Cow's milk allergy in an adult patient

A 22-year-old female patient is described who was repeatedly hospitalised on account of severe asthmatic attacks presumably due to the ingestion of cow's milk or milk-containing products. There were no signs of gastrointestinal disturbance, but some urticaria and angioedema occurred. Strongly positive RASTs were observed in the blood serum against the proteins in cow's milk, bovine serum, egg white, cod fish, and house dust. The symptoms were successfully controlled by rigorous dietary measures.     

Cow's milk allergy in infancy

Cow's milk allergy affects approximately 2% of infants under 2 years of age. This review summarizes the recent advances in understanding its pathophysiology and immunological mechanisms. Apart from IgE-mediated atopic manifestations, T cell-mediated reactions have been demonstrated in infants with cow's milk allergy. The clinical spectrum ranges from immediate-type reactions, presenting with urticaria and angioedema to intermediate and late-onset reactions, including atopic dermatitis, infantile colic, gastro-oesophageal reflux, oesophagitis, infantile proctocolitis, food-associated enterocolitis and constipation. The exact mechanisms of these disorders are still poorly understood. Double-blind, placebo controlled food challenge, the definitive diagnostic test for cow's milk allergy, is increasingly being replaced by the measurement of food-specific antibodies, in combination with skin-prick or atopy patch testing. The treatment of cow's milk allergy relies on allergen avoidance and hypoallergenic formulae, or maternal elimination diets in breast-fed infants.     

Cow's milk allergy as a predictor of bronchial hyperresponsiveness and airway inflammation at school age

Background Cow's milk allergy (CMA) has been found to be associated with an increased incidence of asthma at school age. However, prospective population‐based studies of CMA and the development of airway inflammation and bronchial hyperresponsivess (BHR) are lacking. Objective The aims of this study was to evaluate CMA as a risk factor for BHR and airway inflammation presented later in childhood. Methods We followed prospectively 118 children with CMA and invited them to a clinical visit at a mean age of 8.6 years including the measurement of exhaled nitric oxide (FE_NO) and bronchial challenge with histamine. Ninety‐four patients and 80 control subjects from the same cohort participated. Results At school age, children with a history of CMA had higher FE_NO levels (P=0.0009) and more pronounced responsiveness to histamine (P=0.027) than their controls. Stratified analysis showed a significant difference only in IgE‐positive CMA. Multinomial logistic regression analysis showed that IgE‐positive CMA [odds ratio (OR) 3.51; 95% confidence intervals (CI) 1.56–7.90; P=0.002] and a history of wheeze during the first year of life (OR 2.81; 95% CI 1.16–6.84; P=0.023) were independent explanatory factors for increased FE_NO, and IgE‐positive CMA (OR 3.37; 95% CI 1.03–10.97; P=0.044) and parental smoking (OR 3.41; 95% CI 1.14–10.22; P=0.028) for increased BHR, whereas for IgE‐negative CMA, no associations with FE_NO or BHR were found. In the CMA group, those exposed to CM very early at the maternity hospital, had less BHR (P=0.002). Conclusions Compared with their controls, children with a history of IgE‐positive CMA show signs of airway inflammation, expressed as higher FE_NO, and more pronounced bronchial responsiveness to histamine at school age. In contrast to IgE‐negative CMA, IgE‐positive CMA is a significant predictor of increased FE_NO and BHR at school age. Very early exposure to CM was associated with less BHR. Cite this as: L. P. Malmberg, K. M. Saarinen, A. S. Pelkonen, E. Savilahti and M. J. Mäkelä, Clinical & Experimental Allergy, 2010 (40) 1491–1497.     

Cow's milk allergy and eczema: patterns of the antibody response to cow's milk in allergic skin disease

The pattern of the humoral-immune response to cow's milk was examined in children with eczema and in children who had acute urticarial and/or angioedematous reactions to cow's milk. Each patient group was compared to a group of age-matched controls. Whereas the eczematous patients had significantly elevated IgG, IgA and IgE milk-antibodies, patients, allergic to cow's milk, had elevated IgE milk-antibodies. These differences in the pattern of antibody response to cow's milk suggests that these two patient groups constitute separate allergic populations, and that different pathogenic mechanisms may be operative in these two skin diseases associated with elevated levels of IgE antibodies to cow's milk.     

Cross-reactivity between raw mushroom and molds in a patient with oral allergy syndrome.

BACKGROUND: Oral allergy syndrome, resulting from a cross-reactivity between raw fruits and vegetables and a number of pollens, is well described. However, it has never been associated with mold spore sensitivity and mushrooms. We evaluated a patient with oral allergy symptoms to raw, but not cooked, mushrooms, who also had positive skin testing to molds. OBJECTIVE: To identify and characterize antigenic cross-reactivity between mushroom and mold spores. METHODS: The patient underwent skin prick testing to molds and mushroom. Proteins from raw and cooked mushrooms were extracted and immunoblot/inhibition assays were performed to evaluate for cross-reacting immunoglobulin E antibodies between mushroom and mold extracts to which the patient was sensitive. RESULTS: The patient had a positive skin prick test result to raw mushroom and four types of molds. The immunoblot assay revealed immunoglobulin E antibodies directed against similar molecular weight proteins in the raw mushroom and 3 of the 4 molds: Alternaria tenuis, Fusarium vasinfectum, and Hormodendrum cladosporioides. These protein bands on protein electrophoresis were absent in the cooked mushrooms. Inhibition immunoblot of the raw mushroom with the three molds indicated total inhibition of the 43- and 67-kD protein bands. CONCLUSIONS: We report the first case of cross-reactivity between mushroom and molds in a patient with oral allergy syndrome to raw mushroom and allergic rhinitis secondary to molds.     

Cytokine and chemokine dysregulation in hyper-IgE syndrome.

Hyper-IgE syndrome is characterized by severe recurrent staphylococcal infections, eczema, bone abnormalities, and markedly elevated levels of immunoglobulin E (IgE). The genetic basis is not known and the central immunologic defect is largely undefined. Reduced neutrophil chemotaxis is often described, and variable T cell defects have been demonstrated in some patients. It has been hypothesized that hyper-IgE is associated with a Th1/Th2 imbalance. We wished to characterize cytokine and chemokine imbalances that might reflect the underlying disease process or reflect ongoing pathologic processes. Nine patients with hyper-IgE syndrome and six controls were studied. Radioimmunoassays, flow cytometry, and gene array analyses were performed to characterize cytokine and chemokine production. Hyper-IgE patients express more IL-12, while ENA-78, MCP-3, and eotaxin are markedly underexpressed. Underexpression of a set of chemokines could explain a number of features of hyper-IgE syndrome and may offer a new paradigm for the understanding of this disorder.     

Cow's milk allergy in breast-fed infants: the role of allergen and maternal secretory IgA antibody

The protective effect of breast-feeding in allergy prophylaxis remains controversial despite many epidemiologic studies. One reason for confusion could be heterogeneity of breast milk with regard to its protective capacity. To clarify this issue, we studied 57 mother-infant pairs where breast-feeding was the sole source of infant nutrition. Family history and infant symptom scores suggestive of allergic disease were noted. The presence and quantity in breast milk of a prominent food allergen (beta-lactoglobulin), total IgA, and IgA antibodies to whole cow's milk and casein were measured serially. Eleven infants had symptom scores highly suggestive of allergic disease. The breast milk from mothers of these 11 infants was found to have lower total IgA (p less than 0.01) and IgA antibodies to both whole cow's milk and casein (p less than 0.001 and p less than 0.005, respectively) than milk from mothers whose infants had few or no symptoms. Beta-lactoglobulin was detectable in 45% of breast-milk specimens at concentrations up to 6.4 ng/ml and persisted up to 3 days after maternal dietary milk exclusion but was unrelated to antibody levels or symptom scores. Inadequate quantities of maternal IgA antibodies to food allergens appear to play a permissive role in development of infantile allergic disease in breast-fed infants and are more closely associated with symptoms than parental atopic history.     

Cow's milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE

BACKGROUND: The objective of the present study was to evaluate the relevance of skin tests and the concentration of cow's milk-specific IgE antibodies in correlation with oral cow's milk challenge in infants with suspected cow's milk allergy. METHODS: The study material comprised 143 infants under the age of 2 years who had undergone a diagnostic elimination challenge because of suspected cow's milk allergy in 1996. Cow's milk-specific IgE was measured, and skin prick and patch tests were performed. RESULTS: Of the 143 oral cow's milk challenges performed, 72 (50%) were positive. Of the positive reactions, 22 involved immediate-type reactions. In 50 patients, delayed-onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge-proven cow's milk allergy, 26% showed elevated IgE concentrations to cow's milk, 14% had a positive skin prick test, and 44% had a positive patch test for cow's milk. Interestingly, in most patch test-positive patients, the prick test for cow's milk was negative. CONCLUSIONS: Our study demonstrated that many patients with a negative prick test result had a positive patch test to cow's milk. The patch test was a more sensitive method than the prick test or RAST to detect cow's milk allergy in this study population. Our results indicate that patch testing will significantly increase the probability of early detection of cow's milk allergy. Confirmation of the diagnosis is essential in patients with negative test results but a clinical suspicion of food allergy, and in patch test-positive patients. For this purpose, the most reliable method is the elimination-challenge procedure.