Predictive value ofMP4 (Milk Prick Four), a panel of skin prick test for the diagnosis of pediatric immediate cow's milk allergy.

Background. Oral food challenge (OFC) is the gold standard for the diagnosis of food allergy (FA), but it is risky, expensive and time-consuming. Many studies aimed to avoid OFC by finding a cut off (CO) of skin prick test (SPT) to predict a positive outcome of OFC. Unfortunately the results of these studies are poorly reproducible for various reasons, including the absence of known protein concentration in the extracts. It has also been documented that some doctors mistakenly attributed some symptom/disease, for example recurrent respiratory infections of the upper airways, to the FA, expecially cow milk allergy (CMA). These doctors often performed SPT in their studies to confirm, if the result was positive, their diagnostic suspicion and prescribe an elimination diet without seeking the advice of allergy specialist (AS) and without making an OFC. Objective. To test the diagnostic performances of SPT with fresh cow's milk and commercial extracts of casein, beta-lactoglobulin, alpha-lactoalbumin at known protein concentrations (Milk Prick Four [MP4] test). To look for 2 clusters of SPT CO with positive predictive value (PPV) > 95%, one for AS, one for general practitioner (GP). Methods. A prospective study was carried out on 191 children referred by their GP to the allergy center for suspected immediate-type CMA (iCMA). Based on the history, the allergist has divided the children into two groups: a) group A, children with suspected (subgroup A1, 55 children) or known (subgroup A2, 27 children) diagnosis of iCMA; b) group B, 109 children with a clinical history incompatible with iCMA suspicion according to the AS (in this case the GP was wrong to send those patients to the allergy center). SPT with MP4 test was performed on all patients, and OFC was performed on all patients of group A. CO with PPV > 95% was calculated separately for the entire population of 191 children (CO for GP) and for the only group A (CO for AS). Results. Fresh cow's milk SPT was the most sensitive single prick test (sensitivity [SE] 94%, negative predictive value [NPV] 98%). The positivity to any of 3 SPT extracts (performed at the same time) had the same SE and NPV of the single fresh cow's milk SPT. Moreover, fresh cow's milk SPT or any of 3 SPT extract had 100% SE and 100% NPV, having excluded 2 children with Food Protein Induced Enterocolitis Syndorme from data analysis. MP4 CO for GP allow a total savings of 4% of OFC, a percentage that rises to 22% in the subgroup A2, and does not give false positives. MP4 CO for AS allow a total saving of 33% of OFC, rising to 67% in the subgroup A2, but they give a 7/82 false positives in group A. SPT CO of alpha-lactoalbumin had the best performance in both settings. Conclusion. MP4 is a safe and cheap test, easy to perform. All doctors may be confident in excluding iCMA if fresh cow's milk SPT is negative. GP could perform SPT to fresh milk at his own clinic, and safely diagnose iCMA by using our CO for GP, although this may happen only in a few cases. MP4 test performed by AS can help save a greater number of OFC, especially among children with known diagnosis of iCMA.

Mononuclear cell reactivity to food allergens in neonates, children and adults.

A model of antigen-specific T-cell proliferative responses based on reciprocal patterns of responses to dietary and inhalant allergens has been suggested, the former being frequent in infancy but rare in adults, whereas the latter are preserved and expand between infancy and adulthood. We have evaluated the age-related variations of mononuclear cell reactivity to food allergens. The cord blood mononuclear cells (CBMC) of 30 neonates without family history of atopy and the peripheral blood mononuclear cells (PBMC) of 20 healthy children and of 40 healthy adults were stimulated in vitro with beta-lactoglobulin (BLG) or ovalbumin (OVA) and the cultures were harvested after 7 days. Neonates, children and adults were compared for the percentages of positive responses and for the magnitude of response. Adult subjects showed significantly lower percentages of positive responses and reduced magnitude of response than those observed in neonates and children either in BLG or in OVA cultures. We have not observed a decrease of food allergen mononuclear cell reactivity between neonates and children for the frequency of positive responses. The magnitude of response of neonates was significantly lower than that of children in BLG cultures. Our results seem to confirm the loss of mononuclear cell reactivity to food allergens in adult age. However, other reports show conflicting data. We suggest that a rigorous standardization of the methodological steps of in vitro mononuclear cell stimulation with allergen is necessary.

Immunodeficiency and plasma zinc levels in children with Down's syndrome: a long-term follow-up of oral zinc supplementation.

To evaluate the possible effect of zinc treatment on immune disorders in children with Down's syndrome (DS), 38 noninstitutionalized DS children were investigated. Twenty-four patients (63.2%) had plasmatic zinc levels lower than 0.70 microgram/dl ("hypozinkemic," LZn) and 14 patients (36.8%) had levels higher than 0.75 microgram/dl ("normozinkemic," NZn). No correlation was found between the zinc deficiency and recurrence and/or intensity of infections. The absolute numbers of peripheral lymphocytes, the percentages of B lymphocytes, total T cells, and serum IgG, IgA, and IgM levels did not differ between the DS children and the controls. Eight (21%) patients had CD4+ T cell counts below the lowest value for the controls. Seventeen (44%) DS patients had increased levels of CD8+ T cells. The mean percentage of Leu 7+ cells in DS subjects (22.8 +/- 12.9%) was significantly higher than that in controls (15.8 +/- 4.8%) (P less than 0.01). Notably, Ig levels and numbers of lymphocytes in each subset did not show any significant difference in NZn and LZn trisomic subjects. On the contrary the peripheral blood mononuclear cells (PBMCs) from LZn DS children showed a significantly lower proliferative response to phytohemagglutinin (PHA) (S.I. = 23.4 +/- 22.4) than that of PBMCs from NZn DS children (S.I. = 46.1 +/- 21.5, P less than 0.01). A significant increase in DNA synthesis was obtained after oral administration of zinc sulfate (20 mg/kg/day, for 2 months). The lymphocyte response to PHA appeared to be normal in all patients up to 6 months after the end of the zinc treatment and it became low in half of the patients 22 months after therapy.

Effective high-dose intravenous gammaglobulin therapy for passive immune thrombocytopenia in the neonate.

The second child of a mother with idiopathic thrombocytopenic purpura was given 400 mg/kg per day polyethylenglycol-treated gammaglobulins during the first 5 days of life. Thrombocytes increased from 15 X 10(9)/l to 200 X 10(9)/l within 10 days and remained at this level afterwards.