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April 6, 2017

Earliest age to start skin testing

Question

What is the earliest age at which allergy skin testing can be performed? Ror example, a 5-month old child of both atopic-asthmatic parents came to me for prolonged cough after a respiratory tract infection. The cough prominently is night time although it also occurs during the day. After starting montelukast there is substantial relief in cough, blood investigations are normal. Now I want to do allergy skin testing for the baby for common aeroallergens, should i go forward or not.

Answers

By Prof Larenas-Linneman

When thinking about any testing, the first question is safety. Concerning skin prick testing in children this is a very safe procedure with no anaphylaxis reported in the literature till now. However, intradermal testing has to be done with much more care, as the has been one report of a fatality in a child with cow’s milk allergy being tested with an ID test in the 1st half of the 20th century.(1) It is a procedure that causes some pain and discomfort, though. Thus, then the 2nd question arises: what would be the gain of testing? As holds true for all tests: how would the test results change your treatment? If you suspect a milk-allergy, you can do the SPT with milk, because if positive, you might change the formula. But as your patient’s symptoms are more respiratory, you probably suspect more a respiratory allergen allergy. This might lead you to SPT with a broad range of aeroallergens, thus a lot of discomfort for the baby. And if the test results in 3 allergens with a wheal or flare: would you start immunotherapy? No. First of all because you cannot make a clear diagnosis of symptoms-on-exposure as the classic symptoms of allergic rhinitis are not fully developed yet, and bronquial hyperreactivity generally has no clear time course at such a young age, related to allergen exposure. Thus, the only conclusion you can draw with a positive test is that the child has sensitivity to certain allergen, but this not necessarily is allergy. Secondly, a positive test result might lead you to recommend certain avoidance measures, e.g. For HDM; however, for any atopic child it would be recommendable to avoid HDM exposure and pollen exposure is unavoidable. Thirdly, a positive SPT and history might lead you to start SLIT, but there is no evidence of SLIT efficacy at such young age, thus this is not indicated. Finally we also have to take into account that the skin in such a young child is still immature and it’s reply is generally still reduced, so there is a fair chance you do not get any positive reaction, even though the child is allergic. This might lead to confusion among the parents who could interpret the results as: good, my child is not allergic.

Conclusion: SPT in a very young toddler might be done with very few (food) allergens, to guide in an elimination diet (but a negative SPT does not exclude food allergy). You might consider to do SPT with aeroallergens from 18 months onward, only in well selected patients with a clear symptoms-on-exposure history and atopic background, to guide avoidance and eventually SLIT, for which there is low-quality evidence it has a benefit from 2 years onward (high quality evidence from 4 years onward)(2).

References

1. Larenas Linnemann, D. E. (2012). "One hundred years of immunotherapy: review of the first landmark studies." Allergy Asthma Proc 33(2): 122-128
2. Larenas-Linnemann, D., et al. (2013). "Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009-2012." Ann Allergy Asthma Immunol 110(6): 402-415 e409.

 

By Prof Awad El-Sayed

First described in 1867 by Dr Charles Blackley, skin tests (prick/puncture and intracutaneous) have evolved as reliable, cost effective techniques for the diagnosis of IgE-mediated diseases.  Skin prick tests are used for clinical confirmation of immediate type hypersensitivity to a broad range of allergens such as inhalants, foods, some drugs and few chemicals.1,2 Skin tests represent the first diagnostic method in patients with a suggestive clinical history of allergic rhinitis (conjunctivitis) and/or asthma.3

A positive skin test result indicates only the presence of allergen specific IgE (i.e. sensitization) and does not necessarily mean the presence of clinical allergy. It is important for this reason that the allergy evaluation be based on the patient's history.4

The objective evidence available in the literature supporting the sensitivity, specificity, and positive and negative predictive values of SPT confirms its clinical utility.5  Using positive nasal provocation challenges as a standard, the sensitivity of prick/puncture tests ranges from 85% to 87%, whereas the specificity of these tests is between 79% and 86%.6 Most of the literature suggests that with a negative skin prick test result, a positive Intradermal (ID) skin test result adds little to the diagnostic evaluation of inhalant allergy. 7 ID skin tests are not useful for allergy diagnosis with inhalant allergens.8 Besides, they are less safe to perform.2

Skin tests can be used from infancy to old age. 2 They may be performed in infants as young as 1 month.1 Although an early study observed a clear and significant hyporeactivity to both histamine and codeine phosphate in infancy, especially before the age of 6 mo 9 , a recent investigation of prick/ puncture tests in infants revealed that they exhibit a high degree of reliability.1 Several investigations reported that African American children with or without asthma were more likely to exhibit positive prick/puncture test results to outdoor aeroallergens than their counterpart white cohorts.1

Special clinical situations and exposures must be considered in selecting skin test reagents, and the number of skin tests.1,4  This should be based on the patient’s age, history, environment and living conditions (eg, region of the country), and should be continuously refined in accord with scientific advances, botanic and aerobiologic surveys, demographic trends, and availability of relevant, defined reagents.1  A GA2LEN study clearly showed that many allergens previously regarded as untypical for some regions in Europe had been underestimated and could partly be related to changes in mobility of patients, vegetation or climate in Europe.10 The scope and number of skin tests for allergy diagnosis reflect the clinician’s scientific knowledge and clinical expertise.1

Although recognizing that the history may be a relatively insensitive predictor of clinical sensitivity in some situations, certain historical features serve as important pretest probability guides to the numerical extent of skin tests. Generally, fewer prick/puncture tests need to be performed in infants and very young children (2 years of age) because these children are not likely to be sensitized to as many allergens as older children and adults. In toddlers, sensitization is more apt to reflect intense and prolonged exposure to allergens encountered earliest in life, such as foods, house dust mites, indoor molds, and animal danders rather than pollen. If inhalation allergy is narrowly confined to a single season (eg, ragweed in North America or birch in European northern countries), a limited number of relevant skin tests would suffice for confirmation of the clinical diagnosis and testing to irrelevant inhalant and food allergens would be inappropriate. By contrast, perennial symptoms would require a more extended skin test panel of both indigenous outdoor and indoor inhalants but not foods unless a history of food allergy happened to be a concurrent problem of the patient. 1

The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, interpretation of the tests after 15 – 20 minutes of application, with a positive result defined as a wheal ≥3 mm diameter.11 In a prospective study, 60% of skin sensitive asymptomatic subjects developed clinical allergy suggesting that a positive prick/puncture test result in an asymptomatic person may predict subsequent clinical allergy.12  It was noticed that infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. 13

Identification of specific allergens to which the patient is sensitive can allow therapy to be directed appropriately. Knowing the sensitivities may guide environmental interventions, such as removing an animal from the environment, or selecting appropriate medications during the season when the specific allergen is present.  This would lead to improvement in patient care.14 Nevertheless, skin prick tests with commercial inhalant extracts may exceptionally induce systemic reactions15, yet life-threatening generalized systemic reactions are rare. Caution must be taken to avoid creating a serious systemic reaction by injecting an injudicious amount of antigen into the skin, or in skin-testing a patient whose medical condition or medication profile puts them at increased risk.13

References

1. Bernstein  I, Li JT, Bernstein D I, Hamilton R, Spector S, Tan R, et al. Allergy Diagnostic Testing: An Updated Practice ParameterI.  Ann Allergy Asthma Immunol 2008;100(3 Suppl 3):S1-148.  

2. Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012; 67: 18–24.   

3. Demoly P, Michel F, Bousquet J. In vivo methods for study of allergy. Skin tests, techniques and interpretation. In: Middleton E, Reed C, Ellis E, Adkinson N, Yunginger J, Busse W, editors. Allergy, Principles and Practice, 5th edn. St Louis (Mo): Mosby Co, 1998:530–9.  

4.  Cox L, Williams B, Sicherer S, Oppenheimer J, Sher L, Hamilton R, et al. American College of Allergy, Asthma and Immunology Test Task Force; American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol 2008;101(6):580-92. 

5Day JH, Briscoe MP. Environmental exposure unit: a system to test anti-allergic treatment. Ann Allergy Asthma Immunol 1999;83(2): 83–9. 

6. Krouse JH, Sadrazodi K, Kerswill K. Sensitivity and specificity of prick and intradermal testing in predicting response to nasal provocation with timothy grass antigen. Otolaryngol Head Neck Surg 2004;131(3):215–9.

7. Calabria CW, Hagan L. The role of intradermal skin testing in inhalant allergy. Ann Allergy Asthma Immunol 2008;101(4):337-47; doi: 10.1016/S1081-1206(10)60307-9.

8. Oppenheimer J, Nelson HS. Skin testing. Ann Allergy Asthma Immunol 2006;96(2 Suppl 1):S6–S12

9. Ménardo JLBousquet JRodière MAstruc JMichel FB. Skin test reactivity in infancy. J Allergy Clin Immunol 1985;75:646–51.

10. Heinzerling LM, Burbach GJ, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, et al.  GA2LEN skin test study I: GA²LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe. Allergy 2009;64:1498–506. doi:10.1111/j.1398-9995.2009.02093.x

11.   Heinzerling L,  Mari A,  Bergmann K,Bresciani M, Burbach G, Darsow U, Durham S. The skin prick test – European standards. Clin Transl Allergy 2013; 3: 3. doi:  10.1186/2045-7022-3-3 , 

12.  Bodtger U, Poulsen LK, Malling HJ. Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults: a 3-year follow-up study. J Allergy Clin Immunol 2003;111(1): 149–54

13.  LeMasters GK, Wilson K, Levin L, Biagini J, Ryan P, Lockey J E. High prevalence of aeroallergen sensitization among infants of atopic parents. J Pediatr 2006; 149(4): 505–11. http://doi.org/10.1016/j.jpeds.2006.06.035

14. Fornadley JA. Skin testing for inhalant allergy  Int Forum Allergy Rhinol 2014;4 Suppl 2:S41-5. doi: 10.1002/alr.21393.

15.  Liccardi G, D’Amato G, Canonica GW, Salzillo A, Piccolo A, Passalacqua G. Systemic reactions from skin testing: literature review. J Investig Allergol Clin Immunol 2006;16:75–8.

Zeinab Away El-Sayed, MD, PhD
Professor of Pediatrics
Pediatric Allergy and Immunology Unite
Children’s Hospital, Ain Shams University
Cairo, Egypt

 

By Prof Solé

Skin prick test (SPT) is an important tool in the evaluation of allergic sensitization and can be influenced by several factors: patient age, body area where the test is performed, medication use, systemic and/or topics, type of device used, the allergen chosen, etc. (1-3).

Although there is no lower age limit for the child to be submitted to the SPT, its interpretation must be made with caution. Previous studies have documented a reduction in skin reactivity to histamine and allergens in neonates and infants (4-6). A pioneer study in children, which evaluated the cutaneous response to histamine (1mg/mL) documented an increase in skin reactivity to histamine with increasing age: the average diameter of the wheal induced was 0.77 mm at 3 months old, and tripled at 24 months old, and values ​​above 3 mm were achieved later (4). These findings were corroborated by other authors (5,6). Furthermore, sensitization to airborne allergens has been identified as low in the first two years of life; however, may be present in a significant number of patients (6,7). Because of the low skin reactivity, especially in young children, some authors have proposed the skin index (ratio of allergen-induced wheal diameter and corresponding histamine diameter, SI) as a parameter to assess the allergic sensitization in these patients, and values ​​greater than 0.6 would be indicative of allergic sensitization (8). However, the use of SI has not been established.

References

1 - Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67(1):18-24.

2 - de Vos G. Skin testing versus serum-specific IgE testing: wich is better for diagnosing aeroallergen sensitization and predicting clinical allergy? Curr Allergy asthma Rep 2014;14:430

3 - Sahiner UM, Buyuktiryaki AB, Yavuz ST, Cavkaytar O, Tuncer A, et al. The spectrum of aeroallergen sensitization in children diagnosed with asthma during first 2 years of life. Allergy Asthma Proc. 2013;34(4):356-61.

4 - Menardo JL, Bousquet J, Rodier M, Astruc J, Michel FB. Skin test reactivity in infancy. J Allergy Clin Immunol 1985;75:646–651.

5 - Skassa-Brociek W, Manderscheid JC, Michel FB, Bousquet J. Skin reactivity to histamine from infancy to old age. J Allergy Clin Immunol 1987;80:711-6.

6 - Halász MR, Gonsales SL, Solé D, Naspitz CK. Specific sensitization to Dermatophagoides pteronyssinus and cutaneous reactivity to histamine in Brazilian children. J Investig Allergol Clin Immunol. 1997;7(2):98-102.

7 - Itikawa A, Mallozi MC, Wandalsen GF, Solé D. Skin reactivity to inhalant allergens in allergic children and adolescents from a specialized outpatient clinic – Value of the skin index. Rev Port Imunoalergol 2014;22(4):257-266

8 - Perackis K, Staden U, Mehl A, Niggemann B. Skin prick test with hen's egg: whole egg or egg white? Allergy. 2004;59(11):1236-7.

Dirceu Solé, MD, PhD
Department of Pediatrics
Escola Paulista de Medicina
Universidade Federal de São Paulo
São Paulo, Brazil

 

By Prof Smith

Allergy testing with skin testing can be done at irrespective of their age1. The youngest case where I have seen a positive SPT response reported was a day one infant who had anaphylaxis after a breast feed (his mother ate peanuts from a gift — Poster at AAAAI in NY 2002). Note that the positive predictive value of the SPT wheal differs children under 2 than over 22,3. The negative predictive value of a food allergy test is less in the very young than it is in child >2 years. Always test and manage in the context of history. Also remember the SPT relies on IgE being made in response to the antigen and this has to be distributed peripherally. Both blood and skin test methods detect antigenic responses at a site distal to where the antigen is generally exposed (gut and airways). As part of the allergic march, inhalant allergies start later that food allergies4. If you suspect dust mite causing inhalant disease test for it, but do so in the context that a negative result may just reflect insufficient IgE being present on mast cells in the skin to reflect disease activity at the mucosal airway surfaces and re-testing is warranted in 6 months time if the patient remains symptomatic if you suspect allergic mechanisms.

1. Eigenmann PA et al ,Testing children for allergies: why, how, who and when An updated statement of the European Academy of Allergy and Clinical Immunology (EAACI) Section on Pediatrics and the EAACI-Clemens von Pirquet Foundation. Pediatric Allergy and Immunology 24 (2013) 195–209

http://onlinelibrary.wiley.com/doi/10.1111/pai.12066/pdf <http://onlinelibrary.wiley.com/doi/10.1111/pai.12066/pdf>

2. Sporik R, Hill DJ, Hosking CS. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy. 2000 Nov;30(11):1540-6.

https://www.ncbi.nlm.nih.gov/pubmed/11069561 <https://www.ncbi.nlm.nih.gov/pubmed/11069561>

3. Hill DJ, Hosking CS, Reyes-Benito LV. Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests. Clin Exp Allergy. 2001 Jul;31(7):1031-5.

https://www.ncbi.nlm.nih.gov/pubmed/11467993 <https://www.ncbi.nlm.nih.gov/pubmed/11467993>

4. http://www.worldallergy.org/professional/allergic_diseases_center/allergic_march/

Pete Smith, BmedSci, MBBS, FRACP, PhD
Professor in Clinical Medicine
Griffith University and Bond University
Queensland, Australia


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