European Journal of Pediatrics

, Volume 172, Issue 3, pp 385–391 | Cite as

Towards better triage of infants suspected of cow's milk allergy: development of a preliminary multivariable diagnostic index

  • Anders van Thuijl
  • Anne-Fleur Schoemaker
  • Stef Menting
  • Jennifer van Dulmen
  • Janne Boeting
  • Wim van Aalderen
  • Gerben ter Riet
  • Aline Sprikkelman
Original Article

Abstract

The double-blind placebo-controlled food challenge (DBPCFC) is currently the gold standard to diagnose cow's milk allergy (CMA). However, DBPCFCs are burdensome, expensive and require specialised facilities. For primary care physicians, selective and consistent referral to DBPCFC of infants suspected of CMA may be difficult. The objective of this study was to assess the predictive value of clinical parameters for a positive DBPCFC in infants suspected of CMA. Clinical data from 124 infants suspected of CMA that had undergone a DBPCFC were collected. Out of a total of 23 parameters, nine candidate predictors were selected on clinical grounds. We used bootstrapped logistic regression analysis to find a more parsimonious and practical model. The prevalence of a positive DBPCFC was 34.7 % (95 % CI from 27 to 43). A well-calibrated diagnostic model containing as predictors abdominal cramps, inconsolable crying and the objective SCORAD index discriminated moderately well between infants with and without a positive DBPCFC. The area under the ROC curve was 0.68 (95 % CI from 0.58 to 0.78). The fifth and 95th percentiles of the positive DBPCFC predictive probability distribution were 17 and 73 % (17 and 59 % after correction for over-optimism). We conclude that a diagnostic model with three clinical parameters may be used for better referral of children suspected of CMA and the decision to either initially perform an open food challenge or directly perform a DBPCFC. Large prospective studies are needed to validate these findings and provide additional precision.

Keywords

Cow's milk allergy Infants Diagnosis Logistic regression Retrospective cohort study 

Abbreviations

BIF

Bootstrap inclusion fraction

CMA

Cow's milk allergy

CMP

Cow's milk protein

DBPCFC

Double-blind placebo-controlled food challenge

SCORAD

SCORing atopic dermatitis

IQR

Interquartile range

References

  1. 1.
    Bock SA, Atkins FM (1990) Patterns of food hypersensitivity during sixteen years of double-blind, placebo-controlled food challenges. J Pediatr 117:561–567PubMedCrossRefGoogle Scholar
  2. 2.
    Brouwer ML, Wolt-Plompen SA, Dubois AE, van der Heide S, Jansen DF, Hoijer MA, Kauffman HF, Duiverman EJ (2006) No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Clin Exp Allergy 36:899–906PubMedCrossRefGoogle Scholar
  3. 3.
    Celik-Bilgili S, Mehl A, Verstege A, Staden U, Nocon M, Beyer K, Niggemann B (2005) The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy 35:268–273PubMedCrossRefGoogle Scholar
  4. 4.
    Eigenmann PA, Calza AM (2000) Diagnosis of IgE-mediated food allergy among Swiss children with atopic dermatitis. Pediatr Allergy Immunol 11:95–100PubMedCrossRefGoogle Scholar
  5. 5.
    Flinterman AE, Knulst AC, Meijer Y, Bruijnzeel-Koomen CA, Pasmans SG (2006) Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets. Allergy 61:370–374PubMedCrossRefGoogle Scholar
  6. 6.
    Flokstra-de Blok BM, Dubois AE, Vlieg-Boerstra BJ, Oude Elberink JN, Raat H, Dunngalvin A, Hourihane JO, Duiverman EJ (2010) Health-related quality of life of food allergic patients: comparison with the general population and other diseases. Allergy 65(2):238–244PubMedCrossRefGoogle Scholar
  7. 7.
    Hanifin JM, Rajka G (1980) Diagnostic features of atopic dermatitis. Act Derm Venereol Suppl (Stockh) 92:44–47Google Scholar
  8. 8.
    Keil T, McBride D, Grimshaw K, Niggemann B, Xepapadaki P, Zannikos K, Sigurdardottir ST, Clausen M, Reche M, Pascual C, Stanczyk AP, Kowalski ML, Dubakiene R, Drasutiene G, Roberts G, Schoemaker AF, Sprikkelman AB, Fiocchi A, Martelli A, Dufour S, Hourihane J, Kulig M, Wjst M, Yazdanbakhsh M, Szepfalusi Z, Van Ree RR, Willich SN, Wahn U, Mills EN, Beyer K (2010) The multinational birth cohort of EuroPrevall: background, aims and methods. Allergy 65(4):482–490PubMedCrossRefGoogle Scholar
  9. 9.
    Mills EN, Mackie AR, Burney P, Beyer K, Frewer L, Madsen C, Botjes E, Crevel RW, van Ree RR (2007) The prevalence, cost and basis of food allergy across Europe. Allergy 62:717–722PubMedCrossRefGoogle Scholar
  10. 10.
    Niggemann B, Reibel S, Roehr CC, Felger D, Ziegert M, Sommerfeld C, Wahn U (2001) Predictors of positive food challenge outcome in non-IgE-mediated reactions to food in children with atopic dermatitis. J Allergy Clin Immunol 108:1053–1058PubMedCrossRefGoogle Scholar
  11. 11.
    Novembre E, Vierucci A (2001) Milk allergy/intolerance and atopic dermatitis in infancy and childhood. Allergy 56(Suppl 67):105–108PubMedCrossRefGoogle Scholar
  12. 12.
    Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB (2007) Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol 157:645–648PubMedCrossRefGoogle Scholar
  13. 13.
    Royston P, Sauerbrei W (2008) Multivariable model-building: a pragmatic approach to regression analysis based on fractional polynomials for modelling continuous variables. Wiley Series in Probability and Statistics. Wiley, ChichesterGoogle Scholar
  14. 14.
    Royston P, Sauerbrei W (2003) Stability of multivariable fractional polynomial models with selection of variables and transformations: a bootstrap investigation. Stat Med 22:639–659PubMedCrossRefGoogle Scholar
  15. 15.
    Sampson HA, McCaskill CC (1985) Food hypersensitivity and atopic dermatitis: evaluation of 113 patients. J Pediatr 107:669–675PubMedCrossRefGoogle Scholar
  16. 16.
    Schouten B, van Esch BC, van Thuijl AO, Blokhuis BR, Groot KT, Hofman GA, Moro GE, Boehm G, Arslanoglu S, Sprikkelman AB, Willemsen LE, Knippels LM, Redegeld FA, Garssen J (2010) Contribution of IgE and immunoglobulin free light chain in the allergic reaction to cow's milk proteins. J Allergy Clin Immunol 125:1308–1314PubMedCrossRefGoogle Scholar
  17. 17.
    Schumacher M, Hollander N, Sauerbrei W (1997) Resampling and cross-validation techniques: a tool to reduce bias caused by model building? Stat Med 16:2813–2827PubMedCrossRefGoogle Scholar
  18. 18.
    (1993) Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European Task Force on Atopic Dermatitis. Dermatology 186:23–31Google Scholar
  19. 19.
    Skripak JM, Matsui EC, Mudd K, Wood RA (2007) The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 120:1172–1177PubMedCrossRefGoogle Scholar
  20. 20.
    Sprikkelman AB, Heymans HS, van Aalderen WM (2000) Development of allergic disorders in children with cow's milk protein allergy or intolerance in infancy. Clin Exp Allergy 30:1358–1363PubMedCrossRefGoogle Scholar
  21. 21.
    Verstege A, Mehl A, Rolinck-Werninghaus C, Staden U, Nocon M, Beyer K, Niggemann B (2005) The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin Exp Allergy 35:1220–1226PubMedCrossRefGoogle Scholar
  22. 22.
    Vlieg-Boerstra BJ, van der Heide S, Bijleveld CM, Kukler J, Duiverman EJ, Dubois AE (2007) Placebo reactions in double-blind, placebo-controlled food challenges in children. Allergy 62:905–912PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Anders van Thuijl
    • 1
  • Anne-Fleur Schoemaker
    • 1
  • Stef Menting
    • 1
  • Jennifer van Dulmen
    • 1
  • Janne Boeting
    • 1
  • Wim van Aalderen
    • 1
  • Gerben ter Riet
    • 2
  • Aline Sprikkelman
    • 1
  1. 1.Department of Paediatric Respiratory Medicine and AllergyEmma Children’s HospitalAmsterdamThe Netherlands
  2. 2.Department of General Practice, Division of Clinical Methods and Public Health, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations