A News Letter Devoted To Practical Pediatric Practice Date April 2022

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 PRACTICAL PEDIATRICS

A News Letter Devoted To Practical Pediatric Practice

Volume 4                             Issue 4                         Date April 2022

Editor in Chief :                  

BD Gupta

Ass Editor:

RK Maheshwari

Mohan Makwana

Anil Arora

Regional Editors

Pankaj Agrawal

Avinash Bansal

Anil Jain

PC Khatri

Priyanshu Mathur

Jai Singh Meena

Adarsh Purohit

 

Editorial advisory Board

Neeraj Gupta

Manoj Jangid

Rakesh Jora

Amarjeet Mehta

Lakhan Poswal

GS Sengar

Pramod Sharma

Anurag Singh

Kuldeep Singh

S Sitaraman

 

Approach To Allergic Patient

Dr Purushotam Dan

 

Allergy is a detrimental immune-mediated hypersensitivity response to common environmental substances. The diagnosis of allergies is critically dependent on identifying the immune processes involved in the allergic response. Per se allergy is not a disease, but a mechanism that plays a role in a number of disorders. In allergy practice, clinical examination is usually unremarkable, Moreover, It is not uncommon to find allergen-specific IgE in the serum of people who do not report allergic symptoms. and therefore, clinicians need to place particular and careful emphasis on clinical history for the diagnosis of allergic disorder. Skin testing for IgE-mediated allergy is preferred over ‘in vitro’ testing because skin testing is more rapid, less expensive, and more sensitive.

 

Approach To Allergic Patient

Dr purushotam Dan

 INTRODUCTION

                Allergy can be defined as a detrimental immune-mediated hypersensitivity response to common environmental substances. The word “allergy” can mean many things to the lay person, but the clinician needs to keep in mind that diagnosis of allergies is critically dependent on identifying the immune processes involved in the allergic response. Per se allergy is not a disease, but a mechanism that plays a role in a number of disorders.

MECHANISM OF ALLERGIC REACTION: -So, allergic reaction is one of the immunological reactions. Once a reaction of immunological nature is suspected, the focus should turn towards the mechanism of the reaction. Reaction can be divided into IgE mediated [Type-1] or non-IgE mediated [Type2-4 & eosinophilic disorders].

IgE mediated reactions are caused by mast cell degranulation &  occur soon [maximum up to 2 hours] after allergen exposure. The hallmark symptom of IgE mediated reactions include pruritus, sneezing, urticaria, angioedema, bronchospasm, hypotension & tachycardia, and rarely full-blown anaphylaxis. While Non-IgE mediated reactions are usually delayed. These conditions are known as non-atopic (non-IgE-mediated). The mechanisms of non-atopic diseases are less clearly understood but some disorders (i.e., contact dermatitis) may involve a different subset of immune cells known as T helper 1 (Th1) [Type-4 hypersensitivity].

Generally, when speaking about allergy, it refers to IgE mediated [Type-1 hypersensitivity] reactions, so here we will discuss only IgE mediated [Type-1] allergic disorders.

 

TERMINOLOGY: – The term “atopy,” “sensitization,” and “allergy” are often used loosely in the medical literature, although each has a distinct and clear definition.

ATOPY: Atopy is the genetic predilection to produce specific IgE following exposure to allergens.

SENSITISATION: – Sensitization refers to the production of allergen-specific IgE. Sensitization to an allergen is not synonymous with being allergic to that allergen, because individuals may produce IgE to allergens in a given substance, but not necessarily develop symptoms upon exposure to that substance. It is unclear why some individuals demonstrate only sensitization while others have active allergic disease.

Thus, sensitization is necessary but not sufficient for the development of allergic disease because a person sensitized to an allergen may not react to it upon exposure, thus it is prudent to limit allergy testing to those allergens which are implicated in the disease by the clinical history.

ALLERGY: – Individuals are considered to have clinically significant allergy or allergic disease when they have both allergen-specific IgE and develop symptoms upon exposure to substances containing that allergen.

IGE MEDIATED CLINICAL CONDITIONS: -Allergic rhinitis, allergic conjunctivitis, allergic asthma, atopic dermatitis, food allergy & drug allergy, bee sting reactions.

 HISTORY TAKING

In allergy practice, clinical examination is usually unremarkable, and therefore, clinicians need to place particular and careful emphasis on clinical history.

 

While taking history of patient with allergy, few basic questions need to be addressed: –

1. Is presenting complaint consistent with allergy or allergic like disorder? [Symptoms associated with mast cell degranulation]
2. What could be the underlying mechanism for reaction(s)? [Temporal association with potential triggers consistent with IgE associated reaction]
3. Is there a consistent identifiable trigger(s)?

[Symptoms reappear on re-exposure to potential trigger(s)]

4. Consider past medical history as well as family history.

[Past history or family history of similar or related allergy-like disorder]

 

Characteristics of Allergy/Allergy like disorder

1. Occurs soon after allergen exposure [maximum up to 2 hours].
2. Symptom are associated with same trigger(s).
3. Possibility of Allergic disorder increase if there is Diurnal variation & seasonal variation of symptoms.
4. Night time increase of symptoms.

 

Hallmark symptoms of allergic disorders [associated with release of mediators on mast cell degranulation] [Type-1 hypersensitivity]

Itching

Angioedema

Shortness of breath

Bronchospasm & Wheezing

Vomiting

Diarrhoea

Palpitation

Erythema

Watering of the eyes

Sneezing

Nasal congestion

Urticaria

Throat itching & Tightness

Angioedema

Shortness of breath

Bronchospasm & Wheezing

Vomiting

Diarrhoea

Palpitation

Collapse

 

 

  PHYSICAL EXAMINATION

Clues on physical examination pointing toward allergy/allergy like disorders

1. Face: – Discoloration of the infra-orbital skin or “allergic shiners” may imply nasal congestion and subsequent lymph stasis [? Allergic Rhinitis/Rhinoconjuctivitis]. Extension of the mid-face or adenoid facies in children with adenoid hypertrophy [allergy may be a contributing factor in adenoid hypertrophy].
2. Eyes: – Infra-orbital crease or Dennie’s line, and a transverse crease along the lower half of the nose [Allergy Salute] and degree of injection in conjunctiva [part of Allergic conjunctivitis].
3. Ear: – Sterile fluid behind the eardrum [Secretory otitis media is often associated with allergy in children].
4. Nose: -Congestion & blue tint of nasal turbinates.
5. Lungs: -Pectus excavatum, intercostal retractions, increased anteroposterior diameter of chest, wheezing, reduced air entry all point towards possible Asthma.
6. Skin: -Xerosis, Lichenification [possible atopic dermatitis], Urticarial wheals.

 

 

 

 

 

 ALLERGY SKIN TESTING

1. A positive skin test indicates the presence of specific IgE antibodies on the surface of the mast cells in skin.
2. Skin test is either Epicutaneous [also called Prick, Puncture, and Scratch] or Intradermal. Skin testing should always start with Epicutaneous testing.
3. Method of Prick test: -After placing a drop of antigen, a sharp instrument [needle or lancet] is passed through the drop, penetrating skin at approximately 45 degree creating a small break in the epidermis. Wheal & flare develops within a period of 15-20 minutes.
4. Skin test for a few major & relevant allergens is clinically sufficient.
5. It is important to instruct patients to stay off all antihistamine preparation for a minimum of 3 days prior to the AST.
6. A positive skin test indicates only sensitization & not clinical allergy, for confirmation history should be corroborated.

 

 IN VITRO LABORATORY TESTS

 

TOTAL EOSINOPHIL COUNT: –

1. Eosinophils are often associated with allergy but more commonly, eosinophils are a peripheral marker of inflammation and are elevated in nonallergic as well as allergic asthma.
2. Eosinophils can be measured by means of an automated complete blood count or a manual total eosinophil count. The number is considered abnormal if it is greater than 7% of the total white blood count or greater than 350/ mm³.

 

NASAL SMEAR: –

1. Helpful in distinguishing an infectious process in the nose from an eosinophilic process.
2. Predominance of segmented neutrophils implies underlying bacterial infection; more than10 eosinophils/high-power field as assessed by Wright’s stain are frequent in allergic rhinitis.
3. However, as in peripheral smears, eosinophils are not specific for allergy; they can also be seen in patients with nonallergic rhinitis with eosinophilia syndrome.

 

 

 

MEASUREMENT OF TOTAL IgE: –

1. IgE is measured in international units (1 IU = 2.4 ng IgE, also 1 IU = Ku/ L].
2. Total IgE levels are age related, the level increases during childhood & around 10 years of age & thereafter maintained throughout adulthood.
3. Normal serum levels range from approximately 0 to 100 international units/ml [A new normal adult level ranged from 2 to 214 international units/mL in a study in US in 2014]
4. Though increased serum IgE is seen in allergic diseases, but it is not specific to it & also found in some primary immunodeficiencies, parasitic and viral infections, certain inflammatory diseases, as well as some malignancies also.
5. Individuals with levels of IgE greater than the upper 95 percent confidence limit often have atopic disorders, however an elevated IgE does not prove that a patient’s symptoms are due to allergy & a normal IgE Level does not exclude allergy.

 

MEASUREMENT OF SPECIFIC IgE: –

1. For in-vitro measurement of Allergen specific IgE, Immunoassays are used. They measure free specific IgE, while skin test measures Specific IgE bound to mast cells, so skin test is more clinically relevant.
2. An immunoassay is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule [allergen] in a solution through the use of an antibody.
3. These tests detect allergen-specific IgE in a patient’s serum by incubating the serum with the allergen in question, which has been absorbed on a solid-phase medium. The bound IgE is then detected with an anti-IgE antibody, which, in turn, has a label attached to permit detection.
4. Earlier because radiolabelled antihuman IgE antibody was used in the method so it was called radioallergosorbent test [RAST].
5. Now enzyme conjugated antihuman IgE antibody is used in place of the radiolabelled antibody. So now these are called ELISA Test and the term RAST is inappropriate.
6. There are various IgE Immunoassay systems in the market, e.g.  ImmunoCAP assays (Thermo Fisher Scientific/Phadia, Uppsala, Sweden), Immulite (Siemens Healthcare Diagnostics, Erlangen, Germany), HYTEC 288/Falcon (HYCOR Biomedical, Garden Grove, Calif), and Microtest allergy system (Microtest Diagnostics, London, United Kingdom).
7. In the year 2009, the clinical laboratory standards institute [CLSI] published guidelines to establish uniform reporting of allergen specific IgE results in kUA/L [or kilounits of antibody per liter] using a calibration system linked to WHO IgE standard. However, because of the use of extracts containing different allergen compositions, the inter-assay variation between manufacturers can be significant, thus results from one assay cannot necessarily be compared to the result from another system [e.g., result from ImmunoCAP-assay cannot be compared with Immulite-assay].
8. The likelihood that a positive result will correlate with clinical reactivity is influenced by the degree of positivity, the allergen in question, and the patient’s clinical history.
9. It is not uncommon to find allergen-specific IgE in the serum of people who do not report allergic symptoms. As examples, venom- and food-specific IgE have been reported in up to 25 and 60 percent of the general population respectively.
10. In food allergy, greater serum levels of allergen-specific IgE can better predict anaphylactic reaction as determined by oral food challenge.
11. A typical threshold for positivity is >0.35 kIU/L [likelihood of clinical allergy].
12. The ImmunoCAP has been shown to maintain linearity of results below this threshold and can accurately detect minute quantities of allergen-specific IgE; results can be reported down to 0.15 kIU/L.
13. Patients with higher levels of antibody are more likely to experience symptoms upon exposure to the allergen than patients with lower levels, although strong positive tests do not necessarily predict that a severe reaction (e.g., anaphylaxis) is more likely than a milder type of IgE-mediated reaction (e.g., urticaria). Furthermore, for most allergens, threshold levels above which most patients will react clinically have not been determined. A notable exception to the last statement is the utility of Phadia ImmunoCAP results for certain foods, specifically in paediatric patients, for these foods, the percentage of children with a consistent clinical history who will react to challenge has been determined over a range of food-specific IgE levels.
14. For adults, however, and for most allergens, the patient’s reactivity to the allergen must be determined by the clinical history or by a supervised challenge procedure.

 

PITFALLS OF IN-VITRO SPECIFIC IgE DETERMINATION: –

1. Many plant & invertebrate allergens are glycoproteins containing carbohydrate moieties called N-Glycans, i.e., Cross reactive carbohydrate determinants (CCDs) that interfere with in-vitro specific IgE determination.
2. These CCDs rarely cause allergic reactions but are an important cause of cross reactivity for in vitro specific IgE assays for CCD contain allergens from pollens, plant food, insect & venom. [Skin test is good alternative for circumventing this drawback of in vitro sIgE testing.
3. High total IgE levels may interfere with specific IgE determination & may cause false positive results.
4. In-vitro sIgE determination is costly, & more time consuming than skin test.

 

In conclusion,skin testing for IgE-mediated allergy is preferred over ‘in vitro’ testing because skin testing is more rapid, less expensive, and more sensitive.           

However, in-vitro testing has certain advantages over skin testing: –

1. In vitro testing poses no risk to the patient of an allergic reaction. Hence, it may be preferable in older adults with cardiovascular disease, patients with suspected sensitivities to allergens associated with severe anaphylactic reaction and patients with histories of severe reactions to minute amounts of the allergen.
2. In vitro testing is not affected by medications the patient may be taking, with the possible exception of omalizumab.
3. In vitro testing may be better for patients with certain skin conditions, such as severe and widespread atopic dermatitis or dermographism.

 

 

 CONCLUSION

1. Approach to the allergy patient has its culmination in the discussion of the findings with the patient.
2. Efforts should be made to express optimism that allergic conditions are almost always reversible and controllable.
3. There are many myths and misconceptions among the general population concerning allergy.
4. Adequate time should be given to parents to counsel and explain in simple language about the findings, plan, and prognosis for the patient.

 

REFFERENCES: –

1. Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL &  others, American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008 Mar;100(3 Suppl 3):S1-148. doi: 10.1016/s1081-1206(10)60305-5. PMID: 18431959.
2. Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S73-80. doi: 10.1016/j.jaci.2009.11.017. PMID: 20176269; PMCID: PMC2847274.
3. Hamilton RG, Franklin Adkinson N Jr. In vitro assays for the diagnosis of IgE-mediated disorders. J Allergy Clin Immunol. 2004 Aug;114(2):213-25; quiz 226. doi: 10.1016/j.jaci.2004.06.046. PMID: 15316492.
4. Sampson HA, Ho DG. Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J Allergy Clin Immunol. 1997 Oct;100(4):444-51. doi: 10.1016/s0091-6749(97)70133-7. PMID: 9338535.
5. “Text Book of Allergy for Clinicians” PK Vedanthan, CRC Press.