Category: Allergy

Food allergies are a frequent concern globally, especially in developed countries such as Europe and America (Gowland and Walker, 2014) and this concern is growing rapidly, with prevention as the most recommended treatment (Pieretti et al., 2009). There are cases of allergic reaction ranging from mild to severe, two of which fatal cases happened in the United Kingdom in this last decade. This brings up a question of what we can do to further prevent allergies. This essay will try to summarize these two cases and provide suggestions of what methods or measures that can be taken to prevent more allergy cases from happening.

One case is of a boy named Owen Carey, who suffered a severe allergic reaction to milk in his burger at the Byron restaurant branch in Greenwich in 2017. According to an article in The Guardian (2019), Owen ordered a chicken burger, however, the menu did not inform that the meat was marinated in buttermilk. Although it was said that the restaurant did provide allergy warnings at the back of the menu, it was printed in black font against blue colour of the paper that made it difficult to be read (ibid.). The technical manager of the restaurant believed that the staffs have received adequate training and the restaurant has followed industry standards regarding food allergies at that time, therefore it was the customer’s responsibility to inform the restaurant about their allergies so arrangements can be made (ibid.).

Another case is from last year, where a girl named Natasha Ednan-Laperouse had a fatal response to sesame in her baguette sandwich she had purchased from a Pret a Manger branch at Heathrow Airport. The Guardian (2018) has reported that the wrapper of her sandwich did not have any allergen advice, which is quite common for small sandwich shops. Natasha’s father informed that the signs (that may contain allergy information) on the refrigerated cabinets were placed in the position which is insufficient for good visibility (ibid.). Her case is one of the ten cases of allergies of products from Pret a Manger that year (ibid.).

After some research, I have compiled a few suggestions that can be used to prevent any possible future allergy cases.

Firstly, labelling needs to be improved more. It is common knowledge that who is responsible for the food must ensure that the food is safe, authentic and labelled accordingly, yet labelling has often frustrated consumers with food allergy, mostly because it is not specific, transparent or visible enough to be understood clearly.

Generally, food allergen labelling in UK is regulated by the law in Food Standards Agency, which requires any product that contains one or more of 14 main allergens to be labelled. The 14 main allergens consist of: 1) celery; 2) cereals containing gluten (which includes wheat, rye, barley and oats); 3) crustaceans (such as prawns, crabs and lobsters); 4) eggs; 5) fish; 6) lupin; 7) milk; 8) molluscs (such as mussels and oysters); 9) mustard; 10) tree nuts (including almonds, hazelnuts, walnuts, brazil nuts, cashews, pecans, pistachios and macadamia nuts); 11) peanuts; 12) sesame seeds; 13) soybeans; 14) sulphur dioxide and sulphites (if the concentration exceeds ten parts per million).

The law also encourages food manufacturers to emphasize any allergens in ingredients list of a product, such as making them bold, underline them or to print them in a colour that stand out among other ingredients.

Additionally, Gowland (2002) states that there three categories of food allergen labelling:

1. Contains (where the allergen is the integral component of the product)
2. May contain traces of (possibility of a small amount of allergen; a temporary measure after thorough risk examination)
3. Free of (does not contain the allergen; particularly useful for food that has a clear connection to an allergen)

Despite this, according to Pieretti (2009), there is still a lot of ambiguity in food allergy labelling, especially for the term ‘may contain’ which is frequently not regulated. There have been several cases of costumers incorrectly interpret difference on the risk levels of the term ‘shared equipment’, ‘shared facility’ or ‘may contain’, that could lead to potential risks (ibid.). Furthermore, most labelling often does not contain specification of a certain allergen, for example, a consumer who is allergic to only hazelnut could get confused with the labelling ‘may contain nuts’ since it does not specify what type of nut inside the product, or a person could mistake the term ‘may contain soy’ as warning for soy allergy in general but it could be just a warning for soy lecithin allergy (ibid.). Therefore, it is perhaps the best for food products to have labelling containing a list of the entire ingredients and highlighting any possible allergens.

Labelling is not only limited to food packaging but also applies to displays and places where food was distributed, even in on-line food shops. Start by putting food in a designated section based on allergens (for example putting all products containing sesame in a shelf labelled ‘contains sesame’), display visible stickers, cards or signs on various places in the area and consider the colour contrast, angling, or position of the allergen information in terms of visibility. Following the example of arrangements in supermarkets, for places that has enough area, it is possible to divide into aisles based on ingredients, such as an aisle for meat products, an aisle for dairy products and so on.

Secondly, restaurants should put more effort into providing their employees with more adequate training regarding allergies. Aside from health factors, taking into account that this concern could have an effect on the number of people dining out (Ming Lee and Xu, 2015). This might have an impact on the rating of restaurants and cause a significant loss on revenue of the industry of restaurants as a whole (ibid.). As the number of people suffering from food allergy becoming increasingly prevalent, it is probably best for restaurants to properly consider the severity of this matter and be prepared to meet the needs of people with possible food allergies.

Studies by Ming Lee and Sozen (2016) have revealed that many employees think that the training is not interesting enough, lacks emphasis on the importance of allergy and fairly time-consuming. But now that technology has become more advanced, it may be possible to do training through mobile devices or a website which is more flexible, interactive and consumes less time and energy (ibid.), providing the employees with a good reward system could even motivate them further (Ming Lee and Sozen, 2016). This is not limited to only restaurants but food manufacturing industries as well.

It is also important to train the employees to establish good communication to the costumers so they will feel more at ease to inform the restaurant of any additional inputs, requests and requirements (Ming Lee and Xu, 2015) and to always remember to ask for allergy information beforehand. Making modified versions of the menus for people with allergies, advertising allergens in social platforms and listing out all possible allergens in the menu offered, for both in the restaurant and uploaded to their website is also recommended (Ming Lee and Sozen, 2016), preferably with font colour that can be clearly visible against the background colour.

Thirdly, educating the public about the importance of allergy. It would be even better if this matter was taught since young of an age. Starting from informing the public about basics of allergy, the importance of allergen warnings and learning simple prevention method such as avoiding cross-contamination with any possible allergen (Gowland et al, 2002) and bringing EpiPen in case of emergencies. It is also encouraged for consumers to adopt a habit of read any food labelling very carefully and to always remember to inform food retailers or restaurant employees for any allergy or diet requirements, even bring a food allergen card to further consolidate their stance if their request is met with doubt (Ming Lee and Xu, 2015). This also includes advertising allergy prevention in TV or the streets (posters or banners in public places).

And last but not least, proposing to the government to try creating or enforcing more strict laws or regulations regarding allergens in food processing industries. This includes establishing less leniency and declare a failure to adhere to the laws to be met with a more severe penalty to back it up.

Several laws have been established, however not a small number of people who still think that there is still error in these laws. Most laws require advisory labelling to be truthful and not misleading, however, they often do not provide specific and additional guidelines and some may not be specific enough which could lead to false assumptions by consumers (Pieretti et al., 2009) or even the manufacturers themselves, who could perhaps find a loophole around the rules. This could lead to harmful aftermath.

One of the recommended solutions is to implement higher standards of hygiene in food manufacturing and monitor it regularly (Gowland et al., 2002). Because even though most hard labour now being done by machines, it is still going to have some probability of contamination by allergens and human error. The government must try to make a law that minimizes the risk of error and make allergen warnings as transparent, comprehensive and precise as much as possible. Another suggested solution would be enforcing a law in which food manufacturers, food distributors and restaurants should have a first aid kit containing at least one EpiPen for drastic measures.

Recently, new laws have been created in honour of the two victims above. ‘Natasha’s Law’ which requires food businesses to provide labelling on pre-packaged food which contains the list of the full ingredients and emphasizing allergens that may be inside their product (BBC, 2019) and ‘Owen’s Law’ emphasizes the importance of clarity in food allergy labelling in restaurants (Leigh Day, 2019).

From above, it clear that food allergy still has errors despite its developments. There are several suggested methods, however, it would be great if further research can be conducted to prevent incident as such as the two cases from occurring again in the future.

References

1. BBC News, 13 September 2019, Byron burger allergy death: Owen Carey’s family demand law change. http://www.bbc.co.uk/news/uk-england-49688459
2. Hazel Gowland, M. (2002). Food allergen avoidance: Risk assessment for life. Proceedings of the Nutrition Society, Volume 61, Issue 1, pages 39-43. https://doi.org/10.1079/PNS2001128
3. Hazel Gowland, M. and J. Walker, M. (2014). Food allergy, a summary of eight cases in the UK criminal and civil courts: effective last resort for vulnerable consumers? Journal of the Science of Food and Literature 2015, Volume 95, Issue 10, pages 1979-1990. https://doi.org/10.1002/jsfa.6988
4. Leigh Day, 13 September 2019, Family call for ‘Owen’s Law’ following inquest conclusion. http://www.leighday.co.uk/News/2019/September-2019/Family-call-for-Owens-Law-following-inquest-con
5. Ming Lee, Y. and Sozen, E. (2016) Food allergy knowledge and training among restaurant employees, International Journal of Hospitality Management, Volume 57, pages 52-59. https://doi.org/10.1016/j.ijhm.2016.05.004
6. Ming Lee, Y. and (Michelle) Xu, H. (2015) Food Allergy Knowledge, Attitudes, and Preparedness Among Restaurant Managerial Staff, Journal of Foodservice Business Research, Volume 18, Issue 5, pages 454-469. https://doi.org/10.1080/15378020.2015.1093452
7. M. Pieretti, M., Chung. D., Pacenza, R., Slotkin, T. and H. Sicherer, S. (2009) Audit of manufactured products: Use of allergen advisory labels and identification of labeling ambiguities, Journal of Allergy and Clinical Immunology, Volume 124, Issue 2, pages 337-341. https://doi.org/10.1016/j.jaci.2009.05.032
8. The Guardian, 28 September 2018, Pret allergy death: inquest should be watershed moment, says father. http://www.theguardian.com/uk-news/2018/sep/28/pret-a-manger-gove-tighten-up-food-labelling-rules-teenagers-death-natasha-ednan-laperouse?CMP=share_btn_link
9. The Guardian, 12 September 2019, Teenager who died after burger ‘should have asked about allergens’, says Byron. http://www.theguardian.com/uk-news/2019/sep/12/byron-restaurant-denies-wrongdoing-over-teenagers-allergy-death?CMP=share_btn_link

Apparently, when I was little I was given tennis Ilyn and had terrible hives. And the pediatricians told my parents that, if I was ever given it again I would die. So my entire life I was told that if I ever took penicillin it would kill me. Over 95% of people labeled as penicillin or allergic or not despite the fears expressed by this patient. And those like her for most people penicillin antibiotics are safe. And effective there is also an optimal treatment for many infections. It’s important for individual patients as well as the healthcare system as a whole that these inappropriate diagnoses be removed from the patient’s medical records. So all patients with a penicillin allergy diagnosis should be evaluated the overdiagnosis of a tennis analogy is the subject of a clinical review. This post covers five toolkits from those reviews that are a resource for clinicians interested in performing penicillin allergy testing in their practice.

This post will explain the risk stratification of patients undergoing penicillin allergy testing patient preparation for testing low-risk patients. And management of reactions to oral penicillin challenge including anaphylaxis testing moderate-risk patients. And follow-up management before testing you must first determine your patient’s penicillin allergy risk level. Through a thorough history since there are three parts to penicillin allergy testing skin prick intradermal.

And oral challenge identifying a patient has a low moderate or high risk for having a true penicillin allergy will determine what types of testing they’ll need the history should include details of the past reaction. If the patient knows any including timing relative to the penicillin dose and what treatment the patient received at the time of the reaction.

Some examples of low-risk patients include the patient who says they’re allergic to penicillin but also reports tolerating a course of augmentin prescribed to them at urgent care last year patients like this can be reassured that they’re not allergic to penicillin patients who report reactions to penicillin.

That is consistent within tolerance rather than true allergy nausea vomiting diarrhea or headache can also be reassured through a direct amoxicillin challenge that may be needed to provide maximal reassurance to the patient. On the other hand, patients who have experienced severe reactions to penicillin in the past including blistering rash, hemolytic anemia, thrombocytopenia, nephritis, hepatitis, fever, joint pain or anaphylaxis are considered high-risk and should not be tested. But can be considered for a specialist referral to patients with unstable or compromised hemodynamic or respiratory status. Or pregnancy is always considered to be at least moderate risk for having a true penicillin allergy.

Anyone else with a history of a reaction temporarily associated with penicillin should undergo some form of penicillin allergy testing. Once you’ve determined your patient’s risk level you can move on to testing review what medications.

Your patient is currently taking before beginning any part of penicillin allergy testing for higher-risk patients beta-blockers should be held for two days before testing. Because beta-blockade can inhibit the action of epinephrine during anaphylaxis of challenges are routinely performed, inpatients. On beta-blockers, your anaphylaxis kit should include glucagon to overcome beta-blockade. If necessary for skin testing the patient should not have taken an antihistamine in the last five days tricyclic antidepressants. And antipsychotics can have strong antihistamine activity that can last a week or longer after stopping the medication. High doses of immunosuppressants including steroids are most likely to interfere with a delayed response. But also may interfere with skin testing to rule out IgE mediated reactions.

However, you can do a skin test as long as there’s a positive histamine response. So you can check a histamine prick test before canceling the test after medication review perform.

A physical exam including vitals inspection of the oral pharynx and uvula. If available establishing a baseline peak flow meter reading confirm that the patient is in their usual state of health contraindications to testing include acute illness.

New medications increased rescue, inhaler use increased oxygen requirement or new chest tightness toolkit. I provide a sample anaphylaxis kit checklist prior to any testing you must have an anaphylaxis kit in the clinical area that has medications needed to rescue.

Someone in the event of an anaphylactic reaction. It should also include IV fluids in an IV start kit check the kit. Before each test to make sure nothing missing or expired any drug. Used should be immediately replaced although all sites should have access to a similar kit.

Keep in mind that anaphylaxis resulting from oral amoxicillin challenge testing is an extremely rare event. If your patient is low risk then they can proceed to the direct oral amoxicillin challenge toolkit B covers the oral amoxicillin challenge for low-risk patients. which is a single 250milligram or 500-milligram dose of amoxicillin followed by observation for a minimum of an hour with vital sign checks every 30 minutes going directly to the oral challenges appropriate for patients? The most common reactions will be subjective symptoms such as itching without a rash scratchy.

Throat or vague gastrointestinal symptoms. These symptoms are often side-effects or results from patient anxiety if a patient complains of any of these check their vital signs and examine them. Looking for objective signs of an allergic reaction and observe for an additional 30 minutes.

If at that point there are no objective symptoms the patient can be reassured that the symptoms were likely not an allergic reaction. ।f there are doubts about symptoms resulting from an oral challenge then consider specialty referral the next most common reactions are mild cutaneous ones that can be treated with antihistamines like Racine. Or effects Afeni Deandiphenhydramine can be used. But will cause drowsiness epinephrine may be used for more diffuse urticaria reactions. And will work more rapidly. Than antihistamines again increase the observation period by 30 minutes.

To make sure there are no signs of a systemic reaction and that the cutaneous reactions subside. These symptoms represent a potential penicillin-allergic response. So the patient should remain labeled as penicillin-allergic and specialty referral may be considered anaphylaxis. Typically involves more than two organ systems look for these cutaneous respiratory cardiovascular and gastrointestinal symptoms low blood pressure alone in the setting of known allergen exposure is also considered anaphylaxis. Again epinephrine can be considered for diffuse urticaria to abort a reaction quickly and avoid progression to anaphylaxis. If a patient is having an anaphylactic reaction get out the anaphylactic kit and open it. Uplay the patient supine and elevate their legs. Check the airway breathing circulation. Give up nephron adjunctive medications and IV fluids and call 911.

Determine to be of moderate risk skin testing is performed before an oral amoxicillin challenge for penicillin allergy skin testing. This is what you’ll need these are usually provided in commercially available kits in the U.S. There is one such kit on the market the optimal site for both prick and intradermal skin testing is the volar surface of the forearm. Or extensor surface of the upper arm.

Note any rash irritation or tattoos. You want to avoid these during skin testing use an alcohol swab to clean the skin. Once that’s dried use a permanent marker to mark where each reagent will be placed. Because most negative skin tests are going to be completely invisible. The markings help you remember where you put the skin test we use a plus to indicate the histamine control. And a minus to mark the Saline negative control. We use PHP to indicate pre pen or the major antigenic determinant of the placement. It doesn’t matter though it’s best to place the histamine furthest from the major determinant. Because the flare can bleed into the next test.

If a patient has a very strong reaction to the histamine take the applicator from the reagents then place the applicator on clean dry intact skin. You need to apply a little bit of pressure to break the epidermis. A small drop of the reagent is going to sit on top of the skin and be absorbed through the small punctum. You’ve created repeat with the other reagents set a timer for 15 to 20 minutes. Before interpreting the results the test is interpreted by comparing the reaction to the major determinant with the reactions to histamine. And sailing controls begin by blotting off extra reagents from the skin. Measure the size of the wheel and the flare across the widest diameter at each site there are different acceptable criteria for determining a positive test. One is a wheel larger than five millimeters as long as the flare is larger than the wheel. Another is a wheel larger than three millimeters with a change. In the baseline erythema of the flare larger than five millimeters. This histamine site is about four millimeters across the widest diameter of the wheel. And about 42 millimeters across the widest diameter of the flare. So this is positive as expected this saline control is negative as expected. And at the major determinant site, you see a 5-millimeter Wheeland a 31-millimeter flare. So this skin prick test is positive which is rarely seen the application of topical diphenhydramine or hydrocortisone to the positive histamine control and other positive tests is rarely needed but can be used to relieve short-lived symptoms. The histamine test should be clearly a positive common reason for a negative histamine test. Include inappropriate placement of the test or inhibition by medications often antihistamines. And chronically ill patients may not respond appropriately.

Positive sailing include Dermott agraphia and chronic urticaria. The Saline controls should be clearly negative is common reasons for a positive sailing include Dermott agraphia and chronic urticaria. The next step after negative skin testing intradermal testing. Before proceeding to the final step the oral amoxicillin challenge each step increases the negative predictive value of penicillin allergy testing. The skin preparation and placement of the markings are the same except you don’t have to place an intradermal histamine control for intradermal testing. Onle sterile reagents and vials are used drawn up into tuberculin syringes the technique is similar to that used for placing a PPD injection amount of reagent approximately 0.02milliliters. Just below the epidermis to raise a tiny blip after placing the blabs wait for 15 to 20minutes and interpret the results. Using the same criteria as the skin prick test skin testing is completed wipe the area down with an alcohol swab. You can apply topical diphenhydramine or hydrocortisone to relieve itching from a positive test.

Here we have an example of a negative skin prick test on the left arm followed by a negative intradermal test on the patient’s right arm. This is far more common sight than the positive test demonstrated earlier. If intradermal testing is negative you can proceed to the oral amoxicillin challenge which is the same as the direct oral amoxicillin challenge for low-risk patients. If a patient reacts during either skin test do not proceed with an oral challenge and consider specialty referral most patients. Don’t complain of pain from the skin Creekfest applicators or the small needles used for intradermal testing. Though almost everyone will have itching at the site of the histamine test occasionally bruising seen in patients on antiplatelet drugs or anticoagulants. But this is easy to distinguish from a positive test. Fewer than five and a hundred people undergoing penicillin allergy testing will have a reaction. These are usually the mild skin reactions that can be managed with antihistamine medications as outlined earlier. In this post again anaphylaxis during penicillin allergy testing is extremely rare once testing is complete the patient’s chart needs to be clearly and thoroughly updated.

If testing is negative removing a label of penicillin allergy can be difficult first edit the penicillin allergy entry in the allergy record adding details of the thorough allergy history. You took prior to testing use the free text box. Most DMR’s will have to document the test date and the result. Then delete the allergy from the record some EMRs will require a reason to delete analogy. Something like the resolution of allergy is appropriate second provides for the patient to share with other clinicians and pharmacists. Ideally, your clinic will take the time to communicate directly with the patient’s pharmacy. If you’re not the patient’s primary care clinician the results also need to be communicated directly to the primary care clinician. Finally, communicate to the patient that they should call you if they develop new symptoms like itch or rash in the next 24 hours. Or if the site of a skin test turns hard and itchy a negative test consisting of negative skin testing. And a minimum of one hour of observation.

After an oral challenge means that the patient does not have a risk of an immediate reaction. But the risk of a delayed reaction at the population level is between two and five percent. If a delayed reaction develops either at the site of skin testing or rash this should be clearly documented ideally including a photograph. And specialty referral considered if testing is positive again. You’ll need to first edit the penicillin allergy record in the EMR adding the details about the patient’s allergy history that you’ve elicited and added the test date and results. That demonstrates allergy whether it’s a positive skin test or a reaction to an oral challenge specify the subjective and objective. Findings of the reaction second provide the patient with the documentation for their outside clinicians and pharmacy again ideally you’ll communicate directly with the patient’s pharmacy. And primary care clinician third lets the patient know that positive tests can wane over time.

Avoid all penicillins cephalosporins and carbapenems

So that retesting in five years should be considered finally instruct the patient to avoid all penicillins cephalosporins and carbapenems until they undergo further evaluation specialists.

If deemed appropriate the need for specialty care can be based on the patient’s specific health needs some additional considerations tolerance of a cephalosporin or other beta-lactam in a patient labeled. Penicillin allergy doesn’t rule out penicillin allergy tolerance of penicillin in a patient with a history of cephalosporin allergy does not rule out a cephalosporin allergy. This is because cross-reactivity between different beta-lactams can occur based on shared my chains in the setting of positive penicillin skin testing consider specialty consultation for further testing to assess for cross-reactivity.

Between penicillin and other beta-lactams or if a patient has a history of cephalosporin allergy and negative penicillin skin testing and amoxicillin challenge consider specialty referral for further testing. To address the cephalosporin allergy patients with a history of reacting to augmentin may have reacted to the Clavel innate component rather than amoxicillin.

So negative penicillin skin testing and oral amoxicillin challenge do not exclude augmentin allergy in these patients. A specialist can test for sensitivity to Clavel innate. Finally, the information provided in this post is applicable to adult populations.

In the U.S. there are extra considerations when testing kids hospitalized patients and pregnant women. So these patients should be evaluated by specialists given a large burden of inaccurate. Penicillin allergy diagnosis clinician who starts allergy testing in their practice will be helping their own patients. Should those patients need penicillin therapy in the future and also be contributing to the population level reducing costs and minimizing a major contributing factor in the antimicrobial resistance crisis.

Sneezing, runny nose, red eye, itching… No doubt, the pollens are back. How can we protect ourselves from it? What are effective treatments?

When the good days come, your eyes sting and tearful, your nose runs, you sneeze. The signs don’t deceive, you’re probably allergic to pollen, a common health problem. We tell you more about the symptoms and treatment of this allergy. Pollen allergy is more specific to the age of 20 plus. However, kids can also face pollen allergy.

Pollen allergy is a seasonal allergy. It begins in the spring when nature begins to revive, and continues until September. Pollen dispersed in the air for about 2 months from March for Birch, April for Cypress, plane, oak, and ash, May for grasses, June for herbs, and August for Ambrosia. It is estimated that 20 % of the population is affected by this health problem.

Causes

Every spring, the same nightmare begins again for 10 to 20% of the population. This period when flowering plants reproduction is accompanied by the spread of pollen in the air, and it brings a great displeasure for pollen allergic people! Because the pollen grains, by penetrating the air, are able to trigger in the body of allergic person. The person, who does not recognize these bodies, indeed make every effort to eliminate them, which results in nasal discharge, sneezing, itching, or conjunctivitis. Therefore, we can say that pollen grains (Trees, plants) are the main reason of this allergy.

Symptoms and Indications

The most common symptoms of pollen allergy are: 1) the conjunctivitis; 2) sneezing; 3) nasal congestion; 4) runny nose; 5) cough; 6) dry throat; 7) headaches; 8) red eyes.

The events, their intensity and their duration vary from one individual to another. In the most serious cases, this allergy can cause breathing difficulties or even an asthma attack in the most sensitive subjects. In order to keep hay fever under control, sufferers can do a lot when symptoms occur and also preventatively.

Treatment

With the correct treatment, pollen allergy can be kept in check. Pollen allergy treatment consists of taking antihistamines and corticosteroids which have the effect of calming the attack in the presence of the allergen. But we’ll have to take these drugs every time we have a crisis. To solve the problem more sustainably, it is necessary to meet an allergist who can take stock and propose a desensitization. This therapy removes the allergy by exposing the patient gradually and in small doses to the implicated allergen.

It is important not to take pollen allergy lightly. In most cases, people with hay fever only get medicines from the pharmacy and refrain from a visit to a doctor. Symptom-fighting drugs enough, however, one should warn with hay fever as early as possible to the doctor. Because: “Meanwhile, the risk of an allergic person developing Asthma is already at 46%. A worse asthma attack could even be fatal’, says the Hamburg-based ENT Doctor, Dr. Christa Wilcke.

What to Do Yourself

In order to minimize the effects of pollen on the body, some precautions can be taken. In times of allergic risk, limit your outings in case of peak pollution. This other aggressor weakens your airways and makes you more vulnerable to pollen. Take the same attitude in case of wind, as the pollen is even smaller and can be more easily ingested by the nose or mouth. Anything that can make your respiratory system more fragile should be avoided: smoking. Other measures can also be taken: air your house regularly and dry your clothes inside in order to be as little as possible in contact with the allergen.

The human body has an intricate system of mechanisms that protect and defend the body from germs and disease. As a whole, this system is known as the immune system. Although the whole body is involved in this intricate system, the white blood cells play an extremely important role. There are many different types of white blood cells and they each play a critical role in the case of an allergic reaction.

The first time a person eats a food that they are allergic to they may not notice the common symptoms. However, the proteins and chemicals in the food trigger cause the immune system to react. The chemicals that do this are identified as allergens. When the allergens enter the body the white blood cells called lymphocytes react by creating chemicals called IgE antibodies; These IgE antibodies circle around the bloodstream as they circle they come in contact with other white blood cells called mast cells. The IgE cells latch themselves to the surface of mast cells. These newly equipped cells are ready to “Defend” against that food chemical in the future

The second time a person ingests a food harmful to the body something very different happens. This time the body reacts very quickly and the immune system springs into action. The food proteins interact with the IgE antibodies on the mast cells. This interaction makes the mast cells release the chemicals histamine and other chemicals. These chemicals flow through the bloodstream and once they reach the nose, throat, lungs, and skin they can cause a rash and tingling and make it difficult for the person to breathe. They can also cause other symptoms such as nausea and diarrhea.

If a person ingests a food that they are allergic to they may notice some or all of the following symptoms.

Skin

• Mouth, lips, tongue, and throat may tingle or swell
• Skin and other parts of the body may itch

A bumpy rash may develop.

• Digestion
• Nausea
• Vomiting
• Diarrhea
• Breathing
• Difficulty breathing
• Asthma attack (if asthmatic)
• Circulation

Feeling of faintness

In cases of severe food allergies, the person does not even have to eat the food. Simply touching the food or breathing in particles of it can trigger these reactions.

One of the crazy things about food allergies and intolerances is that different people are affected in different was. This means that two people who are allergic to the same thing can experience two very different experiences. One person with a peanut allergy may only experience a mild rash, while another may experience swelling of the throat and diarrhea. Another strange thing about food allergies is a person may react differently to a food on different days. This might depend on how much of the food they ate, what other foods they have eaten recently, or whether they are moving or resting.

In many cases, it may not be necessary to treat a reaction, for it is very mild. This reaction will cause a faint skin rash or a feeling of mild sickness. After a while, the symptoms will disappear and the body will return back to normal. Some stronger but not severe reactions can be treated with medicines called antihistamines. These can be useful if the allergy causes unpleasant symptoms, such as a lumpy rash or painful stomach cramps. These antihistamines work to reverse the effects of histamine, which is released by the mast cells. If a person’s symptoms include breathing difficulties they may be given a type of inhaler or more commonly known as a puffer. The medicine in these inhalers can help reduce swelling in the airways making it easier to breath. Many allergies can cause what is called a severe reaction. These can only be treated by the ingestion of epinephrine. A person suffering a severe reaction like this will be treated like a medical emergency. They will probably be taken to a hospital so they can be closely examined to make sure they fully recover.

Food allergies are quickly becoming one of the most well-known and chronic medical conditions all over the United States and Canada. At this current time, it is estimated that over 5% of all Canadian and American youth are living with an allergy. Having a food allergy requires constant acknowledgment and attention. It is suspected that food allergies can greatly affect one’s way of living and their physiological health. The rising number of young children being diagnosed with food allergies has caused a spike in children and families who are experiencing mental health problems and depression.

A review published in the The Journal of Allergy and Clinical Immunology in 2017. This review provides an overall synopsis of common physiological concerns of youth with allergies and their families. This review also included how families can deal with anxiety for their allergies for their children. In this journal “The authors report that children with food allergies and their parents tend to report a range of psychosocial concerns that include parenting stress, anxiety, and worries about bullying.” For many families, the first question that must be asked is how to balance surveillance and preparedness for life required for a potentially life-threatening allergy.

The authors said that many families whose children have mental concerns benefit from having an allergist listen to them about their concerns about their allergies. Although when patients need additional psychological health or has extreme anxiety and fear of there allergy, many times a doctor will refer them to a psychologist for additionally support. The mental health professional will conduct a private interview between them and the patient to see if they would benefit from short-term versus long-term psychotherapy and or medication.

With the continuously rising number of allergies every day, it is likely that doctors and medical professionals will continue research and encounter many new questions on how to manage patients’ allergy-related mental concerns. Health care professionals can help normalize the balance of allergy management and activities appropriate to the age group. They can also provide early education on allergies and the psychological impact of them. Additionally, they provide the patient with the information that having anxiety over an allergy is common to try to balance their feelings.

A very common question that is asked about food allergies is can they be prevented. A study conducted in 2013 by American Academy of Pediatrics shows that feeding solid foods to infants could promote allergies. It recommends that solid foods should not be introduced to babies younger than 17 months (1 year and 5 months.) It also suggests that only breastfeeding for as long as possible, but it does not recommend breastfeeding for 6 months straight.

In the well-known case of a peanut allergy your child is more common to have a peanut allergy or an egg allergy if at birth or an infant they have eczema. The guidelines says you should introduce your child to foods with peanut as early as 4-6 months of age for high-risk infants who have already started solid foods. Parents should know that most infants are at a moderate or low risk for developing a peanut allergy, and most peanut-containing foods can be introduced at home.

Some food allergies can develop in the body at birth, some develop during childhood and others don’t appear until adulthood. Some food allergies are outgrown from a child as they grow up, while others are persistent and last throughout one’s lifetime. These patterns vary from the food they are allergic to and the person’s immune system.

Early Childhood

Most children develop a food allergy during the early years of there life. The most common allergies at early ages are those to milk and egg. In recent years, peanut allergies have also become much more common in young children. Parents of very young children who have allergies need to monitor their diets carefully.

Childhood Years

It is thought that, by the young age of five, 80 percent of children who have a milk or egg allergy will have outgrown it. There immune system eventually adapts to this allergen and stops reacting. These allergies often come as a whole: a study done in Australia found that 2 percent of all children who had a milk allergy and 3.2 percent had egg allergy- but more than half of these kids who had a milk allergy also had an egg allergy.

Not all children grow out of there allergies, though. The more severe the allergy is the less likely of a chance that you will outgrow it. Additionally, a child with several allergies are less likely to outgrow their allergy than a child with one allergy. In a small section of children with milk and egg allergies persist throughout childhood and may last for life. An example of this is my teacher Ms.Dubreil. Only about 20 percent of children with nut allergies will outgrow it. Allergic to other foods such as penicillin may also start to develop during childhood. Parents still need to closely monitor their child’s allergy, but as they grow up they become more aware of what they can eat and what they can.

Teenage Years

As a teenager, I can say that I have eaten much more diverse foods than I did when I was younger. This means that as I eat new foods there is more of a chance that I can develop new allergies. Additionally, an allergy can develop to a food which earlier could be eaten without causing a problem. Fish, shellfish, soy, peanut, and wheat allergies can all be developed during teenage years. As they become more independent teenagers can start managing their own allergies.

Adult Years

Most allergies will continue from childhood to adulthood and through the rest of their lives. New allergies particularly to fish, shellfish, soy, peanut, and wheat can arise. Adults who have food allergies have to monitor their diet just as close as a child would have to.

As I said before a food allergy can also affect one’s family and friends. Many different precautions have been taken at school and many other places. However, as long as the necessary precautions are made, having a food allergy should never stop someone from doing anything they want.

Having a child or family member with a serious food allergy means that the rest of the family must be aware of how serious this can be. Foods may have to be stored separately, and different meals might have to be prepared for the person with the allergy. Many people are so allergic to the substance that even being in the same room as the allergen can cause a reaction. This is called a airborne reaction. Even though these reactions are rare they can occur, so the rest of the family should avoid having the substance in the house altogether. Family members can also support the person mentally, by being supportive and knowing what to do in the case of anaphylaxis.

Chapter one. Introduction

1.1 Brief history of inheritance

The origins of genetics i.e study of inheritance lie in the development of theories of evolution. It was in 1858 that the origin of species and how species variability was developed after the research of Charles Darwin and Wallace. They described how new species arose through evolution and how natural selection occurred to evolve new forms. Around the same time Gregor Mendel an Austrian Monk also described the unit of hereditary as a particle that does not change and is passed on to offspring through his experiment on inheritance and genetics of sweet peas plants. His work is the basis of understanding the principles of genetics, therefore, he is regarded as the father of genetics, Also Haeckel and Miescher predicted the location of the hereditary material in the living cell i.e the nucleus and the material is nucleic acid respectively. A chromosome was also discovered during this period.

In the early and mid-20th century some scientists also worked and established the Mendelian Principles and the Chromosomal Theory of Inheritance. They also discovered that DNA is the genetic material and Watson and Crick also determined the structure of DNA, and others suggested that the DNA contains a genetic code. ( Ananya Mandal, MD).

1.2 What is inheritance?

Inheritance is the process by which an offspring cell or organism acquires or becomes predisposed to characteristics of its parent cell or organism. Through inheritance, variation exhibited by individuals can accumulate and cause a species to evolve. the study of biological Inheritance is called Genetics ( Devdutt Saha).

Inheritance can also be defined as the transmission of traits or information from one generation of individuals or cells to the next (encyclopedia of Reproduction,2018).

Inheritance refers to the mechanism that genes, and more specifically the permanent condition, or allele that can be distinguished from other alleles of the same gene, is transmitted from parent to offspring. Also can be referred to as the mechanism for either the transmission of specific traits or the transmission of all biological information required for life without specifying genotypes (J.Merriam, 2001).

1.3 Mechanism of inheritance

There are several ways a gene is inherited, and each has an underlying mechanism, the following are some major mechanisms of inheritance:

1.3.1 Autosomal dominant inheritance

This mode of inheritance refers to the conditions where a mutation in one allele can cause the relevant phenotype. It is not required that both alleles have a mutation for the mutant phenotype to be expressed. This occurs when the amount of protein produced by both the alleles is just sufficient for normal function, when one allele is mutated, the protein produced by the allele becomes insufficient for normal function, leading to the phenotype, which could be a diseased state.

Such inheritance can also occur when a mutated allele produces a new protein that has a deleterious effect on the normal function of a cell.

1.3.2 Autosomal recessive inheritance

This mode of inheritance occurs when both alleles of a gene carry mutations that results in a phenotype, Mutations in one of the alleles does not express the mutant phenotype because enough protein is produced by the allele to continue normal function. Individuals which carry such mutations are called carriers.

1.3.3 X-linked inheritance

This kind of inheritance refers to conditions that are caused by mutations on the X-chromosome, any mutation in this chromosome expresses its phenotype in the males, while females usually remain carriers, because they have two copies of X-chromosomes, and one normal copy of the gene is usually sufficient to mask the deleterious effect of the other copy.

1.3.4 Mitochondrial inheritance

Mitochondrial are cellular organelles which possess their own genetic material. During fertilization, the male sperm does not contribute any mitochondrial DNA to the embryo. (all of the cytoplasms comes from the female). Any defect due to mutations in the mitochondrial DNA follows a maternal pattern of inheritance. Defects in mitochondria generally affect the process that uses energy a lot.

1.4 Brief history of allergy

The term “Allergy” was born on July 24, 1906, in the Münchener Medizinische Wochenschrift as “specifically altered reactivity of the organism”. Today, we define allergy as immunological hypersensitivity that can lead to a variety of different diseases via different pathomechanisms, and thus different approaches in diagnosis, therapy, and prevention can be taken. Several misconceptions can be delineated.

Allergology is the science regarding allergic diseases and their differential diagnoses and mechanisms. It requires clinical experience in allergic diseases, a basic understanding of the immune system in physiology and pathology, and finally extensive knowledge of environmental factors in eliciting or modulating allergic reactions. Allergy is not a disease itself, but a mechanism leading to disease.

In clinical practice, allergy manifests in form of various different conditions such as anaphylaxis, urticaria, angioedema, allergic rhinoconjunctivitis, allergic asthma, serum sickness, allergic vasculitis, Hypersensitivity pneumonitis, atopic dermatitis (eczema), contact dermatitis

1.5 What is an allergy?

An allergy is an abnormal immune response that occurs as a result of exposure to certain substances. An allergic reaction occurs when an allergen-specific antibody called Immunoglobulin E (IgE) which is produced by the immune system and binds to cells in the body, comes into contact with a specific allergen for which it is produced(Micheal Miller, M.D, 2005).

Allergies are associated with serious respiratory illnesses such as allergic rhinitis, asthma, and anaphylaxis.

1.5.1 Allergens

Allergens can be defined as any environmental agent that induced IgE-mediated hypersensitivity reactions following inhalation, ingestion, or injection (M.D.Chapman, Anna Pomes, 2003). From immunological point of view we have two types of allergy; complete allergens(true sensitizing allergens) and incomplete allergens(non-sensitizing) allergens Non-sensitizing allergens are able to interact with IgE antibodies but are unable to induce the production of IgE antibodies.

Examples of allergens include; pollen, pet dander, drugs such as penicillin, chloroquine, and sulfonamide food such as egg, milk, fish, peanut, soy, shellfish, etc.

1.5.2 Risk factors of an allergy

The following are the factors that predisposed to an allergic reaction;

• Genetic factors
• Geographical distribution
• Environmental facsocio-economic status, air pollution, climate
• Hygiene hypothesis
• Exposure to certain foods
• Exposure to antibiotics during infancy

1.5. 3 Pathogenesis of an allergy

Chapter two. Types of allergy; causes, signs and symptoms, pathophysiology.

2.1 There are four major common types of allergy;

• Allergic rhinitis
• Allergic Asthma
• Food allergy
• Atopic dermatitis

2.2.1 Allergic rhinitis

Allergic rhinitis also known as Hay fever is a type of inflammation in the nose which occurs as a result when the immune system overreacts to allergens in the air.

Allergic rhinitis is also an allergic disorder characterized by an exaggerated immune response to pollen grains and other substances.

Allergic rhinitis are of two types: Seasonal which occurs only during the time of the year in which certain plants pollinate. The second type of allergic rhinitis is perennial which occurs all year round.

Allergic rhinitis is the type of allergy that affects the greatest number of people. In western countries, between 10-30% of people are affected in a year. It is very common between the ages of twenty and forty.

2.2.2 Causes

Allergic rhinitis is caused mainly by the pollens of specific seasonal plants. The pollen that causes allergic rhinitis varies between individuals and from region to region; in general, the tiny, hardly visible pollens of wind-pollinated plants are the predominant cause. Examples of plants commonly responsible for allergic rhinitis include:

1. Trees: such as pine(pinus), birch(Betula), alder(Alnus), cedar(Cedrus), hazel(Corylus), hornbeam(Carpinus), horse chestnut(Aesculus) etc.
2. Grasses(Family Poaceae): ryegrass(Lolium sp.) and timothy (Phleum pretense).
3. Weeds: ragweed (Ambrosia), plantain(Plantago) mugwort(Artemisia Vulgaris), etc.

2.2.3 Signs and symptoms

The characteristics and symptoms of allergic rhinitis are rhinorrhea (excess nasal secretion), itching, sneezing fits, and nasal congestion and obstruction.

Physical signs include conjunctival swelling and erythema, eyelid swelling, lower eyelid swelling, lower eyelid venous stasis (rings under the eyes), Swollen nasal turbinate, and middle ear effusion.

There can also be behavioral signs; in order to relieve the irritation or flow of mucus, people may wipe or rubs their nose with the palm of their hand in an upward motion: an action known as nasal salute or the allergic salute.

2.2.4 Pathophysiology of allergic rhinitis

When the antigen enters the body system, the Antigen-presenting cells(APCs) such as the dendritic cells, process the antigen and present some peptides from the allergens on the major histocompatibility complex (MHC) class II molecules ().

This MHC class II and antigen complex serve as the ligand of T-cell receptors on CD4+ cells to allegen-specific Th2 cells. Activated Th2 cells release several cytokines, which trigger isotype switching of B cells to produce specific IgE and proliferation of eosinophils, mast cells, and neutrophils. The produced antigen-specific IgE joins the high-affinity IgE receptors on mast cells or basophils. The stimulated mast cells induce nasal symptoms by secreting chemical mediators such as histamines, prostaglandins, and leukotrienes (). The chemical mediators produced cause eosinophil chemotaxis where several inflammatory cells and T cells migrate to nasal mucosa, break up and remodel normal nasal tissue, and these processes result in nasal obstruction which is the main symptom of Allergic rhinitis patients.

2.3 Allergic Asthma

Allergic asthma is defined as a chronic inflammatory disease of the airways. Chronic inflammation is associated with airway narrowing response to allergens.

Asthma is one of the serious public health problems throughout the world, affecting people of all ages. It is estimated by the World Health Organization that 300 million individuals have asthma worldwide and that with current rising trends this will reach 400 million by 2025. Approximately 250,000 people die prematurely each year from asthma.

2.3.1 Causes

Allergic asthma is mostly caused by aeroallergens such as dust, pollen, pet dander, etc. Also, Other causes of asthma include exposure to environmental tobacco smoke, air pollution, early life respiratory viral infections, certain drugs, and stress.

2.3.2 Signs and symptoms

The characteristics and symptoms of allergic asthma include:

1. Wheezing
2. Coughing, especially early in the morning or at night
3. Chest tightness
4. Shortness of breath

2.3.3 Pathophysiology

Allergic asthma is related to T helper cell type-2(Th2) immune responses various allergens such as dust mites, pollen, etc. triggers produce a cascade of immune-mediated events leading to chronic airway inflammation. High levels of Th2 cells in the airway release specific cytokines including interleukin (IL)-4, IL-5, IL-9, and IL-13 that aids eosinophilic inflammation and IgE production by mast cells, this, in turn, triggers the release of inflammatory mediators such as histamine that causes contraction of the smooth muscle in the airways, swelling and increased mucous secretion which leads to the characteristic symptoms of asthma.

2.4 Food allergy

Food allergy can be define as the adverse immunologic response to a food protein. Many food allergies particularly allergies to milk, egg, soy, and wheat are usually outgrown within the first ten years of life(). While other food allergies such as peanut and shellfish are often lifelong, although 20% of individuals may outgrow peanut allergies.

Food allergy is also a leading cause of anaphylaxis( a severe, potentially fatal allergic reaction).

2.4.1 Causes

Food allergies can arise to any food, but the allergens responsible for more than 85% of food allergies are:

• Milk
• Egg
• Peanut
• Tree nuts
• Shellfish
• Fish
• Wheat
• Soy etc.

2.4.2 Signs and symptoms

Food allergy is associated with a variety of signs and symptoms which can involve many body systems which include the skin, gastrointestinal, respiratory tract, and cardiovascular systems.

Skin-related signs and symptoms include acute urticaria(hives), angioedema (swelling), and erythema(redness of the skin). Respiratory tract symptoms include laryngeal edema, rhinorrhea, and bronchospasm. Gastrointestinal symptoms include nausea, vomiting, abdominal pain, and diarrhea

2.4.3 Pathophysiology

The protein component of these foods i.e milk, egg, peanut, etc. leads to sensitization and allergy. The allergenic components of these proteins rend to be very small in size, water-soluble glycoproteins, and are resistance to denaturation that occur as a result of heat, or acid and therefore remain intact even after cooking or digestion. During initial sensitization to the food, the consumption of the allergenic food protein induces the production of IgE antibodies that is specific to that food which then bind to the tissue basophils and mast cells. When the food is subsequently eaten, they bind to their specific IgE antibodies and trigger the secretion of mediators such as histamine and leukotriene causing clinical reactivity and allergic symptoms.

2.5 Atopic dermatitis

Atopic dermatitis which is also known as atopic eczema is a type of inflammation of the skin It results in itchy, red, swollen, and cracked skin, clear fluid may also be coming out of the affected area which often got thickened over time. Many people with atopic dermatitis develop hay fever or asthma, although the condition may occur at any age, it usually starts in childhood and in severity over the years.

2.5.1 Causes

The cause of atopic dermatitis is unknown, although there is some evidence of genetic, environmental, and immunologic factors. In a small percentage of cases, atopic dermatitis is caused by sensitization to foods, Also exposure to allergens from the environment such as dust mites

2.5.2 Signs and symptoms

People that are affected by atopic dermatitis often have dry and scaly skin that covers the entire body, intensely itchy red, splotchy, raised lesions to form in the bends of the arms, legs, face, and neck.

Flexural distribution with ill-defined edges with or without hyperlinearily on the wrist, finger, knuckles, ankle, feet, and hand are also commonly seen.

2.5.3 Pathophysiology

The pathophysiology may involve a mixture of type 1 and type IV-like hypersensitivity reactions.

Chapter three. Diagnosis, prevention, and management of allergic diseases

3.1 diagnosis

Accurate diagnosis of allergic diseases is essential for the effective management of allergic diseases(). Allergy testing helps to confirm or rule out allergies. There are two different methods that can be used in assessing the presence of allergen-specific IgE antibodies: A skin prick test and an allergy blood test. Early and more accurate diagnoses save cost due to reduced consultations referrals to secondary care, misdiagnosis, etc.

Allergy undergoes frequent changes over time, regular allergy testing of relevant allergens helps to provide information on if and how patient management can be changed, in order to improve health and quality of life.

3.1.1 Skin testing

A skin allergy testing is carried out by using a small plastic or metal device to puncture the skin and a small amount of suspected allergens and or their extract is introduced to the sites on the skin marked with a pen or dye. Sometimes, the allergens are injected intradermally into the patient’s skin, with a needle and syringe. This test is usually carried out inside the forearm and the back.

If the patient is allergic to the substance, a visible inflammatory reaction occurs within 30 minutes. This response ranges from slight reddening of the skin to a full-blown hive. The results is usually interpreted by an allergist. A skin test has been shown to be much better than patient observation to detect allergies.

3.1.2 Patch testing

Patch testing is a method used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed reactions. It is used to confirm the cause of skin contact allergy.

It is usually carried out by using an adhesive patches that has been treated with a number of common allergic chemicals or skin sensitizer which are applied to the back. The skin is then checked for possible local reactions at least usually after 48hours of the application of the patch and two or three days later.

3.1.3 Blood testing

An allergy blood testing can be carried out by collecting the patient’s blood sample, which is then send to the laboratory for further analysis and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. The test measures the concentration of specific IgE antibodies in the blood.

Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity, and pregnancy. The laboratory methods used to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay(ELISA), radioallergosorbent test(RAST), and fluorescent enzyme immunoassay(FEIA)().

3.2 Prevention

There are different preventive measures for allergies they include:

• Early exposure to potential allergens()
• Fish oil supplementation during pregnancy and exclusive breastfeeding
• Probiotic supplements are taken during pregnancy or infancy

3.3 Management

Management of allergies involves avoiding what triggers the allergy and medications to improve the symptoms(). Allergen immunotherapy may be useful for some types of allergies.

3.3.1 Medications

Several medications can be used to block the action of allergic mediators or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine, mast cell stabilizers, and anti-leukotriene agents which are commonly used for the treatment of allergic diseases. The severity of anaphylaxis often requires epinephrine injection(). Anti-cholinergic, decongestants, and other compounds can be used to impair eosinophil chemotaxis

3.3.2 Allergen immunotherapy

Allergen immunotherapy also known as desensitization or hypo-sensitization involves exposing people to a larger amounts of allergens in order to change immune system’s response.() Allergen immunotherapy is very useful in environmental allergy, allergies to insect bites, and asthma.

Studies has shown that injections of allergens under the skin is effective in treatment of allergic rhinitis in children. The benefits of allergen immunotherapy may last for years after treatment is stopped.

There are two different types of allergen immunotherapy:

• Subcutaneous
• Sublingual

In allergen immunotherapy, the aim is to induce or restore tolerance to the allergens by lessening its tendency to induce IgE production through the administration of large amount doses of allergen that gradually reduce the IgE-dominated response. The objective of immunotherapy is to direct immune response away from humoral immunity and toward cellular immunity.

Chapter four. Inheritance and allergy

Most of the allergies are inherited. When one parent has an allergy, the child has a 50% risk of also having one, when both parents are allergic the risk of the child having an allergy increases to 75%. However, although parents may transfer the tendency to be allergic to their children, the children may not inherit an allergy to the exact allergen.

In a study that took place in Arizona in which 344 families were tested to determine if there is a link between genetics and allergic asthma. The result of the study confirmed that allergic asthma can be passed from generation to generation. From families where neither parent had a history of asthma, only 5% of the children suffered from asthma, 20% of children suffered from the condition where either the father or mother suffered from asthma, while in families where both parents had a history of asthma nearly 70% of the children as well.

Studies of the inheritance of human allergic diseases are not likely to give data that are in perfect agreement with Mendelian ratios. For some reasons;

1. It is difficult to tell whether the manifestation was brought about by definite germinal transmission or as a result of sensitization while in utero.
2. It is impossible to control the material; mating occurs as one finds them, not as one wishes.
3. Generations are long and families are not large enough to be sure that all possible combinations of genes are present.
4. Individuals possessing the predisposition may not manifest it at all or may have manifested it in a form not recognized or remembered, while in children the hereditary factor may exist, but not show as a clinical state until later in life.
5. The extreme multiplicity of types and causes and the same type arising from different. causes are a difficulty. All these factors add to the confusion in studies of inherited allergy.

4.1 Study of inheritance and allergy

The inheritance of allergy can be study under the following condition; physiologically, degree of inheritance, mode of inheritance, and sex incidence.

1. Physiology: According to Cooke and Verde it is generally agreed that it is not the specific sensitization that is inherited but rather the predisposition to develop allergic reactions, as they were the first set of people to agree to this principle. For instance, when the shock tissues, in this case, the respiratory tissues, come in contact with the allergen (the critical substance to which the shock tissues are sensitized), a specific antibody is formed in the body cells. The presence of the antibody makes the tissues of the individual permanently hypersensitive to the allergen when introduced. The weather seems to have an effect as an environmental factor.
2. Degree of inheritance: The high incidence of allergy in a family suggests strongly that an hereditary fact, or is involved in the etiology of the disease. For instance in a situation whereby there is bilateral family history i.e both parents had a history of allergy 70% of their offspring suffer from allergy while in the whereby there is unilateral family history i.e one of the parents had a history of allergy 50% of their offspring suffer from allergy.

Chapter 1. Introduction

The suspended pollen grains in the air reach the human respiratory track through inhalation, triggering a type of seasonal allergy called pollen allergy. Pollen is one of the most widespread allergies of all the things that can cause an allergy (PMD, 2017).

Airborne pollen grains are important aeroallergens that may cause allergic rhinitis and asthma in human beings (D’Amato et al., 2007). Pollen grains that cause allergy are usually very small in size and can easily reach the lower respiratory tract (Ciprandi et al., 2005). Allergic rhinitis affects 10–30 % of the global population (Pawankar et al., 2011). Various studies have evidenced the correlation between the high airborne pollen count and allergy symptoms in hypersensitive individuals. (Mandal et al., 2008)

Islamabad is among the cities with the highest pollen counts in the world. The pollen concentration is more in Islamabad as compared to other cities because of population of Paper Mulberry trees. Its population is maximum in Islamabad whereas almost negligible in other cities (PMD, 2017). A preliminary study of atmospheric pollen has been carried out by (Kazmi et al., 1984). A preliminary study of atmospheric pollen also has been carried out in Islamabad (Perveen et al., 2007).

In last five years, the Pollen count is high in Islamabad during the Period of March and April here is the Panted value of the pollen count of last five years (Fig 1).

Fig 1 (Panted value of pollen count of last five years)

Airborne pollen data varies from place to place due to floristic diversities in a geographical region. This data helps to identify the types and count of air spora present in the atmosphere of the study area. Climatic conditions of an area may also aid in increasing the incidence of bronchial allergies as plant growth, dispersion, and quantity of pollen grains are directly correlated with weather conditions of the area (D’Amatoet et al., 1998). Pollen calendar also aids in the appropriate diagnosis of aeroallergens (Puc et al., 2002).

Due to expansion of allergic plants caused by increased carbon dioxide concentration in the air (Ihler et al., 2015). This is most frequently caused by allergens such as pollens from trees and grass. Symptoms of allergic rhinitis and allergic asthma often coexist and it is postulated that they represent a response to the same allergen from upper and lower airways, together named chronic allergic respiratory syndrome (Togias et al., 2003).

Most abundant pollen types in Islamabad are from 08 trees (Paper Mulberry, Acacia, Eucalyptus, Pines, Grasses, Cannabis, Dandelion, and Alternaria). Out of all these plants Paper Mulberry shares about 97 percent of the Total Pollen Count (TPC) during spring season. This calculation was made from daily pollen count data available for the period 2003-2016. Data analysis revealed that concentration of Paper Mulberry grains in the atmosphere resulted in pollen allergy-related diseases. National Institute of Heath Islamabad (NIH) concluded that paper mulberry was the cause of widespread allergy in the city and its neighboring towns (Bennet et al., 1997).

The same inflammatory response is observed in nasal mucosa of patients with allergic rhinitis and bronchial mucosa of patients with asthma. In both of these situations, infiltration by Th2 cells is present (Togias et al., 2003). Less is known about changes in Th17 cells caused by natural seasonal allergen exposure. Systemic reaction caused by contact with allergen has been widely investigated in many studies; however, the immunological mechanisms leading to primary and secondary responses still remain unclear. T cells appear to be strongly involved in this process and its subsets may differ depending on antigen stimulation. The CD45RA marker is characteristic for naïve cells, which proliferate when stimulated with antigens, while the presence of CD45RO is characteristic for memory cells, which proliferate during re-call antigen stimulation (Plebanski et al., 1992).

Changes are also observed depending on whether stimulation is caused by perennial or seasonal allergen. Dust mite-specific cells from mite-allergic patients are mostly of the central memory phenotype, while specific T cells from birch pollen-allergic patients have features of effectors memory cells (Wambre et al., 2011). However, less is known about changes in central memory and effector memory cell subsets in these patients. In particular, studies describing the changes caused by pollen exposure in T cell subpopulations of patients suffering from allergic rhinitis are required. Interestingly, expression of surface antigens CCR4, CXCR1, and CD62L on memory cells increases during pollen season only in symptomatic atopic patients. Explaining the lack of symptoms in patients with asymptomatic skin sensitization and healthy control (Assing et al., 2006).

This was to determine whether natural seasonal allergen exposure causes changes in the percentage and immunological status of T cell subsets in patients with allergic respiratory syndrome. Further, characterize activation of T cells in this condition; production of cytokines by these cells was assessed (Assing et al., 2006).

Haroon and Rasul (2008) reported that the paper mulberry tree has been the focus of attention ever since pollen allergy was first recognized as a threat to human health in Islamabad. Most of the people who suffer from severe allergy symptoms, like asthma attacks, are allergic to the pollen of paper mulberry (Haroon et al., 2008). According to the World Conservation Union, paper mulberry is one of the worst plant invaders in Pakistan (IUCN, 2004).

Chapter 2. Review of literature

Allergic rhinitis (AR) is among the most common diseases globally and ranks first in Europe (over 25percent of the European population). Along with the rapid economic growth and urbanization, the severe and deteriorating regional haze has smothered the eastern region of China. The health effects caused by outdoor air pollution have become a sensitive topic for the public, media, and even the government of China and adjacent countries. The need for a better comprehension to the role of ambient air pollution on human health and implementing of suitable protective policies has fueled related studies in the past decade. A number of adverse health effects, including non-accidental death, respiratory diseases (such as rhinitis, asthma, tracheids, pneumonia), cardiovascular diseases (such as stroke, arrhythmia, ischemic heart disease, cerebrovascular disease), cardiopulmonary diseases (chronic obstructive pulmonary disease, COPD) and, more rarely, conjunctivitis, dermatological disorders, skin allergy and exacerbated cough are associated with ambient air pollution (Zhang et al., 2015).

Most studies regarding respiratory diseases have addressed asthma and COPD, and only limited studies have focused on allergic rhinitis (AR) in China. As a typical respiratory illness, AR affects 20–40percent of the population worldwide, although the prevalence varies with age and region (Greiner et al., 2011-2013). Although it is usually a minor respiratory disease, AR frequently presented with symptoms that affect work performance and quality of daily life and consumes health recourses (Schoenwetter et al., 2004).

According to the Allergies in Asia-Pacific Survey, one of the largest studies of AR on adults and children in Asia, the prevalence of AR was 8.7% in Asia. The prevalence of self-reported AR in adults is much lower in China than in many Western and developed/developing countries (such as Japan and Korea). The age- and gender-adjusted incidence of AR was approximately 14percent in China, ranging from 8.7 percent (Beijing) to 24.1percent (Urumqi). The prevalence of AR for adults was 11.2percent and 15.7percent in Changchun and Shenyang of northeastern China, respectively (Katelaris et al., 2012).

Many plant species are responsible in aggravating pollens allergy by producing pollen that includes Broussonetia papyrifera, Alternanthera pungens, Cannabis sativa, Eucalyptus globules, Grasses, and Pinus sp. It is revealed that percentage of woody taxa in the atmosphere results in pollen allergy-related diseases (Parveen et al., 2012; Ozturk et al., 2013)

In India study have shown that Mulberry tree pollen is a major aeroallergen in northern regions of India(Singh et al., 2003). Already in the early seventies, mulberry tree pollen was considered to cause respiratory allergy in the US (Targow, 1971). Ozone was also associated with AR in children who reside in industrial areas of China (Kim et al., 2011). Moreover, the short-term effects of air pollutants on human health showed seasonal variations with the change of human activity and meteorological factors (Peng et al., 2005).

Chapter 3. Materials and methods

Collection of data

For the Collection of data, I visited Pakistan Meteorological Department Islamabad (PMD). Pakistan Institute of Medical Sciences (PIMS); National Institute of Health (NIH); Federal Government Services Hospital (FGSH). Pakistan Meteorological Department Islamabad (PMD) provides me the information about pollen allergy

The questionnaire contained a separate set of specific questions for those who claimed to have had suffered from allergy symptoms. Questions were asked in view of the availability of the skin tests carried out at the Allergy Center at the National Institute of Health (NIH).

The questionnaires were given in to the following medical centers and related institutions: Pakistan Institute of Medical Sciences (PIMS); National Institute of Health (NIH); Federal Government Services Hospital (FGSH); and Pakistan Meteorological Department (PMD).

From the three major hospitals, responses were attained from PIMS and FGSH, and NIH. Doctors who provided incomplete information or required further elaboration on any particular question were further contacted in person face to face or on telephone. Thus, information was obtained on the factors associated with pollen allergies, as well as, possible solutions for its eradication, including both preventive and curative measures. A separate detailed record of the patients who sought medical advice for purposes of allergy treatment could not be obtained. Therefore, information on variables like the sex of the patient, age, or place of residents is not available from the data collected from the medical centers. In addition, Pakistan Meteorological Department was contacted to provide any information pertaining to the association between the prevailing environmental conditions and pollen allergies.

Test for diagnosis of allergies

Knowing exactly what you are allergic to can help you lessen or prevent exposure and treat your reactions. There are several tests to pinpoint allergies:

Allergy skin testing

Allergy skin testing is considered the most sensitive testing method and provides rapid results. The most common test is the “prick test,” which involves pricking the skin with the extract of a specific allergen, then observing the skin’s reaction.

Serum-specific IgE antibody testing

These blood tests provide information similar to allergy skin testing

How to perform a test

The test used to ascertain the source of allergies is a standard skin test used at the NIH and involves the placement of a drop of a mixture of 25 pollen antigens, prepared at the NIH, on the skin surface under the forearm. Using a sterile needle the antigen is scratched into the surface of the skin and the excess is removed using tissue paper. The patient is kept under observation for 20 minutes. Those positive for pollen allergies are confirmed by signs of erythematic or urticaria in the inoculated area.

Chapter 4. Results and discussion

Results

Analysis of the data collected from the people reveals that of the total 60 patients respondents included in my research, 42 (70%) informed having suffered from one or more of the symptoms associated with some form of pollen allergy during the months of January to April (Pie Chart 1). The medical report of each respondent was seen by the interviewer, to confirm that the respondent had suffered from pollen allergy symptoms.

Pie Chart 1: Percentage symptom distribution

• Variables
• No of Patients and Percentage (%)
• Age of respondent

1. 10-19 years
2. 8(13.33)
3. 20-29 years
4. 26(43.33)
5. 30-39 years
6. 12(20)
7. 40 plus
8. 14(23)

• Gender of respondent
• Male

1. 24(40%)

• Female

1. 34(60%)

• Previous place of residence
• Lived in other parts of Islamabad

1. 28

• Always lived at present place
• 20

1. Live in outside Islamabad

• 12

1. Occupation
2. Private

• 25

1. Public

• 5

1. Housewife

• 10

1. Students/Others

• 20

Table No 1: Allergy distribution sex, gender, age, and occupation vise.

The percentage distribution of the respondents suffering from allergy symptoms by age shows that persons aged 25 years or above were at the highest risk of contracting the allergies. This finding is supported by a senior doctor at the allergy clinic, PIMS, who also found that older persons were more susceptible to contracting pollen allergies compared to young children. However, as is known allergies are not infectious but a disease of the immune system, implying that the older persons included in this study, which were suffering from allergies, were perhaps those who may have had a weekend immune system.

Sex-wise, the percentage distribution of morbidity shows that 60% of the allergy patients were females compared to 40% of males (Table1). Many of these respondents, as indicated above, were older and shared the belief that these illnesses were a recent phenomenon. They were of the opinion that the pervasiveness of the illness was increasing by every year regardless of age and sex. On inquiring about what in their opinion were the causes of these illnesses, most perceived unhygienic living conditions, lack of clean water, and impure food to be the major contributory factors. A few also spoke of the widely propagated opinion that greenery in Islamabad was spreading allergies, a claim refuted by older respondents who said Islamabad was always this green without any allergies in the past.

Symptoms of Allergies

Analysis of the data on various symptoms of allergies shows that of the 33% of respondents suffering from one or more allergy symptoms, 70% experienced the common and simultaneous symptoms of sneezing, running nose and watery, red itchy eyes, followed by constant running and itchy nose (Graph 2). Amongst the symptoms, the more severe cases were found to be those suffering from asthma, other breathing problems, or congestion in the chest (14%).

Graph 2 Percentage symptoms Distribution

As the graphical presentation shows, the figures are high for each allergy, indicating that most of the allergy patients suffered from more than one type of allergy symptom. Results show that about 30% of the respondents suffered from other symptoms along with those already mentioned. The most common problems identified in the category of ‘others’ were headaches, cough, and tiredness.

A variety of non-genetic factors may also play an important role, such as the quantity of exposure, nutritional status of the individual, and the presence of chronic underlying infections or acute viral illnesses9. This factor may also be true for our study where the incidence of allergies was reported to be higher among females. Rural girls/women often work for hours in the fields where the quantity of exposure may be high. In addition, the nutritional status, especially among children, in developing countries like Pakistan is rather poor.

Duration of illness and medical advice sought

Graph 3 presents the incidence of illness by each month of the year and confirms the finding that allergy-related illnesses are at its peak during the months of February and March. As many as 42% of the respondents reported having contracted one or more spring allergies during the month of March alone.

Graph 3 Percentage distribution of the incidence of illness by months

The percentage of the patients declines to a little more than half (29%) during the month of April, followed by a sharp decline in May, leading to negligible cases thereafter. Statistics obtained on allergies in Islamabad indicate a sharp rise in the incidence this year compared to last year. More than half (58%) of the study population suffering from pollen allergies had experienced the symptoms either a season before or the spring this year. Fifteen percent and 18% continued to suffer from allergies, during the spring season.

Pie Chart 2 Allergy symptoms appear season vise

About 66% are suffered in spring season, 4% are suffered in autumn season, 11% in the Winter season, and approx 2% in the summer season are suffered from allergies. From these people, about 17% are those who are suffered all year around.

Discussion

Results of the study conducted in Islamabad, show that of the total 60 respondents, 82% suffered from pollen allergies during the study period of January through April 2017. The findings indicate that most of the patients contracted more than one symptom of allergy and that, more interestingly, the pattern of the symptoms of allergies varied by place of residence. Analysis shows the incidence of pollen allergies to be comparatively more widespread amongst residents of Islamabad with the highest percentage of patients suffering from asthma, difficult breathing, or tightness in the chest. Overall, the most common symptoms of pollen allergies were sneezing/running nose/and itchy, watery eyes, and as high as 70% of the study population suffered from these illnesses. Another important finding of this study reveals that a substantially greater number of females contracted pollen allergies compared to men.

The time of release of pollen grains and identification of their type is useful information for patients suffering from allergic diseases (Scevkova et al., 2010). Broussonetia papyrifera was found to be vulnerable in causing sensitization amongst residents of Islamabad city. Vegetation-covered area correlates significantly with the prevalence of allergies (Khan et al., 2010).

Stratification of the illnesses contracted by age shows that persons at the highest risk of developing allergy-related illnesses belonged to the age bracket of 40 years. Most of the patients developed allergies in the months of March and April and 35 to 50% of them continued to suffer from the illnesses for more than 2 months.

In particular, modifications in pollen and allergen production related to climate change has increased the incidence of illnesses related to asthma and allergies (Shea et al., 2008). On the causes of this widespread morbidity in Islamabad, very few investigations has been conducted so far, primarily leading to inconclusive identification of the allergens or other factors contributing to the pervasiveness of the illnesses. However, many doctors conclude that specific plants and trees which have been identified to trigger pollen allergies are not the only sources. There can be multiple allergens in the environment leading to a high incidence and allergies can occur due to other environmental factors. While the research carried out by PIMS and presented at the International Environment Conference in Islamabad, specifically identified 3 major allergens for most allergies, namely, Bermuda/American Grass (67%), followed by pollens of Bhung (Cannabis sativa) and Paper Mulberry pollen, with the severity of the allergy being in the reverse order.

We observed that the optimum temperature supported the highest pollen numbers in the air of Islamabad city and same is observed when spring pollen count is found highest (Recioet al., 2009).In Norway subjects in summer had higher IgE levels than in other seasons of the year (Omenaas et al., 1994). Probably due to pollen exposure during the summer season another study reported 45% patients of allergic rhinitis to be sensitive to tree pollens and 48.7% to grass pollens (Anwar and Bokhari 2002).A number of studies have attempted to evaluate the correlation between prevalence of pollen and allergic diseases(Behbehani et al., 2004). Only one case of pollinosis to Broussonetia papyrifera has been reported in Italy (Zanforlin and Incovaia, 2004)

Summary

Pollen is fine to coarse powdery substance comprising pollen grains which are male micro gemetophyte of seed plants, which produce male gametes(sperm cells) Nasal allergy to pollen is called pollinosis, and allergy specifically to grass pollen is called hay fever. Generally, pollens that cause allergies are those of anemophilous plants (pollen is dispersed by air currents.) Such plants produce large quantities of lightweight pollen.

Seasonal allergic rhinitis, or hay fever, is an allergic response to pollen. It causes inflammation and swelling of the lining of the nose and of the protective tissue of the eyes (conjunctiva). Symptoms include sneezing, congestion (feeling stuffy), and itchy, watery eyes. Treatment options include over-the-counter and prescription antihistamines, anti-leukotrienes, nasal steroids, and nasal cromolyn. Some people may have allergic asthma symptoms (wheezing, shortness of breath, chest tightness) caused by exposure to pollen.

The present study was planned to determine the effect causes and higher concentration of pollen allergy in Islamabad region. I visited the Pakistan Institute of Medical Sciences (PIMS); National Institute of Health (NIH); Benazir Bhutto Hospital (BBH). The study was conducted from February 2017 to June 2017. The data were collected from 100 people who was suffered from those symptom which are common in pollen allergy patients. The groups range according to age vise 10 to 50 years and above residing in different localities of Islamabad. Various tests were performed to for the confirmation of allergy in these hospitals. These tests are allergy skin tests, and serum-specific IgE antibody tests. On the view of these tests 60(80%) are suffered from one or more symptoms which are showing that they are allergic patients. Few questions were asked from these people for the diagnosis of cause and effect according to season vise. Results of the study conducted in Islamabad, show that of the total 60 respondents, 82% suffered from pollen allergies during the study period of January through April, 2017. . Analysis shows the incidence of pollen allergies to be comparatively more widespread amongst residents of Islamabad with the highest percentage of patients suffering from asthma, difficult breathing or tightness in the chest. Overall, the most common symptoms of pollen allergies were sneezing/running nose/and itchy, watery eyes, and as high as 70% of the study population suffered from these illnesses. Another important finding of this study reveals that a substantially greater number of females contracted pollen allergies compared to men.

Symptom Appear

• Number Of Patients

Year Around Summer Winter Autumn Spring 9 1 6 2 35

• Percentage Symptoms Distribution

Sneezing, running nose, watery, itchy eyes Nasal Congestion Asthama Breathing Problem tightness in the chest, chronic of cough Poor sense of smell headaches Ear Infection Ithicng on skin Others 42 8 3 2 5

• Percentage Symptoms Distribution

Sneezing, running nose, watery, itchy eyes Nasal Congestion Asthama Breathing Problem tightness in the chest, chronic of cough Poor sense of smell headaches Ear Infection Ithicng on skin Others 42 8 3 2 5

• Percentage distribution of the incidence of illness by months

January February March April May June July August September October November December 0.0333 0.05 0.35 0.2833 0.01 0 0.01 0.1 0.2 0 0 0 Months

Having an allergy to peanuts is characterized by serious anaphylactic reactions, which usually has lifelong persistence. In the United States of America, tree nuts and peanuts are among some of the most common food allergens that produce an anaphylactic reaction in humans. This fact is concerning because seemingly harmless substances like dust, gluten, milk, and shellfish should not be of concern to people. If one were to also look at the difference between rates in the United States versus the rest of the world, they will notice a drastic difference in the prevalence of allergies between the two. This begs the question, why is there an alarming rate of food allergies in the United States of America? Along with that, what can everyone do to relieve the symptoms of this hypersensitivity reaction or even prevent it for the next generations to come? In order to get to the root of the problem, scientists have begun to look into these questions a bit deeper. Interestingly enough, even though the fat content is higher in peanuts, it is not the cause of the allergic responses. Most allergens from foods come from the protein component, like gluten. Specifically, food allergists and other researchers have found specific proteins within peanuts that can trigger these immune responses in peanut-allergic persons.

Researchers have found that five of the thirty proteins related to clinical reactions of differing severity; Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. Ara h is associated with the botanical name, Arachis hypogaea and the number next to the h tells you each component. Peanut allergic individuals, they may be allergic to one or more of these proteins. Three of the peanut proteins, Ara h1, Ara h2, and Ara h3 have been most closely linked to serious peanut allergy responses. Ara h 1, 2, and 3 are storage proteins that are heat-resistant and are present in individuals with potentially severe peanut hypersensitive reactions. Out of all of the five proteins that can cause potential hypersensitivity responses, the peanut component Ara h 2 has proven to be the most important predictor of clinical allergies. This specific peanut protein was remarkably more specific than whole peanut extract, used in skin testing or in laboratory blood testing for specific peanut IgE, in the process of distinguishing a clinical peanut allergy.

Another method that can be used is molecular allergy component testing. Molecular allergy component testing has shown to undergo cross-reactivity amid allergens and detects elevation of sIgE to a certain allergen. In general, IgE binding to a specific protein component suggests there is a genuine allergy. These studies have also found that the Ara h 2 measurements are remarkably more precise in determining a true peanut allergy. Ara h 2 shares common IgE-binding epitopes with several types of nuts, which can contribute to the high number of occurrences.

In most people, the immune system learns to accept that the food is foreign and is no real threat to the person. However, in some individuals, the immune system produces a defense against the allergy called an antibody IgE (Immunoglobulin type E). This result is most likely due to the individual’s genetic background. Immunoglobulin E will target one or more of the protein components in peanuts. The antibodies will circulate in the bloodstream, then attach themselves to cells called PMLs or PMNs that are responsible for allergic responses. One type of polymorphonuclear leukocyte are called mast cells which live in the skin, respiratory tract, and gastrointestinal tract. Another example of an allergy cell is called basophils, which live in the blood. Once the antibodies are attached to the surface of the immune cells, the proteins bind to them, causing a chain reaction which triggers the release of histamine (from basophils and mast cells) and other substances from the polymorphonuclear leukocytes. The released materials may cause any conjunction of itch, urticaria, wheezing, swelling, vomiting, red eyes, uterine cramps, runny nose, abdominal pain, low blood pressure, diarrhea, and even death. This combination of symptoms is directly correlated to what is known as a type I hypersensitivity reaction or an immediate hypersensitivity reaction.

A researcher named Klemans went a step further and analyzed the diagnostic value of sIgE to Ara h 2 in order to predict peanut allergy without an oral food challenge. His findings indicated that Ara h 2 testings could differentiate peanut allergy almost equally as well as combining testing for specific IgE to peanut, skin prick testing, and patient characteristics. Along with this, it could reduce the need for food challenges by up to fifty percent. His partner, Dang, designed a study to validate the ability of Ara h 2 to predict an allergy to peanuts and to avoid the need for an oral food challenge in a population-based setting. They had also confirmed that Ara h 2 measurements were more accurate in distinguishing true peanut allergy. “Co-sensitization to Ara h 2 and Ara h 6 was associated with grievous reactions distinguishing severe allergy from mild symptoms,” the team wrote in the European Journal of Allergy and Clinical Immunology. “The sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut-specific IgE,” the authors explained. “We report that when using a combined approach of plasma specific IgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two-thirds.” Therefore, specific binding of the Ara h2 protein is a clear indicator of an allergy. A year later, a third study was published in the Journal of Allergy and Clinical Immunology and reached a similar conclusion. In this study, they found that specific IgE to Ara h 2 alone could predict fifty percent of all peanut allergies and that incorporating this observation into allergy diagnosis could reduce the need for peanut challenges by at least fifty percent.

Allergy skin testing detects an allergen antibody on mast cells. ImmunoCAP allergy blood tests detect an antibody that is floating in the blood. Both of these allergy test types are valid because they provide two different ways of assessing the same problem. In some instances, your allergist may need to do both types of tests to better comprehend your peanut allergy issue. In some people, the ability of these antibodies to cause symptoms becomes weakened as a protective factor; This is known as tolerance. In peanut allergic persons, the allergy tests will present a positive result, yet that person can eat peanuts without any complications. For this individual, the positive peanut allergy test reflects a “peanut sensitivity,” not a clinically relevant “peanut allergy.” On the other hand, someone with a positive skin test who has had symptoms presents both “peanut sensitivity” and clinically relevant “peanut allergy.” When we begin to investigate nurture, we can see a link to how an allergy like this may develop.

After extensive research, scientists have found that this risk was the highest in mothers who consumed peanuts two or more times per week throughout their pregnancy. The number of peanuts eaten as the mother breastfeed showed the same trend, yet it was not statistically significant to this study. As a result of this study, the group of highly allergic families and their infants having a child with high (potentially serious) peanut allergy blood test score by 15 months of age was greatest in mothers who ate peanuts more than 2 times per week throughout their pregnancy. This leads to the question of genetics and how it may have an impact.

Genetic factors most likely play a role since siblings of a peanut allergic child have a four-fold increased chance of developing an allergy to peanuts. However, genetics cannot be the sole problem. For instance, in rural areas of China peanut allergies are rare. Alternatively, in westernized regions of China, such as Hong Kong, the rate of peanut allergies is almost as high as they are in the United States. It has been suspected that this is due to the “hygiene hypothesis”. The hygiene hypothesis is a theory that suggests that westernized children’s reduced exposure to both serious infections and the environment allows their immune system to more readily develop allergic responses to foods and environmental substances. According to this theory, priming the immune system at an early age will help to fight off serious infections that may suppress the immune system’s ability to develop an allergy later in life. This theory has not yet been proven, though there are several examples of how this is believed to be true.

At this time, there are no cures for peanut allergies. Among the several available autoinjector products are the EpiPen, the Adrenaclick, and Auvi-Q. The unequivocal treatment for a child experiencing a type I hypersensitivity reaction to peanuts is injectable epinephrine. All deliver epinephrine intramuscularly, which takes full effect in approximately 8 minutes and reverses more than 90% of systemic reactions. Each product is available loaded with a smaller epinephrine dose for children weighing less than 30 kg. Auvi-Q has the unique ability to voice-activate and instruct the user to deliver the medicine. Delivery of epinephrine via a sublingual tablet is now being studied for the treatment of type I hypersensitivity reaction. In order to use an EpiPen, one does not need a prescription in order to use it. Specifically, while one has to obtain an EpiPen from a primary care provider they do not need to have proof from someone who is experiencing an anaphylactic reaction to administer the medicine to them unless they are an infant.

Today, researchers are also testing to see the effectiveness of immunotherapy which is theorized to lead to the desensitization of the allergen to the person over time. Recent trials have shown the benefit of oral immunotherapy and sublingual immunotherapy. In producing significant tolerance to peanuts in peanut-allergic individuals. It is not unrealistic to hope that in the near future, children with peanut allergy and their parents no longer will have to fear accidental contact or ingestion of peanuts. While molecular allergy testing may not completely eliminate the need for office oral food challenges for patients with unclear peanut allergy, for now being able to diagnose and predict peanut allergy can be as simple as Ara h 1, 2, and 3.

Education by a health care professional is vital for all parents of children with a peanut allergy so that they can learn to avoid accidental peanut exposure. Having a caregiver who is trained in label reading and avoiding foods from places outside of the home, where ingredients are ambiguous, is a high priority in preventing a serious response to peanuts. There is a potential danger of hidden peanut proteins in foods commonly seen in social situations, like birthday parties, Halloween candy, and sauces. Thus, parents have to be diligent in notifying other adults of the food allergies their children are susceptible to and the degree of danger it could cause.

In conclusion, peanut allergies are an increasing problem in the United States of America. When one compares the rates of food allergens to other non-westernized countries, like Israel who feed young children Bamba, allergists can create a solution for future generations. With the use of proper education of nutrition throughout gestation and infancy, other preventative measures, and treatment plans for those at risk for an adverse reaction, the rate of serious immunologic responses can be decreased. Now that scientists have identified the specific proteins causing such cascades, hopefully, solutions can be created for future generations. Further investigation of the hygiene hypothesis is necessary in figuring out whether or not nature and or nurture is to blame. Should Americans go back to their ancestor’s way of life, in some respects, in order to create a safer environment for future generations? Or is it too late to revert back to the old ways of living?

Cow’s milk protein allergy

Abstract

Cow’s milk protein allergy (CMPA) is caused by an immune-mediated response to milk proteins and tends to present during the first year of life. This response can vary greatly from an immediate reaction within 2 hours of ingestion to a more delayed reaction which can occur anywhere between 2 to 72 hours later. Overdiagnosis can lead to an unnecessary elimination diet but a delay in diagnosis can cause child and parental distress. It can also be confused with lactose intolerance which is a non-immune mediated response as a result of enzyme deficiency. We review diagnosis and management in this article along with future directions.

History

Drinking animal milks surfaced into the human diet around 10,000 years ago when cattle began to be domesticated. However, the first reactions to dairy were not described until 2,500 years ago by Hippocrates consisting of skin and gastrointestinal symptoms after consumption. Fast forward to today and cow’s milk has become an important part of a child’s diet providing a source of protein and calcium. Cow’s milk protein allergy (CMPA) occurs due to an immune-mediated response to cow’s milk proteins. These can be classified into IgE-mediated reactions which occur within minutes of exposure to non-IgE mediated reactions which occur hours after ingestion. Mixed forms consisting of IgE and non-IgE mechanisms can also exist.

Epidemiology

CMPA is one of the most common food allergies in the developed world affecting up to 2-7% children in early life. This reduces to 0.5% in exclusively breast-fed infants. The wide variation in prevalence is likely due to different methods of diagnosis and assessment of allergy. Self-reporting results tend to be higher compared to strict food challenge criteria. The Euro-Prevail birth cohort study found incidences of challenge-proven CMPA ranging from 1% in the United Kingdom (UK) and the Netherlands to less than 0.3% in Lithuania, Germany, and Greece in children under 2 years of age. As the natural history of CMPA is one of resolution, analyzing epidemiological data can be difficult. Therefore, the true prevalence probably lies between 2-3% of children.

Pathogenesis and Classification

Classification of CMPA according to mechanism and spectrum is displayed in Figure 1. IgE antibody-mediated or type 1 hypersensitivity reactions occur when an allergen processed by an antigen-presenting cell causes a naïve T cell to become activated to a T helper type 2 (Th2) cell. This Th2 cell produces cytokines which stimulate the B cell to produce IgE antibodies specific to an antigen/allergen. Mast cells and basophils coated by IgE antibodies are now ‘sensitized’ to the allergen. On re-exposure, the allergen binds to the IgE molecules and cross-linking occurs which causes degranulation and release of chemical mediators including histamine, cytokines, leukotrienes, prostaglandins, and tryptase. These cause the wide myriad of clinical features seen and tend to be immediate. They can be limited to one organ like the skin causing urticaria or angioedema to multisystem causing anaphylaxis.

Non-IgE mediated allergy is a delayed cell-mediated type 4 hypersensitivity reaction. This occurs when T helper type 1 cells (Th1) recognize allergens and activate macrophages to produce lytic enzymes and cytotoxic T cells which directly attack host cells causing inflammation. The mechanisms of non-IgE mediated allergy are less well understood and it is thought that other antibody-mediated mechanisms might also be involved.

**talk about FPIES and others here

Figure 1: The spectrum of CMPA

Course

CMPA carries a good prognosis. Studies have shown 2/3rd are tolerant by school age. However, later studies suggest tolerance can also be achieved in adolescence. Non-IgE mediated allergy will resolve earlier than IgE mediated allergy. The predictors of persistence include IgE-mediated allergy, reaction to baked milk on first challenge or exposure, presence of other food allergies especially egg, asthma, and allergic rhinitis.

Diagnosis

History and Examination

IgE-mediated reactions can present with urticaria, angioedema typically of the eyes and lips, and gastrointestinal symptoms like diarrhoea and vomiting. The severe end of the spectrum can include life-threatening anaphylaxis with airway, breathing or circulatory involvement. Non-IgE mediated reactions can also include cutaneous manifestations varying from urticaria to eczema flare-ups. The gastrointestinal system can also be involved including vomiting, diarrhoea or constipation. This can easily be mistaken for other conditions like reflux. Non-IgE mediated reactions can also lead to life-threatening features from gastrointestinal losses secondary to inflammation as seen in food protein-induced enterocolitis syndrome (FPIES). Table 1 summarises the symptoms that can be present in the different types of CMPA according to organ system.

Table 1: Symptoms of CMPA

Investigations

Investigations are dependent on the history and the type of CMPA suspected. The gold standard for diagnosis is a double-blind, placebo-controlled oral food challenge (DBPCFC). In clinical practice, this is not practical, especially in children. Instead, if a non-IgE mediated allergy is suspected then an elimination diet needs to be performed for 2-6 weeks to see if there is a resolution of symptoms followed by reintroduction to see if symptoms reoccur. Again, in clinical practice usually, an elimination diet is commenced to see if symptoms improve, and then this is maintained. Reintroduction is based on reassessment and whether the acquisition of tolerance may have occurred.

Suspected IgE-mediated allergy investigations include the use of serum-specific IgE (sIgE) and skin prick tests (SPT). These tend to be reserved once a referral to secondary care has been made and should only be performed with a history strongly suggestive of CMPA. A positive reaction or sensitization is defined as sIgE ≥ 0.35 kU/L or SPT wheal size ≥3mm.

Moreover, we can start to predict the likely rate of resolution or persistence through the use of component testing (see table 2).

Table 2: Milk components

• Casein (Bosd8)
• Whey

1. 80% of total milk protein
2. 20% of total milk protein

• Heat resistant
• Higher levels associated with being less likely to tolerate baked milk and persistent allergy

1. α-lactalbumin (Bosd4)
2. β-lactoglobulin (Bosd5)

• Bovine serum albumin (Bosd6)
• Extensive heating reduces allergenicity

Differential diagnosis

Management

The majority of infants and children diagnosed with IgE mediated CMPA or non-IgE mediated CMPA will need to undertake full avoidance of all cow’s milk and products containing cow’s milk. If a breastfed infant is reacting to milk protein via the mother’s breast milk, advice on Mum avoiding milk herself will be required. She will also need a supplement of 1000mg Calcium and 10 micrograms of vitamin D daily to prevent nutritional deficiencies. In formula-fed or mixed-fed infants a hypoallergenic formula prescription will be required. In weaned infants and older children, advice on excluding cow’s milk protein from the diet is essential. For suspected non-IgE mediated CMPA individuals then a cow’s milk avoidance diet should be followed for 2-6 weeks followed by reintroduction. If symptoms recur on reintroduction then cow’s milk allergy can be confirmed.

Extensively hydrolyzed formulas (ETFs) are hypoallergenic formulas that are tolerated by the majority (90%) of infants with CMPA. They are either casein or whey dominant formulas based on cow’s milk where the proteins have been extensively broken down into smaller peptides that are less well recognized by the immune system. Examples include Apatmil Pepti, Nutramigen with LGG, Similac Alimentum, and SMA Althera. Some contain lactose which can make them slightly more palatable and one contains a probiotic which has some data to support it aiding faster milk tolerance.

Amino acid formulas (AAFs) are also available on prescription. These are made synthetically and do not contain any cow’s milk protein, making them suitable for those who require halal diet. There has been some debate as to when AAFs should be used in view of their cost burden and because they may affect development of tolerance. The general consensus is that they should only be used when there has been anaphylaxis to cow’s milk protein, in Heiner Syndrome, Eosinophilic Esophagitis, and in severe gastro-intestinal and/or skin presentation, particularly in association with faltering growth. Examples include Neocate LCP/ Neocate Syneo, Nutramigen Puramino, and SMA Alfano.

Soya formula is not advised before the age of 6 months due to the phytate content which may affect nutrient absorption and the isoflavones which may have a weak oestrogenic action. In addition, 25-60% of children with non-IgE mediated CMPA will also react to soya as will a smaller percentage of IgE-mediated CMPA children too.

Calcium-fortified plant drinks can be used as a main cow’s milk alternative over the age of 2 if the child is eating a varied diet with no feeding problems and if growing appropriately. Soya is a good protein source and in the UK there is one suitable brand for children. Fortification is often low in other plant-based drinks and there is no regulation to govern this. There are no growth studies, no data on the absorption of added nutrients (except soya), and no industry regulation on checking the quality of added nutrients. Rice milk has naturally occurring arsenic and is not advised under the age of 4.5 years. Oat drink is low in lysine, an essential amino acid, and nut and seed drinks contain minimal nut/ seed and are very poor nutritionally for young children.

There is no ideal time for testing for development of tolerance. However, it is generally accepted that infants with non-IgE mediated cow’s milk allergy should remain cow’s milk free until the age of 9-12 months or for 6 months post-diagnosis. At this point a milk ladder can be commenced, these start with milk in a baked food as mixing cow’s milk in a flour matrix and heating to high temperature for a long period reduces the milk’s allergenicity. When to start and when and how to progress up the ladder should be ideally supported by a dietitian. Around 75% of children with IgE-mediated cow’s milk allergy will also tolerate cow’s milk in a baked food e.g. cake. Studies have shown that by regularly including such foods in the diets of these children helps to speed up the resolution of their allergy. This may be performed as a hospital oral food challenge or some allergy centers will allow this to be done at home.

Table 3: Brands of formula milks available in the UK for CMPA

• Product name
• Age of suitability
• Type
• Althera
• From birth
• EHF
• Aptamil Pepti 1
• From birth to 6 months
• EHF
• Aptamil Pepti 2
• From 6 months
• EHF
• Nutramigen LGG 1
• From birth to 6 months
• EHF
• Nutramigen LGG 2
• From 6 months
• EHF
• Similac Alimentum
• From birth
• EHF
• Alfamino
• From birth
• AAF
• Neocate LCP
• From birth
• AAF
• Neocate Junior
• From 12 months
• AAF
• Nutramigen Puramino
• From birth
• AAF
• Wysoy
• From 6 months

Soy

UK, United Kingdom; CMPA, Cow’s Milk Protein Allergy; EHF, Extensively Hydrolysed Formula; AAF, Amino Acid Formula

1. Prognosis and explanation to the patient
2. Follow up

• how often?
• by whom?
• how? (e.g. what tests are necessary?)
• complications and disabilities
• rehabilitation

1. Prevention

• Breastfeeding

There is no consistent evidence that breastfeeding is effective for the prevention of allergic diseases. However, breastfeeding is recommended for the many benefits it provides to mother and infant. In the UK exclusive breastfeeding is recommended for the first 6 months of life and to continue breastfeeding during introduction of complementary foods from 6 months. This may help reduce the risk of the infant developing allergies and the acquisition of tolerance, although evidence for this is low. BSACI have produced guidance around preventing food allergy and advocates the early introduction of allergenic foods like egg and peanut (see online resources).

• Probiotics

There is some evidence probiotics can be used as a preventative measure when used antenatally and postnatally to mothers in infants with a high risk of eczema and food allergy. The safety profile of probiotics is good and is one of its main attractions for its use clinically. However, there are a wide variety of commercially available products not subject to the same regulations as medicinal products. There are also many different strains and strengths available and the literature can be quite confusing at times with which one may be more beneficial in a particular condition. Therefore, without further evidence, they should be used cautiously and not routinely.

• Hydrolysed formula

Current consensus is that hydrolyzed formulas should not be used as a means to prevent allergic disease in high-risk infants.

• Online resources

The iMAP Milk Ladder. https://www.allergyuk.org/assets/000/001/297/iMAP_Final_Ladder-May_2017_original.pdf?1502804928

BSACI preventing food allergy in higher risk infants: guidance for healthcare professionals. https://www.bsaci.org/pdf/Early-feeding-guidance-for-HCPs.pdf

References

1. Flom JD, Sicherer SH. Epidemiology of Cow’s Milk Allergy. Nutrients 2019; 11: 1051.
2. Ludman S, Shah N, Fox AT. Managing cow’s milk allergy in children. British Medical Journal 2013; 347: f5424.
3. Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, Clark AT. BSACI guideline for the diagnosis and management of cow’s milk allergy. Clinical & Experimental Allergy 2014; 44: 642.
4. Schoemaker AA, Sprikkelman AB, Grimshaw KE, et al. Incidence and natural history of challenge-proven cow’s milk allergy in European children-EuroPrevall birth cohort. Allergy 2015; 70: 963.
5. Zhang GQ, Hu HJ, Liu CY, Zhang Q, Shakya S, Li ZY. Probiotics for prevention of atopy and food hypersensitivity in early childhood. Medicine 2016; 95: 1-10.

Allergic rhinitis, which affects between 10-40% of the global population and up to 40% of children in the USA (Liu et al., 2010), is a common disabling inflammatory disease of the nasal airways characterized by typical nasal symptoms such as itching, sneezing, rhinorrhoea and airway constriction (Kim et al., 2010).

Extant research has found nasal constriction to be the most dominant symptom resulting from allergic inflammation, and is indeed deemed as a critical symptom in patients presenting with allergic rhinitis (Hellings & Fokkens, 2006; Liu et al., 2010).

In the case scenario, the 4-year old patient has been diagnosed with IgE mediated allergic rhinitis, implying that the infection has an immunologic basis since IgE stands for immunoglobulin E (Burns, 2012; Hellings & Fokkens, 2006).

Recent mechanistic studies have shown that the symptoms of allergic rhinitis “…result as a consequence of allergen-induced release and/or synthesis of a variety of pro-inflammatory mediators (including histamine, cytokines, arachidonic acid metabolites, chemokines, adhesion molecules, etc) from a variety of inflammatory cells (particularly mast cells, eosinophils and T-lymphocytes)” (Liu et al., 2010 p. 1150).

Following from this juxtaposition of facts, the family needs to know that the patient may be having a hereditary condition known as Atopy, which is characterized by excessive production of antibody immunoglobulin E (IgE) in response to specific allergens (e.g., house dust, mite droppings, animal dander and certain types of pollen) that are undisruptive to most individuals (Hellings & Fokkens, 2006; Liu et al., 2010).

In terms of effect, extant literature demonstrates that once IgE is released it circulates around the body and binds itself to specific receptors such as nasal mast cells, leading to symptoms associated with asthma or allergic rhinitis (Burns, 2012).

This view is reinforced by Liu et al (2010), who argue that the production of high levels of allergen-specific IgE in certain individuals adversely interacts with inflammatory cells found in the respiratory and upper airways, particularly the nasal mast cell and eosinophils, leading to symptoms associated with asthma and allergic rhinitis.

The production of IgE is positively correlated to exposure of the mentioned allergens. The development of symptoms in patients with mild or persistent allergic rhinitis follows a similar pattern. The first step is the sensitization of the individual when nasal mast cells, eosinophils and other inflammatory cells found in the respiratory and upper airways become coated with IgE.

On re-exposure the mast cells and other cells release inflammatory mediators such as histamine, cytokines, arachidonic acid metabolites and chemokines (Burns, 2012). These mediators are responsible for the symptoms relevant to the affected organ, including sneezing, mucus production, itching and nasal constriction in allergic rhinitis, and coughing, chest tightness, wheezing and dyspnoea in asthma (Hellings & Fokkens, 2006).

The family needs to have the information regarding the management of allergic rhinitis. Extant literature demonstrates that “…reducing inflammation is a crucial aspect of managing these conditions, which explains the importance of corticosteroids in the treatment of patients with asthma and allergic rhinitis” (Burns, 2012, p. 43).

Many treatment and management guidelines recommend allergen avoidance to prevent allergic rhinitis, but this is not a comprehensive treatment strategy because the condition is triggered by many different allergens and it may be difficult to identify the specific causative agent.

The main pharmacological interventions for allergic rhinitis, according to recent evidence, include: nasal decongestants, antihistamines (topical or systematic), intranasal corticosteroids, leukotriene receptor antagonists, and specialized immunotherapy (Burns, 2012; Kim et al., 2010; Liu et al., 2010).

References

Burns, D. (2012). Management of patients with asthma and allergic rhinitis. Nursing Standard, 26(32), 41-46.

Hellings, P.W., & Fokkens, W.J. (2006). Allergic rhinitis and its impact on otorhinolaryngology. Allergy, 61(6), 656-664.

Kim, T.H., Lee, J.Y., Lee, H.M., Lee, S.H., Cho, W.S., Ju, H…Lee, S.H. (2010). Remodeling of nasal mucosa in mild and severe persistent allergic rhinitis with special reference to the distribution of collagen, proteoglycans, and lymphatic vessels. Clinical & Experimental Allergy, 40(12), 1742-1754.

Liu, F., Zhang, J., Liu, Y., Zhang, N., Holtappels, G., Lin, P., & Bachert, C. (2010). Inflammatory profiles in nasal mucosa of patients with persistent vs. intermittent allergic rhinitis. Allergy, 65(9), 1149-1157.

Although dry eye syndrome (DES) and allergic conjunctivitis (AC) are two different conditions, they share some of the symptoms and can significantly influence school performance, work productivity, and quality of life of the pediatric population. Akil, Celik, Ulas, and Kara (2015) point out that AC can assumingly lead to the tear film dysfunction; since children report symptoms of DES not as frequently as adults, it challenges the clinician’s ability to provide the right diagnosis. Thus, DES remains overlooked in children.

Furthermore, unlike in other studies, Akil et al. (2015) point out that ocular allergy might be more common in the pediatrics population than DES; AC can create an environment that leads to the dry ocular surface. The authors also indicate that the tear film BUT is closely correlated with a patient’s perception of the severity of the disease (Akil et al., 2015). It should also be noted that clinical findings indicate that subjective symptoms of the dry eye are not related to objective findings in the patient. Thus, children’s complaints about the signs of DES do not explicitly indicate that they have DES; however, they might have the dry ocular surface caused by other factors that they confuse with DES.

The authors also point out that “a long-term allergic disease with a chronic traumatic factor on the corneal epithelium could be related to keratoconus” (Akil et al., 2015, p. 470). Furthermore, chronic AC can also be included in the risk factors for myopic refractive error. As it can be seen, AC can be related to various diseases in children, including severe and progressing conditions; it can also be complicated by DES, which is frequently hard to diagnose due to a patient’s unawareness of the condition. Artificial tears can improve the discussed conditions.

Cushing Syndrome in Pediatrics

Cushing syndrome is rather rare in children; according to Stratakis (2012), 2 to 5 cases per million people per year are registered, and only 10% of those occur in children. The common cause of Cushing syndrome in children is the chronic administration of glucocorticoids or ACTH, whereas glucocorticoids are used quite frequently for treatment of various pulmonary, dermatologic, autoimmune, and other diseases.

The most common symptoms include weight gain and lack of height gain, headaches, facial plethora, hirsutism, and delayed sexual development. A low-dose dexamethasone suppression test or a 24-hour urinary free cortisol (UFC) excretion are suitable types of testing for diagnosing Cushing syndrome (Stratakis, 2012).

Almost all patients with an ACTH-secreting pituitary adenoma or Cushing disease will be referred to transsphenoidal surgery (TSS), which is effective in 90% of cases. Treatment failure can happen due to a macroadenoma or a small tumor in the cavernous sinus. Postoperative complications can vary and include transient diabetes insipidus and/or, in some cases, syndrome of inappropriate antidiuretic hormone secretion, as well as “hypogonadism, bleeding, infection (meningitis), and pituitary apoplexy” (Stratakis, 2012, p. 798). It is important to remember that pharmacotherapy can also be used in treating Cushing syndrome if other interventions were unable to help or in ectopic ACTH secretion when it is impossible to identify the source. Mitotane, metyrapone, ketoconazole, and trilostane are suggested as possible medications for controlling hypercortisolism. Nevertheless, if the source of ACTH secretion can be identified, surgical resection of the tumor is the recommended intervention. If the tumor cannot be located at first, annual screenings are necessary. Bilateral adrenalectomy is suggested if neither of the two interventions suggested above is effective or can be performed.

References

Akil, H., Celik, F., Ulas, F., & Kara, I. S. (2015). Dry eye syndrome and allergic conjunctivitis in the pediatric population. Middle East African Journal of Ophthalmology, 22(4), 467-471.

Stratakis, C. A. (2012). Cushing syndrome in pediatrics. Endocrinology and Metabolism Clinics of North America, 41(4), 793-803.