria allergic, due to drug

    Next, select the code for the correct drug below:

    Next, select the code for the correct drug below:

    • Adverse effect of Penicillin T36.0X5A (or D)
    • Adverse effect of Cephalosporins & other beta-lactam antibiotics T36.1X5A (or D) (Be certain to document why penicillin testing is required if the reaction was to a Cephalosporin.)

    T codes require a seventh character of A, D, or S (“S” is rarely used by allergists).

    “A” is used for the initial encounter and continues until athletic treatment has ended. “D” is used for subsequent encounters when the patient is receiving routine care for the condition. Sometimes it is not clear what the correct 7th character should be, and some insurers may own their own unique interpretations. Therefore, you may need to resubmit the claim with a diverse 7th character if the initial claim is denied.

    T codes require a seventh character of A, D, or S (“S” is rarely used by allergists). “A” is used for the initial encounter and continues until athletic treatment has ended.

    “D” is used for subsequent encounters when the patient is receiving routine care for the condition. Sometimes it is not clear what the correct 7th character should be, and some insurers may own their own unique interpretations. Therefore, you may need to resubmit the claim with a diverse 7th character if the initial claim is denied.


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