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BSACI Guideline for the Diagnosis and Management of Cow's Milk Allergy

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BSACI Guideline for the Diagnosis and Management of Cow's Milk Allergy doi: 10.1111/cea.12302 Clinical & Experimental Allergy, 44, 642–672 BSACI GUIDELINES © 2014 John Wiley & Sons Ltd BSACI guideline for the diagnosis and management of cow’s milk allergy D. Luyt1, H. Ball1, N. Makwana2, M. R. Green1, K. Bravin1, S. M. Nasser3 and A. T. Clark3 1University Hospitals of Leicester NHS Trust, Leicester, UK, 2Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK and 3Cambridge University Hospital NHS Foundation Trust, Cambridge, UK Summary Clinical This guideline advises on the management of patients with cow’s milk allergy. Cow’s milk & allergy presents in the first year of life with estimated population prevalence between 2% and 3%. The clinical manifestations of cow’s milk allergy are very variable in type and Experimental severity making it the most difficult food allergy to diagnose. A careful age- and disease- specific history with relevant allergy tests including detection of milk-specific IgE (by skin Allergy prick test or serum assay), diagnostic elimination diet, and oral challenge will aid in diag- nosis in most cases. Treatment is advice on cow’s milk avoidance and suitable substitute milks. Cow’s milk allergy often resolves. Reintroduction can be achieved by the graded exposure, either at home or supervised in hospital depending on severity, using a milk ladder. Where cow’s milk allergy persists, novel treatment options may include oral toler- ance induction, although most authors do not currently recommend it for routine clinical practice. Cow’s milk allergy must be distinguished from primary lactose intolerance. This Correspondence: guideline was prepared by the Standards of Care Committee (SOCC) of the British Society Dr Andy T. Clark, Cambridge for Allergy and Clinical Immunology (BSACI) and is intended for clinicians in secondary University Hospitals NHS Foundation and tertiary care. The recommendations are evidence based, but where evidence is lacking Trust, Box 40, Allergy Clinic, Cambridge CB2 0QQ, UK. the panel of experts in the committee reached consensus. Grades of recommendation are E-mail: [email protected] shown throughout. The document encompasses epidemiology, natural history, clinical pre- Cite this as: D. Luyt, H. Ball, N. sentations, diagnosis, and treatment. Makwana, M. R. Green, K. Bravin, S. M. Nasser and A. T. Clark, Clinical & Keywords aetiology, allergy, anaphylaxis, BSACI, desensitization, diagnosis, food, Experimental Allergy, 2014 (44) 642– management, milk, prevalence, SOCC 672. Submitted 16 July 2013; revised 19 February 2014; accepted 26 February 2014 • Cow’s milk allergy is more likely to persist in IgE- Executive summary (Grades of recommendations, see mediated disease and where there is greater sensitiv- [1]) ity (higher specific IgE levels), multiple food allergies • Cow’s milk allergy may be defined as a reproducible and/or concomitant asthma and allergic rhinitis. (B) adverse reaction of an immunological nature • The clinical diagnosis in IgE-mediated disease is induced by cow’s milk protein. (A) made by a combination of typically presenting • Cow’s milk allergy can be classified into IgE-medi- symptoms, for example urticaria and/or angio- ated immediate-onset and non-IgE-mediated oedema with vomiting and/or wheeze, soon after delayed-onset types according to the timing of ingestion of cow’s milk and evidence of sensitization symptoms and organ involvement. (A) (presence of specific IgE). The spectrum of clinical • The prevalence of cow’s milk allergy is between severity ranges from skin symptoms only to life- 1.8% and 7.5% of infants during the first year of threatening anaphylaxis. Clinical assessment should life. (B) include a severity evaluation to ensure affected indi- • Cow’s milk allergy commonly presents in infancy viduals are managed at the appropriate level. (B) with most affected children presenting with symp- • The clinical diagnosis of non-IgE-mediated disease is toms by 6 months of age. Onset is rare after suspected by the development of delayed gastroin- 12 months. (B) testinal or cutaneous symptoms that improve or • Cow’s milk allergy has a favourable prognosis, as most resolve with exclusion and reappear with reintroduc- children will outgrow their allergy by adulthood. (B) tion of cow’s milk. As with IgE-mediated disease, BSACI Milk allergy guideline 643 non-IgE-mediated disease varies widely in clinical can be performed at home or may need to be super- presentation from eczema exacerbations to life- vised in hospital. (D) threatening shock from gastrointestinal fluid loss • Oral tolerance induction offers a novel treatment secondary to inflammation [food protein-induced option to the small but clinically significant propor- enterocolitis syndrome (FPIES)]. (B) tion of affected individuals whose cow’s milk allergy • Gastrointestinal symptoms of non-IgE-mediated persists. (C) cow’s milk allergy are variable and affect the entire • Cow’s milk allergy in adults more commonly arises gastrointestinal tract. There are some well-recognized in adulthood but may persist from childhood. This is more easily identifiable conditions (e.g. eosinophilic frequently a severe form of allergy where up to 25% proctitis), but symptoms are more commonly non- have experienced anaphylaxis. (C) specific. Cow’s milk allergy should be considered in these circumstances where symptoms fail to respond to standard therapy or where other features of Introduction allergy are present. (B) Cow’s milk protein allergy is most prevalent during • Lactose intolerance can be confused with non-IgE- infancy and early childhood when milk forms the greatest mediated cow’s milk allergy as symptoms overlap. proportion of an individual’s food intake. This guideline The terms are thus frequently mistakenly used inter- for the management of patients with cow’s milk allergy changeably. Lactose intolerance should be considered will focus predominantly on this age group, although it where patients present only with typical gastrointes- will encompass older children and adults as cow’s milk tinal symptoms. (B) allergy persists in a small proportion of patients and can • The reported level of IgE required to support a diag- present in this group in its severest form. The guideline, nosis of IgE-mediated cow’s milk allergy varies which was prepared by an expert group of the Standards between studies and depends on the research popula- of Care Committee (SOCC) of the British Society for Allergy tion. A skin prick test (SPT) weal size ≥ 5mm and Clinical Immunology (BSACI) including a lay commen- (≥ 2 mm in younger infants) is strongly predictive of tator, addresses the clinical manifestations and manage- cow’s milk protein allergy. (C) ment of cow’s milk protein allergy with recommendations • A food challenge may be necessary to confirm the for families with milk allergic children. This guidance is diagnosis in IgE-mediated disease where there is intended for use by specialists involved in the investigation conflict between the history and diagnostic tests. (D) and management of individuals with cow’s milk allergy. • Food elimination and reintroduction is recommended Evidence for the recommendations was obtained from for the assessment of non-IgE-mediated cow’s milk literature searches of MEDLINE/PubMed/EMBASE, NICE, allergy where there is diagnostic uncertainty. (C) and the Cochrane library (from 1946 to the cut-off date, • The management of cow’s milk allergy comprises the March 2012) using the following strategy and key avoidance of cow’s milk and cow’s milk products words – (hypersensitivity OR immune-complex disease and dietary substitution with an allergenically and OR atopic dermatitis OR eczema OR eczematous skin nutritionally suitable milk alternative. (D) diseases OR colitis OR irritable bowel syndrome OR • The choice of cow’s milk substitute should take exanthema OR enteritis OR rash OR oesophagitis OR into account the age of the child, the severity of allergy OR skin prick test OR anaphylaxis OR contrain- the allergy, and the nutritional composition of the dications OR IgE mediated adverse reactions) AND (milk substitute. Nutritionally incomplete substitutes can OR caseins OR lactalbumin OR lactose OR lactic acid OR lead to faltering growth and specific nutritional dairy). The experts’ knowledge of the literature and deficiencies. (D) hand searches as well as papers suggested by experts • As cow’s milk is the major source of calcium in consulted during the development stage were also used infant diets, children on milk exclusion diets are at [2]. Where evidence was lacking, a consensus was risk of a deficient calcium intake. A dietitian should reached amongst the experts on the committee. The assess calcium intake and dietary or pharmaceutical strength of the evidence was assessed by at least 2 supplementation advised where appropriate. (D) experts and documented in evidence tables using the • Cow’s milk allergy will resolve in the majority of grading of recommendations as in a previous BSACI children. Individuals should be reassessed at 6–12 guideline [1], see Box 1. Conflict of interests were monthly intervals from 12 months of age to assess recorded by the BSACI. None jeopardized unbiased for suitability of reintroduction. (B) guideline development. During the development of the • The reintroduction of cow’s milk may be graded guidelines, all BSACI members were consulted using a according to the ‘milk ladder’ with less allergenic web-based system and their comments carefully consid- forms offered initially. More allergenic forms are ered by the SOCC. then eaten sequentially as tolerated. Reintroduction © 2014 John Wiley & Sons Ltd, Clinical & Experimental Allergy, 44 : 642–672 644 D. Luyt et al Box 1. Grades of recommendations [3, 4] and/or eczema. These usually present several hours, and up – Grade of 72 h, after ingestion of larger volumes of milk [5, 7 10]. recommendation Type of evidence Cow’s milk is largely ingested uncooked, but almost all commercially available cow’s milk in the UK is pas- A At least one meta-analysis, systematic review, teurized. Pasteurization involves heating cow’s milk, or RCT rated as 1++, and directly applicable to the target population; but this does not significantly alter its allergenicity.
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