INTRODUCTION
Cow’s milk allergy (CMA) is a significant public health issue worldwide. It is defined as a reproducible adverse reaction to one or more cow’s milk proteins, typically casein or serum beta-lactoglobulin, and is the most common allergen in early life[1]. Epidemiological data indicate that the prevalence of CMA in infants and young children in developed countries ranges from 0.5% to 3%, however, the prevalence of the condition in adults is extremely rare, at around 0.5%, with some regional variations[2]. Milk allergies can be classified into three types based on the immune mechanisms: Ige-mediated, non-Ige-mediated, and a combination of both. This can result in a range of symptoms, including urticaria, angioedema, gastrointestinal symptoms (such as abdominal pain, vomiting, and diarrhea, respiratory symptoms (such as dyspnea, coughing, and wheezing), and cardiovascular symptoms (such as dizziness, confusion, and hypotension). Patients with CMA often experience a severely impacted quality of life, leading to malnutrition, feeding difficulties, as well as the risk of accidental exposure resulting in fatal anaphylactic reactions[3-5].
An accurate diagnosis of milk allergy is critical to managing and preventing severe allergic reactions and preventing unnecessary dietary restrictions[6]. The diagnosis of cow’s milk allergy is confirmed by allergy history, skin prick test (SPT), specific immunoglobulin E (sIgE), atopy patch test (APT), and oral food challenges (OFC), however, SPT and sIgE have low sensitivity and specificity[7], APT is rarely used in the clinic. Although the double-blind oral food challenges (DBOFC) is the gold standard for diagnosis, its limitations have become more apparent over time; this technique is difficult to perform, time-consuming, costly, and may cause severe allergic reactions[8]. In addition, OFC results do not predict the severity of subsequent reactions[9], and there is no direct correlation between the triggering thresholds experienced by patients during OFC and the severity of reactions following accidental exposure[10].
In light of the limitations of traditional methods for diagnosing milk allergy, Component Resolved Diagnostics (CRD) has emerged as a valuable tool in allergology research for measuring specific IgE antibodies over the past decade[11]. This method involves the IgE using a small amount of serum from capillaries, allowing for the identification of the main sensitizing components of milk[12]. The three most significant allergens in milk are casein (Bos d 8), b-lactoglobulin (Bos d 5), and a-lactoglobulin (Bos d 4), with sensitization to other minor proteins, such as bovine serum albumin (Bos d 6), also being reported[13], CRD can distinguish between sensitization due to co-sensitization and cross-reactivity, helping to rule out allergy[12-14]. As CRD technology improves, it can be used not only to assess the risk, severity, persistence, and prognosis of clinical reactions[15], but also to identify those patients who would benefit from it[16, 17], and provide more effective and safer allergy immunotherapy regimens for patients[18]. However, the diagnostic accuracy of the identified components has varied in different studies, so the diagnostic value and clinical application of CRD for milk allergy remain unclear.
Although our previous systematic review evaluated the diagnostic accuracy of various food allergy tests, there have been limited studies on CRD. To our knowledge, only a few studies have addressed the diagnostic test accuracy (DTA) review for CRD, with a primary focus on peanut, hazelnut, and nut allergy diagnosis[19-21]. There is only one systematic review that evaluates the diagnostic accuracy of CRD for milk allergy, but it only includes two studies[22]. With the increasing number of studies on CRD in milk allergy, there is a need for a more comprehensive review of the evidence regarding the diagnostic accuracy of CRD in milk allergy, which would help to reduce overdiagnosis and provide evidence for the necessity of OFC during the final diagnosis. Therefore, we conducted a systematic review to determine the accuracy of CRDs for the diagnosis of milk allergy.